66 results on '"Jiankang Li"'
Search Results
2. Multi-stage metabolomics and genetic analyses identified metabolite biomarkers of metabolic syndrome and their genetic determinants
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Qiong Wu, Jiankang Li, Xiaohui Sun, Di He, Zongxue Cheng, Jun Li, Xuhui Zhang, Yongming Xie, Yimin Zhu, and Maode Lai
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Metabolic syndrome ,Metabolomics ,mGWAS ,Biomarkers ,Zhejiang Metabolic Syndrome Cohort ,Medicine ,Medicine (General) ,R5-920 - Abstract
Background: Metabolic syndrome (MetS) is a cluster of multiple cardiometabolic risk factors that increase the risk of type 2 diabetes and cardiovascular diseases. Identifying novel biomarkers of MetS and their genetic associations could provide insights into the mechanisms of cardiometabolic diseases. Methods: Potential MetS-associated metabolites were screened and internally validated by untargeted metabolomics analyses among 693 patients with MetS and 705 controls. External validation was conducted using two well-established targeted metabolomic methods among 149 patients with MetS and 253 controls. The genetic associations of metabolites were determined by linear regression using our previous genome-wide SNP data. Causal relationships were assessed using a one-sample Mendelian Randomization (MR) approach. Findings: Nine metabolites were ultimately found to be associated with MetS or its components. Five metabolites, including LysoPC(14:0), LysoPC(15:0), propionyl carnitine, phenylalanine, and docosapentaenoic acid (DPA) were selected to construct a metabolite risk score (MRS), which was found to have a dose-response relationship with MetS and metabolic abnormalities. Moreover, MRS displayed a good ability to differentiate MetS and metabolic abnormalities. Three SNPs (rs11635491, rs7067822, and rs1952458) were associated with LysoPC(15:0). Two SNPs, rs1952458 and rs11635491 were found to be marginally correlated with several MetS components. MR analyses showed that a higher LysoPC(15:0) level was causally associated with the risk of overweight/obesity, dyslipidaemia, high uric acid, high insulin and high HOMA-IR. Interpretation: We identified five metabolite biomarkers of MetS and three SNPs associated with LysoPC(15:0). MR analyses revealed that abnormal LysoPC metabolism may be causally linked the metabolic risk. Funding: This work was supported by grants from the National Key Research and Development Program of China (2017YFC0907004).
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- 2021
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3. Application of Whole Exome Sequencing in Six Families with an Initial Diagnosis of Autosomal Dominant Retinitis Pigmentosa: Lessons Learned.
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Berta Almoguera, Jiankang Li, Patricia Fernandez-San Jose, Yichuan Liu, Michael March, Renata Pellegrino, Ryan Golhar, Marta Corton, Fiona Blanco-Kelly, Maria Isabel López-Molina, Blanca García-Sandoval, Yiran Guo, Lifeng Tian, Xuanzhu Liu, Liping Guan, Jianguo Zhang, Brendan Keating, Xun Xu, Hakon Hakonarson, and Carmen Ayuso
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Medicine ,Science - Abstract
This study aimed to identify the genetics underlying dominant forms of inherited retinal dystrophies using whole exome sequencing (WES) in six families extensively screened for known mutations or genes. Thirty-eight individuals were subjected to WES. Causative variants were searched among single nucleotide variants (SNVs) and insertion/deletion variants (indels) and whenever no potential candidate emerged, copy number variant (CNV) analysis was performed. Variants or regions harboring a candidate variant were prioritized and segregation of the variant with the disease was further assessed using Sanger sequencing in case of SNVs and indels, and quantitative PCR (qPCR) for CNVs. SNV and indel analysis led to the identification of a previously reported mutation in PRPH2. Two additional mutations linked to different forms of retinal dystrophies were identified in two families: a known frameshift deletion in RPGR, a gene responsible for X-linked retinitis pigmentosa and p.Ser163Arg in C1QTNF5 associated with Late-Onset Retinal Degeneration. A novel heterozygous deletion spanning the entire region of PRPF31 was also identified in the affected members of a fourth family, which was confirmed with qPCR. This study allowed the identification of the genetic cause of the retinal dystrophy and the establishment of a correct diagnosis in four families, including a large heterozygous deletion in PRPF31, typically considered one of the pitfalls of this method. Since all findings in this study are restricted to known genes, we propose that targeted sequencing using gene-panel is an optimal first approach for the genetic screening and that once known genetic causes are ruled out, WES might be used to uncover new genes involved in inherited retinal dystrophies.
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- 2015
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4. Safety of high-carbohydrate fluid diet 2 h versus overnight fasting before non-emergency endoscopic retrograde cholangiopancreatography: A single-blind, multicenter, randomized controlled trial
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Wenbo Meng, Joseph W. Leung, Zhenyu Wang, Qiyong Li, Leida Zhang, Kai Zhang, Xuefeng Wang, Meng Wang, Qi Wang, Yingmei Shao, Jijun Zhang, Ping Yue, Lei Zhang, Kexiang Zhu, Xiaoliang Zhu, Hui Zhang, Senlin Hou, Kailin Cai, Hao Sun, Ping Xue, Wei Liu, Haiping Wang, Li Zhang, Songming Ding, Zhiqing Yang, Ming Zhang, Hao Weng, Qingyuan Wu, Bendong Chen, Tiemin Jiang, Yingkai Wang, Lichao Zhang, Ke Wu, Xue Yang, Zilong Wen, Chun Liu, Long Miao, Zhengfeng Wang, Jiajia Li, Xiaowen Yan, Fangzhao Wang, Lingen Zhang, Mingzhen Bai, Ningning Mi, Xianzhuo Zhang, Wence Zhou, Jinqiu Yuan, Azumi Suzuki, Kiyohito Tanaka, Jiankang Liu, Ula Nur, Elisabete Weiderpass, Xun Li, Ting Gao, and Xiuyuan Hao
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Medicine - Abstract
Abstract. Background:. Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients' recovery. Methods:. This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group (n = 665) and fasting group (n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results:. The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P
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- 2024
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5. Aloe vera: A Medicinal Plant Used in Skin Wound Healing
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Jingan Li, Kun Zhang, Jiankang Li, Shuaimeng Guan, Longlong Cui, and Jiaheng Liang
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integumentary system ,biology ,Traditional medicine ,Skin wound ,Skin Injury ,business.industry ,0206 medical engineering ,Biomedical Engineering ,Bioengineering ,02 engineering and technology ,021001 nanoscience & nanotechnology ,biology.organism_classification ,020601 biomedical engineering ,Biochemistry ,Aloe vera ,Biomaterials ,hemic and lymphatic diseases ,Wound dressing ,Medicine ,0210 nano-technology ,business ,Wound healing - Abstract
Skin injury is a major problem threatening human physical and mental health, and how to promote wound healing has been the focus. Developing new wound dressings is an important strategy in skin regeneration. Aloe vera is a medicinal plant with a long history, complex constituents, and various pharmacological activities. Many studies have shown that A. vera plays an important role in promoting wound healing. Adding A. vera to wound dressing has become an ideal way. This review will describe the process of skin injury and wound healing and analyze the role of A. vera in wound healing. In addition, the types of wound dressing and the applications of A. vera in wound dressing will be discussed.
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- 2021
6. Single-cell atlas of domestic pig cerebral cortex and hypothalamus
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Shida Zhu, Haoyu Wang, Shiyou Wang, Weiying Wu, Jian Fang, Jinxia Dai, Gen Tang, Sanjie Jiang, Gang Cao, Langchao Liang, Chaochao Chai, Xiumei Lin, Jiankang Li, Feiyue Wang, Jiaying Qiu, Fang Chen, Xin Qiu, Jiacheng Zhu, Jixing Zhong, Xiangning Ding, Dongsheng Chen, Y. Zeng, Xingliang Zhang, Yin Chen, Ping Liu, Fang Li, Chengcheng Sun, Xiaosen Jiang, Zhongmin Liu, Xun Xu, Lihua Luo, Yetian Ruan, and Peiwen Ding
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Cell type ,Multidisciplinary ,Parietal lobe ,Gene mutation ,Biology ,010502 geochemistry & geophysics ,01 natural sciences ,Temporal lobe ,Domestic pig ,medicine.anatomical_structure ,Frontal lobe ,Cerebral cortex ,medicine ,Occipital lobe ,Neuroscience ,0105 earth and related environmental sciences - Abstract
The brain of the domestic pig (Sus scrofa domesticus) has drawn considerable attention due to its high similarities to that of humans. However, the cellular compositions of the pig brain (PB) remain elusive. Here we investigated the single-nucleus transcriptomic profiles of five regions of the PB (frontal lobe, parietal lobe, temporal lobe, occipital lobe, and hypothalamus) and identified 21 cell subpopulations. The cross-species comparison of mouse and pig hypothalamus revealed the shared and specific gene expression patterns at the single-cell resolution. Furthermore, we identified cell types and molecular pathways closely associated with neurological disorders, bridging the gap between gene mutations and pathogenesis. We reported, to our knowledge, the first single-cell atlas of domestic pig cerebral cortex and hypothalamus combined with a comprehensive analysis across species, providing extensive resources for future research regarding neural science, evolutionary developmental biology, and regenerative medicine.
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- 2021
7. A single-cell atlas of mouse olfactory bulb chromatin accessibility
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Qikai Feng, Jiaying Qiu, Haoyu Wang, Rong Xiang, Zhen Huang, Xingliang Zhang, Xiangning Ding, Peiwen Ding, Feiyue Wang, Mingyue Wang, Jiankang Li, Yin Chen, Shengping Tang, Gen Tang, Shiyou Wang, Xiaoling Wang, and Zaoxu Xu
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Epigenomics ,Cell ,Olfaction ,Computational biology ,Biology ,Epigenesis, Genetic ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,medicine ,Animals ,Cluster Analysis ,Cell Lineage ,Gene Regulatory Networks ,Regulatory Elements, Transcriptional ,Epigenetics ,Nucleotide Motifs ,Molecular Biology ,Transcription factor ,Gene ,030304 developmental biology ,0303 health sciences ,RNA ,Olfactory Bulb ,Chromatin ,Olfactory bulb ,medicine.anatomical_structure ,Viruses ,Single-Cell Analysis ,030217 neurology & neurosurgery ,Transcription Factors - Abstract
Olfaction, the sense of smell, is a fundamental trait crucial to many species. The olfactory bulb (OB) plays pivotal roles in processing and transmitting odor information from the environment to the brain. The cellular heterogeneity of the mouse OB has been studied using single-cell RNA sequencing. However, the epigenetic landscape of the mOB remains mostly unexplored. Herein, we apply single-cell assay for transposase-accessible chromatin sequencing to profile the genome-wide chromatin accessibility of 9,549 single cells from the mOB. Based on single-cell epigenetic signatures, mOB cells are classified into 21 clusters corresponding to 11 cell types. We identify distinct sets of putative regulatory elements specific to each cell cluster from which putative target genes and enriched potential functions are inferred. In addition, the transcription factor motifs enriched in each cell cluster are determined to indicate the developmental fate of each cell lineage. Our study provides a valuable epigenetic data set for the mOB at single-cell resolution, and the results can enhance our understanding of regulatory circuits and the therapeutic capacity of the OB at the single-cell level.
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- 2021
8. Novel variants of ABCA4 in Han Chinese families with Stargardt disease
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Jiankang Li, Dan-Dan Wang, Fang-Yuan Hu, Jihong Wu, Ping Xu, Shenghai Zhang, and Feng-Juan Gao
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0301 basic medicine ,Untranslated region ,Male ,ABCA4 ,Gene Expression ,Exon ,0302 clinical medicine ,Panel-based NGS ,Missense mutation ,Stargardt Disease ,Child ,Genetics (clinical) ,Genetics ,biology ,Han Chinese patients ,High-Throughput Nucleotide Sequencing ,Exons ,STGD1 ,Pedigree ,Medical genetics ,Female ,Research Article ,Adult ,medicine.medical_specialty ,lcsh:Internal medicine ,Adolescent ,lcsh:QH426-470 ,Novel mutant variants ,Frameshift mutation ,03 medical and health sciences ,ABCA4 gene ,Asian People ,medicine ,Animals ,Humans ,Family ,Amino Acid Sequence ,lcsh:RC31-1245 ,Sequence Homology, Amino Acid ,medicine.disease ,Human genetics ,Introns ,Stargardt disease ,lcsh:Genetics ,030104 developmental biology ,Mutation ,030221 ophthalmology & optometry ,biology.protein ,ATP-Binding Cassette Transporters ,Sequence Alignment - Abstract
Background Stargardt disease (STGD1) is a common recessive hereditary macular dystrophy in early adulthood or childhood, with an estimated prevalence of 1:8000 to 1:10,000. ABCA4 is the causative gene for STGD1. The current study aims at identifying the novel disease-related ABCA4 variants in Han Chinese families with STGD1 using next-generation sequencing (NGS). Methods In the present study, 12 unrelated Han Chinese families (19 males and 17 females) with STGD1 were tested by panel-based NGS. In order to capture the coding exons and the untranslated regions (UTRs) plus 30 bp of intronic flanking sequences of 792 genes, which were closely associated with usual ophthalmic genetic disease, we designed a customized panel, namely, Target_Eye_792_V2 chip. STGD1 patients were clinically diagnosed by experienced ophthalmologists. All the detected variants were filtered and analyzed through the public databases and in silico programs to assess potential pathogenicity. Results Twenty-one ABCA4 mutant variants were detected in 12 unrelated Han Chinese families with STGD1, containing 14 missense, three splicing, two frameshift, one small deletion, and one nonsense variants. Base on the American College of Medical Genetics (ACMG) guidelines, 8 likely pathogenic and 13 pathogenic variants were determined. The functional consequences of these mutant variants were predicted through in silico programs. Of the 21 mutant variants in ABCA4, two novel coding variants c.3017G > A and c.5167 T > C and one novel null variant c.3051-1G > A were detected in three unrelated probands. Conclusions By panel-based NGS, 21 ABCA4 variants were confirmed in 12 unrelated Han Chinese families. Among them, 3 novel mutant variants were found, which further expanded the ABCA4 mutation spectrum in STGD1 patients.
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- 2020
9. Prevalence and genetic–phenotypic characteristics of patients with USH2A mutations in a large cohort of Chinese patients with inherited retinal disease
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Ping Xu, Fang Chen, Qing Chang, Dan-Dan Wang, Fang-Yuan Hu, Yu-He Qi, Wei Liu, Hao-Xiang Sun, Feng-Juan Gao, Shenghai Zhang, Jihong Wu, Wei Li, Ming Wang, Gezhi Xu, and Jiankang Li
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0301 basic medicine ,Male ,retina ,Usher syndrome ,Visual Acuity ,Disease ,0302 clinical medicine ,Gene Frequency ,USHER-SYNDROME ,Genotype ,Prevalence ,Missense mutation ,genetics ,Child ,Aged, 80 and over ,Extracellular Matrix Proteins ,High-Throughput Nucleotide Sequencing ,Clinical Science ,Middle Aged ,Phenotype ,Sensory Systems ,Pedigree ,Child, Preschool ,Cohort ,Female ,Usher Syndromes ,Retinitis Pigmentosa ,Tomography, Optical Coherence ,Adult ,medicine.medical_specialty ,China ,Adolescent ,Mutation, Missense ,Slit Lamp Microscopy ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Asian People ,Internal medicine ,Retinitis pigmentosa ,SYNDROME TYPE IIA ,medicine ,otorhinolaryngologic diseases ,Humans ,Gene ,Genetic Association Studies ,Aged ,business.industry ,medicine.disease ,Ophthalmology ,030104 developmental biology ,Mutation ,030221 ophthalmology & optometry ,Visual Field Tests ,Visual Fields ,business - Abstract
AimsTo investigate the frequency of USH2A mutation and the clinical and genetic differences between Usher syndrome type II (USH2) and retinitis pigmentosa (RP) in a large cohort of Chinese patients.MethodsA total of 1381 patients with inherited retinal disease (IRD) were recruited. The phenotypic and genotypic information of patients with USH2A mutations was evaluated.ResultsThe prevalence of patients with USH2A mutations was 15.75%, which was the most frequently detected gene in this cohort of patients. Hotspot of USH2A mutations was c.8559-2A >G and c.2802T >G. Patients with USH2 had an earlier and more serious decline of visual function and damage to retina structure than did patients with RP in the first 10 years (p0.05). Missense variants had less severe consequences and were found more commonly in RP, whereas more deleterious genotypes were associated with an earlier onset of disease and were found more commonly in USH2.ConclusionsThis study provides detailed clinical–genetic assessment of patients with USH2A mutations of Chinese origin, enabling precise genetic diagnoses, better management of these patients and putative therapeutic approaches.
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- 2020
10. Environmentally responsive hydrogels for repair of cardiovascular tissue
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Kun Zhang, Jiankang Li, Jingan Li, and Shuaimeng Guan
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Scaffold ,business.industry ,Regeneration (biology) ,medicine.medical_treatment ,Myocardial Infarction ,Heart ,Hydrogels ,030204 cardiovascular system & hematology ,Bioinformatics ,Revascularization ,Cell therapy ,Transplantation ,03 medical and health sciences ,0302 clinical medicine ,Self-healing hydrogels ,Humans ,Medicine ,Cardiovascular Injury ,030212 general & internal medicine ,Stem cell ,Cardiology and Cardiovascular Medicine ,business ,Stem Cell Transplantation - Abstract
Cardiovascular diseases (CVDs) pose a serious threat to human health, which are characterized by high disability and mortality rate globally such as myocardial infarction (MI), atherosclerosis, and heart failure. Although stem cells transplantation and growth factors therapy are promising, their low survival rate and loss at the site of injury are major obstacles to this therapy. Recently, the development of hydrogel scaffold materials provides a new way to solve this problem, which have shown the potential to treat CVD. Among these scaffold materials, environmentally responsive hydrogels have great prospects in repairing the microenvironment of cardiovascular tissues and vascular regeneration. They provide a new method for the treatment of cardiovascular tissue repair and space-time control for the release of various therapeutic drugs, including small-molecule drugs, growth factors, and stem cells. Herein, this article reviews the occurrence and current treatment of CVD, as well as the repair of cardiovascular injury by several environmental responsive hydrogels systems currently used, mainly focusing on the delivery of growth factors or the application of cell therapy to revascularization. In addition, we will also discuss the enormous potential and personal perspectives of environmentally responsive hydrogels in cardiovascular repair.
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- 2020
11. A phenolic amide (LyA) isolated from the fruits of Lycium barbarum protects against cerebral ischemia–reperfusion injury via PKCε/Nrf2/HO-1 pathway
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Fan Wang, Aidong Wen, Jiankang Li, Hai-Feng Tang, Minna Yao, Juan Bai, Yanrong Zhu, Kai Gao, Yanyan Jia, Yi Ding, Jinyi Cao, Jinyi Zhao, Lianghua Cheng, and Meiyou Liu
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Male ,Aging ,Cell Survival ,NF-E2-Related Factor 2 ,Ischemia ,Protein Kinase C-epsilon ,Pharmacology ,medicine.disease_cause ,Neuroprotection ,Brain Ischemia ,Rats, Sprague-Dawley ,Neuroblastoma ,Random Allocation ,Phenols ,In vivo ,Cell Line, Tumor ,medicine ,ischemic stroke ,oxidative stress ,Animals ,Humans ,Protein kinase A ,Gene knockdown ,PKCε ,Chemistry ,Nrf2, HO-1 ,Cell Biology ,Lycium ,medicine.disease ,Lyciumamide A ,Amides ,Rats ,medicine.anatomical_structure ,Neuroprotective Agents ,Gene Expression Regulation ,Cerebral cortex ,Fruit ,Reperfusion Injury ,Reperfusion injury ,Oxidative stress ,Heme Oxygenase-1 ,Research Paper - Abstract
Lyciumamide A (LyA), a dimer of phenolic amide isolated from the fruits of Lycium barbarum, has been confirmed to possess potent antioxidant activity. This study was aimed to investigate the neuroprotection and molecular mechanisms of LyA against cerebral ischemia/reperfusion (I/R) injury via improving antioxidant activity. The model of middle cerebral artery occlusion (MCAO) and SH-SY5Y cells induced by oxygen and glucose deprivation (OGD) were adopted to verify the neuroprotective effects and the potential pharmacology mechanisms of LyA in vivo and in vitro. In MCAO model, treatment with LyA significantly improved neurologic score, reduced infarct volume, and relieved oxidative stress injury at 48 h after reperfusion. Meanwhile, LyA markedly increased the transcription Nrf2 and HO-1 expressions in the ischemic cerebral cortex. In vitro results showed that LyA protected differentiated SH-SY5Y cells against OGD-induced injury. LyA significantly decreased the expression of caspase-3 and the Bax/Bcl-2 ratio. But knockdown of Nrf2 or HO-1 attenuated the protective effect of LyA. Similarly, knockdown of protein kinase Ce (PKCe) inhibited LyA-induced Nrf2/HO-1 activation, and abated its protective effects. In conclusion, this study firstly demonstrated that LyA protects against cerebral I/R injury, ameliorates oxidative damage and neuronal apoptosis, partly via activation of PKCe/Nrf2/HO-1 pathway.
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- 2019
12. Genetic and Clinical Findings in a Large Cohort of Chinese Patients with Suspected Retinitis Pigmentosa
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Wei Li, Feng-Juan Gao, Ping Xu, Yongjin Zhang, Lusheng Wang, Shenghai Zhang, Han Chen, Jiankang Li, Yu-He Qi, Wei Liu, Min Wang, Dan-Dan Wang, Fang Chen, Qing Chang, Fang-Yuan Hu, Jihong Wu, and Gezhi Xu
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Adult ,Male ,China ,medicine.medical_specialty ,Adolescent ,Genetic counseling ,DNA Mutational Analysis ,Population ,Cohort Studies ,Asian People ,Internal medicine ,Retinitis pigmentosa ,Genotype ,Humans ,Medicine ,Genetic Testing ,Age of Onset ,Medical diagnosis ,Child ,Eye Proteins ,education ,Genetic Association Studies ,Aged ,Genetic testing ,Aged, 80 and over ,education.field_of_study ,medicine.diagnostic_test ,business.industry ,High-Throughput Nucleotide Sequencing ,Infant ,Middle Aged ,medicine.disease ,Ophthalmology ,Child, Preschool ,Mutation ,Female ,Age of onset ,business ,Retinitis Pigmentosa ,Cohort study - Abstract
Purpose To characterize the genetic landscape of patients with suspected retinitis pigmentosa (RP) in the Chinese population. Design Cohort study. Participants A total of 1243 patients of Chinese origin with clinically suspected RP and their available family members (n = 2701) were recruited. Methods All patients and available family members were screened using multigene panel testing (including 586 eye disease-associated genes), followed by clinical variant interpretation. Main Outcome Measures Diagnostic yield, the 17 most commonly implicated genes, age at onset, de novo mutations, and clinical usefulness of genetic testing. Results Overall, 72.08% of patients received a molecular diagnosis, and the 17 top genes covered 75.63% of diagnostic cases. Diagnostic yield was higher among patients in the early-onset subgroup (≤5 years old, 79.58%) than in the childhood or adolescence-onset subgroup (6–16 years old, 73.74%) and late-onset subgroup (≥17 years old, 65.99%). Moreover, different genes associated with different onset ages and subgroups with different onset ages showed a diverse mutation spectrum. Only 11 de novo mutations (3.18%) were identified. Furthermore, 16.84% of the patients who received a molecular diagnosis had refinement of the initial clinical diagnoses, and the remaining 83.16% received definite genetic subtypes of RP. Conclusions This large cohort study provides population-based data of the genome landscape of patients with suspected RP in China. The diagnostic yield was significantly higher than that in previous studies, and the mutation spectrum is completely different with other populations. Genetic testing improves the chance to establish a precise diagnosis, identifies features not previously determined, and allows a more accurate refinement of risk to family members. Our results not only expand the existing genotypic spectrum but also serve as an efficient reference for the design of panel-based genetic diagnostic testing and genetic counseling for patients with suspected RP in China.
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- 2019
13. Mutation spectrum of the bestrophin-1 gene in a large Chinese cohort with bestrophinopathy
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Jihong Wu, Ping Xu, Wei Li, Qing Chang, Fang-Yuan Hu, Jingli Guo, Fang Chen, Gezhi Xu, Yongjin Zhang, Yu-He Qi, Dan-Dan Wang, Wei Liu, Feng-Juan Gao, and Jiankang Li
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Adult ,Male ,0301 basic medicine ,China ,Adolescent ,Genetic counseling ,DNA Mutational Analysis ,Population ,medicine.disease_cause ,Young Adult ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,symbols.namesake ,Exon ,0302 clinical medicine ,Retinal Diseases ,Prevalence ,Humans ,Medicine ,Missense mutation ,Bestrophins ,Child ,education ,Aged ,Retrospective Studies ,Aged, 80 and over ,Genetics ,Sanger sequencing ,education.field_of_study ,Mutation ,business.industry ,Eye Diseases, Hereditary ,DNA ,Middle Aged ,Penetrance ,Sensory Systems ,Ophthalmology ,030104 developmental biology ,Child, Preschool ,030221 ophthalmology & optometry ,symbols ,Female ,business ,Biomarkers ,Autosomal recessive bestrophinopathy - Abstract
BackgroundBestrophin-1 (BEST1) gene is associated with a wide range of ocular phenotypes, collectively termed as bestrophinopathy. The aim of the current study was to identify the mutation spectrum ofBEST1in a large cohort of Chinese patients with bestrophinopathy.MethodsPatients clinically suspected of bestrophinopathy were screened using multigene panel testing. AllBEST1variants were confirmed by Sanger sequencing, and validated in the families.FindingsA total of 92 patients (Best vitelliform macular dystrophy (BVMD)=77; autosomal recessive bestrophinopathy (ARB)=15) from 58 unrelated families of Chinese origin and their available family members (n=65) were recruited. Overall, 39 distinct disease-causingBEST1variants were identified, including 13 novel variants, and two reported variants but novel for ARB. Of them, 14 were associated with ARB, 23 with BVMD and two (c.604C>T and c.898G>A) with both BVMD and ARB. Most mutations associated with BVMD were missense (97.78%), while ARB was associated with more complex mutations, including missense (88.46%), splicing effect (3.85%), and frameshifts (15.38%).BEST1hotspots were c.898G>A and c.584C>T among BVMD and ARB patients, respectively. Hot regions were located in exons 8, 2 and 6 in BVMD patients, and in exons 5 and 7 in ARB patients. The overall penetrance ofBEST1in our cohort was 71.30%, no de novo mutations were identified.ConclusionThis is the largest study to date that provides major population-based data of theBEST1mutation spectrum in China. Our results can serve as a well-founded reference for genetic counselling for patients with bestrophinopathy of Chinese origin.
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- 2019
14. Recent Progress of Hydrogel in Skin Tissue Engineering
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Longlong Cui, Kun Zhang, Jiaheng Liang, Shuaimeng Guan, Jiankang Li, and Jingjing Su
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Skin tissue ,business.industry ,Medicine ,business ,Biomedical engineering - Published
- 2021
15. Genotypic spectrum and phenotype correlations of EYS-associated disease in a Chinese cohort
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Jihong Wu, Ping Xu, Dan-Dan Wang, Feng-Juan Gao, Wei Liu, Qing Chang, Fang-Yuan Hu, Jiankang Li, Shenghai Zhang, and Gezhi Xu
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medicine.medical_specialty ,China ,Visual acuity ,Genotype ,DNA Mutational Analysis ,Genes, Recessive ,Disease ,Cataract ,Correlation ,Internal medicine ,Medicine ,Missense mutation ,Humans ,Eye Proteins ,business.industry ,General Arts and Humanities ,Phenotype ,Hyperpigmentation ,Sensory Systems ,Pedigree ,Ophthalmology ,Cohort ,Mutation ,Laminin ,medicine.symptom ,business ,Retinitis Pigmentosa - Abstract
Background To date, certain efforts have been made to investigate the clinical and genetic characteristics of patients with EYS mutations. However, data for Chinese patients are limited. Objectives To perform a detailed phenotyping and genetic characterization of 55 Chinese patients with EYS-RD, and to identify risk factors for these clinical data. Methods A total of 55 patients with EYS-RD were recruited. Best-corrected visual acuity (BCVA), patient age, age at symptom onset, disease duration, and genetic information were collected. Results Thirty-six novel variants, three hot mutations of EYS (30.3%, c.6416G>A, c.6557G>A, c.7492G>C) and one hot region (49.06%, Laminin G domains) were identified. In all, 36.84% of the mutations occurred at base G site, and majority of mutations (56.56%) were missense. Late-truncating mutations are significantly more prevalent (41.30%). The mean age of onset was 15.65 ± 14.67 years old; it had no significant correlation with genotype. The average BCVA was 0.73 ± 0.93 LogMAR, and 61.8% of eyes had a BCVA better than 0.52 logMAR. BCVA was positively correlated with disease duration time. The mean MD was 23.18 ± 7.34 dB, MD showed a significant correlation with genotype and age. Cataract was present in 56.45% of patients, and 42.59% of patients showed an absence of pigmentation in the retina. Cataract and hyperpigmentation both showed a significant correlation with age. Conclusions EYS-RD is associated with a moderate phenotype with onset around adolescence, but great variability. Our study largely enhances the current knowledge of phenotypic and genotypic characteristics of EYS-RD, which could pave the way for better management of these patients.
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- 2021
16. Frequency and phenotypic characteristics of RPE65 mutations in the Chinese population
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Qing Chang, Jiankang Li, Wei Liu, Fang-Yuan Hu, Jihong Wu, Yu-He Qi, Feng-Juan Gao, Wei Li, Shenghai Zhang, Ping Xu, Dan-Dan Wang, Fang Chen, and Gezhi Xu
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Adult ,cis-trans-Isomerases ,phenotype correlations ,0301 basic medicine ,Oncology ,China ,medicine.medical_specialty ,Visual acuity ,Adolescent ,Genotype– ,Genetic counseling ,Genetic enhancement ,Genotype–phenotype correlations ,Visual Acuity ,Disease ,medicine.disease_cause ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Gene ,Genetics (clinical) ,RPE65 gene mutations ,Mutation ,business.industry ,Research ,General Medicine ,Inherited retinal dystrophy ,eye diseases ,Human genetics ,Phenotype ,030104 developmental biology ,RPE65 ,Next-generation sequencing ,030221 ophthalmology & optometry ,Medicine ,sense organs ,Chinese population ,medicine.symptom ,business - Abstract
Background The retinoid isomerohydrolase RPE65 has received considerable attention worldwide since a successful clinical gene therapy was approved in 2017 as the first treatment for vision loss associated with RPE65-mediated inherited retinal disease. Identifying patients with RPE65 mutations is a prerequisite to assessing the patients’ eligibility to receive RPE65-targeted gene therapies, and it is necessary to identify individuals who are most likely to benefit from gene therapies. This study aimed to investigate the RPE65 mutations frequency in the Chinese population and to determine the genetic and clinical characteristics of these patients. Results Only 20 patients with RPE65 mutations were identified, and RPE65 mutations were determined to be the 14th most common among all patients with genetic diagnoses. Ten novel variants and two hotspots associated with FAP were identified. A literature review revealed that a total of 57 patients of Chinese origin were identified with pathogenic mutations in the RPE65 gene. The mean best Snellen corrected visual acuity was worse (mean 1.3 ± 1.3 LogMAR) in patients older than 20 years old than in those younger than 15 years old (0.68 ± 0.92 LogMAR). Bone spicule-like pigment deposits (BSLPs) were observed in six patients; they were older than those without BSLP and those with white-yellow dots. Genotype–phenotype analysis revealed that truncating variants seem to lead to a more severe clinical presentation, while best corrected visual acuity testing and fundus changes did not correlate with specific RPE65 variants or mutation types. Conclusions This study provides a detailed clinical-genetic assessment of patients with RPE65 mutations of Chinese origin. These results may help to elucidate RPE65 mutations in the Chinese population and may facilitate genetic counseling and the implementation of gene therapy in China.
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- 2021
17. Exome sequencing of Saudi Arabian patients with ADPKD
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Tamer S. Ahmed Elsalamouni, Afnan F Almuhanna, Mohammed Shakil Akhtar, Feras A Alkuwaiti, Matthew B. Lanktree, Abdullah M. Al-Rubaish, Arafat Ahmad, Kai Huang, Amein K. Al-Ali, Fahad Al-Muhanna, Shamim S. Mohiuddin, Rudaynah A. Alali, Abdullah Al Hwiesh, Xiaoyan Huang, Chittibabu Vatte, Lusheng Wang, Cyril Cyrus, Mohammad Ahmad Albezra, Brendan J. Keating, and Jiankang Li
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Male ,Pathology ,PKD1 ,DNA Mutational Analysis ,030232 urology & nephrology ,Cystic Fibrosis Transmembrane Conductance Regulator ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,Critical Care and Intensive Care Medicine ,0302 clinical medicine ,Laboratory Study ,Medicine ,CFTR ,Exome sequencing ,Exons ,General Medicine ,Middle Aged ,Polycystic Kidney, Autosomal Dominant ,female genital diseases and pregnancy complications ,Arabs ,Nephrology ,Female ,medicine.symptom ,Adult ,medicine.medical_specialty ,TRPP Cation Channels ,Saudi Arabia ,Mutation, Missense ,Autosomal dominant polycystic kidney disease ,Receptors, Cell Surface ,Kidney cysts ,03 medical and health sciences ,Tuberous Sclerosis Complex 2 Protein ,Exome Sequencing ,Humans ,ADPKD ,EGF ,Aged ,Epidermal Growth Factor ,urogenital system ,business.industry ,medicine.disease ,Diseases of the genitourinary system. Urology ,TSC2 ,Case-Control Studies ,RC870-923 ,Calcium Channels ,Tomography, X-Ray Computed ,business - Abstract
Purpose: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive development of kidney cysts and enlargement and dysfunction of the kidneys. The Consortium of Radiologic Imaging Studies of the Polycystic Kidney Disease (CRISP) cohort revealed that 89.1% had either a PKD1 or PKD2 mutation. Of the CRISP patients with a genetic cause detected, mutations in PKD1 accounted for 85%, while mutations in the PKD2 accounted for the remaining 15%. Here, we report exome sequencing of 16 Saudi patients diagnosed with ADPKD and 16 ethnically matched controls. Methods: Exome sequencing was performed using combinatorial probe-anchor synthesis and improved DNA Nanoballs technology on BGISEQ-500 sequencers (BGI, China) using the BGI Exome V4 (59 Mb) Kit. Identified variants were validated with Sanger sequencing. Results: With the exception of GC-rich exon 1, we obtained excellent coverage of PKD1 (mean read depth = 88) including both duplicated and non-duplicated regions. Of nine patients with typical ADPKD presentations (bilateral symmetrical kidney involvement, positive family history, concordant imaging, and kidney function), four had protein truncating PKD1 mutations, one had a PKD1 missense mutation, and one had a PKD2 mutation. These variants have not been previously observed in the Saudi population. In seven clinically diagnosed ADPKD cases but with atypical features, no PKD1 or PKD2 mutations were identified, but rare predicted pathogenic heterozygous variants were found in cystogenic candidate genes including PKHD1, PKD1L3, EGF, CFTR, and TSC2. Conclusions: Mutations in PKD1 and PKD2 are the most common cause of ADPKD in Saudi patients with typical ADPKD. Abbreviations: ADPKD: Autosomal dominant polycystic kidney disease; CFTR: Cystic fibrosis transmembrane conductance regulator; EGF: Epidermal growth factor; MCIC: Mayo Clinic Imaging Classification; PKD: Polycystic kidney disease; TSC2: Tuberous sclerosis complex 2
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- 2019
18. Bi-allelic variants in SPATA5L1 lead to intellectual disability, spastic-dystonic cerebral palsy, epilepsy, and hearing loss
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Serdal Güngör, Benita Grossmann, Bethany Y. Norton, Zubair M. Ahmed, Wendy K. Chung, John Neidhardt, Julie S. Cohen, Elodie Richard, Yoel Hirsch, Jiankang Li, Jozef Gecz, Ralf A. Husain, Saima Riazuddin, Maria J. Guillen Sacoto, Claudia Steen, Andreas Ziegler, G. Christoph Korenke, Dominic Lenz, Mahim Jain, Urania Kotzaeridou, Henry Houlden, Theresa Brunet, Yavuz Oktay, Semra Hiz, Patricia Cornejo, Sheetal Shetty, Alastair H. MacLennan, Nazira Zharkinbekova, Bader Alhaddad, Dani L. Webber, Mary Alice Abbott, Hanns Lochmüller, Rauan Kaiyrzhanov, Melissa Yelton, Cecilia Mancini, Hakon Hakonarson, Amy Crunk, Simona Amenta, Yiran Guo, Jan Kaslin, Clare L. van Eyk, Richard Webster, Arianna Tucci, Alex M. Pagnozzi, Robert B. Hufnagel, Kirsty McWalter, Sandra M. Nordlie, Kaya Bilguvar, Pasquale Striano, Matias Wagner, Florian Kreuder, Lisa Worgan, Ashley P.L. Marsh, Anna Chassevent, Warren A. Marks, James Liu, Brandon S. Guida, Maria Margherita Mancardi, Kelly Harper, Lance H. Rodan, Rhonda E. Schnur, Dianela Judith Claps Sepulveda, Tzvi Weiden, Michele Pinelli, Marion Rapp, Helen Magee, Jesia G. Berry, Aboulfazl Rad, Michael C. Kruer, Mark A. Corbett, Rita Horvath, Constance Smith-Hicks, Joseph Ekstein, Marta Owczarek-Lipska, Somayeh Bakhtiari, Heinrich Sticht, Thomas Meitinger, Anne M. Comi, Alyssa Blesson, Iris Marquardt, Francesca Clementina Radio, Sergio Padilla-Lopez, Giuseppe Marangi, Christine Makowski, Mona Grimmel, Marco Tartaglia, Sheng Chih Jin, Federico Zara, Andreas Hahn, Shrikant Mane, Michael C Fahey, Marcella Zollino, Barbara Vona, Peter D. Turnpenny, Manuela Morleo, Ute Grasshoff, Amber Begtrup, Richard E. Person, Annalaura Torella, Alexander Münchau, Vincenzo Nigro, Reza Maroofian, John Christodoulou, Tobias B. Haack, Vincenzo Salpietro, Richard, E. M., Bakhtiari, S., Marsh, A. P. L., Kaiyrzhanov, R., Wagner, M., Shetty, S., Pagnozzi, A., Nordlie, S. M., Guida, B. S., Cornejo, P., Magee, H., Liu, J., Norton, B. Y., Webster, R. I., Worgan, L., Hakonarson, H., Li, J., Guo, Y., Jain, M., Blesson, A., Rodan, L. H., Abbott, M. -A., Comi, A., Cohen, J. S., Alhaddad, B., Meitinger, T., Lenz, D., Ziegler, A., Kotzaeridou, U., Brunet, T., Chassevent, A., Smith-Hicks, C., Ekstein, J., Weiden, T., Hahn, A., Zharkinbekova, N., Turnpenny, P., Tucci, A., Yelton, M., Horvath, R., Gungor, S., Hiz, S., Oktay, Y., Lochmuller, H., Zollino, M., Morleo, M., Marangi, G., Nigro, V., Torella, A., Pinelli, M., Amenta, S., Husain, R. A., Grossmann, B., Rapp, M., Steen, C., Marquardt, I., Grimmel, M., Grasshoff, U., Korenke, G. C., Owczarek-Lipska, M., Neidhardt, J., Radio, F. C., Mancini, C., Claps Sepulveda, D. J., Mcwalter, K., Begtrup, A., Crunk, A., Guillen Sacoto, M. J., Person, R., Schnur, R. E., Mancardi, M. M., Kreuder, F., Striano, P., Zara, F., Chung, W. K., Marks, W. A., van Eyk, C. L., Webber, D. L., Corbett, M. A., Harper, K., Berry, J. G., Maclennan, A. H., Gecz, J., Tartaglia, M., Salpietro, V., Christodoulou, J., Kaslin, J., Padilla-Lopez, S., Bilguvar, K., Munchau, A., Ahmed, Z. M., Hufnagel, R. B., Fahey, M. C., Maroofian, R., Houlden, H., Sticht, H., Mane, S. M., Rad, A., Vona, B., Jin, S. C., Haack, T. B., Makowski, C., Hirsch, Y., Riazuddin, S., and Kruer, M. C.
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Male ,Microcephaly ,Pathology ,Settore MED/03 - GENETICA MEDICA ,sensorineural hearing loss ,Epilepsy ,Neurodevelopmental disorder ,sensorineural hearing lo ,Genetics (clinical) ,Allele ,ATPases Associated with Diverse Cellular Activitie ,medicine.anatomical_structure ,Muscle Spasticity ,Child, Preschool ,Sensorineural hearing loss ,Female ,movement disorder ,medicine.symptom ,AAA+ superfamily ,Human ,Adult ,medicine.medical_specialty ,Adolescent ,Hearing loss ,Aaa+ Superfamily ,Atpase ,Spata5l1 ,Cerebral Palsy ,Intellectual Disability ,Movement Disorder ,Neurodevelopmental Disorder ,Sensorineural Hearing Loss ,Biology ,Cerebral palsy ,White matter ,Young Adult ,Report ,Genetics ,medicine ,Animals ,Humans ,ATPase ,Genetic Predisposition to Disease ,Hearing Loss ,SPATA5L1 ,Hearing Lo ,Alleles ,cerebral palsy ,Periventricular leukomalacia ,Animal ,Infant, Newborn ,Infant ,Genetic Variation ,medicine.disease ,neurodevelopmental disorder ,Rats ,ATPases Associated with Diverse Cellular Activities ,Rat - Abstract
Spermatogenesis-associated 5 like 1 (SPATA5L1) represents an orphan gene encoding a protein of unknown function. We report 28 bi-allelic variants in SPATA5L1 associated with sensorineural hearing loss in 47 individuals from 28 (26 unrelated) families. In addition, 25/47 affected individuals (53%) presented with microcephaly, developmental delay/intellectual disability, cerebral palsy, and/or epilepsy. Modeling indicated damaging effect of variants on the protein, largely via destabilizing effects on protein domains. Brain imaging revealed diminished cerebral volume, thin corpus callosum, and periventricular leukomalacia, and quantitative volumetry demonstrated significantly diminished white matter volumes in several individuals. Immunofluorescent imaging in rat hippocampal neurons revealed localization of Spata511 in neuronal and glial cell nuclei and more prominent expression in neurons. In the rodent inner ear, Spata511 is expressed in the neurosensory hair cells and inner ear supporting cells. Transcriptomic analysis performed with fibroblasts from affected individuals was able to distinguish affected from controls by principal components. Analysis of differentially expressed genes and networks suggested a role for SPATA5L1 in cell surface adhesion receptor function, intracellular focal adhesions, and DNA replication and mitosis. Collectively, our results indicate that bi-allelic SPATA5L1 variants lead to a human disease characterized by sensorineural hearing loss (SNHL) with or without a nonprogressive mixed neurodevelopmental phenotype.
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- 2021
19. Comprehensive analysis of genetic and clinical characteristics of 30 patients with X‐linked juvenile retinoschisis in China
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Ying Huang, Jian-Hong Dong, Dan-Dan Wang, Jihong Wu, Gezhi Xu, Jiankang Li, Wei Liu, Feng-Juan Gao, Qing Chang, Fang-Yuan Hu, Ping Xu, and Fang Chen
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Male ,Visual acuity ,RS1 ,DNA Mutational Analysis ,Visual Acuity ,linked retinoschisis ,Gene mutation ,PHENOTYPE ,FAMILIES ,0302 clinical medicine ,RS1 GENE ,Missense mutation ,RETINAL-DETACHMENT ,Child ,Incidence ,General Medicine ,Middle Aged ,Pedigree ,GENOTYPE ,clinical diagnosis ,Child, Preschool ,Cohort ,Female ,Original Article ,Chinese population ,medicine.symptom ,Tomography, Optical Coherence ,Adult ,China ,medicine.medical_specialty ,Adolescent ,Retinoschisis ,Genetic counseling ,Mutation, Missense ,DIAGNOSIS ,Retina ,Young Adult ,03 medical and health sciences ,Ophthalmology ,Molecular genetics ,Electroretinography ,medicine ,Humans ,COHORT ,Genetic Association Studies ,Retrospective Studies ,optical coherence tomography ,MUTATIONS ,business.industry ,Reproducibility of Results ,DNA ,Original Articles ,molecular genetics ,030221 ophthalmology & optometry ,X‐ ,Differential diagnosis ,X‐linked retinoschisis ,business ,RETINOSCHISIN ,030217 neurology & neurosurgery - Abstract
Purpose To provides the clinical and genetic characteristics of a series of Chinese patients with X-linked juvenile retinoschisis (XLRS) through multimodal imaging and next-generation sequencing.Methods Thirty patients (60 eyes) from 29 unrelated families of Chinese origin with XLRS were screened using multigene panel testing, and underwent a complete clinical evaluation. All variants identified in this study and reported in the Human Gene Mutation Database were analysed.Results Twenty-five distinct variants in the retinoschisin gene were identified, of which eight were novel, and one was de novo. Missense mutations were the most prevalent type, and mutation hot spot was localized in the discoidin domain. The mean Snellen best-corrected visual acuity was 0.28 +/- 0.17. Of all eyes presenting with schisis, 92.86% had lamellar schisis and 62.5% had peripheral schisis. Schisis changes mostly involved inner and outer nuclear layers. X-linked juvenile retinoschisis (XLRS) patients had a high incidence of complications, and peripheral schisis was a risk factor for it. No obvious genotype-phenotype association was observed.Conclusion This study provides comprehensive analyses of the genetic and clinical characteristics of XLRS in a cohort of Chinese patients. The fourth de novo mutation in RS1 was identified. And we show that XLRS has a wide spectrum of clinical characteristics; hence, molecular diagnosis is crucial for its diagnosis, differential diagnosis and genetic counselling. Peripheral schisis is a risk factor for the high incidence of complications, and no clear genotype-phenotype correlations were found.
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- 2020
20. Single-cell brain atlas of Parkinson's disease mouse model
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Zhen Huang, Y. Zeng, Fang Chen, Chaochao Chai, Dongsheng Chen, Lihua Luo, Weiying Wu, Feiyue Wang, Langchao Liang, Jiankang Li, Xin Qiu, Ge Li, Hongde Liu, Jixing Zhong, Shengping Tang, Yu Zhang, Jiacheng Zhu, Xiuqing Zhang, Gen Tang, and Xiumei Lin
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Cell type ,Cerebellum ,Parkinson's disease ,Cell ,Muscle Proteins ,Striatum ,Biology ,Pathogenesis ,Transcriptome ,03 medical and health sciences ,Glutamatergic ,Mice ,0302 clinical medicine ,Intermediate Filament Proteins ,Mesencephalon ,Genetics ,medicine ,Animals ,Humans ,RNA-Seq ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,NF-kappa B ,Brain ,Parkinson Disease ,medicine.disease ,Corpus Striatum ,Disease Models, Animal ,medicine.anatomical_structure ,Single-Cell Analysis ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Parkinson's disease (PD) is a neurodegenerative disease, leading to the impairment of movement execution. PD pathogenesis has been largely investigated, either limited to bulk transcriptomic levels or at certain cell types, which failed to capture the cellular heterogeneity and intrinsic interplays among distinct cell types. Here, we report the application of single-nucleus RNA-seq on midbrain, striatum, and cerebellum of the α-syn-A53T mouse, a well-established PD mouse model, and matched controls, generating the first single cell transcriptomic atlas for the PD model mouse brain composed of 46,174 individual cells. Additionally, we comprehensively depicte the dysfunctions in PD pathology, covering the elevation of NF-κB activity, the alteration of ion channel components, the perturbation of protein homeostasis network, and the dysregulation of glutamatergic signaling. Notably, we identify a variety of cell types closely associated with PD risk genes. Taken together, our study provides valuable resources to systematically dissect the molecular mechanism of PD pathogenesis at the single-cell resolution, which facilitates the development of novel approaches for diagnosis and therapies against PD.
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- 2020
21. Correction: Downregulation of microRNA-9-5p promotes synaptic remodeling in the chronic phase after traumatic brain injury
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Xiaocui Tian, Jianjun Zhong, Wei Li, Zhijian Huang, Jingchuan Wu, Shuilian Luo, Junchi He, Hongrong Zhang, Tao Jiang, Jiankang Li, Hui Li, and Xiaochuan Sun
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0301 basic medicine ,Cancer Research ,Traumatic brain injury ,Immunology ,Notch signaling pathway ,Trauma ,Synaptic plasticity ,Synaptotagmin 1 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Downregulation and upregulation ,Neurotrophic factors ,microRNA ,medicine ,lcsh:QH573-671 ,Chemistry ,lcsh:Cytology ,Correction ,Cell Biology ,medicine.disease ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,030217 neurology & neurosurgery ,Astrocyte - Abstract
The level of microRNA-9-5p (miRNA-9-5p) in brain tissues is significantly changed in the chronic phase after traumatic brain injury (TBI). However, the effect of miRNA-9-5p on brain function after TBI has not been elucidated. In this study, we used a controlled cortical impact (CCI) model to induce TBI in Sprague-Dawley rats. Brain microvascular endothelial cells (BMECs), astrocytes, and neurons were extracted from immature Sprague-Dawley rats and cocultured to reconstruct the neurovascular unit (NVU) in vitro. The results showed that downregulation of miRNA-9-5p in the chronic phase contributed to neurological function recovery by promoting astrocyte proliferation and increasing the release of astrocyte-derived neurotrophic factors around injured brain tissues after TBI. A dual-luciferase reporter assay validated that miRNA-9-5p was a post-transcriptional modulator of thrombospondin 2 (Thbs-2), and downregulation of miRNA-9-5p promoted Thbs-2 expression in astrocytes. Furthermore, we verified that Thbs-2 can promote Notch pathway activation by directly binding to Jagged and Notch. Through in vitro experiments, we found that the expression of synaptic proteins and the number of synaptic bodies were increased in neurons in the NVU, which was constructed using astrocytes pretreated with miRNA-9-5p inhibitor. Moreover, we also found that downregulation of miRNA-9-5p promoted Thbs-2 expression in astrocytes, which activated the Notch/cylindromatosis/transforming growth factor-β-activated kinase 1 pathway in neurons and promoted the expression of synaptic proteins, including post-synaptic density protein 95 and synaptotagmin. Based on these results, miRNA-9-5p may be a new promising prognostic marker and treatment target for TBI.
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- 2021
22. The Development of Hyaluronic Acids Used for Skin Tissue Regeneration
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Longlong Cui, Jiaheng Liang, Jiankang Li, Kun Zhang, Jingjing Su, and Shuaimeng Guan
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Wound Healing ,integumentary system ,Tissue Engineering ,Tissue Scaffolds ,business.industry ,Regeneration (biology) ,Pharmaceutical Science ,Scars ,Hydrogels ,Dermal Fillers ,Regenerative medicine ,chemistry.chemical_compound ,Tissue engineering ,chemistry ,Hyaluronic acid ,Poor wound healing ,Medicine ,Humans ,medicine.symptom ,Hyaluronic Acid ,business ,Wound healing ,Biomedical engineering ,Skin - Abstract
Burns, mechanical injuries, skin defects, poor wound healing and scars caused by chronic diseases are serious clinical issues that affect millions of people around the world. Hyaluronic acid (HA) is one of the main components of extracellular matrix, which is widely distributed in human body. Because of its unique physical and chemical properties and diversity of physiological functions, hyaluronic acid is widely used in tissue engineering and regenerative medicine. This paper reviews the application of HA and HA based scaffolds in the regeneration and repair of skin tissue, as well as the application of HA in the fields of skin filler, wound healing, beauty, etc.
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- 2020
23. Next-generation sequencing-based clinical diagnosis of choroideremia and comprehensive mutational and clinical analyses
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Wei Liu, Jihong Wu, Dan-Dan Wang, Feng-Juan Gao, Qing Chang, Gezhi Xu, Fang-Yuan Hu, Guohong Tian, Jiankang Li, and Fang Chen
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0301 basic medicine ,Male ,DNA Mutational Analysis ,Visual Acuity ,Gene mutation ,medicine.disease_cause ,Multimodal Imaging ,Choroideremia ,0302 clinical medicine ,Genotype-phenotype distinction ,lcsh:Ophthalmology ,Age of Onset ,Fluorescein Angiography ,Mutation ,High-Throughput Nucleotide Sequencing ,General Medicine ,Middle Aged ,Pedigree ,Gene mutations ,Female ,Molecular diagnosis ,Tomography, Optical Coherence ,Research Article ,Adult ,medicine.medical_specialty ,Nonsense mutation ,Slit Lamp Microscopy ,DNA sequencing ,03 medical and health sciences ,Asian People ,Ophthalmology ,Retinitis pigmentosa ,medicine ,Humans ,Genetic Association Studies ,Adaptor Proteins, Signal Transducing ,Aged ,Optical coherence tomography ,business.industry ,medicine.disease ,eye diseases ,030104 developmental biology ,lcsh:RE1-994 ,Clinical diagnosis ,030221 ophthalmology & optometry ,sense organs ,CHM ,business - Abstract
Background To report the clinical and genetic findings from seven Chinese patients with choroideremia. Methods Five hundred seventy-eight patients with a clinically suspected diagnosis of retinitis pigmentosa (RP) underwent comprehensive ophthalmic examinations. Next-generation sequencing (NGS) was performed on samples from all patients. Detailed clinical characteristics of the patients with choroideremia identified in this study were assessed using multimodal imaging. Results Seven patients with choroideremia were identified, and six novel variants in CHM (c.1960 T > C p.Ter654Gln, c.1257del p.Ile420*fs1, c.1103_1121delATGGCAACACTCCATTTTT p.Tyr368Cysfs35, c.1414-2A > T, and c.1213C > T p.Gln405Ter, c.117-1G > A) were revealed. All variants were deleterious mutations: two were frameshifts, two were nonsense mutations, two were splicing mutations, and one was a readthrough mutation. The clinical phenotypes of these patients were markedly heterogeneous, and they shared many common clinical features with RP, including night blindness, constriction of the visual field and gradually reduced visual acuity. However, patients with choroideremia showed pigment hypertrophy and clumping, and chorioretinal atrophy, and a majority of patients with choroideremia presented with retinal tubulations in the outer layer of the retina. Conclusions We provide a detailed description of the genotypes and phenotypes of seven patients with choroideremia who were accurately diagnosed using NGS. These findings provide a better understanding of the genetics and phenotypes of choroideremia.
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- 2020
24. Panel‐based targeted exome sequencing reveals novel candidate susceptibility loci for age‐related cataracts in Chinese Cohort
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Shou-Fang Qu, Feng-Juan Gao, Fang-Yuan Hu, Jihong Wu, Li-Li Li, Fang Chen, Lusheng Wang, Wei Li, Jiankang Li, Jie Huang, Zi-Wei Wang, and Shenghai Zhang
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0301 basic medicine ,panel‐based targeted exome sequencing ,Male ,Candidate gene ,lcsh:QH426-470 ,Quantitative Trait Loci ,Disease ,Dopamine beta-Hydroxylase ,030105 genetics & heredity ,Biology ,Polymorphism, Single Nucleotide ,susceptibility ,Cataract ,Dystrophin ,03 medical and health sciences ,Cataracts ,age‐related cataracts ,Genetics ,medicine ,Humans ,Exome ,Molecular Biology ,Gene ,Genetics (clinical) ,Exome sequencing ,Adaptor Proteins, Signal Transducing ,Aged ,Gene map ,Epistasis, Genetic ,Odds ratio ,Original Articles ,Middle Aged ,medicine.disease ,lcsh:Genetics ,Proton-Translocating ATPases ,030104 developmental biology ,Expression quantitative trait loci ,Original Article ,Female - Abstract
Background Age‐related cataracts (ARC) is the most common blinding eye disease worldwide, and its incidence tend to become younger. However, the relationship between genetic factors and mechanisms is not fully understood. The aim of the study was to further clarify the relationship between ARC and genetic mechanisms in East Asian populations and to elucidate the pathogenesis. Methods The study collected 191 sporadic cataracts and 208 healthy people from the eastern provinces of China, with an average age of about 60 years. All participants were subjected to a comprehensive ophthalmic clinical examination and peripheral blood samples were collected and their genomic DNA was extracted. Mutations were screened among 792 candidate genes to enhance understanding of the disease through targeted capture and high‐throughput sequencing. Results We identified novel candidate susceptibility gene, which may serve as a potential susceptibility factor leading to an increase in the incidence of age‐related cataracts. Three novel loci are associated with age‐related cataracts significant significance: rs129882 in DBH (p = 5.27E‐07, odds ratio = 3.9), rs1800280 in DMD (p = 2.85E‐06, odds ratio = 1.4) and rs2871776 in ATP13A2 (p = 4.18E‐05, odds ratio = 0.04). Gene–gene interaction analysis revealed that the most significant interactions between genes include the interaction between DBH and TUB (rs17847537 in TUB, rs129882 in DBH, p‐value = 2.12E‐14), and the interaction between DBH and DMD (rs1800280 in DMD, rs129882 in DBH, p‐value = 2.12E‐14). Pathway analysis shows that the most significant processes are concentrated in response to light stimulation (adjusted p‐Value = 5.56E‐03), response to radiation (adjusted P‐Value = 5.56E‐03), abiotic stimulus (adjusted p‐Value = 5.56E‐03). eQTL analysis shows that DBH rs129882 could regulate the expression of DBH mRNA in various tissues including retina. Conclusion Our study indicates rs129882 and rs1800280 loci are associated with age‐related cataracts, which enlarge the gene map of age‐related cataracts., We identified novel candidate susceptibility gene, which may serve as a potential susceptibility factor leading to an increase in the incidence of age‐related cataracts. Our study indicates rs129882 and rs1800280 loci are associated with age‐related cataracts, which enlarge the gene map of age‐related cataracts.
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- 2020
25. Clinical and Genetic Characteristics of Chinese Patients with Occult Macular Dystrophy
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Jian-Guo Zhang, Feng-Juan Gao, Guohong Tian, Hao-Xiang Sun, Shenghai Zhang, Gezhi Xu, Dan-Dan Wang, Jiankang Li, Fang Chen, Fang-Yuan Hu, Jihong Wu, and Ping Xu
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0301 basic medicine ,Proband ,Adult ,Male ,medicine.medical_specialty ,Visual acuity ,genetic structures ,Adolescent ,early diagnostics ,Visual Acuity ,multimodal imaging ,Retina ,Cohort Studies ,03 medical and health sciences ,Macular Degeneration ,Young Adult ,0302 clinical medicine ,Asian People ,Ophthalmology ,medicine ,Electroretinography ,Humans ,Genetic Predisposition to Disease ,Age of Onset ,Fluorescein Angiography ,Child ,Eye Proteins ,Genetic testing ,medicine.diagnostic_test ,business.industry ,Macular dystrophy ,Middle Aged ,Fluorescein angiography ,eye diseases ,Pedigree ,030104 developmental biology ,Cohort ,Mutation ,030221 ophthalmology & optometry ,occult macular dystrophy ,Female ,RP1L1 ,next-generation sequencing ,sense organs ,Age of onset ,medicine.symptom ,business ,Tomography, Optical Coherence - Abstract
Purpose To investigate the clinical and genetic characteristics of occult macular dystrophy (OMD) based on a Chinese patient cohort. Methods Fifteen Chinese OMD patients from nine unrelated families underwent genetic testing, and all of them harbored a pathogenic RP1L1 variant. Comprehensive ophthalmic examinations were performed in nine probands, including spectral-domain optical coherence tomography (SD-OCT), near-infrared reflectance (NIR), fundus autofluorescence (AF), and multifocal electroretinography. Results The RP1L1 variants p.R45W and p.S1199C were identified in 13 patients and two patients, respectively, and one was a de novo mutation. Among the nine probands, the median ages at onset and examination were 25.0 years (range, 6-51 years) and 27.0 years (range, 14-55 years), respectively. The median decimal visual acuity was 0.20 (range, 0.04-0.5). Foveal photoreceptor thickness and visual acuity showed a significant correlation (r = 0.591; P = 0.01). All eyes presented with an absent interdigitation zone and blurred ellipsoid zone of photoreceptors when examined by SD-OCT. In addition, central round lesions with low NIR reflectance were observed in 66.7% (12/18) of eyes by NIR reflectance imaging, corresponding to the regions with abnormal photoreceptor microstructures observed by SD-OCT. Of the 18 eyes, only four eyes showed ring-like faint hyperfluorescence around the macula by AF. Conclusions To the best of our knowledge, this is the largest study in a cohort of Chinese OMD patients with RP1L1 mutations. Our findings revealed that the two recurrent RP1L1 variants are related to OMD in the Chinese population. Furthermore, multimodal imaging combined with genetic testing is valuable for diagnosing and monitoring OMD progression.
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- 2020
26. Integrated profiling of single cell epigenomic and transcriptomic landscape of Parkinson’s disease mouse brain
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Y. Zeng, Ge Li, W. T. Wu, Langchao Liang, Gen Tang, Shengping Tang, Dongsheng Chen, Chaochao Chai, Xun Xu, Feiyue Wang, Xin Qiu, Zhen Huang, Xiumei Lin, Jixing Zhong, Jiankang Li, Shida Zhu, Fang Chen, Jiacheng Zhu, and Lihua Luo
- Subjects
Transcriptome ,Cell type ,Proteostasis ,medicine.anatomical_structure ,Parkinson's disease ,Cell ,medicine ,Epigenetics ,Biology ,medicine.disease ,Neuroscience ,Neuroinflammation ,Epigenomics - Abstract
Parkinson’s disease (PD) is a neurodegenerative disease leading to the impairment of execution of movement. PD pathogenesis has been largely investigated, but either restricted in bulk level or at certain cell types, which failed to capture cellular heterogeneity and intrinsic interplays among distinct cell types. To overcome this, we applied single-nucleus RNA-seq and single cell ATAC-seq on cerebellum, midbrain and striatum of PD mouse and matched control. With 74,493 cells in total, we comprehensively depicted the dysfunctions under PD pathology covering proteostasis, neuroinflammation, calcium homeostasis and extracellular neurotransmitter homeostasis. Besides, by multi-omics approach, we identified putative biomarkers for early stage of PD, based on the relationships between transcriptomic and epigenetic profiles. We located certain cell types that primarily contribute to PD early pathology, narrowing the gap between genotypes and phenotypes. Taken together, our study provides a valuable resource to dissect the molecular mechanism of PD pathogenesis at single cell level, which could facilitate the development of novel methods regarding diagnosis, monitoring and practical therapies against PD at early stage.
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- 2020
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27. Genetic and clinical findings of panel‐based targeted exome sequencing in a northeast Chinese cohort with retinitis pigmentosa
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Wen Yang, Wang Zhuoshi, Yan Sun, Ling Xu, Lusheng Wang, Jin‐yue Bai, Bo Xing, Wei Li, Wei He, Jiankang Li, Zi-Wei Wang, and Fang Chen
- Subjects
0301 basic medicine ,Proband ,panel‐based targeted exome sequencing ,Adult ,Male ,medicine.medical_specialty ,China ,lcsh:QH426-470 ,Adolescent ,030105 genetics & heredity ,Compound heterozygosity ,digenic inheritance ,Frameshift mutation ,03 medical and health sciences ,Gene Frequency ,Internal medicine ,retinitis pigmentosa ,Retinitis pigmentosa ,Genetics ,Medicine ,Missense mutation ,Humans ,Clinical significance ,Exome ,Genetic Testing ,Child ,Eye Proteins ,Molecular Biology ,Genetics (clinical) ,Exome sequencing ,compound heterozygous ,Aged, 80 and over ,Extracellular Matrix Proteins ,business.industry ,Original Articles ,Middle Aged ,medicine.disease ,eye diseases ,lcsh:Genetics ,030104 developmental biology ,Phenotype ,Original Article ,Female ,Age of onset ,business ,Microtubule-Associated Proteins - Abstract
Background Panel‐based targeted exome sequencing was used to analyze the genetic and clinical findings of targeted genes in a cohort of northeast Chinese with retinitis pigmentosa. Methods A total of 87 subjects, comprising 23 probands and their family members (total patients: 32) with confirmed retinitis pigmentosa were recruited in the study. Panel‐based targeted exome sequencing was used to sequence the patients and family members, all subjects with retinitis pigmentosa underwent a complete ophthalmologic examination. Results Of the 23 probands, the clinical manifestations include night blindness, narrowing of vision, secondary cataracts, choroidal atrophy, color blindness, and high myopia, the average age of onset of night blindness is 12.9 ± 14 (range, 0–65; median, 8). Posterior subcapsular opacities is the most common forms of secondary cataracts (nine cases, 39.1%), and peripheral choroidal atrophy is the most common form of secondary choroidal atrophy (12 cases, 52.2%). Of these probands with complication peripheral choroidal atrophy, there were eight probands (66.7%, 8/12) caused by the pathogenic variation in USH2A gene. A total of 17 genes and 45 variants were detected in 23 probands. Among these genes, the commonest genes were USH2A (40%; 18/45), RP1 (15.6%; 7/45), and EYS (8.9%; 4/45), and the top three genes account for 56.5% (13/23) of diagnostic probands. Among these variants, comprising 22 (48.9%) pathogenic variants, 14 (31%) likely pathogenic variants, and nine (20%) uncertain clinical significance variants, and 22 variants was discovered first time. Most of the mutations associated with RP were missense (53.3%, 24/45), and the remaining mutation types include frameshift (35.6%, 16/45), nonsense (6.7%, 3/45), and spliceSite (4.4%, 2/45). Among the probands with mutations detected, compound heterozygous forms was detected in 13 (56.5%, 13/23) probands, and digenic inheritance (DI) forms was detected in five (21.7%, 5/23) probands. Conclusion Panel‐based targeted exome sequencing revealed 23 novel mutations, recognized different combinations forms of variants, and extended the mutational spectrum of retinitis pigmentosa and depicted common variants in northeast China., We applied panel‐based targeted exome sequencing to explore the pathogenic variation spectrum and genetic characteristics of retinitis pigmentosa populations in northeast China, and have a deeper understanding of the relationship between clinical manifestations and genotypes.
- Published
- 2020
28. Genetic and clinical analysis in Chinese patients with retinitis pigmentosa caused by EYS mutations
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Ling Xu, Jin‐yue Bai, Wei He, Lusheng Wang, Fang Chen, Wei Li, Bo Xing, Yan Sun, Jiankang Li, Wang Zhuoshi, and Jianguo Zhang
- Subjects
0301 basic medicine ,Proband ,panel‐based targeted exome sequencing ,Adult ,Male ,Heterozygote ,lcsh:QH426-470 ,Genetic counseling ,panel-based targeted exome sequencing ,030105 genetics & heredity ,Compound heterozygosity ,blue blindness ,Frameshift mutation ,03 medical and health sciences ,symbols.namesake ,retinitis pigmentosa ,Retinitis pigmentosa ,Genetics ,Medicine ,Humans ,Eye Proteins ,Frameshift Mutation ,Molecular Biology ,Genetics (clinical) ,Exome sequencing ,Sanger sequencing ,business.industry ,Homozygote ,Original Articles ,Middle Aged ,medicine.disease ,Pedigree ,lcsh:Genetics ,030104 developmental biology ,Phenotype ,Mutation (genetic algorithm) ,symbols ,mutation spectrum ,Original Article ,Female ,business - Abstract
Background Panel‐based targeted exome sequencing was applied to identify the pathogenic variants and genetic characteristics of retinitis pigmentosa (RP) in two Chinese families, and to gain a deeper understanding of the relationship between clinical manifestations and genotypes. Methods A total of 17 subjects, comprising two probands (total patients: four subjects) and their family member, were recruited in this study. All subjects underwent comprehensive ophthalmic examinations and clinical evaluations, and the complete history and medical records were collected according to the standard procedures. All participants were screened using the multigene panel test (Target_Eye_792_V2 chip), and Sanger sequencing was used to confirm the candidate variants. Results Among these two families, a total of three novel mutations in the EYS gene were identified in patients, including a homozygous frameshift mutation c.9252_9253insT detected in two patients in one family, and the compound heterozygous splicesite mutation c.5644+2T>C and frameshift mutation c.1920_1923delTGAG detected in two patients in the another family. All patients in both families had early onset of night blindness and poor visual acuity, and with typical posterior capsule opacification. The mutation co‐segregated within all recruited individuals. In addition, one patient with compound heterozygous mutations was found to have typical blue‐blindness symptoms and detected a previously reported disease‐causing mutation c.235G>A in OPN1SW gene, which caused blue blindness manifestations and was first discovered in patient combined with RP causative genes. Conclusions Panel‐based targeted exome sequencing was used to identify three novel variants of RP causative gene, and we also detected a known pathogenic variants of blue‐blindness causative genes in two patients. Our finding will provide a powerful basis for genetic counseling and enhance our current understanding of the genetics factors for RP families., We applied panel‐based targeted exon sequencing to explore the pathogenic variation spectrum and genetic characteristics of retinitis pigmentosa populations in two Chinese families, and have a deeper understanding of the relationship between clinical manifestations and genotypes.
- Published
- 2020
29. LYW-6, a novel cryptotanshinone derived STAT3 targeting inhibitor, suppresses colorectal cancer growth and metastasis
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Maode Lai, Lingnan Guan, Jiankang Li, Siyi Chen, Wenying Yu, Huan Wang, and Zhe Liu
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0301 basic medicine ,STAT3 Transcription Factor ,Apoptosis ,Mice, SCID ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Western blot ,Cell Movement ,Mice, Inbred NOD ,medicine ,Toxicity Tests, Acute ,Animals ,Humans ,Neoplasm Invasiveness ,Viability assay ,Neoplasm Metastasis ,STAT3 ,Cell Proliferation ,Pharmacology ,Mice, Inbred ICR ,biology ,medicine.diagnostic_test ,Chemistry ,Kinase ,Cell Cycle ,Cell cycle ,Phenanthrenes ,medicine.disease ,HCT116 Cells ,Xenograft Model Antitumor Assays ,Molecular Docking Simulation ,030104 developmental biology ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,STAT protein ,Phosphorylation ,Caco-2 Cells ,Colorectal Neoplasms ,Protein Binding - Abstract
The constitutive activation of signal transducer and activator of transcription 3(STAT3) is associated with aggressive development and metastasis in colorectal cancer (CRC), but STAT3-targeting drugs remain elusive in clinic. Here, structure-based strategy was used to remodel the natural compound cryptotanshinone into a more effective STAT3 inhibitor LYW-6. Using the Biolayer Interferometry assay, we observed that LYW-6 exhibited specific interactions with STAT3(KD = 6.6 ± 0.7 μM). Western blot analysis and electrophoretic mobility shift assays (EMSA) showed that LYW-6 inhibited the phosphorylation of STAT3 tyrosine 705 (Tyr-705) and had slight effects on STAT1 and STAT5 phosphorylation. Western blot analysis on the upstream kinases of STAT3 confirmed that the inhibitory mechanism on p-STAT3 was independent of upstream kinases. Further investigation demonstrated that LYW-6 downregulated the expression of downstream oncogenes to inhibit cell viability, cell cycle development, and potently increased cell apoptosis in human CRC cells. The invasion and metastasis linked signaling was also blocked by LYW-6 treatment. LYW-6 was found to reduce the metastasis foci in lung on tail-lung metastasis models. In addition, it was observed that LYW-6 markedly diminished STAT3 phosphorylation in tumor tissue and significantly inhibited tumor growth on xenograft models. Tumor development on chemically-induced colorectal cancer model also significantly inhibited by LYW-6 treatment. These findings provided adequate evidence that STAT3 inhibitor LYW-6 might be a potential candidate agent for CRC treatment.
- Published
- 2019
30. Pollen Competition and Paternal Contribution during Artificially Controlled Pollination of Black Locust (Robinia pseudoacacia L.) without Castration
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Qi Guo, Yingming Fan, Yun Li, Zijie Zhang, Xiuyu Li, Yuhan Sun, Ruiyang Hu, Cui Long, Sen Cao, Li Dong, Peiyao Han, Chao Han, Jiankang Li, and Saleem Uddin
- Subjects
biology ,Pollination ,Offspring ,Selfing ,Zoology ,Forestry ,Outcrossing ,honeybee ,biology.organism_classification ,medicine.disease_cause ,chemistry.chemical_compound ,Castration ,chemistry ,hybridization breeding ,outcrossing rate ,Pollen ,pollen competition ,medicine ,QK900-989 ,without castration ,Mating ,Plant ecology ,Robinia pseudoacacia L ,artificial controlled pollination ,Locust - Abstract
(1) Background: Considering the serious damage caused by castration and the extremely high outcrossing rate in nature, we hypothesized that artificial controlled pollination of black locust without castration could be conducted for hybridization breeding. (2) Methods: The study conducted controlled pollination on 20 mating combinations of black locust without castration using a single or mixed male parent. Offspring of different developmental stages and the leaves of parents were collected to extract DNA and perform paternity analysis using SSR molecular markers. (3) Results: The contribution rate of each male parent differed according to developmental stage after pollination using different pollens mixed in equal proportions. There were significant correlations between the genetic similarity between each male parent and female parent and contribution rate of each male parent at three different developmental stages after pollination. (4) Conclusions: The composition of offspring pollen donors showed no bias toward selfing or outcrossing when artificially pollinated without castration. Hybrid breeding of black locust by artificially controlled pollination without castration may not be feasible, given that our manual method resulted in a large number of abortive and abnormal offspring. Introduction of honeybees in a limited space to conduct controlled pollination of black locust for hybrid breeding may be feasible.
- Published
- 2021
31. Hydrogel Preparation Methods and Biomaterials for Wound Dressing
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Jingan Li, Jiankang Li, Jiaheng Liang, Jingjing Su, and Kun Zhang
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Biocompatibility ,Skin wound ,Science ,wound healing ,Review ,General Biochemistry, Genetics and Molecular Biology ,Synthetic materials ,Preparation method ,Medicine ,hydrogels ,Ecology, Evolution, Behavior and Systematics ,synthetic materials ,integumentary system ,business.industry ,technology, industry, and agriculture ,Paleontology ,equipment and supplies ,Space and Planetary Science ,Wound dressing ,Self-healing hydrogels ,business ,Wound healing ,human activities ,natural biomaterials ,Biomedical engineering - Abstract
Wounds have become one of the causes of death worldwide. The metabolic disorder of the wound microenvironment can lead to a series of serious symptoms, especially chronic wounds that bring great pain to patients, and there is currently no effective and widely used wound dressing. Therefore, it is important to develop new multifunctional wound dressings. Hydrogel is an ideal dressing candidate because of its 3D structure, good permeability, excellent biocompatibility, and ability to provide a moist environment for wound repair, which overcomes the shortcomings of traditional dressings. This article first briefly introduces the skin wound healing process, then the preparation methods of hydrogel dressings and the characteristics of hydrogel wound dressings made of natural biomaterials and synthetic materials are introduced. Finally, the development prospects and challenges of hydrogel wound dressings are discussed.
- Published
- 2021
32. Variants of the ACTG2 gene correlate with degree of severity and presence of megacystis in chronic intestinal pseudo-obstruction
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Margherita Lerone, Yiran Guo, Roberto De Giorgio, Marta Rusmini, Arrigo Barabino, Roberto Ravazzolo, Alessio Pini Prato, Giuseppe Martucciello, Hakon Hakonarson, Jiankang Li, Paolo Nozza, Ivana Matera, Vincenzo Stanghellini, Marcella Devoto, Marco Di Duca, Francesco Morandi, Jianguo Zhang, Manuela Mosconi, Isabella Ceccherini, Matera, Ivana, Rusmini, Marta, Guo, Yiran, Lerone, Margherita, Jiankang, Li, Zhang, Jianguo, Di Duca, Marco, Nozza, Paolo, Mosconi, Manuela, Prato, Alessio Pini, Martucciello, Giuseppe, Barabino, Arrigo, Morandi, Francesco, DE GIORGIO, Roberto, Stanghellini, Vincenzo, Ravazzolo, Roberto, Devoto, Marcella, Hakonarson, Hakon, and Ceccherini, Isabella
- Subjects
Male ,0301 basic medicine ,Intestinal pseudo-obstruction ,Heterozygote ,Genetics ,Genetics (clinical) ,Colon ,Urinary Bladder ,Short Report ,Mutation, Missense ,Locus (genetics) ,Biology ,Bioinformatics ,Chronic intestinal pseudo-obstruction ,NO ,Young Adult ,03 medical and health sciences ,symbols.namesake ,Birth defect ,Genetic ,medicine ,Humans ,Missense mutation ,Abnormalities, Multiple ,Exome ,Child ,Myopathy ,Conserved Sequence ,Exome sequencing ,ACTG2 ,Sanger sequencing ,Intestinal Pseudo-Obstruction ,Infant ,Megacystis ,medicine.disease ,Actins ,Chronic intestinal pseudo-obstruction (CIPO) ,malformation ,ACTG2, mutation ,030104 developmental biology ,symbols ,Female ,mutation ,medicine.symptom - Abstract
Chronic intestinal pseudo-obstruction (CIPO) syndromes are heterogeneous gastrointestinal disorders, caused by either neuropathy or myopathy, resulting in compromised peristalsis and intestinal obstruction. CIPO can have a profound impact on quality of life, leading the most severely affected individuals to life-long parenteral nutrition and urinary catheterization. To search for disease causing gene(s), we performed the whole exome sequencing (WES) in both eight sporadic and two familial cases, followed by targeted sequencing in additional CIPO patients. After identifying a heterozygous missense variant in the ACTG2 gene in one of 10 patients undergone WES, targeted Sanger sequencing of this gene allowed to detect heterozygous missense variants in 9 of 23 further patients with either megacystis-microcolon-intestinal hypoperistalsis syndrome or intestinal pseudo-obstruction. Variants thus identified, one of which still unreported, affect highly conserved regions of the ACTG2 gene that encodes a protein crucial for correct enteric muscle contraction. These findings provided evidence for a correlation between the clinical phenotype and genotype at the ACTG2 locus, a first step to improve the diagnosis and prognosis of these severe conditions.
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- 2016
33. A start codon mutation of the TSPAN12 gene in Chinese families causes clinical heterogeneous familial exudative vitreoretinopathy
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Jin‐yue Bai, Yan Sun, Lusheng Wang, Xiao Sun, Wei He, Zi-Wei Wang, Jiankang Li, Wei Li, Bo Xing, and Wang Zhuoshi
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Male ,0301 basic medicine ,Proband ,China ,medicine.medical_specialty ,lcsh:QH426-470 ,Tetraspanins ,Familial Exudative Vitreoretinopathies ,Genetic counseling ,Mutation, Missense ,Codon, Initiator ,030105 genetics & heredity ,Eye ,Severity of Illness Index ,03 medical and health sciences ,symbols.namesake ,start codon mutation ,Genetics ,Humans ,Medicine ,Missense mutation ,Family history ,Child ,Molecular Biology ,Genetics (clinical) ,Ultrasonography ,Sanger sequencing ,fundus fluorescein angiography ,business.industry ,High-Throughput Nucleotide Sequencing ,Original Articles ,medicine.disease ,Pedigree ,lcsh:Genetics ,Phenotype ,030104 developmental biology ,clinical heterogeneous manifestations ,Mutation (genetic algorithm) ,Familial exudative vitreoretinopathy ,symbols ,Medical genetics ,Original Article ,business - Abstract
Background Familial exudative vitreoretinopathy (FEVR) is a severe clinically and genetically heterogeneous retinal disorder characterized with failure of vascular development of the peripheral retina. The symptoms of FEVR vary widely among patients in the same family, and even between the two eyes of a given patient. The purpose of this study was to investigate the molecular mechanisms by which the start codon mutation of the TSPAN12 causes difference in clinical manifestations between individuals in the same family. Methods Next‐generation sequencing (NGS)‐based target capture sequencing was performed in proband with a diagnosis of FEVR and their normal visual acuity family members. Cosegregation analysis of the candidate causative variant was performed in additional family members by using Sanger sequencing. Complete fundus examination, fundus fluorescein angiography (FFA), and family history collection were performed in all family members. Potential candidate causative variants were verified with reference to guidelines and standards from the American College of Medical Genetics and Genomics. Results We identified a novel heterozygous missense mutation (c.1A>G, p.M1V) localized in the start codon of the TSPAN12 and was detected as a potentially disease‐causing variant for the proband. Retrospective analysis of clinical data, fundus examination, and FFA showed that the mutant carrier presented peripheral retinal vascular anomalies in early stages, and visual acuity did not show significant effects. However, the proband who carried this mutation and his cousin showed typical high‐stage FEVR fundus changes coupled with a sharp decline in vision. Conclusions We report a novel start codon mutation (c.1A>G, p.M1V) in the TSPAN12 that causes clinically heterogeneous manifestations. Our results expand the mutation spectrums of TSPAN12, and will be valuable for disease diagnosis, prognosis, genetic counseling, and enriching our understanding of the role of the tetraspanin‐12 protein in the pathogenesis of FEVR.
- Published
- 2019
34. Next-generation sequencing-aided precise diagnosis of Stickler syndrome type I
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Rui Jiang, Qing Chang, Fang-Yuan Hu, Ping Xu, Jihong Wu, Shenghai Zhang, Jiankang Li, Feng-Juan Gao, and Dan-Dan Wang
- Subjects
Adult ,Male ,China ,Hearing Loss, Sensorineural ,DNA Mutational Analysis ,Computational biology ,DNA sequencing ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,In patient ,Stickler syndrome ,Connective Tissue Diseases ,Collagen Type II ,Genetic testing ,Retrospective Studies ,Chinese population ,medicine.diagnostic_test ,business.industry ,Arthritis ,Incidence ,Retinal Detachment ,High myopia ,High-Throughput Nucleotide Sequencing ,General Medicine ,Gold standard (test) ,DNA ,medicine.disease ,Ophthalmology ,Mutation ,030221 ophthalmology & optometry ,Female ,business ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
PURPOSE To explore an early, rapid and precise diagnosis of Stickler syndrome type I (STL1) and to enrich the spectrum of COL2A1 mutations in the Chinese population, which is poorly studied at present. METHODS In the current study, we analysed 115 patients with high myopia by next-generation sequencing and identified five STL1 patients from four unrelated Chinese families. The clinical features of all patients were reviewed in detail. RESULTS Four variants of COL2A1 were identified, including two novel variants (c.1435delG and c.184delG) and two previously reported variants (c.1221+1G>A and c.1030C>T). Three variants caused premature termination codons which were common in STL1. In addition, we proposed a new diagnostic tactic to improve early diagnostics of STL1 in patients. CONCLUSION In this study, our findings expanded the spectrum of COL2A1 mutations with two novel variants and provided a new diagnostic tactic for reference, which was of great significance. Precise diagnosis on the basis of clinical manifestations and genetic testing will become the gold standard to diagnose inherited ocular disorders or syndromes in the future.
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- 2019
35. Single cell RNA sequencing reveals cellular diversity of trisomy 21 retina
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Shen Xue, Jiacheng Zhu, Feng-Juan Gao, Dan-Dan Wang, Jihong Wu, Wei Li, Shenghai Zhang, Ping Xu, Jixing Zhong, Jun Xia, Shiyou Wang, Ya Gao, Chaochao Chai, Jiankang Li, Yin Chen, Zhikai He, Xiangning Ding, Zaoxu Xu, Qikai Feng, Fang-Yuan Hu, Guanglin Guo, Jingxuan Zhang, Sanjie Jiang, Xinghuai Sun, Xiumei Lin, Daowei Zhang, Fang Chen, Dongsheng Chen, and Langchao Liang
- Subjects
Retina ,Cell type ,genetic structures ,Cell ,Aneuploidy ,RNA ,Computational biology ,Biology ,Cellular level ,medicine.disease ,eye diseases ,medicine.anatomical_structure ,medicine ,sense organs ,Trisomy ,Chromosome 21 - Abstract
Retina is a crucial tissue for the capturing and processing of light stimulus. Characterization of the retina at single cell level is essential for the understanding of its biological functions. A variety of abnormalities in terms of morphology and function were reported in T21 retina. To evaluate the effects of chromosome aneuploidy on retina development, we characterized single cell transcriptional profiles of a T21 fetus and performed comprehensive bioinformatic analyses. Our data revealed the diversity and heterogeneity of cellular compositions in T21 retina. In total, we identified seven major cell types, and detected several subtypes within each cell type, followed by the detection of corresponding molecular markers including previously reported ones and a series of novel markers. Our analyses identified extensive communication networks between distinct cellular types, among which a few ligand-receptor interactions were associated with the development of retina and immunoregulatory interactions. Taken together, our data provided the first single cell transcriptome profile for human T21 retina which facilitates our understanding on the dosage effects of chromosome 21 on the development of retina.
- Published
- 2019
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36. Tyrosine and Glutamine-Leucine Are Metabolic Markers of Early-Stage Colorectal Cancers
- Author
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Maode Lai, Jiankang Li, Lian-Wen Qi, Huan Wang, Zhu Yimin, and Jing Li
- Subjects
Male ,Spectrometry, Mass, Electrospray Ionization ,Colorectal cancer ,Glutamine ,Metabolomics ,Leucine ,medicine ,Biomarkers, Tumor ,Humans ,Tyrosine ,Stage (cooking) ,Aged ,Neoplasm Staging ,Metabolic Syndrome ,Principal Component Analysis ,Hepatology ,business.industry ,Gastroenterology ,Dipeptides ,Middle Aged ,medicine.disease ,Case-Control Studies ,Cancer research ,Biomarker (medicine) ,Female ,Metabolic syndrome ,business ,Colorectal Neoplasms - Published
- 2019
37. Expanding the clinical and genetic spectrum of Heimler syndrome
- Author
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Ping Xu, Qing Chang, Yu-He Qi, Fang-Yuan Hu, Jihong Wu, Gezhi Xu, Feng-Juan Gao, Fang Chen, Jiankang Li, Fang Song, Si-Mai Shen, and Yongjin Zhang
- Subjects
Male ,0301 basic medicine ,Amelogenesis Imperfecta ,Usher syndrome ,lcsh:Medicine ,medicine.disease_cause ,Bioinformatics ,0302 clinical medicine ,Genotype ,Medicine ,Missense mutation ,Pharmacology (medical) ,030212 general & internal medicine ,Child ,Genetics (clinical) ,Heimler syndrome ,Mutation ,High-Throughput Nucleotide Sequencing ,General Medicine ,Middle Aged ,Pedigree ,Phenotype ,Genotype–phenotype ,Genetic diagnosis ,Female ,Adult ,Adolescent ,Hearing Loss, Sensorineural ,Genetic counseling ,Mutation, Missense ,Nails, Malformed ,Young Adult ,03 medical and health sciences ,Retinitis pigmentosa ,Humans ,PEX1 ,business.industry ,Research ,lcsh:R ,Membrane Proteins ,PEX6 ,medicine.disease ,Human genetics ,030104 developmental biology ,Next-generation sequencing ,ATPases Associated with Diverse Cellular Activities ,business - Abstract
Background Heimler syndrome (HS) is a rare hereditary systemic disorder, partial clinically overlapping with Usher syndrome. So far, our knowledge of HS is very limited, many cases are misdiagnosed or may not even be diagnosed at all. This study aimed to analyze the clinical and genetic characteristics of HS, and to evaluate potential phenotype–genotype correlations. Results Two HS cases caused by PEX1 mutations were identified, and a novel likely pathogenic mutation, PEX1 c.895_896insTATA, was found. The main ophthalmic finding of the two patients was consistent with retinitis pigmentosa accompanied by cystoid macular edema, but short axial length and hyperopia were also observed as two previously unreported ocular phenotypes. Analysis of the literature showed that of the 29 HS patients previously reported, 12 had PEX6 mutations, 10 had PEX1 mutations, two had PEX26 mutations, and the remaining patients were not genetically tested. Three novel genotype–phenotype correlations were revealed from analysis of these patients. First, most genotypes of every HS patient include at least one missense variant; second, at least one mutation in PEX1 or PEX6 gene affects the AAA-ATPase region in every HS patient with retinal dystrophy, suggesting AAA-ATPase region is a hypermutable region in patients with a retinal dystrophy; third, there are no significant differences between PEX1-, PEX6-, and PEX26-associated phenotypes. Conclusion Next-generation sequencing is important for the diagnosis of HS. This study expands the clinical and genetic spectrum of HS, and provides additional insights into genotype–phenotype correlations, which is vital for accurate clinical practice, genetic counseling, and pathogenesis studies.
- Published
- 2019
38. Metabolomics Study on the Effects of Salvianolic Acid B and Borneol for Treating Cerebral Ischemia in Rats by Ultra-Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry
- Author
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Xin Ma, Wenting Duan, Xingli Ge, Jiankang Li, Jianzhuang Lv, Lin Wang, Kai Gao, Shaobo Qin, and Yiqing Lu
- Subjects
0301 basic medicine ,Male ,Aging ,Ischemia ,Mass spectrometry ,Neuroprotection ,Mass Spectrometry ,Borneol ,Brain Ischemia ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Metabolomics ,Malondialdehyde ,parasitic diseases ,medicine ,Animals ,cardiovascular diseases ,Stroke ,Chromatography, High Pressure Liquid ,Benzofurans ,Principal Component Analysis ,Chromatography ,Camphanes ,Metabolism ,medicine.disease ,Bioactive compound ,Oxidative Stress ,030104 developmental biology ,chemistry ,Multivariate Analysis ,Metabolome ,Geriatrics and Gerontology ,030217 neurology & neurosurgery ,Metabolic Networks and Pathways - Abstract
Salviae miltiorrliza-borneol Jun-Shi coupled-herbs have been widely used for treatment of ischemia stroke. Salvianolic acid B was the most abundant and bioactive compound of Salviae miltiorrliza and used for prevention and treatment of cerebrovascular diseases. However, the scientific intension and compatible mechanism of Salvianolic acid B - borneol combination were still unknown. A metabolomics study approach based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) combined with a pathological study has been applied to study the metabolic disturbances of cerebral ischemia and evaluate the efficacies of Sal B and Sal B/borneol against cerebral ischemia in middle cerebral artery occlusion (MCAO) rats. The neuroprotection of Sal B and Sal B/borneol was reversed through the evaluation of neurological deficits, infarct volume, and neuronal apoptosis in MCAO model. The metabonomic analysis revealed that the MCAO-induced cerebral ischemia could be ameliorated by Sal B through improving the energy metabolism, lipids metabolism, inflammatory responses, and oxidant stress. Borneol could enhance the neuroprotective effects, was associated with the increased concentration of Sal B, and attenuate the function of sphingolipid metabolism pathway in cerebral ischemia rats. These findings perhaps clarify the mechanism of neuroprotective effects of treating ischemia stroke by Sal B or Sal B/borneol preliminarily through metabolomics and push the quality promotion and the composition of borneol/Sal B in secondary development of prescription.
- Published
- 2018
39. Congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty have distinct genetic architectures
- Author
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Johannes R. Lemke, Daniel Konrad, Jean-Marc Ferrara, Nelly Pitteloud, Lucie Favre, Christian De Geyter, Özlem Turhan Iyidir, Federico Santoni, Duarte Pignatelli, Vera Popovic, Franziska Phan-Hug, Sandra Pekic, Sara Santini, Richard Quinton, Huanming Yang, Waljit S. Dhillo, James S Acierno, Saba Sharif, Cheng Xu, Dagmar l'Allemand, Jiankang Li, Laura Marino, Jenny Meylan, Brian Stevenson, Michael Hauschild, Georgios Papadakis, Xuanzhu Liu, Mariarosaria Lang-Muritano, Attila Nemeth, Sasha Howard, Anne De Paepe, Christa E. Flück, Caroline Chambion, Gabor Szinnai, Leo Dunkel, Andrew A. Dwyer, Pierre-Marc Bouloux, Jianguo Zhang, Gerasimos P. Sykiotis, and Daniele Cassatella
- Subjects
0301 basic medicine ,Proband ,Delayed puberty ,Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Early adolescence ,030209 endocrinology & metabolism ,610 Medicine & health ,Biology ,Delayed diagnosis ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Internal medicine ,medicine ,Humans ,In patient ,Exome sequencing ,Finland ,Growth Disorders ,Aged ,Puberty, Delayed ,Female ,Finland/epidemiology ,Growth Disorders/diagnosis ,Growth Disorders/epidemiology ,Growth Disorders/genetics ,Hypogonadism/diagnosis ,Hypogonadism/epidemiology ,Hypogonadism/genetics ,Middle Aged ,Mutation/genetics ,Puberty, Delayed/diagnosis ,Puberty, Delayed/epidemiology ,Puberty, Delayed/genetics ,business.industry ,Hypogonadism ,General Medicine ,030104 developmental biology ,Mutation ,Clinical Study ,Congenital Hypogonadotropic Hypogonadism ,Differential diagnosis ,medicine.symptom ,business - Abstract
Objective Congenital hypogonadotropic hypogonadism (CHH) and constitutional delay of growth and puberty (CDGP) represent rare and common forms of GnRH deficiency, respectively. Both CDGP and CHH present with delayed puberty, and the distinction between these two entities during early adolescence is challenging. More than 30 genes have been implicated in CHH, while the genetic basis of CDGP is poorly understood. Design We characterized and compared the genetic architectures of CHH and CDGP, to test the hypothesis of a shared genetic basis between these disorders. Methods Exome sequencing data were used to identify rare variants in known genes in CHH (n = 116), CDGP (n = 72) and control cohorts (n = 36 874 ExAC and n = 405 CoLaus). Results Mutations in at least one CHH gene were found in 51% of CHH probands, which is significantly higher than in CDGP (7%, P = 7.6 × 10−11) or controls (18%, P = 5.5 × 10−12). Similarly, oligogenicity (defined as mutations in more than one gene) was common in CHH patients (15%) relative to CDGP (1.4%, P = 0.002) and controls (2%, P = 6.4 × 10−7). Conclusions Our data suggest that CDGP and CHH have distinct genetic profiles, and this finding may facilitate the differential diagnosis in patients presenting with delayed puberty.
- Published
- 2018
40. Novel variants associated with Stargardt disease in Chinese patients
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Fang-Yuan Hu, Jihong Wu, Feng-Juan Gao, Jiankang Li, Shenghai Zhang, Ping Xu, Fang Chen, and Dan-Dan Wang
- Subjects
Adult ,Genetic Markers ,Male ,0301 basic medicine ,Untranslated region ,ABCA4 ,medicine.disease_cause ,Genetic analysis ,Young Adult ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Asian People ,Genetics ,medicine ,Humans ,Stargardt Disease ,Missense mutation ,Child ,Eye Proteins ,Gene ,Mutation ,biology ,Genetic Variation ,High-Throughput Nucleotide Sequencing ,Membrane Proteins ,General Medicine ,medicine.disease ,Pedigree ,Stargardt disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,biology.protein ,ATP-Binding Cassette Transporters ,Female - Abstract
Purpose Stargardt disease (STGD) is the most frequent cause of hereditary macular dystrophy in childhood. Variants in the ABCA4, ELOVL4, PROM1, BEST1, and PRPH2 genes have been detected in patients with autosomal recessive or dominant STGD. This study was aimed at identifying the novel disease-associated variants in Chinese patients with STGD. Methods Ten Chinese families and two sporadic cases with STGD (n = 32) were enrolled in the study. All subjects underwent genetic analysis with next-generation sequencing (NGS), which was based on a specially customized capture panel targeting exons and untranslated regions (UTRs) of 792 genes related to common hereditary ophthalmopathy. Variants were analyzed to assess possible pathogenicity. Results Fourteen disease-associated variants of ABCA4 were detected in 9 Chinese families with autosomal recessive STGD, including 11 pathogenic variants and 3 likely pathogenic variants. Variant c.4253 + 4C > T in ABCA4 was identified as one de novo variant. Of the 14 distinct variants in ABCA4, 7 novel variants were found. In addition, one known variant of PROM1, c.1117C > T (p.Arg373Cys), was detected in one family and one sporadic case with autosomal dominant STGD, respectively. One novel missense variant of ELOVL4, c.59A > G (p.Asn20Ser), was found in one sporadic case with autosomal dominant STGD. The potential deleterious effects of these novel variants were confirmed through intensive analysis. Conclusion By panel-based NGS, 8 novel disease-associated variants are identified in two genes responsible for STGD, including ABCA4 and ELOVL4. Our results further extend the mutation spectrum of these two genes in Chinese patients with STGD. One ABCA4 c.4253 + 4C > T variant is identified as a de novo splicing variant.
- Published
- 2020
41. Pharmacokinetics and bioavailability in healthy Chinese volunteers of a novel rabeprazole sterile powder formulation for injection
- Author
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Fan Li, Jiankang Li, Xueqing Li, Chengtao Lu, Zhongying Ma, Ying Song, Aidong Wen, and Jie Ge
- Subjects
Adult ,Male ,Pharmacology ,Chemistry ,Chemistry, Pharmaceutical ,Enteric coated tablets ,Rabeprazole ,Cmax ,Biological Availability ,Healthy Volunteers ,Treatment period ,Injections ,Bioavailability ,Single oral dose ,Pharmacokinetics ,Oral administration ,Area Under Curve ,medicine ,Humans ,Female ,Pharmacology (medical) ,Powders ,medicine.drug - Abstract
Rabeprazole sterile powder for injection (RSPI) is a new formulation, compared with rabeprazole enteric coated tablets. The aim of this study was to evaluate the pharmacokinetic properties and bioavailability of RSPI in healthy Chinese volunteers. Pharmacokinetic studies included an ascending single dose of 10, 20, 40 mg, and a multiple doses of 20 mg. A bioavailability study was evaluated following a single dose of 20 mg between RSPI and Pariet® Pharmacokinetic parameters of rabeprazole given in each treatment period were calculated using non-compartmental analysis. In the PK study, after a single intravenous dose of 10, 20, and 40 mg, the main pharmacokinetic parameters for rabeprazole were as follows: Cmax 566.88, 897.23, 2,171.6 ng/mL; AUClast/794.31, 1,122.76, 2,446.85 ng×h/mL, respectively. After multiple doses of 20 mg, the main pharmacokinetic parameters for rabeprazole were Cmax 991.90 ng/mL, AUClast 1,261.08 ng×h/mL. In the BA study, after a single oral dose of Pariet® 20 mg, the main pharmacokinetic parameters for rabeprazole were Cmax 582.74 ng/mL, AUClast 1,135.5 ng×h/mL. RSPI produced a less-than-proportional increase in exposure with increasing dose in healthy subjects. The accumulation ratio was 1.0, suggesting RSPI displayed no accumulation after repeated administration. The bioavailability of RSPI was increased by ~ 11% as measured by AUClast compared with Pariet® after a single oral administration.
- Published
- 2016
42. Safflower yellow B suppresses HepG2 cell injury induced by oxidative stress through the AKT/Nrf2 pathway
- Author
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Chengtao Lu, Aidong Wen, Xiaohu Zhai, Caixia Li, Jing Niu, Qian Ren, Jin Sun, Wei Song, Yi Qiao, Jiankang Li, and Zhongying Ma
- Subjects
0301 basic medicine ,NF-E2-Related Factor 2 ,medicine.disease_cause ,Superoxide dismutase ,03 medical and health sciences ,chemistry.chemical_compound ,Chalcone ,0302 clinical medicine ,Genetics ,medicine ,Humans ,Viability assay ,Propidium iodide ,HepG2 cells ,Protein kinase B ,Membrane Potential, Mitochondrial ,chemistry.chemical_classification ,biology ,Superoxide Dismutase ,Akt ,Glutathione peroxidase ,Articles ,Hep G2 Cells ,Hydrogen Peroxide ,General Medicine ,Malondialdehyde ,Molecular biology ,Heme oxygenase ,Oxidative Stress ,030104 developmental biology ,nuclear factor erythroid 2-related factor 2 ,Biochemistry ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,safflower yellow B ,Oxidation-Reduction ,Oxidative stress - Abstract
Oxidative stress plays an important role in the pathogenesis of various liver diseases. Safflower yellow B (SYB) has been reported to protect the brain against damage induced by oxidative stress; however, whether SYB can also protect hepatocytes from oxidative stress remains unknown. In the present study, to determine whether pre-treatment with SYB reduces hydrogen peroxide (H2O2)‑induced oxidative stress in HepG2 cells, we investigated H2O2-induced oxidative damage to HepG2 cells treated with or without SYB. Cell viability was measured by MTT assay and cytotoxicity was evaluated by lactate dehydrogenase (LDH) assay. The activities of the antioxidant enzymes, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were determined using respective kits. Intracellular reactive oxygen species (ROS) accumulation in the HepG2 cells was monitored using the fluorescent marker, 2',7'-dichlorodihydrofluorescein diacetate (H2DCF-DA). Cell apoptosis was evaluated by determining the activity of caspase-3 and by Annexin V/propidium iodide (PI) double staining. Protein expression levels were measured by western blot analysis, and the levels of related cellular kinases were also determined. H2O2 induced pronounced injury to the HepG2 cells, as evidenced by increased levels of malondialdehyde (MDA) and ROS, the decreased activity of SOD and GSH-Px, the increased activitation of caspase-3 and cell apoptosis, and the loss of mitochondrial membrane potential. SYB significantly inhibited the damaging effects of H2O2, indicating that it protected the cells against H2O2-induced oxidative damage. Moreover, pre-treatment with SYB increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1) and NAD(P)H dehydrogenase, quinone 1 (NQO1) which are peroxiredoxins. SYB also significantly increased the phosphorylation of AKT. However, this inductive effect was blunted in the presence of the AKT inhibitor, LY294002. The findings of our study suggest that the activation of the AKT/Nrf2 pathway is involved in the cytoprotective effects of SYB against oxidative stress. Our findings provide new insight into the cytoprotective effects of SYB and the possible mechanisms underlying these effects. Thus, SYB may prove to be of therapeutic value for the treatment of various liver diseases.
- Published
- 2016
43. Effect of Food on the Single-dose Pharmacokinetics and Tolerability of Subutinib and its Active Metabolite in Chinese Healthy Volunteers
- Author
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Wei Song, Likun Ding, M.-h. Wang, Chao Wang, Na Jia, Lijun Yang, X.-h. Gao, Jiankang Li, and Aidong Wen
- Subjects
Adult ,Indoles ,Cmax ,Biological Availability ,Capsules ,Pharmacology ,Eating ,Food-Drug Interactions ,Young Adult ,Asian People ,Pharmacokinetics ,Drug Discovery ,Healthy volunteers ,Humans ,Medicine ,Pyrroles ,Active metabolite ,FOOD EFFECT ,Cross-Over Studies ,business.industry ,Fasting ,General Medicine ,Crossover study ,Healthy Volunteers ,Tolerability ,Food ,Area Under Curve ,Female ,Drug intoxication ,business - Abstract
The aim of this study is to investigate a food effect on the single-dose pharmacokinetics and tolerability of subutinib maleate capsules in healthy Chinese volunteers. The author evaluated the effect of being under a fasting or fed state at the time of drug intake on the single-dose of subutinib maleate capsules in a randomized, balanced, single-dose, 2-treatment (fasting and fed), 2-period design with a 3-week washout period. The end points were the maximum plasma drug concentration (Cmax) and areas under the plasma-concentration curve (AUC) for 336 h exposure (AUC0-336) and total exposure (AUC0-∞). All volunteers completed the whole study without side effects being observed. For subutinib, Cmax were 6.13 and 5.04 ng·mL(-1), and AUC0-336 were 278.4 and 304.5 h·ng·mL(-1) in the fasting and the fed state, respectively. For active metabolite, Cmax were 0.90 and 0.61 ng·mL(-1), and AUC0-336 were 65.5 and 56.4 h·ng·mL(-1) in the fasting and the fed state, respectively. The authors showed that food intake was associated with a slight increase in AUC values but decrease in Cmax of subutinib, and it was associated with a decrease both in AUC and Cmax of active metabolite.
- Published
- 2015
44. Mutation Screening of mtDNA Combined Targeted Exon Sequencing in a Cohort With Suspected Hereditary Optic Neuropathy
- Author
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Fang Chen, Shou-Fang Qu, Li-Li Li, Feng-Juan Gao, Jihong Wu, Shenghai Zhang, Jie Huang, Lusheng Wang, Zi-Wei Wang, Wei Li, Fang-Yuan Hu, Yong Qiu, and Jiankang Li
- Subjects
0301 basic medicine ,Proband ,Genetic counseling ,Biomedical Engineering ,Optic Atrophy, Hereditary, Leber ,DNA, Mitochondrial ,Genetic analysis ,Article ,Haplogroup ,Optic neuropathy ,panel-based targeted exon sequencing ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Optic Nerve Diseases ,autosomal dominant optic atrophy ,Humans ,Medicine ,Exome sequencing ,Genetics ,mtDNA ,business.industry ,Membrane Proteins ,Exons ,medicine.disease ,eye diseases ,Ophthalmology ,030104 developmental biology ,Mutation ,autosomal recessive optic atrophy ,030221 ophthalmology & optometry ,ntDNA ,Leber hereditary optic neuropathy ,business ,Optic nerve disorder - Abstract
Purpose Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) are the two commonest forms of hereditary optic neuropathy. The aim of this study was to comprehensively investigate the incidence and spectrum of mutations in patients with suspected hereditary optic neuropathy by combining mitochondrial DNA (mtDNA) genome-wide and targeted exon sequencing. Methods A cohort of 1101 subjects were recruited to participate in the study, comprising 177 families (177 probands and their family members, a total of 537 subjects, including 254 patients) and 164 sporadic cases with suspected hereditary optic neuropathy, and 400 unrelated control subjects for genetic analysis: all subjects (including control subjects) underwent a comprehensive ophthalmologic examination and were subjected to sequencing analysis of mtDNA genome-wide and targeted exon. Overall, targeted exon sequencing was used to screen 792 genes associated with common hereditary eye diseases, and the mtDNA genome-wide were screened by next-generation sequencing. Results We found variants detected in 168 (40.2%, 168/418) of the 418 patients screened. Among these, 132 cases (78.6%, 132/168) were detected with known LHON disease-causing mtDNA variants; 40 cases (23.8%, 40/168) were detected with nuclear DNA (ntDNA) variants, which included 36 cases (21.4%, 36/168) with detected OPA1 mutations, 4 patients (2.4%, 4/168) with detected OPA3 mutations, and 2 patients (1.2%, 2/168) with detected TMEM126A homozygous mutation. Coexistence variation (mtDNA/mtDNA [n = 16], ntDNA/ntDNA [n = 4], mtDNA/ntDNA [n = 7]) was found in 27 patients (16.4%, 27/165), including mtDNA/ntDNA coexistence variation that was detected in seven patients. Among these ntDNA mutations, 38 distinct disease-causing variants, including autosomal recessive heterozygous mutations, were detected, which included 22 novel variants and two de novo variants. Total haplogroup distribution showed that 34.5% (29/84) and 28.6% (24/84) of the affected subjects with m.11778G>A belonged to haplogroup D and M, with a high frequency of subhaplogroups D4, D5, and M7. Conclusions The LHON-mtDNA mutations are the commonest genetic defects in this Chinese cohort, followed by the OPA1 mutations. To our knowledge, this is the first comprehensive study of LHON, ADOA, and autosomal recessive optic atrophy combined with mtDNA genome-wide and targeted exon sequencing, as well as haplogroup analysis, in a large cohort of Chinese patients with suspected hereditary optic neuropathy. Our findings provide a powerful basis for genetic counseling in patients with suspected hereditary optic neuropathy. Translational Relevance We applied mtDNA genome-wide sequencing combined with panel-based targeted exon sequencing to explore the pathogenic variation spectrum and genetic characteristics of patients with suspected hereditary optic neuropathy, providing a comprehensive research strategy for clinical assistant diagnosis, treatment, and genetic counseling.
- Published
- 2020
45. Protective Effects of Lycium barbarum Polysaccharide on 6-OHDA-Induced Apoptosis in PC12 Cells through the ROS-NO Pathway
- Author
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Jinyi Cao, Aidong Wen, Yun-Yang Lu, Jiankang Li, Kai Gao, Zhifu Yang, Meiyou Liu, Minna Yao, and Xiaohe Zhu
- Subjects
Nitric Oxide Synthase Type II ,Pharmaceutical Science ,Caspase 3 ,Nitric Oxide Synthase Type I ,Mitochondrion ,Pharmacology ,medicine.disease_cause ,PC12 Cells ,Article ,Analytical Chemistry ,Nitric oxide ,lcsh:QD241-441 ,chemistry.chemical_compound ,lcsh:Organic chemistry ,nitric oxide ,LBP ,Drug Discovery ,medicine ,Animals ,mitochondrion ,Physical and Theoretical Chemistry ,Oxidopamine ,reactive oxygen species ,chemistry.chemical_classification ,Reactive oxygen species ,PC cells ,biology ,Organic Chemistry ,apoptosis ,Caspase 9 ,Rats ,Nitric oxide synthase ,nervous system ,Biochemistry ,chemistry ,Chemistry (miscellaneous) ,Apoptosis ,Parkinson’s disease ,biology.protein ,Molecular Medicine ,Intracellular ,Oxidative stress ,Drugs, Chinese Herbal - Abstract
Oxidative stress plays an important role in Parkinson’s disease and other neurodegenerative disorders. Lycium barbarum polysaccharides (LBP), the main active ingredients extracted from the fruits of Lycium barbarum L., have been shown to be a potent antioxidant. In the present study, we investigated the protective effects, and the possible mechanism of action of LBP against 6-hydroxydopamine (6-OHDA)-induced apoptosis in PC12 cells. Our data demonstrated that LBP significantly reversed the 6-OHDA-induced decrease in cell viability, prevented 6-OHDA-induced changes in condensed nuclei and decreased the percentage of apoptotic cells in a dose-dependent manner. Furthermore, LBP also slowed the accumulation of reactive oxygen species (ROS) and nitric oxide (NO), decreased the level of protein-bound 3-nitrotyrosine (3-NT) and intracellular free Ca2+, and inhibiting the overexpression of nuclear factor κB (NF-κB), neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS). These results demonstrate that LBP prevents 6-OHDA-induced apoptosis in PC12 cells, at least in part through the ROS-NO pathway.
- Published
- 2014
46. Inherited bone marrow failure associated with germline mutation of ACD, the gene encoding telomere protein TPP1
- Author
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Hakon Hakonarson, Juliana Teo, Yiran Guo, Xun Xu, Jiankang Li, Yulan Chen, Tatjana Kilo, Melissa Kartawinata, Tracy M. Bryan, Roger R. Reddel, Hilda A. Pickett, Lifeng Tian, Ahmad Al-Odaib, Brendan J. Keating, John Christodoulou, and Pasquale M Barbaro
- Subjects
Adult ,Male ,Telomerase ,Molecular Sequence Data ,Telomere-Binding Proteins ,Immunology ,Plenary Paper ,Inheritance Patterns ,Biology ,Biochemistry ,Shelterin Complex ,Telomerase RNA component ,Germline mutation ,Bone Marrow ,Neoplasms ,medicine ,Humans ,Exome ,Telomerase reverse transcriptase ,RNA, Messenger ,Aplastic anemia ,Child ,Bone Marrow Diseases ,Alleles ,Germ-Line Mutation ,Genome, Human ,Telomere Homeostasis ,Anemia ,Cell Biology ,Hematology ,Middle Aged ,Telomere ,medicine.disease ,Molecular biology ,Pedigree ,Phenotype ,medicine.anatomical_structure ,Cancer research ,Mutant Proteins ,Female ,Bone marrow ,Serine Proteases ,Dyskeratosis congenita - Abstract
Telomerase is a ribonucleoprotein enzyme that is necessary for overcoming telomere shortening in human germ and stem cells. Mutations in telomerase or other telomere-maintenance proteins can lead to diseases characterized by depletion of hematopoietic stem cells and bone marrow failure (BMF). Telomerase localization to telomeres requires an interaction with a region on the surface of the telomere-binding protein TPP1 known as the TEL patch. Here, we identify a family with aplastic anemia and other related hematopoietic disorders in which a 1-amino-acid deletion in the TEL patch of TPP1 (ΔK170) segregates with disease. All family members carrying this mutation, but not those with wild-type TPP1, have short telomeres. When introduced into 293T cells, TPP1 with the ΔK170 mutation is able to localize to telomeres but fails to recruit telomerase to telomeres, supporting a causal relationship between this TPP1 mutation and bone marrow disorders. ACD/TPP1 is thus a newly identified telomere-related gene in which mutations cause aplastic anemia and related BMF disorders.
- Published
- 2014
47. Genetic analysis of impaired trimethylamine metabolism using whole exome sequencing
- Author
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Hui Jiang, Xiao Chang, Jianguo Zhang, Chung Wen Yu, Liang-Dar Hwang, Brendan J. Keating, George Preti, Danielle R. Reed, Yiran Guo, Paul V. Fennessey, Jason Eades, Yulan Chen, Fujiko Duke, Hakon Hakonarson, Corrine Mansfield, Alexis Burdick-Will, Steven Fakharzadeh, and Jiankang Li
- Subjects
Adult ,Male ,0301 basic medicine ,dbSNP ,Adolescent ,Genotype ,Biology ,Polymorphism, Single Nucleotide ,Genetic analysis ,Choline ,Methylamines ,03 medical and health sciences ,INDEL Mutation ,Genetics ,medicine ,Humans ,Genetics(clinical) ,Genetic Testing ,Exome ,Allele frequency ,Genetics (clinical) ,Exome sequencing ,Aged ,Genetic testing ,medicine.diagnostic_test ,DNA ,Sequence Analysis, DNA ,Middle Aged ,Human genetics ,3. Good health ,Smell ,030104 developmental biology ,Biochemistry ,Oxygenases ,Female ,Metabolism, Inborn Errors ,Research Article - Abstract
Background Trimethylaminuria (TMAU) is a genetic disorder whereby people cannot convert trimethylamine (TMA) to its oxidized form (TMAO), a process that requires the liver enzyme FMO3. Loss-of-function variants in the FMO3 gene are a known cause of TMAU. In addition to the inability to metabolize TMA precursors like choline, patients often emit a characteristic odor because while TMAO is odorless, TMA has a fishy smell. The Monell Chemical Senses Center is a research institute with a program to evaluate people with odor complaints for TMAU. Methods Here we evaluated ten subjects by (1) odor evaluation by a trained sensory panel, (2) analysis of their urine concentration of TMA relative to TMAO before and after choline ingestion, and (3) whole exome sequencing as well as subsequent variant analysis of all ten samples to investigate the genetics of TMAU. Results While all subjects reported they often emitted a fish-like odor, none had this malodor during sensory evaluation. However, all were impaired in their ability to produce >90% TMAO/TMA in their urine and thus met the criteria for TMAU. To probe for genetic causes, the exome of each subject was sequenced, and variants were filtered by genes with a known (FMO3) or expected effect on TMA metabolism function (other oxidoreductases). We filtered the remaining variants by allele frequency and predicated functional effects. We identified one subject that had a rare loss-of-function FMO3 variant and six with more common decreased-function variants. In other oxidoreductases genes, five subjects had four novel rare single-nucleotide polymorphisms as well as one rare insertion/deletion. Novel in this context means no investigators have previously linked these variants to TMAU although they are in dbSNP. Conclusions Thus, variants in genes other than FMO3 may cause TMAU and the genetic variants identified here serve as a starting point for future studies of impaired TMA metabolism. Electronic supplementary material The online version of this article (doi:10.1186/s12881-017-0369-8) contains supplementary material, which is available to authorized users.
- Published
- 2017
48. Synergistic efficacy of meropenem and rifampicin in a murine model of sepsis caused by multidrug-resistant Acinetobacter baumannii
- Author
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Shang Gangwei, Lei Wang, Chongbo Zhao, Jiankang Li, Yuan Sun, Jinyi Zhao, Shan Wang, Chengtao Lu, Yanyan Jia, Meiyou Liu, and Aidong Wen
- Subjects
Acinetobacter baumannii ,Male ,Combination therapy ,medicine.drug_class ,Antibiotics ,Microbial Sensitivity Tests ,Pharmacology ,Meropenem ,Microbiology ,Sepsis ,Mice ,In vivo ,Drug Resistance, Multiple, Bacterial ,polycyclic compounds ,medicine ,Animals ,Humans ,Mice, Inbred BALB C ,Dose-Response Relationship, Drug ,biology ,business.industry ,Therapeutic effect ,Drug Synergism ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,medicine.disease ,biology.organism_classification ,Anti-Bacterial Agents ,Disease Models, Animal ,Treatment Outcome ,Thienamycins ,Rifampin ,business ,Rifampicin ,Acinetobacter Infections ,medicine.drug - Abstract
Multidrug-resistant Acinetobacter baumannii becomes an increasing challenge due to the overuse of antibiotics. Combination therapies are considered as effective options to overcome this matter. The present study was to investigate the synergistic activity of meropenem combined with other antibiotics in vitro and in vivo. Checkerboard assay and time-kill assay were performed to study the combination effects in vitro. For the animal model, a murine sepsis model injected with inoculums intraperitoneally was used. Susceptibility test showed that all the twelve strains in this study were resistant to most of the antibiotics except rifampicin. In combination, meropenem plus rifampicin exhibited synergistic activity against six of twelve strains. In the sepsis model, meropenem monotherapy had no therapeutic effect in this model while it can enhance the activity of rifampicin in both survival rate and bacterial clearance from blood. Moreover, combination therapy significantly reduced plasma IL-6 levels compared with rifampicin monotherapy. Pharmacokinetic analysis of rifampicin was also performed in this study. These data above showed that there was synergistic activity between meropenem and rifampicin against multidrug-resistant Acinetobacter baumannii both in vitro and for experimental model of sepsis. It suggested that combining meropenem with rifampicin may be appropriate in treating multidrug-resistant Acinetobacter baumannii infections.
- Published
- 2014
49. Effect of food on the single-dose pharmacokinetics and tolerability of clinofibrate tablets in Chinese healthy volunteers
- Author
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Wei Song, MinChun Chen, Jing Yang, Lei Wang, Xue-qin Li, Likun Ding, Yanyan Jia, Jiankang Li, Ying Song, and Aidong Wen
- Subjects
Adult ,Male ,Pharmacology ,FOOD EFFECT ,Cross-Over Studies ,business.industry ,Cmax ,Phenoxyacetates ,Food-Drug Interactions ,Tolerability ,Pharmacokinetics ,Area Under Curve ,Healthy volunteers ,medicine ,Humans ,Female ,Pharmacology (medical) ,Clinofibrate ,Drug intoxication ,business ,Fasting state ,Tablets ,medicine.drug - Abstract
The aim of this study is to investigate a food effect on the single-dose pharmacokinetics and tolerability of clinofibrate tablets in 12 Chinese healthy volunteers. The authors evaluated the effect of being under a fasting or fed state at the time of drug intake on the single-dose of clinofibrate 400 mg tablets in a randomized, balanced, single-dose, two-treatment (fed and fasting), two-period, two-sequence study design with a 7-day washout period. The end points were the maximum plasma drug concentration (Cmax) and areas under the plasma-concentration curve (AUC) for 72 hours exposure (AUC0-72) and total exposure (AUC0-∞). All participants completed the whole study without side effects being observed. The Cmax mean of clinofibrate glucuronides and parent clinofibrate were 21.91, 17.85 μ/ml for the fasting state and 13.14, 11.25 μ/ml for the fed state, respectively. The AUC0-72 and AUC0-∞ of clinofibrate glucuronides and parent clinofibrate were 381.60, 307.07 μ/ ml and 404.55, 342.24 μ/ml for the fasting state and 379.02, 321.14 μ/ml and 432.24, 351.80 μ/ml for the fed state. The authors showed that food intake was associated with a significant decrease in Cmax, but no significant change in AUC values.
- Published
- 2013
50. Uncertainty evaluation for the determination of repaglinide in human plasma by LC–MS/MS
- Author
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Aidong Wen, Yanyan Jia, MinChun Chen, Jing Yang, Ying Song, Chao Wang, Jiankang Li, and Yan Li
- Subjects
Chemistry ,General Chemical Engineering ,Analytical chemistry ,General Chemistry ,Repeatability ,Repaglinide ,Mass spectrometry ,Human plasma ,Calibration ,medicine ,Measurement uncertainty ,Sample preparation ,Safety, Risk, Reliability and Quality ,Instrumentation ,Reliability (statistics) ,medicine.drug - Abstract
Measurement uncertainty although introduced to medical laboratories some years ago, this concept is not familiar to all medical researchers, especially for the measurement of biological samples. Therefore, it is important to highlight the evaluation and expression of measurement uncertainty using a practical example. In accordance with published procedures for evaluating and expressing uncertainty, we analyzed the sources of uncertainty in the determination of repaglinide in human plasma using liquid chromatography–tandem mass spectrometry (LC–MS/MS). We investigated each component of uncertainty and calculated the combined and expanded uncertainties. We evaluated the uncertainty associated with repeatability, weighing, purity, solution and sample preparation, recovery, calibration fitting, and temperature. The expanded uncertainty for low, medium, and high concentrations of repaglinide was 0.090, 0.25, and 3.16 ng/mL, respectively (p = 95 %, k = 2). This example provides an important reference for the evaluation of uncertainty in biological sample determinations using LC–MS/MS and human plasma and will be helpful in explaining the reliability of test results.
- Published
- 2012
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