20 results on '"Shaoling Yu"'
Search Results
2. Circadian rhythm modulates endochondral bone formation via MTR1/AMPKβ1/BMAL1 signaling axis
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Shaoling Yu, Qingming Tang, Guangjin Chen, Xiaofeng Lu, Ying Yin, Mengru Xie, Yanlin Long, Wenhao Zheng, Fengyuan Guo, Longquan Shao, Anbing Shi, and Lili Chen
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Osteogenesis ,Receptors, Melatonin ,ARNTL Transcription Factors ,Cell Biology ,Molecular Biology ,Article ,Circadian Rhythm ,Melatonin - Abstract
The circadian clock is a master regulator in coordinating daily oscillations of physiology and behaviors. Nevertheless, how the circadian rhythm affects endochondral ossification is poorly understood. Here we showed that endochondral bone formation exhibits circadian rhythms, manifested as fast DNA replication in the daytime, active cell mitosis, and matrix synthesis at night. Circadian rhythm disruption led to endochondral ossification deformities. The mechanistic dissection revealed that melatonin receptor 1 (MTR1) periodically activates the AMPKβ1 phosphorylation, which then orchestrates the rhythms of cell proliferation and matrix synthesis via destabilizing the clock component CRY1 and triggering BMAL1 expression. Accordingly, the AMPKβ1 agonist is capable of alleviating the abnormity of endochondral ossification caused by circadian dysrhythmias. Taken together, these findings indicated that the central circadian clock could control endochondral bone formation via the MTR1/AMPKβ1/BMAL1 signaling axis in chondrocytes. Also, our results suggested that the AMPKβ1 signaling activators are promising medications toward endochondral ossification deformities. more...
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- 2022
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3. Role of the oral microbiota in cancer evolution and progression
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Shaoling Yu, Qingming Tang, Jiwei Sun, Guangjin Chen, Yanling Xie, Mengru Xie, and Lili Chen
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0301 basic medicine ,Cancer Research ,Aerobic bacteria ,Firmicutes ,Reviews ,Review ,Alphapapillomavirus ,medicine.disease_cause ,lcsh:RC254-282 ,Malignant transformation ,03 medical and health sciences ,Bacteria, Anaerobic ,0302 clinical medicine ,Neoplasms ,medicine ,Immune Tolerance ,Humans ,cancer ,Radiology, Nuclear Medicine and imaging ,Porphyromonas gingivalis ,Cancer Biology ,Mouth ,biology ,Fusobacterium nucleatum ,Molecular pathology ,Microbiota ,Fungi ,Cancer ,biology.organism_classification ,medicine.disease ,oral microbiota ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,infection ,Bacteria, Aerobic ,Oropharyngeal Neoplasms ,stomatognathic diseases ,030104 developmental biology ,Cell Transformation, Neoplastic ,Oncology ,Tumor progression ,030220 oncology & carcinogenesis ,Bacterial Translocation ,Immunology ,Disease Progression ,Dysbiosis ,Carcinogenesis ,carcinogenesis - Abstract
Bacteria identified in the oral cavity are highly complicated. They include approximately 1000 species with a diverse variety of commensal microbes that play crucial roles in the health status of individuals. Epidemiological studies related to molecular pathology have revealed that there is a close relationship between oral microbiota and tumor occurrence. Oral microbiota has attracted considerable attention for its role in in‐situ or distant tumor progression. Anaerobic oral bacteria with potential pathogenic abilities, especially Fusobacterium nucleatum and Porphyromonas gingivalis, are well studied and have close relationships with various types of carcinomas. Some aerobic bacteria such as Parvimonas are also linked to tumorigenesis. Moreover, human papillomavirus, oral fungi, and parasites are closely associated with oropharyngeal carcinoma. Microbial dysbiosis, colonization, and translocation of oral microbiota are necessary for implementation of carcinogenic functions. Various underlying mechanisms of oral microbiota‐induced carcinogenesis have been reported including excessive inflammatory reaction, immunosuppression of host, promotion of malignant transformation, antiapoptotic activity, and secretion of carcinogens. In this review, we have systemically described the impact of oral microbial abnormalities on carcinogenesis and the future directions in this field for bringing in new ideas for effective prevention of tumors., Oral microbiota has been playing an important role in the development of cancer throughout human body. Thus we try to summarize the current researches about this topic. more...
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- 2020
4. F. nucleatum facilitates oral squamous cell carcinoma progression via GLUT1-driven lactate production
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Jiwei Sun, Qingming Tang, Shaoling Yu, Mengru Xie, Wenhao Zheng, Guangjin Chen, Ying Yin, Xiaofei Huang, Keqi Wo, Haoqi Lei, Junyuan Zhang, Qian Wan, and Lili Chen
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General Medicine ,General Biochemistry, Genetics and Molecular Biology - Published
- 2023
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5. Insight into the roles of melatonin in bone tissue and bone-related diseases (Review)
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Xiaofeng Lu, Shaoling Yu, Lili Chen, Wenhao Zheng, Guangjin Chen, Xiaofei Huang, and Jinfeng Peng
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0301 basic medicine ,Osteoporosis ,melatonin ,Osteoarthritis ,Bone tissue ,Bioinformatics ,Bone and Bones ,Melatonin ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,medicine ,Animals ,Humans ,Periodontitis ,Dental alveolus ,Dose-Response Relationship, Drug ,business.industry ,Bone Injury ,Cartilage ,bone injury ,General Medicine ,Articles ,medicine.disease ,osteoporosis ,osteoarthritis ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,business ,medicine.drug - Abstract
Bone-related diseases comprise a large group of common diseases, including fractures, osteoporosis and osteoarthritis (OA), which affect a large number of individuals, particularly the elderly. The progressive destruction and loss of alveolar bone caused by periodontitis is a specific type of bone loss, which has a high incidence and markedly reduces the quality of life of patients. With the existing methods of prevention and treatment, the incidence and mortality of bone-related diseases are still gradually increasing, creating a significant financial burden to societies worldwide. To prevent the occurrence of bone-related diseases, delay their progression or reverse the injuries they cause, new alternative or complementary treatments need to be developed. Melatonin exerts numerous physiological effects, including inducing anti-inflammatory and antioxidative functions, resetting circadian rhythms and promoting wound healing and tissue regeneration. Melatonin also participates in the health management of bone and cartilage. In the present review, the potential roles of melatonin in the pathogenesis and progression of bone injury, osteoporosis, OA and periodontitis are summarized. Furthermore, the high efficiency and diversity of the physiological regulatory effects of melatonin are highlighted and the potential benefits of the use of melatonin for the clinical prevention and treatment of bone-related diseases are discussed. more...
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- 2021
6. Melatonin regulates the immune response and improves Sjögren’s syndrome-like symptoms in NOD/Ltj Mice
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Yi, Liu, Xiuhong, Weng, Mingbo, Wei, Shaoling, Yu, Yumei, Ding, and Bo, Cheng
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Pharmacology ,Disease Models, Animal ,Mice ,Sjogren's Syndrome ,Mice, Inbred NOD ,Immunity ,Animals ,Humans ,Biochemistry ,Salivary Glands ,Autoimmune Diseases ,Melatonin - Abstract
Primary Sjögren's syndrome (pSS) is an autoimmune disease that primarily affects exocrine glands and is characterized by sicca syndrome and systemic manifestation. Mounting evidence indicates that circadian clocks are involved in the onset and progression of autoimmune diseases, including rheumatic arthritis, multiple sclerosis, and systemic lupus erythematosus. However, few studies have reported the expression of clock genes in pSS. There is no ideal therapeutic method for pSS, the management of pSS is mainly palliative, aims to alleviate sicca symptoms. Melatonin is a neuroendocrine hormone mainly secreted by the pineal gland that plays an important role in the maintenance of the circadian rhythm and immunomodulation. Hence, this study aimed to analyse the circadian expression profile of clock genes in pSS, and further evaluate the therapeutic potential of melatonin in pSS. We discovered a distinct clock gene expression profile in the salivary glands of pSS patients and pSS animal model. More importantly, melatonin administration improved the hypofunction of the salivary glands, inhibited inflammatory development, and regulated clock gene expression in animal model of pSS. Our study suggested that the pathogenesis of pSS might correlate with abnormal expression of circadian genes, and that melatonin might be a potential candidate for prevention and treatment of pSS. more...
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- 2022
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7. PLAU Promotes Cell Proliferation and Epithelial-Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma
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Guangjin Chen, Jiwei Sun, Mengru Xie, Shaoling Yu, Qingming Tang, and Lili Chen
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Cell growth ,EMT ,Tissue migration ,TNFRSF12A ,Biology ,QH426-470 ,medicine.disease ,head and neck squamous cell carcinoma ,Head and neck squamous-cell carcinoma ,PLAU ,Downregulation and upregulation ,Tumor progression ,Cancer research ,medicine ,Genetics ,Gene silencing ,Molecular Medicine ,Extracellular matrix binding ,Epithelial–mesenchymal transition ,prognostic biomarker ,Genetics (clinical) ,Original Research - Abstract
Plasminogen activator, urokinase (uPA) is a secreted serine protease whose Dysregulation is often accompanied by various cancers. However, the biological functions and potential mechanisms of PLAU in head and neck squamous cell carcinoma (HNSCC) remain undetermined. Here, the expression, prognosis, function, and coexpression genetic networks of PLAU in HNSCC were investigated by a series of public bioinformatics tools. A Higher PLAU level predicted a poorer clinical outcome. Meanwhile, functional network analysis implied that PLAU and associated genes mainly regulated cell-substrate adhesion, tissue migration, and extracellular matrix binding. The top 4 significantly associated genes are C10orf55, ITGA5, SERPINE1, and TNFRSF12A. Pathway enrichment analysis indicated that PLAU might activate the epithelial-to-mesenchymal transition (EMT) process, which could explain the poor prognosis in HNSCC. Besides, genes associated with PLAU were also enriched in EMT pathways. We further validated the bioinformatics analysis results by in vivo and in vitro experiments. Then, we found that much more PLAU was detected in HNSCC tissues, and the silencing of PLAU inhibit the proliferation, migration, and EMT process of CAL27 cell lines. Notably, the downregulation of PLAU decreased the expression of TNFRSF12A. Moreover, knockdown TNFRSF12A also inhibits cell proliferation and migration. In vivo experiment results indicated that PLAU inhibition could suppress tumor growth. Collectively, PLAU is necessary for tumor progression and can be a diagnostic and prognostic biomarker in HNSCC. more...
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- 2021
8. Porphyromonas gingivalis disrupts vascular endothelial homeostasis in a TLR-NF-κB axis dependent manner
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Qingming Tang, Mengru Xie, Feng Mei, Jiajia Zhao, Lili Chen, Jiwei Sun, and Shaoling Yu
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0301 basic medicine ,Endothelium ,Cell ,030204 cardiovascular system & hematology ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Homeostasis ,Endothelial dysfunction ,General Dentistry ,Porphyromonas gingivalis ,biology ,business.industry ,Cell growth ,NF-kappa B ,Endothelial Cells ,NF-κB ,Bacterial pathogenesis ,medicine.disease ,biology.organism_classification ,Cell biology ,lcsh:RK1-715 ,Endothelial stem cell ,Mechanisms of disease ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,lcsh:Dentistry ,business ,Signal Transduction - Abstract
Cardiovascular disease is still the leading cause of mortality worldwide. Vascular endothelial dysfunction is viewed as the initial step of most cardiovascular diseases. Many studies have indicated that periodontal pathogens, especially Porphyromonas gingivalis, are closely correlated with vascular endothelial homeostasis, but the function of P. gingivalis and the underlying mechanisms are still elusive. To illuminate the effects and elucidate the mechanisms of P. gingivalis on endothelial structural integrity, we developed P. gingivalis infection models in vivo and in vitro. Endothelial cell proliferation, differentiation and apoptosis were detected. Here, we showed that P. gingivalis can impair endothelial integrity by inhibiting cell proliferation and inducing endothelial mesenchymal transformation and apoptosis of endothelial cells, which reduce the cell levels and cause the endothelium to lose its ability to repair itself. A mechanistic analysis showed that TLR antagonist or NF-κB signalling inhibitor can largely rescue the damaged integrity of the endothelium caused by P. gingivalis, suggesting that TLR-NF-κB signalling plays a vital role in vascular endothelial homeostasis destroyed by P. gingivalis. These results suggest a potential intervention method for the prevention and treatment of cardiovascular disease. more...
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- 2020
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9. Combined Mode of Courses on Dental Virtual Clerkship During COVID-19 Pandemic for Final-year Undergraduates in Wuhan
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Ran Yu, Yuelin Wu, Jiajia Zhao, Xin Zhou, Xiaofei Huang, Chen Lili, Shue Li, and Shaoling Yu
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Medical education ,Mode (computer interface) ,Coronavirus disease 2019 (COVID-19) ,Computer science ,Pandemic - Abstract
BackgroundOnline teaching is being widely adopted to achieve medical teaching objectives during the COVID-19 pandemic. To explore the dental virtual clerkship so as to continue the education of final-year dental undergraduate interns, combined mode of courses including small private online course, problem-based learning, online dental practice broadcasting and dental practice based on relatives’ or friends’ oral health management were applied for clerkship education for final-year interns.MethodsCombined courses of virtual clerkship was conducted from March to May, 2020 for final-year interns, while online preclerkship curriculum teaching was conducted for non-final-year students. Using the online students’ engagement scale (OSE), Biggs’ revised two-factor version of the study process questionnaire (R-SPQ-2F), student engagement and study process were evaluated for both. Teaching efficacy were evaluated via teachers' sense of efficacy scale (TSES) as well. ResultsStudents’ engagement was higher in final-year students, especially the emotion and participation categories (P0.05).ConclusionThis combined mode of courses on dental virtual clerkship could be potentially applied during the pandemic or be supplementary for traditional by-chair clerkship after the pandemic. more...
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- 2020
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10. Bmal1 Regulates Coagulation Factor Biosynthesis in Mouse Liver in Streptococcus oralis Infection
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Lili Chen, Shue Li, Jiaming Nie, Jiajia Zhao, Shaoling Yu, Yaoxu Li, and Jinfeng Peng
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0301 basic medicine ,Microbiology (medical) ,endocrine system ,medicine.medical_treatment ,030106 microbiology ,Immunology ,lcsh:QR1-502 ,FXII ,Coagulation Factor XII ,FVII ,Microbiology ,lcsh:Microbiology ,Sepsis ,03 medical and health sciences ,Cellular and Infection Microbiology ,Downregulation and upregulation ,In vivo ,bmal1 ,Fibrinolysis ,medicine ,Pathogen ,Original Research ,biology ,business.industry ,S. oralis ,biology.organism_classification ,medicine.disease ,coagulation factor biosynthesis ,030104 developmental biology ,Infectious Diseases ,Streptococcus oralis ,Coagulation ,business - Abstract
Streptococcus oralis (S. oralis) has been recognized as a fatal pathogen to cause multiorgan failure by contributing to the formation of microthrombus. Coagulation and fibrinolysis systems have been found under the control of circadian clock genes. This study aimed to explore the correlation between BMAL1 and coagulation factor biosynthesis in S. oralis infection. Mice were administered S. oralis to induce sepsis, and HepG2 cells were also infected by S. oralis. The expression of BMAL1 of hepatocytes was downregulated in the S. oralis infection group, leading to the downregulation of coagulation factor VII (FVII) and the upregulation of the coagulation factor XII (FXII) in vitro and in vivo. Furthermore, we confirmed that the deficiency of BAML1 contributed to the elevation of FVII and the decline in FXII by constructing BMAL1-deficiency (Bmal1−/−) mice. The current result showed that BMAL1 regulates FVII directly. Thus, a novel insight into the coagulation abnormality in S. oralis infection was gained that may optimize the treatment of sepsis by rescuing the expression of BMAL1 in the liver. more...
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- 2020
11. Melatonin alleviated the immune response and improved the salivary gland function in primary Sjögren’s syndrome
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Yi Liu, Yumei Ding, Xiuhong Weng, Bo Cheng, and Shaoling Yu
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Melatonin ,stomatognathic diseases ,Immune system ,stomatognathic system ,business.industry ,Immunology ,Salivary gland function ,Medicine ,Sjogren s ,business ,medicine.drug - Abstract
Background Excessive inflammatory reactions participate in primary Sjögren’s syndrome (pSS) progression. In addition, biological clock genes have been detected in the salivary glands, which indicates that clock genes regulate the growth and development of the salivary glands as well as the quality and quantity of saliva secretion. Melatonin is an amine hormone secreted by the pineal gland that has many physiological functions, such as regulating immunity and correcting disorder in the biological clock rhythm. The purpose of this study was to clarify the correlation between pSS and the biological clock rhythm and explore the possibility of applying melatonin to treat pSS. Methods Melatonin (10 mg/kg/d or 15 mg/kg/d) or vehicle was administered to NOD/Ltj mice by intraperitoneal injection for 4 weeks. Clock gene expression levels in labial gland biopsy specimens from pSS patients and submandibular gland specimens from mice were measured by Western blotting (WB) and RT-PCR. The salivary flow rate of mice was measured at 12, 14, and 16 weeks. The severity of lymphocyte infiltration in the salivary glands was analysed by haematoxylin and eosin (H&E) staining. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining were used to detect the expression levels of related inflammatory factors in mice. The percentages of Th17, Th2, and Treg cells were analysed by flow cytometry. Results There was a distinct expression profile for clock genes in pSS patients compared with controls. Continuous melatonin administration improved salivary gland function in NOD/Ltj mice, with decreased lymphocyte infiltration in the submandibular glands and reduced related inflammatory factor expression in the serum and salivary glands. Melatonin treatment skewed T cells towards the Treg and Th2 subsets while suppressing Th17 responses. Additionally, melatonin administration regulated clock gene expression in NOD/Ltj mice. Conclusion pSS pathogenesis and progression are correlated with abnormal circadian gene expression. Melatonin improves the hypofunction of the salivary glands and inhibits the inflammatory development of pSS in NOD/Ltj mice. This study provides a theoretical basis and potential approach for the clinical prevention and treatment of pSS. more...
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- 2020
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12. BMAL1-Downregulation Aggravates Porphyromonas Gingivalis -Induced Atherosclerosis by Encouraging Oxidative Stress
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Lili Chen, Xiang Cheng, Chao Zhang, Qingming Tang, Nianguo Dong, Yu Hu, Mengru Xie, Xin Zhou, Jiwei Sun, Shaoling Yu, and Jiaming Nie
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biology ,Physiology ,business.industry ,Inflammation ,medicine.disease_cause ,biology.organism_classification ,Downregulation and upregulation ,Immunology ,medicine ,Circadian rhythm ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Porphyromonas gingivalis ,Oxidative stress - Abstract
Rationale: Atherosclerotic cardiovascular diseases are the leading cause of mortality worldwide. Atherosclerotic cardiovascular diseases are considered as chronic inflammation processes. In addition to risk factors associated with the cardiovascular system itself, pathogenic bacteria such as the periodontitis-associated Porphyromonas gingivalis ( P gingivalis ) are also closely correlated with the development of atherosclerosis, but the underlying mechanisms are still elusive. Objective: To elucidate the mechanisms of P gingivalis -accelerated atherosclerosis and explore novel therapeutic strategies of atherosclerotic cardiovascular diseases. Methods and Results: Bmal1 −/− (brain and muscle Arnt-like protein 1) mice, ApoE −/− mice, Bmal1 −/− ApoE −/− mice, conditional endothelial cell Bmal1 knockout mice ( Bmal1 fl/fl ; Tek -Cre mice), and the corresponding jet-legged mouse model were used. P gingivalis accelerates atherosclerosis progression by triggering arterial oxidative stress and inflammatory responses in ApoE −/− mice, accompanied by the perturbed circadian clock. Circadian clock disruption boosts P gingivalis -induced atherosclerosis progression. The mechanistic dissection shows that P gingivalis infection activates the TLRs-NF-κB signaling axis, which subsequently recruits DNMT-1 to methylate the BMAL1 promoter and thus suppresses BMAL1 transcription. The downregulation of BMAL1 releases CLOCK, which phosphorylates p65 and further enhances NF-κB signaling, elevating oxidative stress and inflammatory response in human aortic endothelial cells. Besides, the mouse model exhibits that joint administration of metronidazole and melatonin serves as an effective strategy for treating atherosclerotic cardiovascular diseases. Conclusions: P gingivalis accelerates atherosclerosis via the NF-κB-BMAL1-NF-κB signaling loop. Melatonin and metronidazole are promising auxiliary medications toward atherosclerotic cardiovascular diseases. more...
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- 2020
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13. BMAL1-Downregulation Aggravates
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Mengru, Xie, Qingming, Tang, Jiaming, Nie, Chao, Zhang, Xin, Zhou, Shaoling, Yu, Jiwei, Sun, Xiang, Cheng, Nianguo, Dong, Yu, Hu, and Lili, Chen
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DNA (Cytosine-5-)-Methyltransferase 1 ,Male ,Toll-Like Receptors ,NF-kappa B ,ARNTL Transcription Factors ,CLOCK Proteins ,Down-Regulation ,Atherosclerosis ,Antioxidants ,Anti-Bacterial Agents ,Circadian Rhythm ,Mice, Inbred C57BL ,Mice ,Oxidative Stress ,Apolipoproteins E ,Metronidazole ,Bacteroidaceae Infections ,Animals ,Female ,Endothelium, Vascular ,Porphyromonas gingivalis ,Melatonin ,Signal Transduction - Abstract
Atherosclerotic cardiovascular diseases are the leading cause of mortality worldwide. Atherosclerotic cardiovascular diseases are considered as chronic inflammation processes. In addition to risk factors associated with the cardiovascular system itself, pathogenic bacteria such as the periodontitis-associatedTo elucidate the mechanisms of more...
- Published
- 2020
14. BMAL1 Deficiency Contributes to Mandibular Dysplasia by Upregulating MMP3
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Jun Han, Lili Chen, Ran Yu, Jeremy J. Mao, Anbing Shi, Xiong Chen, Cen Cao, Qingming Tang, Shaoling Yu, Yanlin Long, Jiajia Zhao, and Xin Zhou
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0301 basic medicine ,circadian rhythm ,Male ,medicine.medical_specialty ,MMP3 ,endocrine system ,Circadian clock ,Biology ,Biochemistry ,circadian clock gene ,Article ,Gene Expression Regulation, Enzymologic ,Pathogenesis ,03 medical and health sciences ,Mice ,Downregulation and upregulation ,Internal medicine ,skeletal mandibular hypoplasia ,Genetics ,medicine ,Animals ,Humans ,Mandibular Diseases ,Craniofacial ,Child ,lcsh:QH301-705.5 ,Mice, Knockout ,lcsh:R5-920 ,p65 ,BMAL1 ,metallopeptidase 3 ,ARNTL Transcription Factors ,Cell Biology ,medicine.disease ,Hypoplasia ,Up-Regulation ,Mandibuloacral dysplasia ,Obstructive sleep apnea ,030104 developmental biology ,Endocrinology ,lcsh:Biology (General) ,Female ,Matrix Metalloproteinase 3 ,lcsh:Medicine (General) ,Developmental Biology - Abstract
Summary Skeletal mandibular hypoplasia (SMH), one of the common types of craniofacial deformities, seriously affects appearance, chewing, pronunciation, and breathing. Moreover, SMH is prone to inducing obstructive sleep apnea syndrome. We found that brain and muscle ARNT-like 1 (BMAL1), the core component of the molecular circadian oscillator, was significantly decreased in mandibles of juvenile SMH patients. Accordingly, SMH was observed in circadian-rhythm-disrupted or BMAL1-deficient mice. RNA sequencing and protein chip analyses suggested that matrix metallopeptidase 3 (MMP3) is the potential target of BMAL1. Interestingly, in juvenile SMH patients, we observed that MMP3 was obviously increased. Consistently, MMP3 was upregulated during the whole growth period of 3–10 weeks in Bmal1−/− mice. Given these findings, we set out to characterize the underlying mechanism and found BMAL1 deficiency enhanced Mmp3 transcription through activating p65 phosphorylation. Together, our results provide insight into the mechanism by which BMAL1 is implicated in the pathogenesis of SMH., Highlights • Juvenile SMH patients express lower BMAL1 levels in the mandibular tissues • Circadian rhythm disruption or BMAL1 deficiency leads to SMH • MMP3 upregulation is involved in SMH caused by BMAL1 deficiency • BMAL1 controls the expression of MMP3 indirectly via p65 phosphorylation modulation, Chen et al. found that BMAL1 expression decreased significantly in the mandibles of juvenile SMH patients, and SMH was observed in circadian-rhythm-disrupted mice or Bmal1−/− mice. Moreover, they demonstrated that MMP3 is an indispensable factor in BMAL1-deficiency-induced SMH. Given these findings, they set out to characterize the underlying mechanism and found that BMAL1 deficiency enhanced Mmp3 transcription through activating p65 phosphorylation. more...
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- 2017
15. Circadian BMAL1 regulates mandibular condyle development by hedgehog pathway
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Mengru Xie, Shaoling Yu, Qingming Tang, Lili Chen, Yanlin Long, Fengyuan Guo, Yanling Xie, and Xin Zhou
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0301 basic medicine ,endocrine system ,Morphogenesis ,Biology ,genome‐wide RNA sequencing ,Chondrocyte ,prepuberty and early puberty periods ,Mice ,03 medical and health sciences ,Chondrocytes ,0302 clinical medicine ,medicine ,Animals ,Hedgehog Proteins ,Endochondral ossification ,Mice, Knockout ,patched homologue 1 (PTCH1) ,BMAL1 ,Mandibular Condyle ,ARNTL Transcription Factors ,food and beverages ,Cell Differentiation ,Original Articles ,Cell Biology ,General Medicine ,chondrogenesis and endochondral ossification ,Chondrogenesis ,Embryonic stem cell ,Phenotype ,Hedgehog signaling pathway ,Circadian Rhythm ,Cell biology ,Patched-1 Receptor ,Cartilage ,030104 developmental biology ,medicine.anatomical_structure ,PTCH1 ,030220 oncology & carcinogenesis ,Original Article ,Signal Transduction - Abstract
Objective Chondrogenesis and endochondral ossification in mandibular condyle play crucial roles in maxillofacial morphogenesis and function. Circadian regulator brain and muscle arnt‐like 1 (BMAL1) is proven to be essential for embryonic and postnatal development. The goal of this study was to define the functions of BMAL1 in the embryonic and postnatal growth of mandibular condylar cartilages (MCC). Materials and Methods Micro‐CT, TUNEL staining and EdU assay were performed using BMAL1‐deficient mice model, and in vitro experiments were performed using rat chondrocytes isolated from MCC. RNA sequencing in mandibular condyle tissues from Bmal1 ‐/‐ mice and the age‐matched wild‐type mice was used for transcriptional profiling at different postnatal stages. Results The expression levels of BMAL1 decrease gradually in MCC. BMAL1 is proved to regulate sequential chondrocyte differentiation, and its deficiency can result in the impairment of endochondral ossification of MCC. RNA sequencing reveals hedgehog signalling pathway is the potential target of BMAL1. BMAL1 regulates hedgehog signalling and affects its downstream cascades through directly binding to the promoters of Ptch1 and Ihh, modulating targets of hedgehog signalling which is indispensable for endochondral ossification. Importantly, the short stature phenotypes caused by BMAL1 deficiency can be rescued by hedgehog signalling activator. Conclusions Collectively, these results indicate that BMAL1 plays critical roles on chondrogenesis and endochondral ossification of MCC, giving a new insight on potential therapeutic strategies for facial dysmorphism. more...
- Published
- 2019
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16. Periodic Oxaliplatin Administration in Synergy with PER2‐Mediated PCNA Transcription Repression Promotes Chronochemotherapeutic Efficacy of OSCC
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Yanling Xie, Qingming Tang, Mengru Xie, Guangjin Chen, Fengyuan Guo, Lili Chen, Xin Zhou, and Shaoling Yu
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endocrine system ,General Chemical Engineering ,Circadian clock ,Regulator ,General Physics and Astronomy ,Medicine (miscellaneous) ,circadian clock genes ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Transcription (biology) ,medicine ,General Materials Science ,lcsh:Science ,Cytotoxicity ,DNA‐damaging repair ,biology ,Full Paper ,business.industry ,chronochemotherapeutic strategy ,oxaliplatin ,General Engineering ,Full Papers ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Proliferating cell nuclear antigen ,Oxaliplatin ,PER2 ,oral squamous cell carcinoma ,stomatognathic diseases ,Apoptosis ,biology.protein ,Cancer research ,lcsh:Q ,0210 nano-technology ,business ,medicine.drug - Abstract
Developing chemotherapeutic resistance affects clinical outcomes of oxaliplatin treatment on various types of cancer. Thus, it is imperative to explore alternative therapeutic strategies to improve the efficacy of oxaliplatin. Here, it is shown that circadian regulator period 2 (PER2) can potentiate the cytotoxicity of oxaliplatin and boost cell apoptosis by inhibiting DNA adducts repair in human oral squamous cell carcinoma (OSCC) cells. The circadian timing system is closely involved in controling the activity of DNA adducts repair and gives it a 24 h rhythm. The mechanistic dissection clarifies that PER2 can periodically suppress proliferating cell nuclear antigen (PCNA) transcription by pulling down circadian locomotor output cycles kaput–brain and muscle arnt‐like 1 heterodimer from PCNA promoter in a CRY1/2‐dependent manner, which subsequently impedes oxaliplatin‐induced DNA adducts repair. Similarly, PER2 is capable of improving the efficacy of classical DNA‐damaging chemotherapeutic agents. The tumor‐bearing mouse model displays PER2 can be deployed as an oxaliplatin administration timing biomarker. In summary, it is believed that the chronochemotherapeutic strategy matching PER2 expression rhythm can efficiently improve the oxaliplatin efficacy of OSCC., Circadian regulator period 2 (PER2) potentiates the cytotoxicity of oxaliplatin depending on suppressing proliferating cell nuclear antigen (PCNA) transcription periodically by pulling down circadian locomotor output cycles kaput–brain and muscle arnt‐like 1 heterodimer from PCNA promoter in a CRY1/2‐dependent manner, which subsequently impedes oxaliplatin‐induced DNA adducts repair. Oxaliplatin administration in synergy with PER2 can efficiently improve chemotherapeutic efficacy of oral squamous cell carcinoma (OSCC). more...
- Published
- 2019
17. Hypoxic Preconditioning Enhances Dental Pulp Stem Cell Therapy for Infection-Caused Bone Destruction
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Fang Huang, Shue Li, Juan Wang, Qingming Tang, Shaoling Yu, Wu Yan, Xin Zhou, and Lili Chen
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Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Alveolar Bone Loss ,Biomedical Engineering ,Bioengineering ,Biochemistry ,CXCR4 ,Biomaterials ,Mice ,03 medical and health sciences ,Dental pulp stem cells ,Animals ,Humans ,Medicine ,Child ,Ischemic Preconditioning ,Periodontitis ,Bone regeneration ,Dental Pulp ,Dental alveolus ,Mice, Inbred BALB C ,business.industry ,Stem Cells ,Correction ,Stem-cell therapy ,medicine.disease ,Cell Hypoxia ,Transplantation ,030104 developmental biology ,Female ,Stem cell ,business ,Stem Cell Transplantation - Abstract
The use of biological repair in infectious bone defects has been a major challenge for clinicians. With potential for bone regeneration, stem cell therapy could be an effective biological restoration measure for infection-caused bone destruction. In this study, we propose a new stem cell therapy strategy for infectious bone defect repair through systemic transplantation of human dental pulp stem cells (hDPSCs). Hypoxic preconditioning (HP) is thought to be able to enhance duration of survival and therapeutic potency of engrafted stem cells; therefore, we examined the role of HP on hDPSC therapeutic efficacy. Our results show that HP significantly enhanced hDPSC survival rate and osteogenic differentiation. hDPSCs were all CXCR4 positive under hypoxic pretreatment and their migration in response to SDF-1 was increased in vitro. hDPSC migration increase can be abolished after application of CXCR4 antagonist, AMD3100. In a mouse apical periodontitis bone destruction model, after transplantation of hypoxic preconditioned hDPSCs through intravenous injection, upregulated hDPSC recruitment and recovery of alveolar bone mass were observed in infected periapical tissue, and osteogenesis and bone mineralization were enhanced. Significantly, in periapical lesions, we found increased SDF-1 production and CXCR4/CFSE+ colabeled cells. Together, our results suggested that hypoxic preconditioned hDPSCs are capable of repairing infectious bone defects through the SDF-1/CXCR4 axis. Our investigation provides a novel infection-caused bone loss therapeutic strategy using hDPSC transplantation, and HP is an effective way of improving hDPSC survival rate, recruitment, and osteogenesis. more...
- Published
- 2016
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18. The biological function of BMAL1 in skeleton development and disorders
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Shaoling Yu, Shue Li, Guangjin Chen, Lili Chen, Qingming Tang, Yanling Xie, and Jiwei Sun
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0301 basic medicine ,endocrine system ,Osteoporosis ,Osteoclasts ,Osteoarthritis ,Biology ,030226 pharmacology & pharmacy ,Bone and Bones ,General Biochemistry, Genetics and Molecular Biology ,Bone resorption ,Bone remodeling ,03 medical and health sciences ,Chondrocytes ,0302 clinical medicine ,Bone Density ,Osteogenesis ,Circadian Clocks ,medicine ,Animals ,Humans ,Bone Resorption ,General Pharmacology, Toxicology and Pharmaceutics ,Endochondral ossification ,Bone Development ,Osteoblasts ,Cartilage ,Mesenchymal stem cell ,ARNTL Transcription Factors ,Cell Differentiation ,Mesenchymal Stem Cells ,General Medicine ,medicine.disease ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,Intramembranous ossification ,Chondrogenesis ,Tooth - Abstract
BMAL1 is a core component of the circadian clock loop, which directs the sophisticated circadian expression of clock-controlled genes. Skeletal Bone development is a complex biological process involving intramembranous ossification, endochondral ossification and bone remodeling, as well as specific cells, such as mesenchymal cells, osteoblasts, osteoclasts, chondrocytes, etc. Growing evidences suggest that BMAL1 is indispensable for hard tissue development, including bone, cartilage and teeth. Loss of BMAL1 in animals can inhibit bone and cartilage development, and result in abnormal bone mass. In mesenchymal cells, BMAL1 defect inhibits osteoblastic and chondrocytic differentiation. Inactivation of BMAL1 also can promote the differentiation and formation of osteoclasts and increase bone resorption. Specifically, preclinical data demonstrate that the abnormity of BMAL1 expression is associated with skeletal disorders such as skeletal mandibular hypoplasia, osteoarthritis, osteoporosis, etc. In this review, we systemically describe the impact of BMAL1 in skeletal development and homeostasis, and devote to searching new therapy strategies for bone disorders. more...
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- 2020
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19. New Insights Into the Circadian Rhythm and Its Related Diseases
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Shaoling Yu, Lili Chen, Mengru Xie, Guangjin Chen, Jiajia Zhao, Qingming Tang, and Yanling Xie
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0301 basic medicine ,circadian rhythm ,Future studies ,Physiology ,Circadian clock ,Disease ,Review ,rhythm monitoring ,influence factors ,lcsh:Physiology ,03 medical and health sciences ,Human health ,0302 clinical medicine ,Physiology (medical) ,Medicine ,Circadian rhythm ,Cognitive impairment ,lcsh:QP1-981 ,business.industry ,disorder ,Experimental research ,030104 developmental biology ,business ,Internal time ,Neuroscience ,synchronization ,030217 neurology & neurosurgery - Abstract
Circadian rhythms (CR) are a series of endogenous autonomous oscillators generated by the molecular circadian clock which acting on coordinating internal time with the external environment in a 24-h daily cycle. The circadian clock system is a major regulatory factor for nearly all physiological activities and its disorder has severe consequences on human health. CR disruption is a common issue in modern society, and researches about people with jet lag or shift works have revealed that CR disruption can cause cognitive impairment, psychiatric illness, metabolic syndrome, dysplasia, and cancer. In this review, we summarized the synchronizers and the synchronization methods used in experimental research, and introduced CR monitoring and detection methods. Moreover, we evaluated conventional CR databases, and analyzed experiments that characterized the underlying causes of CR disorder. Finally, we further discussed the latest developments in understanding of CR disruption, and how it may be relevant to health and disease. Briefly, this review aimed to synthesize previous studies to aid in future studies of CR and CR-related diseases. more...
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- 2019
20. BMAL1 deficiency promotes skeletal mandibular hypoplasia via OPG downregulation
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Xin Zhou, Ran Yu, Lili Chen, Shaoling Yu, Yanlin Long, Jiajia Zhao, and Qingming Tang
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0301 basic medicine ,musculoskeletal diseases ,medicine.medical_specialty ,endocrine system ,Circadian clock ,Down-Regulation ,Osteoclasts ,Biology ,Craniofacial Abnormalities ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Downregulation and upregulation ,Western blot ,Osteoclast ,Internal medicine ,Circadian Clocks ,medicine ,Animals ,Humans ,Mandibular Diseases ,Circadian rhythm ,Child ,Muscle, Skeletal ,Promoter Regions, Genetic ,Mice, Knockout ,Gene knockdown ,medicine.diagnostic_test ,Osteoprotegerin ,ARNTL Transcription Factors ,Cell Differentiation ,030206 dentistry ,Cell Biology ,General Medicine ,Original Articles ,Up-Regulation ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Immunohistochemistry ,Chromatin immunoprecipitation - Abstract
Objectives Skeletal mandibular hypoplasia (SMH), a common type of developmental deformities, results in impaired aesthetics of facial profile, occlusal dysfunction and poor life quality. In this study, BMAL1 deficiency leads to SMH formation, and we aim to investigate the mechanism by which BMAL1 deficiency induces SMH. Materials and methods Circadian rhythm-disordered mouse models were constructed by placing animals in a jet lag schedule of 6-h light advance every 7 days for 4 or 8 weeks. The OPG expression was evaluated by histomorphometry, immunohistochemistry and western blot analysis. The mechanism by which BMAL1 affects OPG expression was investigated by chromatin immunoprecipitation and luciferase reporter assays. The phenotypes caused by BMAL1 knockout can be rescued by exogenous supplementation with OPG. Results We demonstrate that the expressions of BMAL1 and OPG decreased in SMH patients. Circadian rhythm-disordered mice and Bmal1-/- mice exhibited decreased expression of OPG, reduced bone mass and bone size of mandibles. Our results revealed that BMAL1 bound directly to the Opg promoter and upregulated its expression, thus inhibiting osteoclast differentiation. BMAL1 deficiency increased osteoclast differentiation by downregulating OPG expression. In vitro, the enhancement effect of osteoclast differentiation caused by BMAL1 knockdown was significantly reversed by exogenous supplementation with OPG. Importantly, bone loss caused by BMAL1 knockout can be partially reversed by injecting OPG Intraperitoneally. Conclusions These results indicate that the circadian clock plays a critical role in the growth and development of mandible by regulating OPG expression, and present a potential therapeutic strategy to prevent SMH. more...
- Published
- 2018
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