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Cisplatin (DDP) resistance is a principal cause leading to poor prognosis in females suffering from ovarian cancer (OC). Long non-coding RNA (lncRNA) has been shown to have an involvement in regulating cellular processes; chemoresistance being one of them the precise object of this work was to probe into the role of lncRNA ACTA2-AS1 in OC cells that have developed DDP resistance. We developed DDP-resistant OC cell lines (A2780/DDP and SKOV3/DDP). The influence of the ACTA2-AS1/miR-378a-3p/Wnt5a axis on DDP chemoresistance of DDP-resistant OC cells was ascertained using real-time PCR, Elisa, and CCK-8, and dual-luciferase reporter assay. In DDP-resistant cells and tissues, ACTA2-AS1 was increased, while a substantial downregulation in miR-378a-3p was noticed. In cells manifesting DDP-resistance, knocking down ACTA2-AS1 boosted the expression of miR-378a-3p. Further research into the mechanism of ACTA2-AS1 revealed that it acted as a 'sponge' by getting involved in a competition against miR-378a-3p binding to modify its target Wnt5a. The suppression of DDP-resistance in OC cells caused by ACTA2-AS1 downregulation was reversed by silencing miR-378a-3p. Furthermore, via inhibition of Wnt5a, miR-378a-3p alleviated DDP resistance in OC cells. These findings show that for miR-378a-3p, ACTA2-AS1 works like a sponge thus preventing it from binding to Wnt5a and boosting OC cell DDP resistance. Our research will aid the expansion of plausible therapeutic options for treating OC.

Background: With increasing research on Alzheimer's disease and periodontitis, many studies suggest a close correlation between Alzheimer's disease and periodontitis, but the underlying pathophysiological mechanisms remain unclear. The aim of this study was to identify potential pivotal genes and pathways associated with both diseases by using a bioinformatics approach. Materials/Methods: The GEO dataset GSE5281 for Alzheimer's disease patients and normal controls was downloaded from the GEO database. The GSE10334 dataset for periodontitis patients and healthy controls was also obtained. Differentially expressed genes (DEGs) for the Alzheimer's disease and periodontitis datasets were obtained, as well as genes common between them. Further GO and KEGG enrichment analyses were performed on the common genes. To determine the pathogenesis associated with Alzheimer's disease and periodontitis, protein-protein interaction (PPI) networks were constructed. Finally, the diagnostic value of HUB genes in the Alzheimer's disease and periodontitis datasets was analyzed separately using SPSS software. Results: A total of 16 common genes were obtained for Alzheimer's disease and periodontitis with a P value

Background: As a major cause of liver disease worldwide, metabolic associated fatty liver disease (MAFLD) comprises non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Due to the high prevalence and poor prognosis of NASH, it is critical to understand its mechanisms. However, the etiology and mechanisms remain largely unknown. Methods: We first identified differential genes in NASH by single-cell analysis of the GSE129516 and expression profiling data analysis of the GSE184019 dataset from the GEO database. Then single-cell trajectory reconstruction and analysis, immune gene score, cellular communication, key Gene Screening, functional enrichment analysis, and immune microenvironment analysis were carried out. Finally, cell experiments were performed to verify the role of key genes in NASH. Results: We show transcriptome profiling of 30,038 single cells—including hepatocyte and non-hepatocyte—from normal and steatosis adult mouse liver. Comparative analysis of hepatocyte and non-hepatocyte revealed pronounced heterogeneity as well as specific utilization of non-hepatocyte types as major cell-communication hubs. The results showed that Hspa1b, Tfrc, Hmox1 and Map4k4 effectively distinguish NASH tissues from normal samples. The results of scRNA-seq and qPCR indicated that the expression levels of hub genes in NASH were significantly higher than in normal cells or tissues. Further immune infiltration analysis showed significant differences in Macrophages M2 distribution between healthy and metabolic associated fatty liver samples. Conclusions: Our results suggest that Hspa1b, Tfrc, Hmox1 and Map4k4 are all potential biomarkers for NASH diagnosis and prognosis may also be potential therapeutic targets for NASH.

Many patients of choroidal neovascularization (CNV) are unresponsive to the current anti-VEGF treatment. The mechanisms for anti-VEGF resistance are poorly understood. We explore the unique property of the apolipoprotein A-I (apoA-I) binding protein (AIBP) that enhances cholesterol efflux from endothelial cells and macrophages to thereby limit angiogenesis and inflammation to tackle anti-VEGF resistance in CNV. We show that laser-induced CNV in mice with increased age showed increased resistance to anti-VEGF treatment, which correlates with increased lipid accumulation in macrophages. The combination of AIBP/apoA-I and anti-VEGF treatment overcomes anti-VEGF resistance and effectively suppresses CNV. Furthermore, macrophage depletion in old mice restores CNV sensitivity to anti-VEGF treatment and blunts the synergistic effect of combination therapy. These results suggest that cholesterol-laden macrophages play a critical role in inducing anti-VEGF resistance in CNV. Combination therapy by neutralizing VEGF and enhancing cholesterol removal from macrophages is a promising strategy to combat anti-VEGF resistance in CNV., By combining advanced age and laser photocoagulation, Zhu et al. establish a novel CNV model of anti-VEGF resistance. They show that lipid accumulation in old macrophages promote angiogenesis, and that apoA-I binding protein (AIBP) inhibits angiogenesis by reducing this lipid accumulation. They further show that the combination of AIBP/apoA-I and anti-VEGF treatment overcomes anti-VEGF resistance and effectively suppresses CNV.

Plant polyketides are well-known for their crucial functions in plants and their importance in the context of human health. They are synthesized by type III polyketide synthases (PKSs) and their final functional diversity is determined by post-PKS tailoring enzymes. Gerbera hybrida is rich in two defense-related polyketides: gerberin and parasorboside. Their synthesis is known to be initiated by GERBERA 2-PYRONE SYNTHASE 1 (G2PS1), but the polyketide reductases (PKRs) that determine their final structure have not yet been identified. We identified two PKR candidates in the pathway, GERBERA REDUCTASE 1 (GRED1) and GRED2. Gene expression and metabolite analysis of different gerbera tissues, cultivars, and transgenic gerbera plants, and in vitro enzyme assays, were performed for functional characterization of the enzymes. GRED1 and GRED2 catalyze the second reduction step in parasorboside biosynthesis. They reduce the proximal keto domain of the linear CoA bound intermediate before lactonization. We identified a crucial tailoring step in an important gerbera PKS pathway and show that plant polyketide biosynthesis shares processing strategies with fungi and bacteria. The two tailoring enzymes are recruited from the ancient sporopollenin biosynthetic pathway to a defense-related PKS pathway in gerbera. Our data provide an example of how plants recruit conserved genes to new functions in secondary metabolism that are important for environmental adaptation.

This study aimed to determine whether skin flap warming after an operation interferes with temperature monitoring. The postoperative nursing workflow of subabdominal deep inferior epigastric artery perforator (DIEP) flap breast reconstruction was optimized.A retrospective analysis involving 69 patients who received one-stage breast reconstruction at the Huashan Hospital from July 2017 to December 2019 was performed. The postoperative physical care of patients, including flap temperature monitoring and flap warming, was reviewed.All patients had successful operations. After surgery, all flaps were warmed following the standard protocol. Abnormal temperature and compromised circulation of flaps were observed in three of the patients. These patients received re-exploration surgery and all three flaps survived. A postoperative follow-up shows a high level of patient satisfaction in most cases.The appropriate warming of transplanted flaps did not interfere with temperature monitoring. This helped determine whether there was compromised circulation, leading to increased skin flap survival and improved patient satisfaction.

Angiogenesis, the fundamental process that generates new blood vessels from parental vessels, is essential for embryogenesis and pathogenesis. A variety of underlying molecular and cellular mechanisms control angiogenesis. In this review, we focus on a unique mechanism of action – cholesterol-regulated angiogenesis. We will discuss lipoproteins, including low-density lipoprotein and high-density lipoprotein, cholesterol-rich lipid rafts/caveolae, apoA-I-binding protein (AIBP, also known as NAXE)-regulated cholesterol efflux, the effect of the hydroxycholesterol-activated nuclear receptor liver X receptor α/β on the proangiogenic vascular endothelial growth factor receptor 2 and antiangiogenic Notch signaling, and cholesterol-modified sonic hedgehog signaling. These pathways can be exploited, either alone or in conjunction with the currently available regimen for angiogenesis treatment, to control neovascularization in dyslipidemia. A treatment protocol for angiogenesis that takes into consideration cholesterol management might constitute an important component in precision and personalized medicine.

Lingping Zhu,1,2 Zhiqun Shu,3 Xiaoming Sun2,3 1Department of General Practice, Shenzhen Longhua District Central Hospital, Shenzhen, People’s Republic of China; 2Department of General Practice, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Pudong Institute for Health Development, Shanghai, People’s Republic of China Background: The purpose of this study was to investigate the expression of different miRNAs in nonmetastatic and metastatic endometrial cancer Existing evidence indicates that there are many factors affecting the metastasis of endometrial cancer, and miRNAs play an unique role in many processes of endometiral cancer. Materials and methods: miRNA sequences were downloaded from The Cancer Genome Atlas Project database, and Bioinformatics technique was used to deal with those data. Results: We elucidated the relation between differentially expressed miRNAs and clinical information for a total of 260 tumor tissues and 22 tumor tissues that had metastasized. We used the threshold of P 1.2 to identify potential miRNAs. Four differentially expressed miRNAs were identified in nonmetastatic and metastatic endometrial cancers. Further differential analysis of metastatic tissue revealed that miR-1247 is associated with metastasis of endometrial cancer to the lung, and miR-3200 is associated with the clinical stage of endometrial cancer. A functional enrichment analysis showed that the four miRNAs may be involved in multiple pathways of cancer, including the Wnt, NOTCH, and TGF-β signaling pathways and signaling pathways regulating pluripotency of stem cells. Protein–protein interaction analysis showed that PAK6, SNAP25, MAN1A1, MYB, ZBTB4, UST, ALDH1A3, and NRP2 are hub genes of relevant miRNAs in endometrial cancers. Conclusion: The current study indicates that these four miRNAs may be related to molecular markers of metastasis of endometrial cancer. Keywords: endometrial cancer, bioinformatics, miR-1247, protein analysis

Alkaloids are the most relevant bioactive components in lotus, a traditional herb in Asia, but little is known about their qualitative and quantitative distributions. Here, we report on the alkaloid composition in various lotus organs. Lotus laminae and embryos are rich in isoquinoline alkaloids, whereas petioles and rhizomes contain trace amounts of alkaloids. Wide variation of alkaloid accumulation in lamina and embryo was observed among screened genotypes. In laminae, alkaloid accumulation increases during early developmental stages, reaches the highest level at full size stage, and then decreases slightly during senescence. Vegetative and embryogenic tissues accumulate mainly aporphine-type and bisbenzylisoquinoline-type alkaloids, respectively. Bisbenzylisoquinoline-type alkaloids may be synthesized mainly in lamina and then transported into embryo via latex through phloem translocation. In addition, mechanical wounding was shown to induce significant accumulation of specific alkaloids in lotus leaves.

The objective of this study was to compare the efficacy and side effects of acupuncture, sham acupuncture and drugs in the treatment of chronic constipation. Randomized controlled trials (RCTs) assessing the effects of acupuncture and drugs for chronic constipation were comprehensively retrieved from electronic databases (such as PubMed, Cochrane Library, Embase, CNKI, Wanfang Database, VIP Database and CBM) up to December 2017. Additional references were obtained from review articles. With quality evaluations and data extraction, a network meta-analysis (NMA) was performed using a random-effects model under a frequentist framework. A total of 40 studies (n = 11032) were included: 39 were high-quality studies and 1 was a low-quality study. NMA showed that (1) acupuncture improved the symptoms of chronic constipation more effectively than drugs; (2) the ranking of treatments in terms of efficacy in diarrhoea-predominant irritable bowel syndrome was acupuncture, polyethylene glycol, lactulose, linaclotide, lubiprostone, bisacodyl, prucalopride, sham acupuncture, tegaserod, and placebo; (3) the ranking of side effects were as follows: lactulose, lubiprostone, bisacodyl, polyethylene glycol, prucalopride, linaclotide, placebo and tegaserod; and (4) the most commonly used acupuncture point for chronic constipation was ST25. Acupuncture is more effective than drugs in improving chronic constipation and has the least side effects. In the future, large-scale randomized controlled trials are needed to prove this. Sham acupuncture may have curative effects that are greater than the placebo effect. In the future, it is necessary to perform high-quality studies to support this finding. Polyethylene glycol also has acceptable curative effects with fewer side effects than other drugs.

Background. The objective of this study was to compare the efficacy and side effects of acupuncture, sham acupuncture, and drugs in the treatment of diarrhoea-predominant irritable bowel syndrome. Methods. Randomized controlled trials (RCTs) assessing the effects of acupuncture and drugs were comprehensively retrieved from electronic databases (such as PubMed, Cochrane Library, Embase, CNKI, Wanfang Database, VIP Database, and CBM) up to December 2017. Additional references were obtained from review articles. With document quality evaluations and data extraction, Network Meta-Analysis was performed using a random-effects model under a frequentist framework. Results. A total of 29 studies (n = 9369) were included; 19 were high-quality studies, and 10 were low-quality studies. NMA showed the following: (1) the ranking of treatments in terms of efficacy in diarrhoea-predominant irritable bowel syndrome is acupuncture, sham acupuncture, pinaverium bromide, alosetron = eluxadoline, ramosetron, and rifaximin; (2) the ranking of treatments in terms of severity of side effects in diarrhoea-predominant irritable bowel syndrome is rifaximin, alosetron, ramosetron = pinaverium bromide, sham acupuncture, and acupuncture; and (3) the treatment of diarrhoea-predominant irritable bowel syndrome includes common acupoints such as ST25, ST36, ST37, SP6, GV20, and EX-HN3. Conclusion. Acupuncture may improve diarrhoea-predominant irritable bowel syndrome better than drugs and has the fewest side effects. Sham acupuncture may have curative effect except for placebo effect. In the future, it is necessary to perform highly qualified research to prove this result. Pinaverium bromide also has good curative effects with fewer side effects than other drugs.

The predominant alkaloids in lotus leaves are aporphine alkaloids. These are the most important active components and have many pharmacological properties, but little is known about their biosynthesis. We used digital gene expression (DGE) technology to identify differentially-expressed genes (DEGs) between two lotus cultivars with different alkaloid contents at four leaf development stages. We also predicted potential genes involved in aporphine alkaloid biosynthesis by weighted gene co-expression network analysis (WGCNA). Approximately 335 billion nucleotides were generated; and 94% of which were aligned against the reference genome. Of 22 thousand expressed genes, 19,000 were differentially expressed between the two cultivars at the four stages. Gene Ontology (GO) enrichment analysis revealed that catalytic activity and oxidoreductase activity were enriched significantly in most pairwise comparisons. In Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, dozens of DEGs were assigned to the categories of biosynthesis of secondary metabolites, isoquinoline alkaloid biosynthesis, and flavonoid biosynthesis. The genes encoding norcoclaurine synthase (NCS), norcoclaurine 6-O-methyltransferase (6OMT), coclaurine N-methyltransferase (CNMT), N-methylcoclaurine 3'-hydroxylase (NMCH), and 3'-hydroxy-N-methylcoclaurine 4'-O-methyltransferase (4'OMT) in the common pathways of benzylisoquinoline alkaloid biosynthesis and the ones encoding corytuberine synthase (CTS) in aporphine alkaloid biosynthetic pathway, which have been characterized in other plants, were identified in lotus. These genes had positive effects on alkaloid content, albeit with phenotypic lag. The WGCNA of DEGs revealed that one network module was associated with the dynamic change of alkaloid content. Eleven genes encoding proteins with methyltransferase, oxidoreductase and CYP450 activities were identified. These were surmised to be genes involved in aporphine alkaloid biosynthesis. This transcriptomic database provides new directions for future studies on clarifying the aporphine alkaloid pathway.

Association mapping was used to identify candidate molecular markers associated with four flower-related traits-flower color, petal number per flower, flowering time, and flowering duration-in a collection of lotus (Nelumbo Adans.) accessions evaluated over two years. Significant phenotypic variations (P 0.5, indicating a low level of LD between the markers. Using the general linear model considering population structure, association mapping identified several significant markers (P

Rhizome is the storage organ of lotus derived from modified stems. The development of rhizome is a complex process and depends on the balanced expression of the genes that is controlled by environmental and endogenous factors. However, little is known about the mechanism that regulates rhizome girth enlargement. In this study, using RNA-seq, transcriptomic analyses were performed at three rhizome developmental stages—the stolon, middle swelling and later swelling stage —in the cultivars ‘ZO’ (temperate lotus with enlarged rhizome) and ‘RL’ (tropical lotus with stolon). About 348 million high-quality reads were generated and 88.5% of the data were mapped to the reference genome. Of 26783 genes identified, 24069 genes were previously predicted in the reference and 2714 genes were novel transcripts. Moreover, 8821 genes were differentially expressed between the cultivars at the three stages. Functional analysis identified that these genes were significantly enriched in pathways carbohydrate metabolism and plant hormone signal transduction. Twenty-two genes involved in photoperiod pathway, starch metabolism and hormone signal transduction were candidate genes inducing rhizome girth enlargement. Comparative transcriptomic analysis detected several differentially expressed genes and potential candidate genes required for rhizome girth enlargement, which lay a foundation for future studies on molecular mechanisms underlying rhizome formation.

PurposeThe association between menopause and overactive bladder is controversial. The purpose of this study was to determine the association between menopausal symptoms and overactive bladder, and identify the risk factors for overactive bladder.MethodsA cross-sectional study was performed. The study included 403 women aged 36-76 years who visited the menopause clinic at Peking University First Hospital between September 2012 and December 2013. The overactive bladder symptom score and modified Kupperman index questionnaires were used. Differences were assessed using descriptive statistics to determine any association between the overactive bladder symptom score and modified Kupperman index score, and to evaluate the risk factors for overactive bladder.ResultsA total of 304 women were finally enrolled. The prevalence of overactive bladder was 9.43%, and the modified Kupperman index score; number of sexual problems; and frequency of urinary tract infections, vertigo, melancholia, and mood swings were significantly higher in patients with overactive bladder than in the patients without overactive bladder (p < 0.05). Menopausal symptoms (modified Kupperman index score ≥ 15) (odds ratio: 1.049, 95% confidence interval: 1.006-1.095, p = 0.025) and a low frequency of sexual intercourse in the last 6 months (odds ratio: 2.580, 95% confidence interval: 1.228-5.422, p = 0.012) were identified as independent risk factors for overactive bladder. The frequency of sexual intercourse was found to decrease with an increase in the severity of overactive bladder (p = 0.004, linear-by-linear association = 0.001).ConclusionMenopausal symptoms may be closely associated with overactive bladder, and sexual activity may be associated with the severity of overactive bladder. Moreover, sexual problems, urinary tract infections, vertigo, melancholia, and mood swings may be associated with overactive bladder.