Deficiency of neutral cholesterol ester hydrolase 1 (NCEH1) impairs endothelial function in diet-induced diabetic mice.

BACKGROUND: Neutral cholesterol ester hydrolase 1 (NCEH1) plays a critical role in the regulation of cholesterol ester metabolism. Deficiency of NCHE1 accelerated atherosclerotic lesion formation in mice. Nonetheless, the role of NCEH1 in endothelial dysfunction associated with diabetes has not been explored. The present study sought to investigate whether NCEH1 improved endothelial function in diabetes, and the underlying mechanisms were explored. METHODS: The expression and activity of NCEH1 were determined in obese mice with high-fat diet (HFD) feeding, high glucose (HG)-induced mouse aortae or primary endothelial cells (ECs). Endothelium-dependent relaxation (EDR) in aortae response to acetylcholine (Ach) was measured. RESULTS: Results showed that the expression and activity of NCEH1 were lower in HFD-induced mouse aortae, HG-exposed mouse aortae ex vivo, and HG-incubated primary ECs. HG exposure reduced EDR in mouse aortae, which was exaggerated by endothelial-specific deficiency of NCEH1, whereas NCEH1 overexpression restored the impaired EDR. Similar results were observed in HFD mice. Mechanically, NCEH1 ameliorated the disrupted EDR by dissociating endothelial nitric oxide synthase (eNOS) from caveolin-1 (Cav-1), leading to eNOS activation and nitric oxide (NO) release. Moreover, interaction of NCEH1 with the E3 ubiquitin-protein ligase ZNRF1 led to the degradation of Cav-1 through the ubiquitination pathway. Silencing Cav-1 and upregulating ZNRF1 were sufficient to improve EDR of diabetic aortas, while overexpression of Cav-1 and downregulation of ZNRF1 abolished the effects of NCEH1 on endothelial function in diabetes. Thus, NCEH1 preserves endothelial function through increasing NO bioavailability secondary to the disruption of the Cav-1/eNOS complex in the endothelium of diabetic mice, depending on ZNRF1-induced ubiquitination of Cav-1. CONCLUSIONS: NCEH1 may be a promising candidate for the prevention and treatment of vascular complications of diabetes.

Exploring the Diversity and Specificity of Secondary Biosynthetic Potential in Rhodococcus.

The actinomycete genus Rhodococcus is known for its diverse biosynthetic enzymes, with potential in pollutant degradation, chemical biocatalysis, and natural product exploration. Comparative genomics have analyzed the distribution patterns of non-ribosomal peptide synthetases (NRPSs) in Rhodococcus. The diversity and specificity of its secondary metabolism offer valuable insights for exploring natural products, yet remain understudied. In the present study, we analyzed the distribution patterns of biosynthetic gene clusters (BGCs) in the most comprehensive Rhodococcus genome data to date. The results show that 86.5% of the gene cluster families (GCFs) are only distributed in a specific phylogenomic-clade of Rhodococcus, with the most predominant types of gene clusters being NRPS and ribosomally synthesized and post-translationally modified peptides (RiPPs). In-depth mining of RiPP gene clusters revealed that Rhodococcus encodes many clade-specific novel RiPPs, with thirteen core peptides showing antibacterial potential. High-throughput elicitor screening (HiTES) and non-targeted metabolomics revealed that a marine-derived Rhodococcus strain produces a large number of new aurachin-like compounds when exposed to specific elicitors. The present study highlights the diversity and specificity of secondary biosynthetic potential in Rhodococcus, and provides valuable information for the targeted exploration of novel natural products from Rhodococcus, especially for phylogenomic-clade-specific metabolites.

Disrupted cardiac fibroblast BCAA catabolism contributes to diabetic cardiomyopathy via a periostin/NAP1L2/SIRT3 axis.

BACKGROUND: Periostin is an extracellular matrix protein that plays a critical role in cell fate determination and tissue remodeling, but the underlying role and mechanism of periostin in diabetic cardiomyopathy (DCM) are far from clear. Thus, we aimed to clarify the mechanistic participation of periostin in DCM. METHODS: The expression of periostin was examined in DCM patients, diabetic mice and high glucose (HG)-exposed cardiac fibroblasts (CF). Gain- and loss-of-function experiments assessed the potential role of periostin in DCM pathogenesis. RNA sequencing was used to investigate the underlying mechanisms of periostin in DCM. RESULTS: A mouse cytokine antibody array showed that the protein expression of periostin was most significantly upregulated in diabetic mouse heart, and this increase was also observed in patients with DCM or HG-incubated CF. Periostin-deficient mice were protected from diabetes-induced cardiac dysfunction and myocardial damage, while overexpression of periostin held the opposite effects. Hyperglycemia stimulated the expression of periostin in a TGF-ß/Smad-dependent manner. RNA sequencing results showed that periostin upregulated the expression of nucleosome assembly protein 1-like 2 (NAP1L2) which recruited SIRT3 to deacetylate H3K27ac on the promoters of the branched-chain amino acid (BCAA) catabolism-related enzymes BCAT2 and PP2Cm, resulting in BCAA catabolism impairment. Additionally, CF-derived periostin induced hypertrophy, oxidative injury and inflammation in primary cardiomyocytes. Finally, we identified that glucosyringic acid (GA) specifically targeted and inhibited periostin to ameliorate DCM. CONCLUSION: Overall, manipulating periostin expression may function as a promising strategy in the treatment of DCM.

Accuracy of computed tomographic angiography in the diagnosis of patients with inferior vena cava partial obstruction in Budd-Chiari syndrome.

BACKGROUND AND AIM: The diagnosis of the partially obstructed inferior vena cava (IVC) in Budd-Chiari syndrome (BCS) patients has received little attention. We aimed to evaluate the diagnostic accuracy of computed tomographic angiography (CTA) for patients with BCS and a partially obstructed IVC. METHODS: A total of 329 patients with BCS and an obstructed IVC were endovascularly treated with balloon dilation and/or stent placement. All patients underwent a CTA examination prior to endovascular treatment, and the data were retrospectively reviewed. The presence of a round, oval, irregular shape or jet sign low-density area without enhancement within the enhanced proximal IVC was considered a sign of a partially obstructed IVC. Digital subtraction angiography was used as the gold standard. RESULTS: The results from the digital subtraction angiography revealed a partially obstructed IVC in 108 BCS patients and a complete obstruction in 221 patients. The CTA discovered a partially obstructed IVC in 99 patients and a completely obstructed IVC in 230 patients. From the CTA results, 15 were false negatives, and six were false positives. The patient-based evaluation yielded an accuracy of 93.6%, a sensitivity of 86.1%, specificity of 97.3%, positive predictive value of 93.9%, and negative predictive value of 93.5% for the detection of BCS patients with a partial IVC obstruction. CONCLUSIONS: Computed tomographic angiography offered a high diagnostic accuracy and sensitivity in BCS patients with a partially obstructed IVC. The low-density area within the enhanced proximal IVC above the membrane in artery phase can be considered a reliable indicator of a stenotic IVC in BCS patients.

[Bushen Huoxue Recipe Inhibited Vascular Calcification in Chronic Renal Failure Rats by Regulating BMP-2/Runx2/Osterix Signal Pathway].

OBJECTIVE: To observe the effect of Bushen Huoxue Recipe (BHR) on inhibiting vascular calcification (VC) in chronic renal failure (CRF) rats by regulating BMP-2/Runx2/Osterix signal pathway, and to explore its possible mechanism. METHODS: Thirty SD rats were randomly divided into the normal group, the model group, and the BHR group, 10 in each group. Rats in the model group and the BHR group were administered with 250 mg/kg adenine suspension by gastroagavage and fed with 1.8% high phosphorus forage, once per day in the first 4 weeks, and then gastric administration of adenine suspension was changed to once per two days in the following 5-8 weeks. Rats in the BHR group were administered with BHR at the daily dose of 55 g/kg by gastrogavage in the first 8 weeks, once per day. Equal volume of normal saline was given to rats in the normal group by gastrogavage for 8 weeks. Histological changes in renal tissue and aorta VC were observed by HE staining and alizarin red staining respectively. Levels of calcium (Ca), phosphorus (P), serum creatinine (Cr), blood urea nitrogen (BUN), and intact parathyroid hormone (iPTH) in serum were detected. Protein expression levels of bone morphogenetic protein (BMP-2), Runt related transcription factor (Runx2) , and Osterix were detected by Western blot. RESULTS: HE staining showed that compared with the normal group, disordered glomerular structure, tubular ectasia and dropsy, intracavitary inflammatory cell infiltration, dark brown crystal deposition in kidney tubules, renal interstitial fibrosis, and decreased number of renal blood vessels in the model group. Compared with the model group, normal glomerular numbers increased more, reduced degree of tubular ectasia, decreased number of inflammatory cells, and reduced adenine crystal deposition in the BHR group. Alizarin red staining showed that compared with the normal group, calcified nodes could be found in the model group, with extensive deposition of red particle in aorta. Compared with the model group, calcified nodes were reduced in the BHR group. Compared with normal group, serum levels of P, SCr, BUN, and iPTH significantly increased, serum Ca level significantly decreased, protein expressions of BMP-2, Runx2, Osterix also increased in the model group (P < 0.05, P < 0.01). Compared with the model group, serum levels of P, SCr, BUN, and iPTH levels significantly decreased, serum Ca level significantly increased, protein expressions of BMP-2, Runx2, Osterix also decreased in the BHD group (P < 0.05, P < 0.01). CONCLUSION: BHD could improve renal function, Ca-P metabolism, and renal histological changes in CHF rats, down-regulate the expression level of BMP-2/Runx2/Osterix signal pathway in vascular calcification of CRF, which might be one of the mechanisms for inhibiting VC in CHF.

Placement of a duodenal stents bridge the duodenal papilla may predispose to acute pancreatitis.

BACKGROUND/AIMS: To retrospective evaluate the incidence, predictive factors, and management of acute pancreatitis after placement of duodenal stent in patients with malignant gastroduodenal obstruction. METHODOLOGY: Among 242 patients with symptomatic malignant gastroduodenal obstruction successfully treated with duodenal stent placement, acute pancreatitis occurred in 10 (4.1%) of the patients 1-7 days after stent placement. The variables were analyzed. Univariate and multivariate analysis was performed to evaluate factors predictive of acute pancreatitis. Management of acute pancreatitis also was evaluated. RESULTS: All patients with acute pancreatitis were presented with abdominal pain and distention with vomiting 1-7 days after stent placement, in which 7 patients developed acute janudice. Four patients were cured by fasting and intravenous nutrition, and the remaining 6 cases were managed with percutaneous cholangiography and drain placement (PTCD). Univariate analysis showed acute pancreatitis was associated with location in the descending duodenum (p = 0.001) and stent bridge the duodenal papilla (p < 0.001). Multivariate analysis exhibited that the presence of stent bridged the duodenal papilla (odds ratio (OR), 18.48; 95% CI, 2.298-148.48; p = 0.006) was independent predictors of acute pancreatitis. CONCLUSIONS: Acute pancreatitis is an uncommon early complication of placement of duodenal stents in patients with malignant gastroduodenal obstruction. Acute pancreatitis occurred most commonly in descending duodenum, and in patients with stent bridged the duodenal papilla. Stent bridged the duodenal papilla may be the most important predictors for acute pancreatitis. Acute pancreatitis can be managed conservatively or by PTCD when developed to acute jaundice.

Influence of nonalcoholic fatty liver disease on response to antiviral treatment in patients with chronic hepatitis B: A meta-analysis.

BACKGROUND: Although hepatitis B virus infection is the leading cause of chronic liver injury globally, nonalcoholic fatty liver disease (NAFLD) is gradually gaining attention as another major chronic liver disease. The number of patients having chronic hepatitis B (CHB) with concomitant hepatic steatosis has increased. AIM: To analyze the effect of NAFLD on the response to antiviral treatment in patients with CHB. METHODS: Relevant English studies were systematically searched across PubMed, EMBASE, Web of Science, and Cochrane Library until October 2023. Studies in which the treatment outcomes were compared between patients with CHB only and those with CHB and hepatic steatosis were included. RESULTS: Of the 2502 retrieved studies, 11 articles were finally included. Biochemical response until 48 wk (OR = 0.87, 95%CI: 0.50-1.53, P = 0.000) and 96 wk (OR = 0.35, 95%CI: 0.24-0.53, P = 0.24) and virological response until 96 wk (OR = 0.80, 95%CI: 0.43-1.49, P = 0.097) were lower in patients with hepatic steatosis than in patients with CHB alone. CONCLUSION: Hepatic steatosis lowers the biochemical response to antiviral treatment in patients with CHB.

Tumor immunity: A brief overview of tumor­infiltrating immune cells and research advances into tumor­infiltrating lymphocytes in gynecological malignancies (Review).

Tumor immunity is a promising topic in the area of cancer therapy. The 'soil' function of the tumor microenvironment (TME) for tumor growth has attracted wide attention from scientists. Tumor-infiltrating immune cells in the TME, especially the tumor-infiltrating lymphocytes (TILs), serve a key role in cancer. Firstly, relevant literature was searched in the PubMed and Web of Science databases with the following key words: 'Tumor microenvironment'; 'TME'; 'tumor-infiltrating immunity cells'; 'gynecologic malignancies'; 'the adoptive cell therapy (ACT) of TILs'; and 'TIL-ACT' (https://pubmed.ncbi.nlm.nih.gov/). According to the title and abstract of the articles, relevant items were screened out in the preliminary screening. The most relevant selected items were of two types: All kinds of tumor-infiltrating immune cells; and advanced research on TILs in gynecological malignancies. The results showed that the subsets of TILs were various and complex, while each subpopulation influenced each other and their effects on tumor prognosis were diverse. Moreover, the related research and clinical trials on TILs were mostly concentrated in melanoma and breast cancer, but relatively few focused on gynecological tumors. In conclusion, the present review summarized the biological classification of TILs and the mechanisms of their involvement in the regulation of the immune microenvironment, and subsequently analyzed the development of tumor immunotherapy for TILs. Collectively, the present review provides ideas for the current treatment dilemma of gynecological tumor immune checkpoints, such as adverse reactions, safety, personal specificity and efficacy.

Asymmetric total synthesis of polycyclic xanthenes and discovery of a WalK activator active against MRSA.

The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro-hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective construction mechanism of the three contiguous stereocenters. Additionally, this work leads to the discovery of an antibacterial agent against both drug-sensitive and drug-resistant S. aureus. This compound operates through a unique mechanism that promotes bacterial autolysis by activating the two-component sensory histidine kinase WalK. Our research holds potential for future antibacterial drug development.

[Intervention of chronic hepatitis B liver fibrosis patients in different stages by syndrome typing and different activating blood removing stasis methods: a clinical study].

OBJECTIVE: To observe the clinical efficacy of treating chronic hepatitis B liver fibrosis (CHBLF) in different stages by syndrome typing and different activating blood removing stasis methods (ABRSM). METHODS: Totally 100 CHBLF patients of vital qi deficiency blood stasis syndrome (VQDBSS) treated at the Department of Liver Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences from July 2008 to December 2011, were randomly assigned to the treatment group and the control group, 50 in each group. Those in the treatment group were treated by self-formulated decoctions for activating blood nourishing blood (ABNB), activating blood removing stasis (ABRS), and activating blood softening hard mass (ABSHM) according to their stages of disease conditions (mild, moderate, and severe). Those in the control group were treated with Compound Biejia Ruangan Tablet (CBRT). Integrals of Chinese medical syndromes, liver functions [mainly including alanine aminotransferase (ALT), albumin/globulin (A/ G)], ultrasonographic examinations of liver (mainly including echoes of liver, width of spleens, width of portal vein), four indicators of serum hepatic fibrosis [including serum hyaluronic acid (HA), laminin (LN), type IV collagen (IV-C), type III collagen peptide (P-III-P)] were statistically analyzed. The therapeutic course was 6 months for all. RESULTS: Compared with before treatment in the same group, the integrals of Chinese medical syndromes both decreased after treatment in the two groups (P < 0.05). The width of spleens decreased in the treatment group more obviously after treatment than before treatment (P < 0.05). Compared with the control group, the integrals of Chinese medical syndromes and the width of spleens were more obviously improved in the treatment group, showing statistical difference (P < 0.05). Compared with before treatment in the same group, levels of ALT, HA, and LN significantly decreased, and the level of A/G significantly increased after treatment in the two groups, showing statistical difference (P < 0.05). Compared with the control group, the A/G level, HA, and LN were more obviously improved in the treatment group, showing statistical difference (P < 0.05). The total effective rate was 76% in the treatment group and 46% in the control group, showing statistical difference (P < 0.05). CONCLUSIONS: Treating CH-BLF in different stages by ABRSM got better effect than using CBRT alone. It could favorably improve clinical symptoms of CHBLF patients and their serum biochemical indicators.

QiHuangYiShen Granules Modulate the Expression of LncRNA MALAT1 and Attenuate Epithelial-Mesenchymal Transition in Kidney of Diabetic Nephropathy Rats.

Background: QiHuangYiShen granules (QHYS), a traditional Chinese herbal medicine formula, have been used in clinical practice for treating diabetic kidney disease for several years by our team. The efficacy of reducing proteinuria and delaying the decline of renal function of QHYS has been proved by our previous studies. However, the exact mechanism by which QHYS exerts its renoprotection remains largely unknown. Emerging evidence suggests that lncRNA MALAT1 is abnormally expressed in diabetic nephropathy (DN) and can attenuate renal fibrosis by modulating podocyte epithelial-mesenchymal transition (EMT). Objective: In the present study, we aimed to explore whether QHYS could modulate lncRNA MALAT1 expression and attenuate the podocyte EMT as well as the potential mechanism related to the Wnt/ß-catenin signal pathway. Methods: SD rats were fed with the high-fat-high-sucrose diet for 8 weeks and thereafter administered with 30 mg/kg streptozotocin intraperitoneally to replicate the DN model. Quality control of QHYS was performed using high-performance liquid chromatography. QHYS were orally administered at 1.25, 2.5, and 5 g/kg doses, respectively, to the DN model rats for 12 weeks. Body weight, glycated haemoglobin, blood urea nitrogen, serum creatinine, 24-h proteinuria, and kidney index were measured. The morphologic pathology of the kidney was evaluated by Hematoxylin-eosin and Masson's trichrome staining. The expression level of lncRNA MALAT1 was determined by quantitative real-time polymerase chain reaction. In addition, the expression levels of podocyte EMT protein markers and Wnt/ß-catenin pathway proteins in renal tissues were evaluated by Western blotting and immunohistochemistry. Results: The results showed that QHYS significantly reduced 24-h proteinuria, blood urea nitrogen, kidney index, and ameliorated glomerular hypertrophy and collagen fiber deposition in the kidney of DN rats. Importantly, QHYS significantly downregulated the expression level of lncRNA MALAT1, upregulated the expression of nephrin, the podocyte marker protein, downregulated the expression of desmin and FSP-1, and mesenchymal cell markers. Furthermore, QHYS significantly downregulated the expression levels of Wnt1, ß-catenin, and active ß-catenin. Conclusion: Conclusively, our study revealed that QHYS significantly reduced proteinuria, alleviated renal fibrosis, and attenuated the podocyte EMT in DN rats, which may be associated with the downregulation of lncRNA MALAT1 expression and inhibition of the Wnt/ß-catenin pathway.

The clinical value of miRNA-21 in cervical cancer: A comprehensive investigation based on microarray datasets.

Previous work has demonstrated that the expression of microRNA-21 (miR-21) is implicated in cervical cancer (CC). However, little is known regarding its associations with clinical parameters. We first conducted a meta-analysis using data from Gene Expression Omnibus (GEO) microarrays and The Cancer Genome Atlas (TCGA). Then, enrichment analysis and hub gene screening were performed by bioinformatic methods. Finally, the role of the screened target genes in CC was explored. According to the meta-analysis, the expression of miR-21 in cancer tissues was higher than in adjacent nontumor tissues (P < 0.05). In addition, 46 genes were predicted as potential targets of miR-21. After enrichment analyses, it was detected that these genes were enriched in various cancer pathways, including the phosphatidylinositol signaling system and mammalian target of rapamycin (mTOR) signaling pathway. In this study, bioinformatic tools and meta-analysis validated that miR-21 may function as a highly sensitive and specific marker for the diagnosis of CC, which may provide a novel approach to the diagnosis and treatment of CC.

The Mechanism of Insulin-Like Growth Factor II mRNA-Binging Protein 3 Induce Decidualization and Maternal-Fetal Interface Cross Talk by TGF-ß1 in Recurrent Spontaneous Abortion.

Recurrent spontaneous abortion (RSA) is defined as the loss of two or more consecutive intrauterine pregnancies that are clinically established early in pregnancy. To date, the etiology and underlying mechanisms of RSA remain unclear. It is widely thought that the impairment of decidualization is inclined to induce subsequent pregnancy failure and leads to the dysregulation of extra-villous trophoblast invasion and proliferation through maternal-fetal cross talk. However, the mechanism of decidualization in RSA has yet to be understood. In our study, we demonstrate that decidual samples from RSA patients have significantly higher insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and lower TGF-ß1 levels compared to healthy controls. In addition, the overexpression of IGF2BP3 in human endometrial stromal cells (hESCs) can lead to the impairment of decidualization in vitro-induced model and the abnormal cell cycle regulation. Furthermore, TGF-ß1 and MMP9 levels were greatly increased after decidualization, whereas IGF2BP3 overexpression inhibited endometrial mesenchymal decidualization by downregulating TGF-ß1, impeding maternal-fetal interface cytokine cross talk, and limiting the ability of trophoblast invasion. In conclusion, our investigation first demonstrates that abnormal elevation of IGF2BP3 in the pregnant endometrium leads to the impairment of decidualization and abnormal trophoblast invasion, thereby predisposing individuals to RSA.

Landscape of Immune Microenvironment in Epithelial Ovarian Cancer and Establishing Risk Model by Machine Learning.

BACKGROUND: Epithelial ovarian cancer (EOC) is an extremely lethal gynecological malignancy and has the potential to benefit from the immune checkpoint blockade (ICB) therapy, whose efficacy highly depends on the complex tumor microenvironment (TME). METHOD AND RESULT: We comprehensively analyze the landscape of TME and its prognostic value through immune infiltration analysis, somatic mutation analysis, and survival analysis. The results showed that high infiltration of immune cells predicts favorable clinical outcomes in EOC. Then, the detailed TME landscape of the EOC had been investigated through "xCell" algorithm, Gene set variation analysis (GSVA), cytokines expression analysis, and correlation analysis. It is observed that EOC patients with high infiltrating immune cells have an antitumor phenotype and are highly correlated with immune checkpoints. We further found that dendritic cells (DCs) may play a dominant role in promoting the infiltration of immune cells into TME and forming an antitumor immune phenotype. Finally, we conducted machine-learning Lasso regression, support vector machines (SVMs), and random forest, identifying six DC-related prognostic genes (CXCL9, VSIG4, ALOX5AP, TGFBI, UBD, and CXCL11). And DC-related risk stratify model had been well established and validated. CONCLUSION: High infiltration of immune cells predicted a better outcome and an antitumor phenotype in EOC, and the DCs might play a dominant role in the initiation of antitumor immune cells. The well-established risk model can be used for prognostic prediction in EOC.

TMEM206 is a potential prognostic marker of hepatocellular carcinoma.

Transmembrane proteins are involved in the transportation of materials into and out of cells. The transmembrane protein (TMEM) family is a collection of poorly described transmembrane proteins that serve important roles in tumor development and progression. A number of TMEM proteins have been discovered. A newly discovered TMEM protein, TMEM206, transports ions across the membrane under physiological and pathological conditions, generating an acidic environment, which serves an important role in the microenvironment. However, the prognostic value and regulatory mechanisms of action of TMEM206 in tumors is unclear. The aim of the present study was to evaluate the prognostic value and regulation mechanisms of TMEM206 in tumors. Firstly, the expression of TMEM206 in tumors and normal tissues was assessed using the GEPIA and Oncomine databases and the results revealed that TMEM206 expression increased or decreased depending on the type of tumor. Subsequently, using the Human Protein Atlas and the Kaplan-Meier plotter, the findings of the present study revealed that TMEM206 is related to the prognosis of hepatocellular carcinoma. In order to explore the mechanism of TMEM206 in promoting tumor progression, GEO and cBioPortal were used to determine genes that may be co-expressed with TMEM206. MetaScape was used to identify the signaling pathways that TMEM206 may participate in. Finally, miRWalk, miRDB and TargetScan were used to identify miRNAs that may regulate the expression of TMEM206 and the findings revealed that 2 miRNA (hsa-miR-325 and hsa-miR-510-5p) were involved. In conclusion, upregulation of TMEM206 is associated with poor prognosis in patients with hepatocellular carcinoma.

Identification of differentially expressed genes and signaling pathways involved in endometriosis by integrated bioinformatics analysis.

Endometriosis is a common gynecological disease characterized by the presence and growth of endometrial tissue outside the uterus, including the pelvis and abdominal cavity. This condition causes various clinical symptoms, such as non-menstrual pelvic pain, dysmenorrhea and infertility, seriously affecting the health and quality of life of women. To date, the specific mechanism and the key molecules of endometriosis remain uncertain. The purpose of the present study was to elucidate the mechanisms involved in the development and persistence of the disease. A number of mRNA expression profile datasets (namely GSE11691, GSE23339, GSE25628 and GSE78851) were downloaded from the Gene Expression Omnibus (GEO) database. These gene expression profiles were normalized, and the differentially expressed genes (DEGs) were identified by integrated bioinformatics analysis. A total of 103 DEGs were screened upon excluding the genes that exhibited inconsistency of expression (P<0.05). Furthermore, the Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and construction of protein-protein interaction networks of DEGs were performed using online software. The results revealed that the DEGs were closely associated with cell migration, adherens junction and hypoxia-inducible factor signaling. In addition, immunohistochemical assay results were found to be consistent with the bioinformatics results. The present study may help us understand underlying molecular mechanisms and the development of endometriosis, which has a great clinical significance for early diagnosis of the disease.

Efficacy and safety of the Fu-Zheng-Qu-Zhuo method on retarding the progress of chronic kidney disease (stage 3-4): a systematic review and meta-analysis.

BACKGROUND: To evaluate the efficacy and safety of a traditional Chinese medicine (TCM), Fu-Zheng-Qu-Zhuo, on retarding the progress of stage 3-4 chronic kidney disease (CKD). METHODS: We searched the relevant randomized controlled trials (RCTs) from the Medline, Cochrane Library, Embase, SinoMed, Wanfang, CNKI, and Weipu (VIP) databases from their inception to June 2018. Conference proceedings, and reference lists of relevant articles and two reviewers, independently identified the relevant studies. RevMan software was used for statistical analysis. The fixed-effect model was applied if there was either no or low heterogeneity, and pooled odds ratios (ORs) were estimated using the Mantel-Haenszel method. Publication bias was assessed if there were more than ten studies in one outcome. All hypotheses were tested at the alpha =0.05 level. RESULTS: Ten studies with 1,308 participants were included, and eight studies were included in the meta-analysis. Compared with the control group, the occurrence of composite endpoint events (defined as the initiation of dialysis, CKD-related death, or the doubling of serum creatinine) was significantly reduced in the treatment group [risk ratio (RR) =0.56, 95% CI: 0.33-0.94, P=0.029, I2=0.0%]. In addition, it did not increase the risk of hyperkalemia (RR =1.43, 95% CI: 0.85-2.42, P=0.180, I2=0.0%). CONCLUSIONS: In conclusion, the Fu-Zheng-Qu-Zhuo method combined with integrated therapy decreased the occurrence of composite endpoint events and retarded the progress of stage 3-4 CKD. In addition, there was no increase in the risk of hyperkalemia. We recommend the use of the Fu-Zheng-Qu-Zhuo method combined with integrated therapy for stage 3-4 CKD.

Effect of Bushen Huoxue decoction on inhibiting osteogenic differentiation of vascular smooth cells by regulating OPG/RANK/RANKL system in vascular calcification.

BACKGROUND: To investigate the effects of Bushen Huoxue Decoction (BSHXD) and its underlying molecular mechanisms on inhibiting osteogenic differentiation of vascular smooth muscle cells (VSMCs) in vascular calcification via regulating the mRNA expression of osteoprotegerin (OPG) and the receptor activator of the nuclear factor-kappa B ligand (RANKL). METHODS: VSMCs from the aortas of rats were cultured in vitro. Osteogenic differentiation of VSMCs was induced by high levels of an inorganic phosphate medium (2.4 mM). BSHXD-containing serum was prepared using the serum-pharmacological method. VSMCs were plated using 6-well plates at an approximate density of 4.0×104 cells/mL and cultured for 10 days. This was followed by the application of different concentrations of BSHXD-containing serum. The percentage of concentrations of BSHXD-containing serum in high, middle and low dosage group was 20%, 10% and 5%, respectively. Calcium nodules were evaluated by alizarin red S staining, and alkaline phosphatase (ALP) activity and calcium deposition were both examined as per the instruction of the test kits on the 3rd, 6th, and 10th days. Protein expression level of ALP and α-smooth muscle actin (α-SMA) were detected by Western blot on the 3rd, 6th, and 10th days. The mRNA expression of the OPG and RANKL were also detected by real-time PCR on the 3rd, 6th, and 10th days. RESULTS: Compared with the control group, BSHXD significantly attenuated the calcium nodules that were examined by alizarin red-S staining. Protein expression levels of α-SMA were up-regulated and ALP were down-regulated on the BSHXD group (P<0.05). BSHXD also attenuated the ALP activity and calcium deposition of the VSMCs (P<0.05). These changes were associated with the effect of BSHXD on up-regulating the expression of OPG mRNA and down-regulating the expression of RANKL mRNA in the process of osteogenic differentiation of VSMCs. CONCLUSIONS: BSHXD has a beneficial effect on inhibiting osteogenic differentiation of VSMCs induced by high levels of phosphate. The underlying mechanism appears to be related to the modulation of expressions of OPG mRNA and RANKL mRNA in the VSMCs, thereby preventing the phenotypic changes of VSMCs to an osteogenic phenotype.

Plasma extracellular vesicle microRNAs for pulmonary ground-glass nodules.

In this study, we evaluated the diagnostic value and molecular characteristics of plasma extracellular vesicles (EVs)-derived miRNAs for patients with solitary pulmonary nodules (SPNs), particularly ground-glass nodules (GGNs). This study was registered at www.clinicaltrials.gov under registration number NCT03230019. Small RNA sequencing was performed to assess plasma EVs miRNAs in 59 patients, including 12 patients with benign nodules (2017, training set). MiRNA profiles of 40 an additional individuals were sequenced (2018, validation set). Overall, 16 pure GGNs, 21 mixed GGNs, and 42 solid nodules were included, with paired post-operative plasma samples available for 20 patients. The target miRNA/reference miRNA ratio was used to construct a support vector machine (SVM) model. The SVM model with the best specificity showed 100% specificity in both the training and validation sets independently. The model with the best sensitivity showed 100% and 96.9% sensitivity in the training and validation sets, respectively. Principal component analysis revealed that pure GGN distributions were distinct from those of solid nodules, and mixed GGNs had a diffuse distribution. Among differentially expressed miRNAs, miR-500a-3p, miR-501-3p, and miR-502-3p were upregulated in tumor tissues and enhanced overall survival. The SVM classifier accurately distinguished malignant GGNs and benign nodules. The distinct profile characteristics of miRNAs provided insights into the feasibility of EVs miRNAs as prognostic factors in lung cancer.