Identification of metabolism-related key genes as potential biomarkers for pathogenesis of immune thrombocytopenia.

Immune thrombocytopenia (ITP), an acquired autoimmune disease, is characterized by immune-mediated platelet destruction. A biomarker is a biological entity that contributes to disease pathogenesis and reflects disease activity. Metabolic alterations are reported to be associated with the occurrence of various diseases. As metabolic biomarkers for ITP have not been identified. This study aimed to identify metabolism-related differentially expressed genes as potential biomarkers for pathogenesis of ITP using bioinformatic analyses.The microarray expression data of the peripheral blood mononuclear cells were downloaded from the Gene Expression Omnibus database (GSE112278 download link: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112278 ). Key module genes were intersected with metabolism-related genes to obtain the metabolism-related key candidate genes. The hub genes were screened based on the degree function in the coytoscape sofware. The key ITP-related genes were subjected to functional enrichment analysis. Immune infiltration analysis was performed using a single-sample gene set enrichment analysis algorithm to evaluate the differential infiltration levels of immune cell types between ITP patient and control. Molecular subtypes were identified based on the expression of hub genes. The expression of hub genes in the ITP patients was validated using quantitative real-time polymerase chain reaction analysis. This study identified five hub genes (ADH4, CYP7A1, CYP1A2, CYP8B1, and NR1H4), which were be associated with the pathogenesis of ITP, and two molecular subtypes of ITP. Among these hub genes, CYP7A1 and CYP8B1 involved in cholesterol metabolism,were further verified in clinical samples.

Cationic Alternating Polypeptide Fixed on Polyurethane at Multiple Sites for Excellent Antibacterial and Antifouling Properties.

Bacterial infection and blockage are severe problems for polyurethane (PU) catheters and there is an urgent demand for surface-functionalized polyurethane. Herein, a cationic alternating copolymer comprising allyl-substituted ornithine and glycine (allyl-substituted poly(Orn-alter-Gly)) with abundant carbon-carbon double bond functional groups (C═C) is designed. Polyurethane is prepared with a large quantity of C═C groups (PU-D), and different amounts of allyl-substituted poly(Orn-alter-Gly) are grafted onto the PU-D surface (PU-D-2%AMPs and PU-D-20%AMPs) via the C═C functional groups. The chemical structures of the allyl-substituted poly(Orn-alter-Gly) and polyurethane samples (PU, PU-D, PU-D-2%AMPs, and PU-D-20%AMPs) are characterized and the results reveal that allyl-substituted poly(Orn-alter-Gly) is decorated on the polyurethane. PU-D-20%AMPs shows excellent antibacterial activity against Escherichia coli, Enterococcus faecalis, and Staphylococcus aureus because of the high surface potential caused by cationic allyl-substituted poly(Orn-alter-Gly), and it also exhibits excellent long-term antibacterial activity and antibiofilm properties. PU-D-20%AMPs also has excellent antifouling properties because the cationic copolymer is fixed at multiple reactive sites, thus avoiding the formation of movable long chain brush. A strong surface hydration barrier is also formed to prevent adsorption of proteins and ions, and in vivo experiments reveal excellent biocompatibility. This flexible strategy to prepare dual-functional polyurethane surfaces with antibacterial and antifouling properties has large potential in biomedical implants.

Traditional Chinese medicine for the treatment of pulmonary fibrosis: A protocol for systematic review and meta-analysis of overview.

BACKGROUND: Since December 2019, there have been many cases of viral pneumonia of unknown causes in Wuhan City, Hubei Province. During the period of novel coronavirus, according to the observation of limited autopsy and biopsy pathological results, pulmonary interstitial fibrosis appeared in some pathological changes of lung. Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial pneumonia with unknown etiology and pathological changes limited to the lung. At present, there is still a lack of reevaluation of systematic evaluation of traditional Chinese medicine treatment IPF. Therefore, a systematic re-evaluation of the systematic evaluation of traditional Chinese medicine in the treatment of pulmonary fibrosis may help to understand the effective treatment scheme of traditional Chinese medicine in the treatment of pulmonary fibrosis and provide more reliable evidence for the first-line clinicians to treat novel coronavirus. METHODS: We will search 3 foreign electronic databases (Cochrane Library, Embase, PubMed) and 4 Chinese electronic databases (China National Knowledge Infrastructure [CNKI], WangFang Database, Chinese Biomedical Literature Database [CBM], and Chinese Scientific Journal Database [VIP]) to collect potential systematic reviews from their inceptions to February 2020. The language of publication is limited to Chinese or English. We will consider SRs and meta-analysis of Traditional Chinese Medicine for the Treatment of pulmonary fibrosis. Two reviewers will identify relevant studies, and then assess the methodological quality by assessment of multiple systematic reviews-2 tool. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) report checklist to assess the quality of reports included in the study. In order to better evaluate the systematic evaluation included in this research, risk of bias in systematic review tool is included in this research to evaluate the methodological quality. The quality of evidence of the included systematic reviews was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The Primary outcomes include: Clinical total effective rate, curative effect of TCM symptoms, pulmonary function and blood gas analysis. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSIONS: We expect to obtain reliable evidence from systematic analysis of traditional Chinese medicine treatment of pulmonary fibrosis in an available and useful document. REGISTRATION NUMBER: INPLASY202060029.

Tianma Gouteng Decoction combined with Qiju Dihuang Pill for the treatment of essential hypertension: A protocol for systematic review and meta-analysis.

BACKGROUND: Essential hypertension is one of the risk factors of cardiovascular and cerebrovascular diseases, which can cause target organ damage such as heart, brain and kidney, and has extremely high disability rate and death rate. With the development of economy and society, the prevalence rate of hypertension in China has increased rapidly from 9.8% in the 1980s to over 30% in the 21st century. According to the data published in "China Cardiovascular Disease Report 2018," China currently has 245 million hypertension patients. Comprehensive prevention and treatment of hypertension has become one of the major public health problems in China. The clinical practice and theoretical innovation of traditional Chinese medicine in the prevention and treatment of hypertension have been carried out for decades. Relevant literature points out that Tianma Gouteng Decoction combined with Qiju Dihuang Pill has ideal effect in the treatment of primary hypertension. However, most of the literatures are small sample studies, with uneven quality and clinical evidence, and lack of evidence-based medical evidence for clinical efficacy. Therefore, this study makes further meta-analysis of Tianma Gouteng Decoction combined with Qiju Dihuang Pill in the treatment of primary hypertension, with a view to providing evidence-based medical evidence for the treatment of primary hypertension. METHODS: We will search 3 foreign electronic databases (Cochrane Library, Embase, PubMed) and 4 Chinese electronic databases (China National Knowledge Infrastructure, WangFang Database, Chinese Biomedical Literature Database, and Chinese Scientific Journal Database) to collect potential systematic reviews from their inceptions to February 2020. The language of publication is limited to Chinese or English. First, the quality of randomized controlled trials documents included in this study was evaluated by using the improved Jadad scoring scale. Then, the 2 researchers conducted the evaluation independently according to Cochrane bias risk tools. The evidence level of the results will be evaluated by using the recommended evaluation, development and evaluation grading of recommendations assessment, development, and evaluation method. Statistical analysis will be conducted using Revman 5.3. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSIONS: The conclusion of this study will provide evidence for the efficacy of Tianma Gouteng Decoction combined with Qiju Dihuang Pills in the treatment of primary hypertension due to the efficacy of western medicine alone in treating primary hypertension. REGISTRATION NUMBER PROSPERO: INPLASY202050088.

A comprehensive evaluation of association between homocysteine levels and single nucleotide polymorphisms with hypertension risk: A protocol of systematic review and network meta-analysis.

BACKGROUND: According to the relevant reports that single nucleotide polymorphisms (SNPs) may contribute to change of homocysteine (HCY) levels and increase the risk of hypertension (HTN). During the inconsistent results, this meta-analysis purpose is systematically review and synthesized relevant data on HCY levels and SNPs in HTN. METHODS: The systematic search database, from the following database to find out the association studies of SNPs and HTN publications up until March 2020 from the databases of PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), the Chinese Science and Technology Periodical Database (VIP) and Wan fang databases, and Chinese Biomedical Literature Database (CBM). Network meta-analysis and Thakkinstian's algorithm were used to select the most appropriate genetic model, along with false positive report probability (FPRP) for noteworthy associations. All statistical analyses were calculated with STATA software (version 14.0; StataCorp, College Station, TX). RESULTS: This meta-analysis will provide high-quality evidence to the effects of SNP on HTN and levels of HCY, and find between SNPs and HTN susceptibility on in all the genetic models, and choose the best one. CONCLUSIONS: This meta-analysis will research which SNP is the most correlated with HTN risk. REGISTRATION: INPLASY202050002.

Salidroside affects proliferation, invasion and apoptosis of cervical squamous cell carcinoma C33Acells through JAK2/STAT3 pathway / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the effects of salidroside on the proliferation, invasion and apoptosis of cervical squamous cell carcinoma C33A cells and explore its possible mechanism. Methods: C33A cells were divided into 4 groups: control group, low-dose group (salidroside 50 μg/mL), high-dose group (salidroside 150 μg/mL), and AG490 group (inhibitor of JAK2/STAT3 signaling pathway, 50 μmol/L). Effects of salidroside and AG490 on the proliferation, invasion and apoptosis of C33A cells were detected by MTT method, EdU labeling experiment, Transwell assay, Rh123 staining and Flow cytometry, respectively. Western blotting was used to detect the effects of salidroside and AG490 on the expressions of JAK2/STAT3 pathway-related proteins (p-JAK2, p-STAT3) and apoptosis-related proteins (Bax, Bcl-2, caspase-3) in C33A cells. Result: Compared with the control group, the proliferation and DNA synthesis as well as the invasion of C33Acells in the low-dose group were significantly inhibited (all P<0.05), while the apoptosis was significantly enhanced (P<0.05); in the meanwhile, the fluorescence intensity of Rh123 was significantly reduced (all P<0.05) and the membrane structure of C33A cells were destroyed; moreover, the expressions of p-JAK2, p-STAT3 and Bcl-2 were significantly decreased while the expressions of Bax and caspase-3 were significantly increased (all P<0.05). Compared with the low-dose group, the effects of high-dose salidroside and AG490 on the proliferation, invasion, apoptosis and related protein expressions in C33A cells were more significant (all P<0.05), but there was no difference between the high-dose group and the AG490 group. Conclusion: Salidroside can inhibit the proliferation and invasion of C33A cells and promote cell apoptosis. Its mechanism may be related to inhibition of JAK2/ STAT3 signaling pathway.

Expression of Long Noncoding RNA LIPCAR Promotes Cell Proliferation, Cell Migration, and Change in Phenotype of Vascular Smooth Muscle Cells.

BACKGROUND The long noncoding RNA LIPCAR is a type of transcription product (>200 nucleotides long). Recent studies demonstrated that LIPCAR is a potential biomarker in cardiovascular disease and can predict survival in patients with cardiovascular disease. Therefore, the present study explored the role of LIPCAR in the regulation of proliferation, migration, and change in phenotype of vascular smooth muscle cells. MATERIAL AND METHODS Human vascular smooth muscle cells (VSMCs) were treated with 20 g/mL oxidatively modified low-density lipoprotein (ox-LDL) or 20 ng/ml platelet-derived growth factor BB (PDGF-BB) for 24 h, then the expression levels of LIPCAR were detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay. LIPCAR-overexpressing plasmids were transfected into VSMCs. After transfection, cell proliferation and migration were measured using the Cell Counting Kit-8 (CCK-8) and Transwell assays, respectively. The levels of a-smooth muscle actin (a-SMA) a molecular marker of the contractile VSMC phenotype, were measured using Western blot and immunofluorescence assays. Protein levels of cyclin-dependent kinase-2 (CDK2), proliferating cell nuclear antigen (PCNA), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor A (VEGF-A), and angiopoietin-2 (Ang-2) were assessed by Western blot. The level of tissue factor (TF) was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS Treatment with PDGF-BB or ox-LDL significantly increased levels of LIPCAR in VSMCs. Overexpression of LIPCAR markedly promoted cell proliferation and migration. Further, upregulation of LIPCAR increased CDK2, p21, PCNA, MMP2, MMP9, VEGF-A, Ang-2, and TF expression and decreased p21 expression. In addition, LIPCAR significantly decreased a-SAM expression. CONCLUSIONS Together, our data suggest that overexpression of LIPCAR promotes cell proliferation, migration, and phenotypic switch of vascular smooth muscle cells.

MicroRNA-125a inhibits tumorigenesis by targeting Smurf1 in colorectal carcinoma.

Aberrant expression of microRNAs (miRNAs) may contribute to the initiation and development of multiple types of human cancer. Several miRNAs have been found to be strongly correlated with the diagnosis, progression, and prognosis of colorectal carcinoma (CRC), but the role of miR-125a in CRC remains unclear. In the present study, the function of miR-125a on the expression of Smad ubiquitin regulatory factor 1 (Smurf1) was investigated in vitro and in vivo. We verified that Smurf1 is a downstream target gene of miR-125a and is involved in miR-125a-mediated regulation of CT26 cell (colon cancer cell) proliferation and migration. Overexpression of miR-125a suppresses CT26 cell growth by inhibiting cell proliferation. Additionally, wound healing assays were performed to show that overexpression of miR-125a significantly reduced CT26 cell migration, which was reversed by overexpression of Smurf1. In vivo, miR-125a overexpression downregulated the expression of Ki67 and Smurf1, thus leading to a marked reduction in tumor growth. These results revealed that miR-125a plays a critical role in CRC by directly targeting Smurf1, a finding that may facilitate the development of improved diagnostic and therapeutic techniques for CRC.

Application of embolization microspheres in interventional therapy of malignant non-hypervascular tumor of liver.

OBJECTIVE: To investigate the efficacy and safety of transarterial embolization (TAE) using embolization microspheres in the treatment of non-hypervascular malignant liver tumors. METHODS: Patients with malignant non-hypervascular liver tumors, who were treated with TAE using embolization microspheres, were selected and analyzed retrospectively. The technical success rate, tumor response, and complications were assessed. RESULTS: Six patients were included in the study: 1 patient each with hepatocellular-cholangiocarcinoma, intrahepatic cholangiocarcinoma, hepatic metastasis after resection of common bile duct carcinoma, liver metastasis from colon cancer, liver metastasis from esophageal cancer, and liver metastasis from pancreatic cancer. The technical success rate was 100%. At 1 and 3 months after TAE, tumor local reactions were seen in 6/6 and 2/6 patients, respectively, and the tumor necrosis rates were 48%-73% and 22%-68%, respectively. The main complications were those related to the embolization syndrome, including 1 case of liver abscess and 1 case of severe pain on the first day after embolization. CONCLUSION: TAE with embolization microspheres is safe and effective in non-hypervascular liver tumors. It is a feasible option for palliative therapy of these tumors.

Application of molecular modelling and spectroscopic approaches for investigating binding of vanillin to human serum albumin.

In the present study, the interaction of vanillin and human serum albumin (HSA) has been characterised by molecular modelling, fluorescence, Fourier transform infrared (FT-IR) and circular dichroism (CD) spectroscopic methods. The results of molecular modelling suggested that vanillin was located within the binding pocket of subdomain IIA of HSA mainly by hydrophobic forces. The quenching of HSA fluorescence takes place with a binding constant (K) of 8.8, 7.7, 5.7, 4.2×10(4)M(-1) at four different temperatures (288, 298, 308, 318K), respectively. Meanwhile, the number of binding site (n≈1) was also obtained from fluorescence titration data. The enthalpy change ΔH(0) and the entropy change ΔS(0) were calculated to be -20kJmol(-1) and 5.8Jmol(-1)K(-1) according to the Van't Hoff equation. Furthermore, the alterations of protein secondary structure in the presence of vanillin were explored by FT-IR and CD spectra.

Investigation of the interaction between endocrine disruptor bisphenol A and human serum albumin.

In this study, the interaction of the endocrine disruptor bisphenol A (BPA) and human serum albumin (HSA) was investigated by molecular modelling, fluorescence, ultraviolet-visible spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FT-IR) and circular dichroism spectroscopy (CD). The association constants between BPA and HSA were determined using the Scatchard equation. The thermodynamic parameters of the binding reaction (DeltaG0, DeltaH0 and DeltaS0) were measured, and they indicated the presence of hydrophobic forces in the BPA-HSA interaction, which agreed well with the results from molecular modelling. The alterations of protein secondary structure in the presence of BPA were confirmed by UV-vis, FT-IR and CD spectroscopy. Lastly, the average binding distance, r, between BPA and HSA was evaluated and found to be 1.82 nm according to Förster's theory of non-radiation energy transfer.