Background Numerous reports have shown the role of human leukocyte antigen (HLA) alleles in the induction of cutaneous adverse drug reactions by moderating drug metabolism. We therefore aimed to investigate the docking patterns of four HLA alleles (HLA-B x 5101, HLA-B x 1501, HLA-A x 02:06 and HLA-B x 57:01) against four commercial drugs. Methodology   Four drugs (phenytoin (PHT), amoxicillin (AMX), aceclofenac (ACE) and ciprofloxacin (CIP)) were investigated for their docking behavior against four HLA alleles (HLA-B x 5101, HLA-B x 1501, HLA-A x 02:06, and HLA-B x 57:01) using the SwissDock method. In addition, toxicity (Tox) and the search tool for interactions of chemicals (STITCH) (protein-drug interaction) analyses were also carried out using the predicating the small molecule pharmaco-kinetic (pk) properties using graph-based signature method (pkCSM) and STITCH free online servers, respectively. Results Toxicity analysis showed that two drugs (amoxicillin and ciprofloxacin) exhibit hepatotoxicity. The STITCH analysis of the drug amoxicillin revealed its interaction with two human proteins. The drug phenytoin exhibited the lowest binding energy (LBE) with all four HLA alleles (HLA-B x 5101, HLA-B x 1501, HLA-A x 02:06, and HLA-B x 57:01). Conclusions The present findings provide new knowledge about the four drugs (phenytoin (PHT), amoxicillin (AMX), aceclofenac (ACE) and ciprofloxacin (CIP)) and their binding affinities with HLA alleles, which may cause cutaneous adverse drug reactions.

UNASSIGNED: Wood apple (Limonia acidissima) has been reported to possess various pharmacological activities. The present study aimed to evaluate the 11 selected constituents of Wood apple (L. acidissima) as potent anti-dandruff and anti-acne agents using a molecular docking approach.
UNASSIGNED: The 11 selected constituents of Wood apple were studied on the molecular docking behavior of Malassezia globosa Lipase-1 and Cutibacterium acnes beta-keto acyl synthase-III enzymes by using the patchdock method. Furthermore, STITCH analysis was carried out to determine the ligand-protein interactions. STITCH analysis reveals that two ligands, namely, psoralen and umbelliferone, have exhibited interactions with both the M. globosa and P. acnes KPA 171202 proteins.
UNASSIGNED: The docking studies revealed that isopimpinellin and saponarin exhibited the highest (ACE) atomic contact energy (-162.32 and - 318.63 kcal/mol) with that of M. globosa Lipase-1 and C. acnes beta-ketoacyl synthase-III, respectively.
UNASSIGNED: Thus, the present finding provides new knowledge for understanding the 11 selected ligands of Wood apple (L. acidissima) as potent anti-dandruff and anti-acne agents.

暂无摘要。

Uterine fibroid is the most common non-cancerous tumor with no satisfactory options for long-term pharmacological treatment. Fibroblast activation protein-α (FAP) is one of the critical enzymes that enhances the fibrosis in uterine fibroids. Through STITCH database mining, we found that dipeptidyl peptidase-4 inhibitors (DPP4i) have the potential to inhibit the activity of FAP. Both DPP4 and FAP belong to the dipeptidyl peptidase family and share a similar catalytic domain. Hence, ligands which have a binding affinity with DPP4 could also bind with FAP. Among the DPP4i, linagliptin exhibited the highest binding affinity (Dock score = -8.562 kcal/mol) with FAP. Our study uncovered that the differences in the S2 extensive-subsite residues between DPP4 and FAP could serve as a basis for designing selective inhibitors specifically targeting FAP. Furthermore, in a dynamic environment, linagliptin was able to destabilize the dimerization interface of FAP, resulting in potential inhibition of its biological activity. True to the in-silico results, linagliptin reduced the fibrotic process in estrogen and progesterone-induced fibrosis in rat uterus. Furthermore, linagliptin reduced the gene expression of transforming growth factor-β (TGF-β), a critical factor in collagen secretion and fibrotic process. Masson trichrome staining confirmed that the anti-fibrotic effects of linagliptin were due to its ability to reduce collagen deposition in rat uterus. Altogether, our research proposes that linagliptin has the potential to be repurposed for the treatment of uterine fibroids.

BACKGROUND: The hallmark of non-alcoholic fatty liver disease (NAFLD) is aberrant buildup of triglycerides (TGs) in hepatocytes. Many genes promote NAFLD development. Using bioinformatics tools, we investigated the possible effect of statins on genes involved in NAFLD progression.
METHODS: Protein interactions of statins and NAFLD were searched in gene-drug and gene-disease databases. A Protein-Protein interaction (PPI) network was constructed to find hub genes and Molecular Complex Detection (MCODE) of NAFLD-related genes. Shared protein targets between protein targets of statins and NAFLD-associated genes were identified. Next, targets of each statin were assayed with all modular clusters in the MCODEs related to NAFLD. Biological process and pathway enrichment analysis for shared proteins was performed.
RESULTS: Screening protein targets for conventional statins and curated NAFLD-related genes identified 343 protein targets and 70 genes, respectively. A Venn diagram of NAFLD-related genes and protein targets of statins showed 24 shared proteins. The biological pathways on KEGG enrichment associated with the 24 shared protein sets were evaluated and included cytokine-cytokine receptor interaction, adipocytokine, PPAR, TNF and AMPK signaling pathways. Gene Ontology analysis showed major involvement in lipid metabolic process regulation and inflammatory response. PPI network analysis of 70 protein targets indicated 13 hub genes (PPARA, IL4, CAT, LEP, SREBF1, PRKCA, CYP2E1, NFE2L2, PTEN, NR1H4, ADIPOQ, GSTP1 and TGFB1). Comparing all seven statins with the three MCODE clusterings and 13 hub genes revealed that simvastatin as the most associated statin with NAFLD.
CONCLUSIONS: Simvastatin has the most impact on NAFLD-related genes versus other statins.

Cervical cerclage has been used for decades to reduce preterm birth. The Shirodkar and McDonald cerclage are the most commonly used techniques with no current consensus on the preferred technique.
To compare the efficacy of the Shirodkar and McDonald cerclage techniques in preventing preterm birth.
Studies were sourced from six electronic databases and reference lists.
Studies including women with a singleton pregnancy, requiring a cervical cerclage, using either the Shirodkar or McDonald technique that ran comparative analyses between the two techniques.
The primary outcome was preterm birth before 37 weeks, with analyses at 28, 32, 34 and 35 weeks. Secondary data were also collected on neonatal, maternal and obstetric outcomes.
Seventeen papers were included: 16 were retrospective cohort studies and one was a randomised controlled trial. The Shirodkar technique was significantly less likely to result in preterm birth before 37 weeks than the McDonald technique (relative risk [RR] 0.91, 95% CI 0.85-0.98). This finding was supported by a statistically significant reduction in rates of preterm birth before 35, 34 and 32 weeks, PPROM, difference in cervical length, cerclage to delivery interval, and an increase in birthweight in the Shirodkar group. No difference was seen in preterm birth rates <28 weeks, neonatal mortality, chorioamnionitis, cervical laceration or caesarean section rates. The RR for preterm birth prior to 37 weeks was no longer significant when sensitivity analyses were performed removing studies with a serious risk of bias. However, similar analyses removing studies that utilised adjunctive progesterone strengthened the primary outcome (RR 0.83, 95% CI 0.74-0.93).
Shirodkar cerclage reduces the rate of preterm birth prior to 35, 34 and 32 weeks\' gestation when compared with McDonald cerclage; however, the overall quality of the studies in this review is low. Further, large, well-designed randomised controlled trials are required to address this important question to optimise care for women who may benefit from cervical cerclage.

BACKGROUND: Diabetes is an increasingly prevalent global disease caused by the impairment in insulin production or insulin function. Diabetes in the long term causes both microvascular and macrovascular complications that may result in retinopathy, nephropathy, neuropathy, peripheral arterial disease, atherosclerotic cardiovascular disease, and cerebrovascular disease. Considerable effort has been expended looking at the numerous genes and pathways to explain the mechanisms leading to diabetes-related complications. Curcumin is a traditional medicine with several properties such as being antioxidant, anti-inflammatory, anti-cancer, and anti-microbial, which may have utility for treating diabetes complications. This study, based on the system biology approach, aimed to investigate the effect of curcumin on critical genes and pathways related to diabetes.
METHODS: We first searched interactions of curcumin in three different databases, including STITCH, TTD, and DGIdb. Subsequently, we investigated the critical curated protein targets for diabetes on the OMIM and DisGeNET databases. To find important clustering groups (MCODE) and critical hub genes in the network of diseases, we created a PPI network for all proteins obtained for diabetes with the aid of a string database and Cytoscape software. Next, we investigated the possible interactions of curcumin on diabetes-related genes using Venn diagrams. Furthermore, the impact of curcumin on the top scores of modular clusters was analysed. Finally, we conducted biological process and pathway enrichment analysis using Gene Ontology (GO) and KEGG based on the enrichR web server.
RESULTS: We acquired 417 genes associated with diabetes, and their constructed PPI network contained 298 nodes and 1651 edges. Next, the analysis of centralities in the PPI network indicated 15 genes with the highest centralities. Additionally, MCODE analysis identified three modular clusters, which highest score cluster (MCODE 1) comprises 19 nodes and 92 edges with 10.22 scores. Screening curcumin interactions in the databases identified 158 protein targets. A Venn diagram of genes related to diabetes and the protein targets of curcumin showed 35 shared proteins, which observed that curcumin could strongly interact with ten of the hub genes. Moreover, we demonstrated that curcumin has the highest interaction with MCODE1 among all MCODs. Several significant biological pathways in KEGG enrichment associated with 35 shared included the AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, PI3K-Akt signaling pathway, TNF signaling, and JAK-STAT signaling pathway. The biological processes of GO analysis were involved with the cellular response to cytokine stimulus, the cytokine-mediated signaling pathway, positive regulation of intracellular signal transduction and cytokine production in the inflammatory response.
CONCLUSIONS: Curcumin targeted several important genes involved in diabetes, supporting the previous research suggesting that it may have utility as a therapeutic agent in diabetes.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder. Defects in function/expression of genes/proteins are critical in initiation/progression of NAFLD. Natural products may modulate these genes/proteins. Curcumin improves steatosis, inflammation, and fibrosis progression. Here, bioinformatic tools, gene−drug and gene-disease databases were utilized to explore targets, interactions, and pathways through which curcumin could impact NAFLD. METHODS: Significant curcumin−protein interaction was identified (high-confidence:0.7) in the STITCH database. Identified proteins were investigated to determine association with NAFLD. gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed for significantly involved targets (p < 0.01). Specificity of obtained targets with NAFLD was estimated and investigated in Tissue/Cells−gene associations (PanglaoDB Augmented 2021, Mouse Gene Atlas) and Disease−gene association-based EnrichR algorithms (Jensen DISEASES, DisGeNET). RESULTS: Two collections were constructed: 227 protein−curcumin interactions and 95 NAFLD-associated genes. By Venn diagram, 14 significant targets were identified, and their biological pathways evaluated. Based on gene ontology, most targets involved stress and lipid metabolism. KEGG revealed chemical carcinogenesis, the AGE-RAGE signaling pathway in diabetic complications and NAFLD as the most common significant pathways. Specificity to diseases database (EnrichR algorithm) revealed specificity for steatosis/steatohepatitis. CONCLUSION: Curcumin may improve, or inhibit, progression of NAFLD through activation/inhibition of NAFLD-related genes.

Preterm birth (PTB) is the leading cause of death in children under five years. Spontaneous preterm birth (SPTB) is the major cause of preterm delivery. The key risk factors for SPTB are women who have a short cervix and women who have had previous preterm birth. Cervical cerclage has been used for several decades and has shown to decrease rates of preterm birth. The most commonly used cerclage techniques were described by Shirodkar and McDonald, with no current consensus on the preferred technique. The objective of this review is to determine and compare the effectiveness of both techniques.
Studies will be sourced from six electronic databases, as well as from experts in the field, reference lists, and grey literature. Eligible studies will include pregnant women, with a singleton or twin pregnancy, requiring a cervical cerclage, using either the Shirodkar or McDonald technique and run comparative analyses between the two techniques. Randomized control trials (RCT)s, non-randomized control trials, and cohort studies will be eligible. Two independent reviewers will conduct study screening at abstract and full-text level, data extraction and risk of bias assessment. Discrepancies will be resolved by a consensus third reviewer if required. Fixed-effects or random-effects models will be used where appropriate to synthesize results. Alternative synthesis methods will be investigated in instances where a meta-analysis is not appropriate, such as summarizing effect estimates, combining P values, vote counting based on direction of effect, or synthesis in narrative form.
This review will synthesize the evidence on both the Shirodkar and McDonald cerclage method, and will help clinicians and health services to determine and deliver best practice antenatal care that has the potential to make an impact on preterm birth.
PROSPERO on 25 of May, 2020 with registration number CRD42020177386.

UNASSIGNED: The aim of this study was to determine if there is an association between the salivary protein profile and disease control in asthma.
UNASSIGNED: Thirty asthmatic patients (17 adults and 13 children) participated in this study. Saliva samples were collected from healthy subjects, controlled and uncontrolled asthmatics. Individual samples from each group were combined to form a pooled sample, from which proteomic analysis was performed using gel-based quantitative proteomics.
UNASSIGNED: Fourteen out of thirty asthmatics were classified to be controlled asthma. Most of asthmatics received inhaled corticosteroids as the controller medications. SDS-PAGE showed predominant bands at high molecular weight in asthmatic saliva compared to that of the controls. Shotgun proteomic analyses indicated that 193 salivary proteins were expressed in both controlled and uncontrolled asthmatics. They were predicted to associate with proteins involved in pathogenesis of asthma including IL-5, IL-6, MCP-1, VEGF, and periostin and asthma medicines (Cromolyn, Nedocromil, and Theophylline). Nucleoside diphosphate kinase (NME1-NME2) only expressed in controlled asthmatics whereas polycystic kidney and hepatic disease 1 (PKHD1)/fibrocystin, zinc finger protein 263 (ZNF263), uncharacterized LOC101060047 (ENSG00000268865), desmoglein 2 (DSG2) and S100 calcium binding protein A2 (S100A2) were only found in uncontrolled asthma. Therefore, the six proteins were associated with disease control in children and adults with asthma.
UNASSIGNED: Our findings suggest that NME1-NME2, PKHD1, ZNF 263, uncharacterized LOC101060047, DSG 2 and S100 A2 in saliva are associated with disease control in asthma.