P24 Antigen Research Articles

Mass Spectrometry based identification of site-specific proteomic alterations and potential pathways underlying the pathophysiology of schizophrenia.

Schizophrenia (SZ) is a complex multifactorial disorder that affects 1% of the population worldwide with no available effective treatment. Although proteomic alterations are reported in SZ however proteomic expression aberrations among different brain regions are not fully determined. Therefore, the present study aimed spatial differential protein expression profiling of three distinct regions of SZ brain and identification of associated affected biological pathways in SZ progression. Comparative protein expression profiling of three distinct autopsied human brain regions (i.e., substantia nigra, hippocampus and prefrontal cortex) of SZ was performed with respective healthy controls. Using two-dimensional electrophoresis (2DE)-based nano liquid chromatography tandem mass spectrometry (Nano-LC MS /MS) analysis, 1443 proteins were identified out of which 58 connote to be significantly dysregulated, representing 26 of substantia nigra,14 of hippocampus and 18 of prefrontal cortex. The 58 differentially expressed proteins were further analyzed using Ingenuity pathway analysis (IPA). The IPA analysis provided protein-protein interaction networks of several proteins including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kb), extracellular signal regulated kinases 1/2 (ERK1/2), alpha serine / Threonine-protein kinase (AKT1), cellular tumor antigen p53 (TP53) and amyloid precursor protein (APP), holding prime positions in networks and interacts with most of the identified proteins and their closely interacting partners. These findings provide conceptual insights of novel SZ related pathways and the cross talk of co and contra regulated proteins. This spatial proteomic analysis will further broaden the conceptual framework for schizophrenia research in future.

The Antiviral Compound PSP Inhibits HIV-1 Entry via PKR-Dependent Activation in Monocytic Cells.

Actin depolymerization factor (ADF) cofilin-1 is a key cytoskeleton component that serves to lessen cortical actin. HIV-1 manipulates cofilin-1 regulation as a pre- and post-entry requisite. Disruption of ADF signaling is associated with denial of entry. The unfolded protein response (UPR) marker Inositol-Requiring Enzyme-1α (IRE1α) and interferon-induced protein (IFN-IP) double-stranded RNA- activated protein kinase (PKR) are reported to overlap with actin components. In our published findings, Coriolus versicolor bioactive extract polysaccharide peptide (PSP) has demonstrated anti-HIV replicative properties in THP1 monocytic cells. However, its involvement towards viral infectivity has not been elucidated before. In the present study, we examined the roles of PKR and IRE1α in cofilin-1 phosphorylation and its HIV-1 restrictive roles in THP1. HIV-1 p24 antigen was measured through infected supernatant to determine PSP's restrictive potential. Quantitative proteomics was performed to analyze cytoskeletal and UPR regulators. PKR, IRE1α, and cofilin-1 biomarkers were measured through immunoblots. Validation of key proteome markers was done through RT-qPCR. PKR/IRE1α inhibitors were used to validate viral entry and cofilin-1 phosphorylation through Western blots. Our findings show that PSP treatment before infection leads to an overall lower infectivity. Additionally, PKR and IRE1α show to be key regulators in cofilin-1 phosphorylation and viral restriction.

Phylogenetic identification of feline leukemia virus A and B in cats with progressive infection developing into lymphoma and leukemia

To date, only a few studies have examined the impacts of feline leukemia virus (FeLV) subgroups on disease development in spontaneously infected cats. The present study identified FeLV-A and FeLV-B subgroups in cats with lymphoma and leukemia and explored the phylogenetic relationships of env sequences. Twenty-six cats with lymphoma (n=16) or leukemia (n=10) were selected. FeLV p27 antigen positivity was determined using ELISA, and proviral DNA in blood samples was detected using nested PCR. Positive animals in both tests were classified as cases of FeLV progressive infection and subjected to a second nested PCR for env amplification and subgroup determination. Six samples of FeLV-A and five samples of FeLV-B were sequenced using the Sanger method, and the results were used to build a phylogenetic tree and estimate evolutionary divergence. Among cats with lymphoma, 68.8% carried FeLV-AB and 31.2% FeLV-A. Among cats with leukemia, 70% carried FeLV-AB and 30% FeLV-A. Regarding cat characteristics, 50% were young, 30.8% young adults, and 19.2% adults; 88.5% were mixed-breed and 11.5% pure breed; and 42.3% were males and 57.7% were females. Among lymphomas, 62.5% were mediastinal, 31.3% multicentric, and 6.3% extranodal. Regarding histological classification, lymphoblastic and small non-cleaved-cell lymphomas were the most frequently detected. Among leukemia cases, 30% were acute lymphoid, 30% chronic myeloid, and 40% acute myeloid. Phylogenetic analysis showed that FeLV-A SC sequences were closely related to the Arena, Glasgow-1, and FeLV-FAIDS variants. Meanwhile, FeLV-B SC sequences were divergent from one another but similar to the endogenous FELV env gene (enFeLV). In conclusion, FeLV-AB is prevalent in cats with lymphoma and leukemia, highlighting the genetic diversity involved in the pathogenesis of these neoplasms in Brazil.

Potential targets and mechanisms of Guarana in the treatment of Alzheimer’s disease based on network pharmacology

ObjectiveTo dig the main active components and predict potential mechanisms of Guarana in the treatment of Alzheimer’s disease (AD) by network pharmacology method and molecular docking. MethodsBy digging into papers relating to this topic, chemical components in Guarana were obtained and used for drug-likeness analysis. Databases including HERB and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) were used to obtain potential targets that the active components in Guarana might have effects on, and to find out diseases in association with the potential targets. Other databases such as GeneCards, a human gene database, and DisGeNET were used to identify the genes relating to AD, and a Wayne diagram was drawn to get the intersected targets in Guarana and AD. Subsequently, CytoScape software was adopted for the construction of a Guarana-intersected targets-AD map. After that, the intersected targets were uploaded to the Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) database to acquire a protein-protein interaction (PPI) network diagram. Then, the key target proteins were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). In terms of molecular docking verification, AutoDock software was used to verify whether the crucial active compounds of Guarana’s components could bind to the key targets. ResultsA total of 140 potential targets for Guarana to treat AD were obtained. The results of PPI network analysis showed that interleukin 6 (IL-6), tumor necrosis factor (TNF), insulin (INS), mitogen-activated protein kinase 3 (MAPK3), transcription factor (JUN), cell tumor antigen p53 (TP53), caspase3 (CASP3), protein c-Fos (FOS), catalase (CAT), and Catenin beta-1 (CTNNB1) might be the key targets of Guarana in the treatment of AD. It was found by GO and KEGG analyses that the mechanism of Guarana in the treatment of AD might be the bindings between Guarana compounds and protease outside the cell membranes. The molecular docking results showed that the small molecules of various components in Guarana binding to target proteins such as TNF, IL-6, MAPK3, and FOS needed relatively less energy. ConclusionThe treatment of AD with Guarana involves the participation of multiple targets, among which IL-6, TNF, and MAPK3 might be the key ones. These key targets might take effects through the biological process in their bindings to β-amyloid and involving signaling pathways in cancer. Hopefully, our research could offer some scientific foundations as well as references for in-depth studies on the treatment of AD with Guarana.

Field Performance of a Rapid Test to Detect Progressive, Regressive, and Abortive Feline Leukemia Virus Infections in Domestic Cats in Australia and Germany.

Different feline leukemia virus (FeLV) infection outcomes are possible in cats following natural exposure, such as progressive infections (persistent viremia), regressive infections (transient or no viremia followed by proviral persistence) and abortive infections (presence of only antibodies). Laboratory-based testing is currently required for categorization of infection outcomes in cats. The aim of this study was to evaluate the field performance of a novel, rapid, combination point-of-care (PoC) test kit commercially available in Europe (v-RetroFel®Ag/Ab; 2020-2021 version) to determine different FeLV infection outcomes by concurrent detection of FeLV antigen (p27) and antibodies against FeLV transmembrane envelope protein (p15E). A secondary aim was to evaluate the performance of the same test kit (v-RetroFel®FIV) to determine positive/negative feline immunodeficiency virus (FIV) infection status by the detection of antibodies to FIV capsid protein (p24) and transmembrane glycoprotein (gp40). Two cohorts of domestic cats were recruited and tested with v-RetroFel® using plasma or serum, including cats in Australia (n = 200) and cats in Germany (n = 170). Results from p27 antigen PoC testing, proviral DNA PCR, and neutralizing antibody testing or testing for antibodies against non-glycosylated surface unit envelope protein (p45) were used to assign cats to groups according to different FeLV infection outcomes. Testing with a laboratory-based FeLV p15E antibody ELISA was also performed for comparison. In the first cohort, v-RetroFel®Ag/Ab correctly identified 89% (109/122) FeLV-unexposed cats and 91% (21/23) progressive infections, but no regressive (0/23) or abortive (0/32) infections. In the second cohort, v-RetroFel®Ag/Ab correctly identified 94% (148/158) FeLV-unexposed cats and 100% (4/4) progressive infections, but no regressive (0/2) and only 17% (1/6) abortive infections. There was test agreement between v-RetroFel®Ab and the p15E laboratory ELISA in 58.9% of samples. As a secondary outcome of this study, the sensitivity and specificity of v-RetroFel®FIV testing in cohort 1 were 94.7% (18/19) and 98.3% (178/181), and in cohort 2, 30.0% (3/10) and 100.0% (160/160), respectively. Prior history of FIV vaccination did not produce any false-positive FIV results. In conclusion, v-RetroFel®Ag/Ab (2020-2021 version) was unable to accurately determine different FeLV infection outcomes in the field. Improvements of the test prior to application to field samples are required.

Screening and diagnostic testing protocols for HIV and Syphilis infections in health care setting in Qatar: Evaluation and recommendations.

HIV and Syphilis are common STIs, which have become a concern and burden on healthcare systems, as many infections go untreated and lead to potentially serious complications. HIV is usually diagnosed with Western blot, PCR, and p24 antigen testing. Whereas, Syphilis is mainly diagnosed through clinical findings and serologic testing. The Medical Commission Department (MC) under MOPH is responsible for screening all newcomers to Qatar, aiming to keep the country free from serious infectious diseases. We aimed to evaluate the diagnostic efficiency of the protocols used in the MC for screening HIV and Syphilis infections. We conducted a retrospective study of samples analyzed by 4th Generation ARCHITECT® HIV Ag/Ab Combo and Rapid Plasma Reagin (RPR) between January to December 2019. ARCHITECT® HIV Ag/Ab Combo positive samples were confirmed by INNO-LIA™ HIVI/II and RT-PCR. RPR-reactive samples were confirmed by ARCHITECT® Syphilis Treponema pallidium Antibody (Syphilis TPA) assay. For HIV, data were collected from 585,587 individuals, of which 595 (0.1%) were positive by the ARCHITECT® HIV Ag/Ab Combo (Analyzer A). When all initially positive sera were re-tested on newly collected blood samples using different ARCHITECT® HIV Ag/Ab Combo analyzer (analyzer B), 99.8% (594/595) of samples were also positive, suggesting high reproducibility. The positive predictive value (PPV) between ARCHITECT® HIV Ag/Ab Combo and the INNO-LIA™ HIVI/II confirmatory assay was 31.8%. The PPV between ARCHITECT® HIV Ag/Ab Combo and HIV-PCR assay was 26.8%. Retrospective data for Syphilis were collected from a total of 97,298 individuals who visited the MC, of which 198 (0.20%) were initially positive by RPR. The PPV between RPR and Syphilis TPA confirmatory assay was 36.6%. Despite the high rate of false positivity using ARCHITECT® HIV Ag/Ab Combo and RPR screening assays, both assays have proven to be highly effective as screening testing methods.

Natural Bioactive Compounds Promote Cell Apoptosis in Gastric Cancer Treatment: Evidence from Network Pharmacological Study and Experimental Analysis

Background. Gastric cancer (GC) is one of the most lethal cancers. Shenlian capsule (SLC) is a Chinese patent medicine made from 11 herbs containing numerous plant-derived compounds, and the clinical trials of SLCs confirmed that they had effective adjuvant therapy for a variety of cancer such as lung cancer and gastric cancer. Moreover, the HPLC fingerprint of SLCs was established from other research to find potential components. In this study, network pharmacology-based research was used to identify combinations with molecules, targets, and pathways to explore their interaction mechanisms. Methods. The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and the Traditional Chinese Medicine Integrated Database (TCMID) were widely implemented in selecting the active chemical components of SLCs with an oral bioavailability (OB) ≥ 30% and drug-likeness (DL) ≥ 18%. In addition, the TCMSP and TCMID databases obtained the targets of SLCs, and PharmMapper (PM) was used to predict targets of SLCs. Gastric cancer-related genes were provided by the GeneCards and TTD databases. Subsequently, the drug/target/pathway network was established and visualized using Cytoscape software. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) enrichment analyses were used to predict the potential genes and pathways of gastric cancer. Molecular docking was performed to study the interaction between ligands and targets; the interaction was visualized using Discovery Studio and PyMOL. Finally, the potential primary mechanism used by SLCs against gastric cancer was verified by cell experiments, including MTT cell apoptosis assay, flow cytometry cell cycle assay, and western blotting with HGC-27 cells (undifferentiated). Results. Of 213 active chemical components from SLCs, 35 primary active chemical components were identified, and 10 potential critical targets were selected from the 185 intersections of the targets of SLCs and GC, such as RAC-alpha serine/threonine kinase 1 (AKT1), cellular tumor antigen p53 (TP53), interleukin-6 (IL6), caspase-3 (CASP3), vascular endothelial growth factor A (VEGFA), and epidermal growth factor receptor (EGFR). GO and KEGG enrichment analysis provided the PI3K/AKT, TNF, and p53 signaling pathways, which may be the primary signaling pathways modulating gastric cancer. Molecular docking verified targets such as AKT1, TP53, EGFR, and CASP3, which exhibited satisfactory binding capacity with active ingredients. Experiments with HCG-27 cells confirmed that SLCs may provide favorable treatment for GC by promoting CASP3 and TP53 expression to induce cell apoptosis and provided the predictions for network pharmacology and molecular docking. MTT and flow cytometry assays verified that SLCs promoted cell apoptosis and inhibited cell proliferation by triggering G0/G1 and S cell cycle arrest. In addition, western blot analysis confirmed that SLCs promoted TP53 and CASP3 overexpression, which led to HGC-27 gastric cell apoptosis. Conclusions. Our results confirmed that SLCs inhibit proliferation of HGC-27 gastric cell by promoting cell apoptosis and, therefore, have potential in the treatment of advanced gastric cancer. P53 signaling pathway was the key pathway. In addition, quercetin, matrine, and ursolic acid might be the main active ingredients.

The contemporary immunoassays for HIV diagnosis: a concise overview.

Recent advances in human immunodeficiency virus (HIV) diagnostics have improved the management of disease progression significantly, which have also boosted the efficacy of antiviral therapies. The detection of HIV at the earliest is very important. A highly recognized and effective virological biomarker for acute HIV infections is p24 antigen. This brief overview is based on advances of HIV diagnosis while focusing on the latest HIV testing technologies including HIV-specific antigens detecting assays of both anti-HIV antibodies and p24 antigen. In addition to other emerging molecular diagnostics for acute HIV infection, the utilization of p24 antigen has been summarized. Moreover, it has been explained how these immunoassays have reduced the window period for detection of HIV in the acute stage of infection.

Targets of total glucosides of paeony in the treatment of Sjogren syndrome: A network pharmacology study.

We aimed to explore the underlying mechanism of the total glucoside of peony (TGP) in treating Sjogren syndrome (SS) using the network pharmacology approach. The protein targets of TGP and SS were identified by database search. Then, the intersection of the two groups was studied. The drug-target network between TGP and the overlapping genes was constructed, visualized, and analyzed by Cytoscape software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment were performed to analyze these genes. Finally, the predictions of potential targets were evaluated by docking study. Forty-six overlapping genes were discovered. The results suggested that TGP used in the treatment of SS is associated with cellular tumor antigen p53, neurotrophic tyrosine kinase receptor type 1, and epidermal growth factor receptor, as well as their related 3372 protein networks, which regulate intrinsic apoptotic signaling pathway, cellular response to oxidative stress, rhythmic process, and other processes. Molecular docking analysis proved that hydrogen bonding is the main form of interaction. Our research provided the protein targets affected by TGP in SS treatment. The key targets (caspase 3, vascular endothelial growth factor A, glyceraldehyde-3-phosphate dehydrogenase, etc.), which involve 3372 proteins, are the multitarget mechanism of TGP in SS treatment.

A More Comprehensive Clinical and Laboratory Characterization of 61 Acute HIV Infection Patients in Southwest China

Acute HIV infection (AHI), i.e., the early stage of HIV infection, plays an important role in immune system failure and HIV transmission, but most AHI patients are missed due to their non-specific symptoms. To facilitate the identification of patients with high AHI risk and reduction of missed diagnosis, we characterized 61 AHI patients in a Southwest China hospital with 4300 beds; specifically, we characterized their general clinical characteristics, evolution in results of a novel HIV screening assay called Elecsys® HIV Duo, and by programming, we analyzed the ability of all routine laboratory tests (e.g., routine blood analysis) to identify AHI patients. Among 61 AHI patients, 85.2% were male and the median age was 42 (interquartile range, 25-62) years. A total of 61.9% of patients visit the emergency department first during AHI. Clinical presentation of AHI patients included fever, fatigue, chills, rash, and various respiratory, digestive, and nervous system symptoms. Two of three results from Elecsys® HIV Duo show clear evolution trends: HIV P24 antigen decreased while HIV antibody increased in consecutive samples of nearly all patients. High fluorescence lymphocytes have a very high positive likelihood ratio (LR+) of 10.33 and a relatively high "rate of out-of-range tests" of 56.8% (21 in 37 patients who received this test had a result outside the reference range). In addition, we identified more than ten tests with LR+ greater than two. In summary, the emergency department is important for AHI screening. The evolution of HIV P24 Ag and HIV Ab and those laboratory tests with a high "rate of out-of-range tests" or high LR+ may aid the AHI identification and missed diagnosis reduction.

Observation of Serological Index and Efficacy of Abiraterone Hydrochloride Tablets Combined with Endocrine Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer.

This study reviewed and analysed the serological indexes, clinical efficacy and common clinical indexes of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with combination of abiraterone hydrochloride tablets and endocrine therapy. This study is a retrospective analysis. A total of 133 mCRPC patients who were admitted to our hospital from January 2019 to December 2021 were selected as the study subjects. The patients were categorised into the experimental group (n = 51) and control group (n = 82) according to their treatment method. The control group was treated with docetaxel combined with endocrine therapy, whilst the experimental group was treated with combination therapy with abiraterone hydrochloride tablets. Subsequently, the clinical data of the two groups, including serum insulin-like growth factor-1 (IGF-1), human glandular kallikrein 2 (hK2), prostate specific antigen (PSA), vascular endothelial growth factor (VEGF) and serum carcinoembryonic antigen (CEA), were analysed. The overall response rate of the experimental group (84.3%) was higher than that of the control group (72.0%). The serum levels of CEA, total prostate specific antigen, free prostate specific antigen, testosterone and androgen receptor splice variant 7 in both groups were lower than those of before treatment, and the values obtained by the experimental group were lower than those of the control group (p < 0.05). After treatment, the levels of CD3+, CD4+ and CD4+/CD8+ in both groups were higher than those before treatment, and the levels of CD8+, IGF-1, hK2, PSA and VEGF in the two groups decreased after treatment (p < 0.05). The use of abiraterone hydrochloride tablet combined with endocrine therapy for patients with mCRPC is effective and can improve clinical symptoms and serum cytokine levels.

Mucuna cinerea Seeds: Levodopa Extraction Using Deep Eutectic Solvent and Its Mammalian Cell Activity

A new class of deep eutectic solvents (DES) was used in the extraction of levodopa (L-dopa) present in Mucuna cinerea, which has been termed “green” or “designer” solvents, with notable productive and economic/environmental benefits. The seeds of Mucuna cinerea were prepared and submitted to extraction with heating and agitation in a solvent mixture of DES with citric acid, urea, or glycerol. The extracts were analyzed by high performance liquid chromatography (HPLC) which confirmed the efficiency of DES in extracting L-dopa. These extractions were carried out to determine the L-dopa extracts in DES with regard to the induction of cellular response activity, demonstrating the synergy between L-dopa and DES. The DES-glycerol extract exhibited a higher proliferative activity than commercial L-dopa after 24 h of treatment. The human glandular kallikrein-1 gene (hGK3) demonstrated higher expression in the treatment with the DES-urea, while the G protein-coupled receptor kinase-6 gene (GRK6) showed higher expression for all extracts compared to commercial L-dopa, with a higher value obtained for DES-glycerol, followed by DES-urea extract. The DES extraction method is therefore promising and unprecedented, confirming its possible use in the replacement of expensive solvents, supporting the use of ecologically viable DES in the extractions of other plant species.

Using Network Pharmacology to Explore the Mechanism of Huanglian Jiedu Decoction in the Treatment of Ulcerative Colitis

The aim of this study was to identify the potential compounds, core targets and possible mechanism of Huanglian Jiedu decoction in treating ulcerative colitis based on network pharmacology and molecular docking. At first, potential compounds of Huanglian Jiedu decoction were retrieved from traditional Chinese medicine systems pharmacology. And then, the targets related to compounds and ulcerative colitis was obtained from traditional Chinese medicine systems pharmacology, Online Mendelian Inheritance in Man, GeneCards and DisGeNET. Next, Cytoscape was used to visualize drug-compound-common target-disease network and protein-protein interaction network. Moreover, gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis was performed by database for annotation, visualization and integrated discovery to investigate possible mechanism of Huanglian Jiedu decoction against ulcerative colitis. At last, molecular docking verified the reliability of the prediction results. 55 compounds and 84 targets of Huanglian Jiedu decoction were screened out as potential players on ulcerative colitis. After network analyses, 10 core compounds (quercetin, kaempferol, wogonin, baicalein, acacetin, 5-hydroxy-7-methoxy-2-(3,4,5- trimethoxyphenyl) chromone, beta-sitosterol, moslosooflavone, 5,7,4'-trihydroxy-8-methoxyflavone, oroxylin A) and 10 core targets (interleukin-6, interleukin-1 beta, tumor necrosis factor-alpha, threonine-protein kinases, tumor antigen p53, prostaglandin-endoperoxide synthase 2, JUN, CXCL8, C-C motif chemokine 2, matrix metalloproteinase-9) were identified. Furthermore, the inflammatory response, tumor necrosis factoralpha signaling pathway, pathways in cancer, T cell receptor signaling pathway, toll-like receptor signaling pathway and nuclear factor kappa B signaling pathway may be involved in the treatment of ulcerative colitis using Huanglian Jiedu decoction. This study reveals that Huanglian Jiedu decoction contains multiple ingredients, multiple targets and multiple pathways in treating ulcerative colitis, which provides a basis for further research.

Relationship Between Obesity and Hypertension From Bioinformatics Analysis

Abstract Background To explore the relationship between obesity and hypertension using bioinformatics analyses. Methods Disease databases (GeneCards, OMIM, CTD, TTD, DisGeNET, and Drugbank) were used to obtain hypertension and obesity-related targets. The intersection targets of obesity and hypertension were constructed using Venn diagrams. STRING online platform was used to obtain protein–protein interaction networks of common targets, and Cytohubba plug-in was used to screen the core targets. Gene ontology (GO) analysis and the enrichment analysis of Kyoto encyclopedia of genes and genomes (KEGG) were carried out using DAVID database. Results A total of 459 and 551 targets were obtained for obesity and hypertension, respectively. Among them, 135 were targets for both obesity and hypertension in which tumor necrosis factor (TNF), cell tumor antigen p53 (TP53), chemokine 2 (CCL2), Toll-like receptor 4 (TLR4), interleukin (IL) 1B, nitric oxide synthase 3 (NOS3), IL-6, and serine/threonine protein kinase 1 (AKT1) were key targets for regulating obesity and hypertension. Enrichment analysis yielded 306 GO entries [P &amp;lt; 0.05, false discovery rate (FDR) &amp;lt;0.05], which were involved in positive regulation of mitogen-activated protein kinase (MAPK) cascade, positive regulation of nitric oxide biosynthetic process, cilium basal body, hormone activity, and RNA polymerase II repeating transcription factor binding. The 86 enriched KEGG entries (P &amp;lt; 0.05, FDR &amp;lt;0.05) included adipocytokine signaling pathway, regulation of lipolysis in adipocytes, PI3K–Akt signaling pathway and forkhead transcription factor O (FoxO) signaling pathway. Conclusions TNF, TP53, CCL2, TLR4, IL-1B, NOS3, IL-6, AKT1, and the key pathways including adipocytokine signaling pathway, regulation of adipocyte lipolysis, PI3K–Akt and FoxO signaling pathway play a regulatory role in interactions between obesity and hypertension. These findings provide new insights into the complex interactions between obesity and hypertension.

Exploring the therapeutic mechanisms of Gleditsiae Spina acting on pancreatic cancer via network pharmacology, molecular docking and molecular dynamics simulation.

Pancreatic cancer is one of the most aggressive tumors and also has a low survival rate. The dried spines of Gleditsia sinensis Lam are known as "Gleditsiae Spina" and they mostly contain flavonoids, phenolic acids, terpenoids, steroids, and other chemical components. In this study, the potential active components and molecular mechanisms of Gleditsiae Spina for treating pancreatic cancer were systematically revealed by network pharmacology, molecular docking and molecular dynamics simulations (MDs). RAC-alpha serine/threonine-protein kinase (AKT1), cellular tumor antigen p53 (TP53), tumor necrosis factor α (TNFα), interleukin-6 (IL6) and vascular endothelial growth factor A (VEGFA) were common targets of Gleditsiae Spina, human cytomegalovirus infection signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and MAPK signaling pathway were critical pathways of fisetin, eriodyctiol, kaempferol and quercetin in the treatment of pancreatic cancer. Molecular dynamics simulations (MDs) results showed that eriodyctiol and kaempferol have long-term stable hydrogen bonds and high binding free energy for TP53 (-23.64 ± 0.03 kcal mol-1 and -30.54 ± 0.02 kcal mol-1, respectively). Collectively, our findings identify active components and potential targets in Gleditsiae Spina for the treatment of pancreatic cancer, which may help to explore leading compounds and potential drugs for pancreatic cancer.

Development and Validation of a Rapid Screening Test for HTLV-I IgG Antibodies.

Initial diagnosis of human T cell lymphotropic virus (HTLV) infections is mainly based by detecting antibodies in plasma or serum using laboratory-based methods. The aim of this study was to develop and evaluate a rapid screening test for HTLV-I antibodies. Our rapid screening test uses HTLV-I p24 antigen conjugated to gold nanoparticles and an anti-human IgG antibody immobilized to a nitrocellulose strip to detect human HTLV-I p24-specific IgG antibodies via immunochromatography. Performance of the rapid screening test for HTLV-I was conducted on a total of 118 serum specimens collected in Salvador, Bahia, the epicenter for HTLV-1 infection in Brazil. Using a Western blot test as the comparator, 55 serum specimens were HTLV-I positive, 5 were HTLV-I and HTLV-II positive, and 58 were negative. The sensitivity of the rapid screening test for HTLV-1 was 96.7% and the specificity was 100%. The rapid screening test did not show cross-reaction with serum specimens from individuals with potentially interfering infections including those caused by HTLV-II, HIV-I, HIV-II, hepatitis A virus, hepatitis B virus, hepatitis C virus, herpes simplex virus, Epstein-Barr virus, SARS-CoV-2, Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, Toxoplasma gondii, and Plasmodium falciparum. The rapid screening test also did not show cross-reaction with potentially interfering substances. Strategies for HTLV diagnosis in non- and high-endemic areas can be improved with low-cost, rapid screening tests.

Cerrahpaşa Medical Faculty Hospital HIV-1/-2 Serological Test Data: 2019-2022 Retrospective Evaluation

Objective: The aim of this study was to retrospectively discuss the human immunodeficiency virus (HIV) scanning and verification test results and demographics of patients who were admitted to the Istanbul University Cerrahpaşa Medical Faculty’s Medical Microbiology Laboratory Center Serology/ELISA division with suspected HIV infection or pre-operative serologic screening. In addition, the study aimed to compare HIV seroprevalence with data from the center’s previous period. Materials and Methods: HIV-1/-2 antibody +P24 antigen (HIV-1/-2 Ab/Ag) was studied routinely using the chemiluminescent microparticle immunoassay (CMIA) method with the same method also being used as the second repeat test. The sera verifications of patients who showed repeated reactivity after the HIV Ab/Ag test were studied using the line immunoassay (LIA) method. Results: The study retrospectively studied 156,542 cases between 2019-2022, of which 237 (0.17%) showed repeated anti-HIV-1/-2 reactivity. From the repeated reactivity serum samples, LIA testing was performed to confirm the remaining 181 serum samples after excluding the previously confirmed samples, with 175 (96.6%) coming back positive. All these samples showed sgp120 and gp41 band positivity, thus confirming HIV1 positivity. Conclusion: These retrospective data from one center regarding HIV seroprevalence for the 2019-2022 period are in line with other national studies. However, due to the COVID-19 pandemic, HIV prevalence during this period may have been higher than detected. HIV prevalence in Istanbul, being a cosmopolitan city that receives immigrants, should be monitored in the future.

Network pharmacology, molecular docking and bioinformatics reveal the mechanism of Tripterygii Wilfordii against Osteosarcoma

Osteosarcoma (OS) is a malignant bone tumor of mesenchymal origin. Tripterygii Wilfordii (TW) is a traditional Chinese medicine widely used for its anti-inflammatory and immunomodulatory effects. Various components of TW have been shown to have antitumor effects, however, no systematic study has been conducted to prove the anti-OS effects of TW. This study aimed to investigate the effects of TW on OS and its mechanism based on network pharmacology and molecular docking. The web pharmacology section includes the gathering of the active components of TW, the collection of predicted targets of TW and OS-related targets, the analysis of therapeutic targets of TW, the enrichment of gene ontology (GO), and the enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG). The Veen diagram showed 451 targets for OS treatment in TW. The therapeutic target enrichment analysis results showed that TW treated OS via multiple targets and pathways. TW can affect OS proliferation, apoptosis, migration, infiltration, and angiogenesis through a signaling network formed by hub genes that cascade through numerous signaling pathways. In addition, molecular docking results showed that triptolide, kaempferol, and 5,8-Dihydroxy-7-(4-hydroxy-5-methyl-coumarin-3)-coumarin have relatively high potential to become drugs for patients with OS and improve the 5-year survival rate of patients with OS. Network pharmacology and molecular docking suggest that TW affects the biological behavior of OS through multiple pathways involving multiple targets, such as proliferation, apoptosis, migration, and infiltration. Upregulation of the cellular tumor antigen p53 (TP53) gene and downregulation of peroxisome proliferator-activated receptor gamma (PPARG) and signal transducer and activator of transcription 1-alpha/beta (STAT1) genes can prolong the survival time of patients with OS. Triptolide, kaempferol, and 5,8-Dihydroxy-7-(4-hydroxy-5 methyl-coumarin-3)-coumarin have a relatively high potential to become a treatment for patients with OS and improve 5-year survival of OS patients.

Extraction and Characterization of Fucoidan Derived from Sargassum ilicifolium and Its Biomedical Potential with In Silico Molecular Docking

Fucoidan, a polymer derived from seaweed, poses a broad range of biological applications, and its potential medicinal benefits have been widely studied over the past decade. In this study, fucoidan was extracted from marine macroalga Sargassum ilicifolium and its bioactive potential for in silico molecular docking was investigated. Additionally, the computational in silico docking studies were applied on the fucoidan against anticancer and antioxidant target proteins by using Glide ligand docking, Schrodinger software. The FT-IR analysis revealed that fucoidan mainly consisted of the fucose residues (59.1%) and a few monosaccharides, such as uronic acid (11.7%) and sulphate (18.3%). The in vitro tests revealed that fucoidan possessed various antioxidative properties and anticoagulant activities. Fucoidans played an inhibitory role in the colony formation of HepG2 cells. The NADPH oxidase (−7.169 Kcal/mol) and cellular tumor antigen p53 protein (−6.205 Kcal/mol) exhibited the highest antioxidant and anticancer proteins, respectively. Overall, the present study results provide a theoretical foundation for broadening the application of fucoidan from S. ilicifolium as a pharmaceutical ingredient.

Network-based pharmacology and molecular docking exploring the "Bupleuri Radix-Scutellariae Radix" mechanism of action in the viral hepatitis B treatment.

Viral hepatitis B is caused by the hepatitis B virus, which is characterized by liver lesions. Bupleuri Radix and Scutellariae Radix are the main traditional medicine pairs with remarkable efficacy in hepatitis B. However, their molecular mechanisms are incompletely understood. The main active components of Bupleuri Radix and Scutellariae Radix, as well as therapeutic targets for the treatment of hepatitis B, were identified through network pharmacology techniques. We identified viral hepatitis B targets using the GeneCards, online mendelian inheritance in man, and therapeutic target databases. We discovered the active components of Bupleuri Radix and Scutellariae Radix as well as therapeutic targets using the encyclopedia of traditional Chinese medicine, HERB, traditional Chinese medicine systems pharmacology database, and a bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine databases. VENNY obtained the intersections. Cytoscape and STRING were used to create the "active ingredient-potential target" network and protein interaction network. The DAVID database was used to enrich GO and KEGG pathways. The results were confirmed using the molecular docking method. There were 1827 viral hepatitis B targets, and 37 active ingredients for Bupleuri and Scutellariae Radix, with the main components being quercetin, wogonin, baicalein, and kaempferol. Tumor necrosis factor (TNF), mitogen-activated protein kinase 3 (MAPK3), interleukin-6 (IL-6), vascular endothelial growth factor A, cysteinyl aspartate specific proteinase 3, transcription factor AP-1 (JUN), RAC-alpha serine/threonine-protein kinase, and cellular tumor antigen p53 are among the 78 common targets of Bupleuri Radix and Scutellariae Radix intervention in viral hepatitis B. KEGG enrichment resulted in 107 pathways, including cancer, hepatitis B, and TNF signaling pathways. According to the molecular docking technique, quercetin, wogonin, baicalein, and kaempferol had strong binding activities with TNF, MAPK3, and IL-6. In this study, we initially identified various molecular targets and multiple pathways involved in hepatitis B treatment with Bupleuri Radix and Scutellariae Radix.