Venn Diagram Research Articles

Network Pharmacology and Bioinformatics Analyses Identify the Core Genes and Pyroptosis-Related Mechanisms of Nardostachys Chinensis for Atrial Fibrillation.

Nardostachys chinensis is an herbal medicine widely used in the treatment of atrial fibrillation (AF), but the mechanism is unclear. To explore the molecular mechanism of N. chinensis against AF. The TCMSP was used to screen the active N. chinensis compounds and their targets. Differentially expressed genes (DEGs) for AF were identified using open-access databases. Using Venn diagrams, the cross-targets of N. chinensis, pyroptosis, and AF were obtained. The genes underwent molecular docking as well as gene set enrichment analysis (GSEA). A nomogram based on candidate genes was constructed and evaluated with the clinical impact curve. After that, the immune infiltration of the dataset was analyzed by single sample GSEA (ssGSEA). Finally, microRNAs (miRNAs) and transcription factors (TFs) were predicted based on candidate genes. Tumor necrosis factor (TNF) and caspase-8 (CASP8) were obtained as candidate genes by taking the intersection of DEGs, targets of N. chinensis, and pyroptosis-related genes. Tolllike receptor (TLR) and peroxisome proliferator-activated receptor (PPAR) signaling pathways were linked to candidate genes. Additionally, immune cell infiltration analysis revealed that CASP8 was associated with natural killer T cells, natural killer cells, regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSC), macrophages, CD8 T cells, and CD4 T cells. Finally, miR-34a-5p and several TFs were found to regulate the expression of CASP8 and TNF. CASP8 and TNF are potential targets of N. chinensis intervention in pyroptosisrelated AF, and the TLR/NLRP3 signaling pathway may be associated with this process.

Targets and Mechanisms of Xuebijing in the Treatment of Acute Kidney Injury Associated with Sepsis: A Network Pharmacology-based Study.

Sepsis is a state of the systemic inflammatory response of the host induced by infection, frequently affecting numerous organs and producing varied degrees of damage. The most typical consequence of sepsis is sepsis-associated acute kidney injury(SA-AKI). Xuebijing is developed based on XueFuZhuYu Decoction. Five Chinese herbal extracts, including Carthami Flos, Radix Paeoniae Rubra, Chuanxiong Rhizoma, Radix Salviae, and Angelicae Sinensis Radix, make up the majority of the mixture. It has properties that are anti-inflammatory and anti-oxidative stress. Xuebijing is an effective medication for the treatment of SA-AKI, according to clinical research. But its pharmacological mechanism is still not completely understood. First, the composition and target information of Carthami Flos, Radix Paeoniae Rubra, Chuanxiong Rhizoma, Radix Salviae, and Angelicae Sinensis Radix were collected from the TCMSP database, while the therapeutic targets of SA-AKI were exported from the gene card database. To do a GO and KEGG enrichment analysis, we first screened the key targets using a Venn diagram and Cytoscape 3.9.1. To assess the binding activity between the active component and the target, we lastly used molecular docking. For Xuebijing, a total of 59 active components and 267 corresponding targets were discovered, while for SA-AKI, a total of 1,276 targets were connected. There were 117 targets in all that was shared by goals for active ingredients and objectives for diseases. The TNF signaling pathway and the AGE-RAGE pathway were later found to be significant pathways for the therapeutic effects of Xuebijing by GO analysis and KEGG pathway analysis. Quercetin, luteolin, and kaempferol were shown to target and modulate CXCL8, CASP3, and TNF, respectively, according to molecular docking results. This study predicts the mechanism of action of the active ingredients of Xuebijing in the treatment of SA-AKI, which provides a basis for future applications of Xuebijing and studies targeting the mechanism.

Genome-wide identification of HIPP and mechanism of SlHIPP4/7/9/21/26/32 mediated phytohormones response to Cd, osmotic, and salt stresses in tomato

Heavy-metal-associated isoprenylated plant proteins (HIPPs) contributed to abiotic tolerance in vascular plants. Up to now, the HIPP gene family of tomato (Solanum lycopersicum L.) had not been thoroughly understood. In the present study, 34 SlHIPP genes were identified from the tomato genome using the Hidden Markov Model (HMM). The phylogenetic analysis revealed that the evolution of SlHIPPs was highly conserved. The cis-acting element analysis indicated that SlHIPP genes might be involved in phytohormones and abiotic stresses. We constructed venn diagram with 17 genes containing stress-related motifs as well as 15 genes and 19 genes expressing in leaves and roots in RNA-seq data, suggesting that SlHIPP4/7/9/21/26/32 were selected as candidate genes for study. The quantitative real-time PCR (qRT-PCR) analysis showed that 6 candidate genes were indicated to be involved in osmotic and salt stress tolerance and SlHIPP7/21/26/32 responded to cadmium (Cd) tolerance. The virus-induced silencing of 6 candidate genes caused growth inhibition in stress conditions, further illustrating that 6 candidate genes played a positive role in abiotic conditions. Importantly, the phytohormone analysis implied that 6 candidate genes mediated abscisic acid (ABA), salicylic acid (SA), gibberellin (GA3), auxin (IAA), or methyl jasmonate (MeJA) responses to Cd, osmotic, or salt stress tolerance. These findings indicated that SlHIPP4/7/9/21/26/32 were key regulators of abiotic stress responses in tomato seedlings, functioning through multiple phytohormone pathways.

ANGPTL4 promotes choroidal neovascularization and subretinal fibrosis through the endothelial‒mesenchymal transition.

This study aimed to investigate the possible mechanisms by which ANGPTL4 is involved in the pathogenesis of choroidal neovascularization (CNV) and subretinal fibrosis. Differentially expressed genes in retinal pigmented epithelium (RPE)-choroid-sclera complex tissues from nAMD patients and control individuals were identified via the GEO database, followed by GO and KEGG analyses. A Venn diagram was used to identify EndMT-related DEGs. A logistic regression model was constructed to screen for prognostic genes. Laser-induced CNV mouse models were established and validated with FFA and OCTA. The expression of ANGPTL4 and EndMT-related markers in the RPE-choroid-sclera complex was measured via RT‒qPCR and Western blotting. TGF-β2-induced HUVECs were used as EndMT cell models, and specific siRNAs targeting ANGPTL4 (si-ANGPTL4) were designed and screened. The effects of ANGPTL4 knockdown on the migration and invasion of HUVECs were also examined. Laser-induced CNV mouse models were constructed, and an intravitreal injection of cholesterol-modified si-ANGPTL4 was used to knock down ANGPTL4. FFA, OCTA and immunofluorescence staining were used to observe CNV formation and subretinal fibrosis, and the expression of ANGPTL4 and EndMT-related markers was determined. ANGPTL4 expression was significantly increased in mice with CNV and colocalized with IB4. In TGF-β2-induced EndMT, ANGPTL4 was also upregulated, and its knockdown led to the inhibition of EndMT and cell migration and invasion, while its overexpression promoted the EndMT process. ANGPTL4 knockdown reduced the formation of CNV and subretinal fibrosis in mice with CNV by suppressing EndMT. ANGPTL4 may promote CNV and subretinal fibrosis through EndMT, suggesting that ANGPTL4 may be a novel potential target for nAMD therapy.

APAtizer: a tool for alternative polyadenylation analysis of RNA-Seq data.

APAtizer is a tool designed to analyze alternative polyadenylation events on RNA-sequencing data. The tool handles different file formats, including BAM, htseq and DaPars bedGraph files. It provides a user-friendly interface that allows users to generate informative visualizations, including Volcano plots, heatmaps and gene lists. These outputs allow the user to retrieve useful biological insights such as the occurrence of polyadenylation events when comparing two biological conditions. Additionally, it can perform differential gene expression, gene ontology analysis, visualization of Venn diagram intersections and correlation analysis. Source code and example case studies for APAtizer are available at https://github.com/GeneRegulationi3S/APAtizer/.

Exploration of Astragaloside IV in multiple organ dysfunction syndrome and hippocampus damage through network pharmacological analysis

Background: This study aims to investigate the potential therapeutic effect of Astragaloside IV on the hippocampus in multiple organ dysfunction syndrome (MODS) and its underlying mechanisms. Methods: Targets related to "Multiple Organ Dysfunction Syndrome," "Hippocampus," and "Astragaloside IV" were collected from the GeneCards database. Co-existing intersection targets were identified using a Venn diagram via the bioinformatics platform. A protein interaction network was constructed using the String database, and core targets were screened with the cytoHubba plug-in of Cytoscape software. GO functional enrichment and KEGG pathway enrichment analyses were performed using the DAVID database, and a "disease-site-drug-key target-KEGG pathway" network map was constructed to reveal the mechanisms of Astragaloside IV. Results: Two intersection targets were identified, and the protein interaction network showed their interactions. GO and KEGG analyses indicated that these targets are mainly involved in biological processes and pathways such as efferocytosis. The "disease-site-drug-key targets-KEGG pathway" network map further clarified that Astragaloside IV may treat MODS by affecting specific signaling pathways. Conclusion: Astragaloside IV may exert a therapeutic effect on the hippocampus in MODS by influencing pathways such as efferocytosis, offering new perspectives and potential targets for future research.

Systematic review of Buzhong Yiqi method in alleviating cancer-related fatigue: a meta-analysis and exploratory network pharmacology approach.

Cancer-related fatigue (CRF) is a prevalent and distressing symptom experienced by many cancer patients, necessitating effective treatments. This study utilizes meta-analysis and network pharmacology to comprehensively assess the efficacy of the Buzhong Yiqi prescription in alleviating cancer-related fatigue and to preliminarily explore the mechanism of its core drugs. We included randomized controlled trials (RCTs) in cancer patients. The inclusion criteria encompassed a diagnosis of cancer-related fatigue, without limitation on cancer type, the experimental group receiving Buzhong Yiqi prescription, the control group receiving conventional treatment, patients awaiting treatment, and articles published in either English or Chinese. We conducted a search through 29 February 2024, across PubMed, Cochrane Database of Systematic Reviews, Cochrane Controlled Clinical Trials (CENTRAL), China Biomedical Literature Service (CBM), China National Knowledge Infrastructure (CNKI), WANFANG Database, and Weipu Database (VIP). Journal articles that met the inclusion criteria were selected for inclusion. Two independent investigators evaluated the quality of the included studies. A meta-analysis was performed utilizing the Stata 12.0 software package, where estimates of cancer-related fatigue were aggregated through the application of a random-effects model. We employed the Cochrane Risk of Bias Tool to evaluate potential biases in RCTs. The primary outcome measures utilized to assess the efficacy and safety of CRF treatment comprised the Revised Piper Fatigue Scale (PFS-R) and the Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). The secondary outcomes encompassed the KPS score, the effective rate, the TCM syndrome score, and an evaluation of adverse reactions. The Traditional Chinese Medicine Systems Pharmacology (TCMSP) was utilized to identify the active ingredients and targets of BZD. Additionally, the Drug bank, Therapeutic Target Database (TTD), DiaGeNET, and GeneCards databases were utilized to retrieve relevant targets for CRC. The Venn diagram was employed to identify overlapping targets. Cytoscape software was utilized to construct a network of "herb-ingredient-target" and identify core targets. GO and KEGG pathway enrichment analyses were performed using R language software. In comparison to the control group, patients with CRF who received BZYQ prescription exhibited marked improvements in KPS score, QLQ-C30 quality of life score, and effective rate. Conversely, PFS, TCM syndrome score, and adverse reaction assessments significantly decreased. The primary active ingredients in its core drugs may exert a positive therapeutic effect on CRF by targeting molecules such as AKT1, IL6, IL1B, PTGS2, CASP3, ESR1, and BCL2, as well as through signaling pathways including TNF, IL17, TLR, NF-κB, and C-type lectin receptor. BZYQ demonstrates significant efficacy in treating CRF with minimal adverse reactions. It can serve as a fundamental treatment for CRF in clinical practice, and the medication can be tailored to individual patients for personalized therapy. The potential pharmacological mechanism of BZYQ in treating CRF, as predicted by network pharmacology, offers a molecular foundation for clinical CRF treatment. https://inplasy.com, identifier INPLASY202430025.

Streptococcus canis transcriptomic modifications in host cell entry environments of human keratinocytes

BackgroundStreptococcus canis is a commensal bacterium in companion animals. This microorganism can infect humans who have been in deep contact with or bitten by pet dogs, suggesting that the skin/soft tissue is one of infection entry sites. To understand pathological process in human cells, we aimed to determine S. canis transcriptomic changes in invasive environments of human keratinocytes.MethodsWe selected one isolate from candidates with whole-genome sequences, based on re-obtained cell invasion ability (CIA) data into human keratinocytes along with bacterial cytotoxicity. RNA-sequencing was conducted for the samples at baselines and 2 h/5 hr post-inoculation using NovaSeq 6000. Global/differential gene expression analyses [principal component analysis (PCA)/k-means clustering analysis/differentially expressed gene (DEG) analyses] were performed. We classified DEGs into their functional categories. To validate transcriptomic results, we did quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays.ResultsFU1 isolate was selected from seven candidates, based on re-obtained CIA data with less cytotoxicity. Total read bases of 6.17–9.02 Gbp were obtained by RNA-sequencing. PCA and k-means clustering analysis indicated clustering according to their inoculation times. Volcano plots and Venn diagrams revealed that S. canis invasion into keratinocytes produced altered distributions of many genes. Gene ontology enrichment analysis showed most of the gene expressions were downregulated. DEG functional analysis showed the downregulated DEGs belonging to energy production and conversion/carbohydrate transport and metabolism/amino acid transport and metabolism/nucleotide transport and metabolism, with the upregulated DEGs belonging to transcription. qRT-PCR assays for downregulated/upregulated expressions of four genes (pgk–slo/opuAA–kdpB) validated transcriptomic results.ConclusionOur observations suggest that S. canis can downregulate its metabolism-associated gene expressions in human keratinocyte environments. The observed gene expression changes can imply the latent infection in human cells. Further investigation is needed to elucidate the underlying mechanisms for the latent infection.

Identification of key genes in diabetic nephropathy based on lipid metabolism.

Diabetic nephropathy (DN) is a common systemic microvascular complication of diabetes with a high incidence rate. Notably, the disturbance of lipid metabolism is associated with DN progression. The present study aimed to identify lipid metabolism-related hub genes associated with DN for improved diagnosis of DN. The gene expression profile data of DN and healthy samples (GSE142153) were obtained from the Gene Expression Omnibus database, and the lipid metabolism-related genes were obtained from the Molecular Signatures Database. Differentially expressed genes (DEGs) between DN and healthy samples were analyzed. The weighted gene co-expression network analysis (WGCNA) was performed to examine the relationship between genes and clinical traits to identify the key module genes associated with DN. Next, the Venn Diagram R package was used to identify the lipid metabolism-related genes associated with DN and their protein-protein interaction (PPI) network was constructed. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. The hub genes were identified using machine-learning algorithms. The Gene Set Enrichment Analysis (GSEA) was used to analyze the functions of the hub genes. The present study also investigated the immune infiltration discrepancies between DN and healthy samples, and assessed the correlation between the immune cells and hub genes. Finally, the expression levels of key genes were verified by reverse transcription-quantitative (RT-q)PCR. The present study determined 1,445 DEGs in DN samples. In addition, 694 DN-related genes in MEyellow and MEturquoise modules were identified by WGCNA. Next, the Venn Diagram R package was used to identify 17 lipid metabolism-related genes and to construct a PPI network. GO analysis revealed that these 17 genes were markedly associated with 'phospholipid biosynthetic process' and 'cholesterol biosynthetic process', while the KEGG analysis showed that they were enriched in 'glycerophospholipid metabolism' and 'fatty acid degradation'. In addition, SAMD8 and CYP51A1 were identified through the intersections of two machine-learning algorithms. The results of GSEA revealed that the 'mitochondrial matrix' and 'GTPase activity' were the markedly enriched GO terms in both SAMD8 and CYP51A1. Their KEGG pathways were mainly concentrated in the 'pathways of neurodegeneration-multiple diseases'. Immune infiltration analysis showed that nine types of immune cells had different expression levels in DN (diseased) and healthy samples. Notably, SAMD8 and CYP51A1 were both markedly associated with activated B cells and effector memory CD8 T cells. Finally, RT-qPCR confirmed the high expression of SAMD8 and CYP51A1 in DN. In conclusion, lipid metabolism-related genes SAMD8 and CYP51A1 may play key roles in DN. The present study provides fundamental information on lipid metabolism that may aid the diagnosis and treatment of DN.

Metabolic Differences among Patients with Cirrhosis Using Q Exactive Hybrid Quadrupole Orbitrap Mass Spectrometry Technology.

The hospitalization and mortality rates of patients gradually increase following the onset and progression of liver cirrhosis (LC). We aimed to help define clinical stage and better target interventions by detecting the expression of specific metabolites in patients with different stages of LC via Q Exactive hybrid quadrupole orbitrap mass spectrometry (UPLC-Q-Exactive) technology. This noninterventional observation case-control study involved 139 patients with LC or acute-on-chronic liver failure (ACLF) in a Chinese hospital between October 2022 and April 2023. Serum specimens were analyzed for multiple metabolite levels using UPLC-Q-Exactive. Data were processed to screen for differentially accumulated metabolites (DAMs). Short time-series expression miner (STEM) analysis and enrichment analysis were performed to assess cirrhosis progression biomarkers. Following univariate and multivariate analyses, a Venn diagram indicated nine significant DAMs in common among groups. STEM analysis showed 8'-hydroxyabscisic acid, HDCA, pyruvate-3-phosphate, indospicine, eplerenone, and DEHP as significant; their levels first peaked [Child-Turcotte-Pugh (CTP) class B peaked] and then decreased with CTP grade aggravation. Significant differences among 8'-hydroxyabscisic acid, eplerenone, and DEHP were observed among LC comorbidities and between subgroups. Therefore, serum levels of six DAMs may characterize metabolomic changes, determine the severity of LC, and predict the development of ACLF.

Evaluation of Rhus Tox, a homeopathic formulation for treatment of Parkinson’s and Alzheimer’s disease: a network pharmacology and ex-vivo approach

Rhus toxicodendron, commonly known as Rhus tox, is a potent homeopathic medication widely used in the treatment of rheumatoid arthritis and is claimed to have potential benefits for neurodegenerative disorders. Given the ability of homeopathic medications to address the root causes of diseases, our study aimed to evaluate Rhus tox for Parkinson’s Disease (PD) and Alzheimer’s Disease (AD) using in-silico, ex-vivo, and network pharmacology approaches to obtain comprehensive information on its multi-component and multi-target effects. Phytoconstituents of Rhus tox were collected from PubMed and screened for ADMET properties. Targets for these constituents were predicted using the Binding Database and DisGeNET, resulting in 61 targets for Parkinsonism and 85 targets for alzhiemer’s disease. Protein-protein interactions (PPIs) were analysed using the STRING database. A Venn diagram was constructed for all these targets, and 5 out of 13 common targets were selected for docking studies. From these analyses, kaempferol and quercetin were identified as promising neuroprotective agents with good blood-brain barrier (BBB) permeation. The docking studies validated these predictions as most of the constituents showed good binding affinity with EGFR, SNCA and MAO-B. It was further validated using MAO inhibition assay, in which Quercetin was found to be highly efficacious, with an IC50 value of 32.69 μg/mL among the other flavonoids studied for MAO inhibition assay. The Rhus Tox also showed MAO inhibition assay similar to the standard seligiline. To conclude, we can propose that Rhus Tox primarily acts on the dopaminergic pathway, serotonergic pathway, and EGFR signaling pathway. Further in vitro and in vivo studies are needed to confirm the mechanism action and efficacy of Rhus Tox for treatment of neurodegenerative diseases.

The Ihya' As-Sunnah Movement Of Rice By Lazismu At The Darul Arqom Mosque, Batu Rinngit Kel. Karang Pule, Mataram, NTBArticle Sidebar

This article will discuss the ihya' as-sunnah movement for rice by lazismu at the darul arqom mosque, batu ringgit kel. karang pule, mataram, NTB. This study aims to see how Lazismu performs in an effort to revive the sunnah (Living Qur`an-Hadith) through the distribution of shadaqah lunches for Friday prayers in congregation at the Darul-Arqam Batu Ringgit mosque, Karang Pule sub-district. Even beyond that, Lazismu has also indirectly preached Islamic teachings in the form of hadiths of Rasulullah SAW which are very rarely known by the local community. Looking at the results of the research above, the author can describe the pattern of interaction of Living Qur'an-Hadith with traditions built by Lazismu through its program is the puritanism-based Living Qur'an-Hadith model, namely a pure understanding of the text which is lived in the form of tradition once a week. When depicted in the form of a Venn diagram, the diagram patterns are not separate from one another, nor are they intersected, but all parts of one set are part of another set.

Changes in the expression profile of serum lncRNAs in pregnant women with high hepatitis B viral load during antiviral and non-antiviral treatment

ObjectiveThis research analyzes the potential of long non-coding RNAs (lncRNAs) as markers in determining the necessity of antiviral treatment in pregnant women by examining alterations in the expression profile of serum lncRNAs in pregnant women with elevated hepatitis B viral load (HBVL) under antiviral and non-antiviral treatment regimens between the second trimester and delivery.MethodsSerum was obtained from 6 s-trimester pregnant women with high HBVL and no intrauterine infection. Then, 3 of these women were randomly selected for antiviral treatment, with the remaining 3 women undergoing non-antiviral treatment as control. Serum samples were again collected from these 6 women before delivery. The expression profile of lncRNAs was analyzed with microarray technology, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The axes of hub lncRNA-miRNA-mRNA were identified based on the competing endogenous RNA (ceRNA) network.ResultsThe expression profile of serum lncRNAs in pregnant women with high HBVL changed significantly from the second trimester of pregnancy until delivery under antiviral or non-antiviral treatment. The Venn diagram was utilized to screen out the jointly up-regulated and down-regulated lncRNAs in the serum of pregnant women under antiviral and non-antiviral treatment before delivery. Additionally, the KEGG pathway enrichment analysis results showed that lncRNAs might mediate the Hippo pathway in HBV infection. Based on the ceRNA network, 3 hub lncRNAs (CATG00000076041.1, LINC01310, and G014655) were found to potentially regulate the key gene TP73 in the Hippo pathway.ConclusionIn this study, we retrieved co-differentially expressed lncRNAs in pregnant women with high HBVL under antiviral or non-antiviral treatment, which may be used as markers for evaluating whether pregnant women with high HBVL may be free of antiviral treatment. This study may provide a basis for preventing potential adverse effects of antiviral treatment on maternal and fetal health.

Operating itself safely: merging the concepts of ‘safe to operate’ and ‘operate safely’ for lethal autonomous weapons systems containing artificial intelligence

ABSTRACT The Ministry of Defence, specifically the Royal Navy, uses the ‘Duty Holder Structure’ to manage how it complies with deviations to maritime laws and health and safety regulations where military necessity requires it. The output statements ensuring compliance are ‘safe to operate’ certification for all platforms and equipment, and the ‘operate safely’ declaration for people who are suitably trained within the organisation. Together this forms the Safety Case. Consider a handgun; the weapon has calibration, design and maintenance certification to prove it is safe to operate, and the soldier is trained to be qualified competent to make predictable judgement calls on how and when to pull the trigger (operate safely). Picture those statements as separate circles drawn on a Venn diagram. As levels of autonomy and complexity are dialled up the two circles converge. Should autonomy increase to the point that the decision to fire be under the control of an Artificial Intelligence within the weapon’s software then the two circles will overlap. This paper details research conclusions within the overlap, and proposes a new methodology able to certify that an AI based autonomous weapons system is “safe to operate itself safely” when in an autonomous state.

Exploring the Key Pathogenesis and Potential Intervention Targets of Sulforaphane in Acute Kidney Injury in Sepsis Based on Bioinformatics.

The objective was to use bioinformatics to analyze the potential key genes involved in the mechanism of sulforaphane's protective effects in sepsis-associated acute kidney injury (SA-AKI) and to identify potential intervention targets. Gene Expression Omnibus (GEO) gene chip datasets containing gene expression profiles from kidney tissues of SA-AKI patients and normal controls were selected. Upregulated differentially expressed genes (DEGs) were identified using GEO2R. Protein-protein interaction (PPI), GO, and KEGG enrichment analyses were performed. Allyl isothiocyanate's target genes were analyzed in the ChEMBL database, and intersections with the above DEGs were presented in Venn diagrams. Rat tissues were examined for FKBP1A expression using qRT-PCR. A total of 17 DEGs related to SA-AKI were obtained (|log fold change| > 0 and P < .05). KEGG pathway analysis indicated that the primary pathways linked to the elevated DEGs were glycogen breakdown, leukocyte trans-endothelial migration, and T-cell receptor, TNF, and NF-κB signaling. The module and PPI network analysis of common DEGs revealed one cluster and four candidate genes, including OASL, TRRAP, FKBP1A, and BANF. ChEMBL database analysis identified 339 target genes for allyl isothiocyanate, and the intersection with upregulated DEGs related to SA-AKI injury yielded two co-expressed genes, FKBP1A and TRRAP. According to the findings of the qRT-PCR assay, the kidney tissues of the model cohort showed significantly higher expression levels of FKBP1A mRNA than the control cohort (P = .0142). Allyl isothiocyanate may alleviate SA-AKI injury by targeting FKBP1/NF-κB.

The role of NOP58 in prostate cancer progression through SUMOylation regulation and drug response.

Prostate cancer is one of the leading causes of cancer-related deaths in men. Its molecular pathogenesis is closely linked to various genetic and epigenetic alterations, including posttranslational modifications like SUMOylation. Identifying biomarkers that predict outcomes and specific therapeutic targets depends on a comprehensive understanding of these processes. With growing interest in SUMOylation as a mechanism affecting prostate cancer-related genes, this study aimed to investigate the central role of SUMOylation in prostate cancer prognostics, focusing on the significance of NOP58. We conducted a comprehensive bioinformatics analysis, integrating differential expression analysis, survival analysis, gene set enrichment analysis (GSEA), and single-cell transcriptomic analyses using data from The Cancer Genome Atlas (TCGA). Key genes were identified through intersections of Venn diagrams, Boralta algorithm signatures, and machine learning models. These signaling mechanisms were validated through experimental studies, including immunohistochemical staining and gene ontology analyses. The dual-gene molecular subtype analysis with SUMO1, SUMO2, and XPO1 genes revealed significant differences in survival outcomes across molecular subtypes, further emphasizing the potential impact of NOP58 on SUMOylation, a key post-translational modification, in prostate cancer. NOP58 overexpression was strongly associated with shorter overall survival (OS), progression-free interval (PFI), and disease-specific death in prostate cancer patients. Immunohistochemical analysis confirmed that NOP58 was significantly overexpressed in prostate cancer tissues compared to normal tissues. ROC curve analysis demonstrated that NOP58 could distinguish prostate cancer from control samples with high diagnostic accuracy. Gene Ontology analysis, along with GSVA and GSEA, suggested that NOP58 may be involved in cell cycle regulation and DNA repair pathways. Moreover, NOP58 knockdown led to increased BCL2 expression and decreased Ki67 levels, promoting apoptosis and inhibiting cell proliferation. Colony formation assays further showed that NOP58 knockdown inhibited, while its overexpression promoted, colony formation, highlighting the critical role of NOP58 in prostate cancer cell growth and survival. Additionally, NOP58 was linked to drug responses, including Methotrexate, Rapamycin, Sorafenib, and Vorinostat. NOP58 is a key regulator of prostate cancer progression through its mediation of the SUMOylation pathway. Its expression level serves as a reliable prognostic biomarker and an actionable therapeutic target, advancing precision medicine for prostate cancer. Targeting NOP58 may enhance therapeutic efficacy and improve outcomes in oncology.

FUNDAMENTAL PRINCIPLES OF SUSTAINABLE DEVELOPMENT AS A BASIS FOR THE FORMATION OF HUMAN CAPITAL IN RURAL AREAS

The article is dedicated to the analysis of economic, social, and environmental problems that intensified at the end of the 20th century and the beginning of the 21st century, stimulating the development of the concept of sustainable development. The authors examine contemporary challenges related to inequality between rich and poor countries, rising greenhouse gas emissions, and the consequences for the environment and society. The aim of the study is to systematize and generalize the existing theoretical and methodological foundations of sustainable development and to clarify them in the context of human capital formation in rural areas. The historical development of the concept of sustainable development, which was established at the UN conference in Rio de Janeiro in 1992, is considered, and three main components of this concept are presented: economic, social, and environmental. The study addresses the classical concept of sustainable development based on the Venn diagram, illustrating the harmonious combination of these components. Special attention is given to the analysis of indicators used for assessing sustainable development in rural areas. Specifically, both domestic and foreign methodological approaches to measuring the effectiveness and inclusiveness of the development of these areas are studied. The article examines various methodological approaches to assessing sustainable development, particularly in rural areas, with a focus on the Sustainable Development Goals (SDGs) of the UN. The study presents an analysis of 17 Global Goals adopted for the period until 2030, aimed at achieving peace, prosperity, and sustainable development in all countries. It is revealed that Ukraine, as a UN member, has actively participated in the implementation of the SDGs, particularly through the national report “Sustainable Development Goals: Ukraine” in 2017. The study substantiates the importance of adapting global goals to the national characteristics of Ukraine, taking into account the specifics of the socio-economic and ecological system. A list of key goals for sustainable development in rural areas of Ukraine is provided, including poverty eradication, agricultural development, ensuring quality education, clean water, decent work, innovation, and infrastructure. The research identifies the importance of indicators for monitoring the achievement of goals and comparing them with the target values planned for 2030. However, considering the current situation with Russian aggression, the achievement of these goals is only possible in the long-term perspective.

Exploring Molecular Signatures in Early-Stage Pancreatic Ductal Adenocarcinoma: Implications for Patient Management and Therapeutic Strategies

Abstract Introduction/Objective Pancreatic ductal adenocarcinoma (PDAC) poses significant challenges to patient survival, predominantly due to its tendency for late-stage diagnosis and high rates of post-surgical cancer recurrence. Therefore, a comprehensive understanding of the molecular characteristics associated with the early stages of PDAC is imperative. This understanding holds the potential to improve patient treatment strategies by enabling targeted interventions and personalized therapies. Methods/Case Report Initially, RNA-seq datasets of early-stage PDAC cases (stages IA, IB, IIA, and IIB, all without distant metastasis; M0) were extracted from the GEO database. Subsequently, the datasets were analyzed in four distinct groups, and differentially expressed genes were identified within each group. Group 1 compared T1T2 cases with T3 cases (T: primary tumor), irrespective of N status (N: regional lymph nodes), while group 2 compared N0 cases with N1 cases, regardless of T status. Group 3 included comparisons between T1T2N0 cases and T3N0 cases, and group 4 compared T1T2N1 cases with T3N1 cases. Utilizing a Venn diagram, commonalities between gene expression profiles were isolated. Afterward, gene ontology and signaling pathways were determined using KEGG and Enrichr. Finally, a protein network was constructed, and the proteins were evaluated using the GEPIA and TCGA clinical databases. Results (if a Case Study enter NA) The study encompassed a total of 43 cases, with 25 (58.1%) being male and 18 (41.9%) female. The mean age of the participants was 64.4 years. In group 1, the expression levels of MUC5AC, AKAP13, and SPG7 were significantly upregulated in T3 cases. In group 2, STAB1, PDLIM1, and MTUS1 emerged as the top upregulated genes in N1 cases. Group 3 exhibited notable upregulation of CCNL2, CEACAM6, and TSPAN3 in T3N0 cases, while group 4 demonstrated marked upregulation of LTBR, AKAP12, and BOP1 in T3N1 cases. These genes exhibited diverse functions in PDAC progression. They contributed to the regulation of gene expression and cell cycle progression, modulating cell proliferation, inhibiting tumor growth, regulating cell signaling, and were involved in cytoskeletal organization. Conclusion The upregulated genes in cases with the T3 and/or N1 staging components may shed light on the potential mechanisms of progression from stage IA/B to stage IIA/B in PDAC cases. Furthermore, the identified genetic alterations may hold potential therapeutic and prognostic applications for future use in the early stages of PDAC.

Exploring the mechanisms of Cornus officinalis in the treatment of non-alcoholic steatohepatitis using network pharmacology, molecular docking and molecular dynamics simulations

Non-alcoholic steatohepatitis (NASH) is a predominant metabolic liver disease, typically characterized by hepatic steatosis, oxidative stress, and inflammation. The traditional Chinese medicine Cornus officinalis possesses anti-inflammatory and hepatoprotective pharmacological properties and has shown ameliorative effects on NASH. however, its mechanism of action remains unclear. This study aims to elucidate the mechanisms by which C. officinalis ameliorates NASH. The active components of C. officinalis were analyzed using the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), and the corresponding targets were predicted. Subsequently, the DisGeNET, GeneCards, and GEO databases were employed to identify NASH-related targets. Venn diagrams were used to intersect the C. officinalis targets with the NASH targets. Protein–protein interaction (PPI) networks were constructed using the STRING database, and PPI network analysis was performed using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the Database for Annotation, Visualization, and Integrated Discovery (DAVID), followed by molecular docking validation. Cornus officinalis was found to contain 20 major active ingredients corresponding to 672 potential targets, 61 of which overlapped with NASH targets. PPI network, GO, and KEGG pathway analyses identified four targets with the highest correlation, and molecular docking results indicated that the active ingredients of C. officinalis exhibited strong binding affinities to NASH targets. The treatment of NASH with C. officinalis is characterized by multiple active ingredients and multiple targets, underscoring the major advantage of traditional Chinese medicine in treating NASH.

Comparison of intestinal and pharyngeal microbiota in preterm infants on the first day of life and the characteristics of pharyngeal microbiota in infants delivered by cesarean section or vaginally.

This study aimed to explore the distribution of intestinal and pharyngeal microbiota on the first day of life in preterm infants and compare the composition of microbiota in infants delivered by cesarean section or vaginally. This study included 44 late preterm infants with a gestational age of 34-36 + 6 weeks. Stool and throat swab samples were collected from the preterm infants on the first day of life. The infants were divided into cesarean section and vaginal delivery groups. Illumina NovaSeq high-throughput sequencing technology was used to sequence the V3-V4 hypervariable region of the 16S rRNA gene of all bacteria in the samples. Venn diagram was used to identify shared operational taxonomic units (OTUs) in the intestines and pharynges. Microbial analysis was conducted at the phylum and genus levels, and α and β diversity comparisons were performed. (1) Gestational age may have significantly affected the microbial colonization of the intestines and pharynges of preterm infants on the first day after birth (p ≤ 0.001). (2) More OTUs were detected in the pharynx than in the intestines, both have a total of 819 shared OTUs. Proteobacteria, Firmicutes, and Bacteroidota were the dominant phyla in both. At the genus level, Streptococcus had a lower relative abundance in stool samples (0.5%) compared to throat samples (0.5% vs. 22.2%, p = 0.003). 3) The relative abundance of Streptococcus in pharyngeal samples was 26.2% in the cesarean section group much higher than the 3.8% in the vaginal delivery group (p = 0.01). The early postnatal period is a critical time for the establishment of an infant's microbiota. Gestational age at birth may influence microbial colonization, while birth weight, gender, and mode of delivery do not. The intestinal and pharyngeal microbiota composition of preterm infants on the first day after birth showed high similarity, but larger samples are needed for further validation.