KEGG Analysis Research Articles

Identification of crucial LncRNAs associated with testicular development and LOC108635509 as a potential regulator in black goat spermatogenesis

The establishment and maintenance of spermatogenesis is a complex process involving a vast of regulatory pathways. There is growing evidence revealing that long noncoding RNAs (lncRNA) play important roles in regulating testicular development and spermatogenesis in a stage-specific way. However, our understanding of how lncRNA regulates testicular development and spermatogenesis in black goats is quite limited. In the current study, we screened the transcriptomes (lncRNA and mRNA) of testicular from Guangxi black goats before puberty (3 days old, D3; 30 days old, D30), puberty (90 days old, D90) and postpuberty (180 days old, D180), in order to identify the lncRNA interaction with mRNAs contributes to goat spermatogenesis. The RNA-sequencing (RNA-seq) analysis showed that there were 1211, 12,180, 834 differential lncRNAs and 1196, 8838,269 differential mRNAs at the ages of D30 vs. D3, D90 vs. D30, and D180 vs. D90. The lncRNAs showed the most significantly changes from D30 to D90, which indicated that D90 was a key node of lncRNAs participated in the regulation of testicular development and spermatogenesis in black goat. According to functional enrichment analysis of GO and KEGG, we found that differentially expressed lncRNAs (DE lncRNAs) and their target genes regulated spermatogenesis through signal pathways including MAPK, Ras, and PI3K-Akt. Using cis- and trans-acting, 39 DE lncRNAs-targeted genes were found to be enriched for male reproduction. Of these, LOC108635509, which specific expressed in testis and upregulated the expression levels at D90, was found participated in the regulation of testicular development through promoting the proliferation of Sertoli cells (SCs). Overall, this study provides new insight into the regulatory mechanisms that support spermatogenesis and testicular development in black goats.

GG-NER’s role in androgen receptor signaling inhibitor response for advanced prostate cancer

BackgroundAdvanced prostate cancer (PCa) often initially responds to androgen receptor signaling inhibitors (ARSI) but frequently develops resistance, driven by tumor heterogeneity and therapeutic pressure. Addressing the clinical challenge of identifying non-responsive patients and discovering new therapeutic targets is urgently needed.MethodsWe utilized single-sample gene set enrichment analysis (ssGSEA) to elucidate the influence of the GG-NER pathway on ARSI response in PCa. We then constructed and validated a prognostic model based on this pathway using LASSO regression, Kaplan-Meier analysis, Cox regression, and ROC analysis. Additionally, we mapped tumor mutations to delineate the mutational landscapes across different risk groups and explored functional pathways through GO, KEGG, and GSEA analyses. The impact of the GG-NER pathway on enzalutamide sensitivity and DNA repair in PCa was further validated through CCK-8 assays, colony formation assays, in vivo experiments, and immunofluorescence.ResultsssGSEA indicated a trend of GG-NER pathway upregulation in patients with poor ARSI response. The GG-NER characteristic gene score (NECGS) identified a high-risk group with diminished ARSI response, serving as an independent prognostic indicator with strong predictive power. This high-risk group exhibited elevated TP53 mutation frequencies and significant enrichment in key pathways such as ribosome and mitochondrial functions, as well as MYC and E2F signaling. Experimental validation confirmed that targeting the GG-NER pathway or its key gene, ACTL6A, significantly reduces enzalutamide resistance in resistant cell lines and increases γH2AX expression.ConclusionNECGS effectively predicts ARSI response in PCa, and our comprehensive analysis underscores the critical role of the GG-NER pathway in enzalutamide resistance, positioning ACTL6A as a potential therapeutic target for PCa.

Interferon-stimulated gene subtypes as key indicators of immune landscape and survival outcomes in ovarian cancer

PurposeOvarian cancer (OV) remains the most lethal gynecological malignancy, underscoring the critical need for robust prognostic biomarkers to enhance patient outcomes. In this study, we classified OV patients by their interferon-stimulated gene (ISG) expression profiles and investigated the associations between these subtypes, the immune microenvironment, and survival outcomes.MethodsWe employed consensus clustering in the TCGA-OV cohort (n = 376) to classify patients into ISG-related subgroups. Survival analysis, differential gene expression (DESeq), KEGG and GSEA pathway enrichment analyses, genomic variation assessments, immune cell profiling using the CIBERSORT algorithm, and TIDE analysis were conducted in the TCGA-OV cohort. In addition, immune checkpoint marker expressions were assessed using data from the TCGA-OV cohort and multiplex immunofluorescence (mIF) staining on an independent cohort (n = 80).ResultsTwo distinct ISG subtypes were identified: ISG Cluster A and ISG Cluster B. Patients in ISG Cluster B exhibited significantly improved overall survival (OS) (p = 0.0442). A total of 328 dysregulated genes were identified, with Cluster B showing overexpression of immune-related genes and enhanced involvement in immune signaling pathways. ISG Cluster B also presented higher tumor mutation burden (TMB) and an enriched immune profile, including M1 macrophages and CD8 + T cells. TIDE analysis indicated a more favorable response to immune checkpoint inhibitors in this cluster, corroborated by high expressions of PD-L1 and ISG15, which were associated with prolonged OS.ConclusionsOur findings demonstrate that ISG-related subtypes are significantly associated with the immune microenvironment and survival outcomes in OV. The biomarkers identified in this study have the potential to inform precision therapy development, thereby enhancing treatment efficacy and personalized care for OV patients.

Metabolite profiling of PGPR Bacillus subtilis BGKMR1: A potential strategy for managing Fusarium equiseti causing wilt in bitter gourd (Momordica charantia L.)

Wilt caused by Fusarium equiseti is one of the most destructive diseases that leads to substantial yield loss in bitter gourd. The F. equiseti strain CBEFE1((PQ111513.1) which was identified morphologically with falcate shaped three septate macroconidia and oval shaped microconidia and molecularly confirmed through amplification of the ITS region at 560bp was used for this study. Plant growth promoting rhizobacteria (PGPR) act as a sustainable biocontrol agent against major plant pathogens through multiple mode of actions. PGPR were isolated from native rhizopshere region in bitter gourd. The isolated PGPR Bacillus subtilis BGKMR 1 shows maximum mycelial inhibition of 68.73 % against F. equiseti in dual plate assay. The presence of metabolites produced by B. subtilis and F. equiseti along with its interaction were identified through the GCMS profiling. Primarily, pathogenic compound squalene (8.88 %) was identified in F. equiseti and antifungal compound 1,4-benzenedicarboxylic acid (6.1 %) was identified in B. subtilis. Further, B. subtilis BGKMR 1 during its interaction shows propanoic acid (14.69 %) which was found to have effectiveness against F. equiseti. KEGG analysis revealed pyrimidine metabolism in F. equiseti and nitrogen, alanine, aspartate and glutamate metabolism in B. subtilis and propanoate metabolism pathways were detected during its interaction. B. subtilis BGKMR 1 promote the seed germination rate upto 96 % and vigor index to 1919.04 when compared to control. The seed treatment with soil application of B. subtilis BGKMR1 reduced disease incidence upto 25.95 % under glass house condition. Moreover, B. subtilis BGKMR1 treated plants shows enhanced defense enzymes activity such as peroxidase, polyphenol oxidase and phenylalanine ammonia-lyase indicating induction of systemic resistance. Therefore, B. subtilis BGKMR 1 contains novel antifungal metabolites which were identified via GC-MS and induced defense enzyme activity highlights its practical application as a sustainable and eco-friendly solution for managing wilt disease in bitter gourd.

The expression of glycolysis-related proteins in urine significantly increases after running

ObjectiveGlucose metabolism is the main way in which cells obtain energy during exercise and plays an important role in exercise. The purpose of this study was to explore the changes in the expression of glucose metabolism-related proteins in urine after running, and finally applied to the monitoring of running training.MethodsUrine samples were collected before and after running, and urine proteomics information was collected to explore the expression of proteins in the urine using LC-MS/MS in DDA mode and DIA mode. Receiver operating characteristic (ROC) curve was drawn to evaluate the value of target proteins in monitoring running training.ResultsA total of 140 proteins were identified using LC-MS/MS in DDA mode, of which 49 urine proteins showed increased expression after running. KEGG analysis revealed that glucose metabolism-related proteins are mainly concentrated in glycolysis. There were six glycolysis-related proteins, among which urine proteins PKM, TPI1, ENO1 and LDHB were significantly increased after running (P < 0.05). This changes in urine proteins PKM, TPI1, ENO1 and LDHB were further verified by the results of LC-MS/MS in DIA mode. The concentrations of the urine proteins TPI1, ENO1 and LDHB showed a significant linear relationship with PKM. ROC curve analysis showed that PKM, TPI1, ENO1 and LDHB proteins in urine had good monitoring values for running training.ConclusionThe expression of glycolysis-related proteins PKM, TPI1, ENO1 and LDHB in urine was significantly increased after running, which may be applied to the monitoring of running training.

Expression of ALG8 in hepatocellular carcinoma and its diagnostic and prognostic significance

Background Alpha-1,3-glucosyltransferase (ALG8), a key enzyme in protein glycosylation, is implicated in the oncogenesis and progression of several human malignancies. This study aimed to define the role of ALG8 in hepatocellular carcinoma (HCC) and uncover its mechanisms of action. Methods ALG8 expression in HCC and normal tissues was analyzed using the TCGA and GEO databases, validated by RT-qPCR and western blot. Survival outcomes were evaluated via Cox analyses, and ALG8’s impact on HCC behavior was examined through functional assays. GO, KEGG, and GSEA identified ALG8-related pathways, validated by biochemical assays. Results In bioinformatics analyses, ALG8 was overexpressed in HCC tissues (p < 0.05 for all comparisons) and correlated with poorer survival (p = 0.006 and p = 0.025, respectively), establishing its role as an independent prognostic factor. In vitro experiments showed that knockdown of ALG8 reduced HCC cell proliferation, migration, and invasion. Using the STRING platform and TCGA-LIHC dataset, we identified ALG8-interacting genes and their associated differentially expressed genes (DEGs). GO and KEGG analyses further linked ALG8 to genes involved in glycosylation, signal release, and other processes, as well as pathways including neuroactive ligand-receptor interaction and N-Glycan biosynthesis. GSEA, corroborated by western blot and immunofluorescence, points to the Wnt/β-catenin signaling cascade as a probable mechanistic pathway through which ALG8 may modulate HCC progression. Conclusion Elevated ALG8 expression in HCC is linked to worse outcomes and increased tumor aggressiveness, with silencing ALG8 reducing Wnt/β-catenin signaling, highlighting ALG8 as a potential therapeutic target.

Revealing the core active pharmaceutical ingredients and targets of Jie-gu capsules for fracture treatment through network pharmacology and mendelian randomization.

Jie-gu capsules are widely used for the treatment of fractures in China. However, the core active pharmaceutical ingredients of Jie-gu capsules and the potential mechanisms for treating fractures remain unclear. This study aims to preliminarily elucidate the potential mechanisms of Jie-gu capsules in the treatment of fractures through network pharmacology and mendelian randomization methods. Data of fracture patients were obtained from the GEO database (GSE93215), and the active pharmaceutical ingredients and therapeutic targets of Jie-gu capsules were retrieved from the TCMSP and TCMID databases to identify the intersection genes. Subsequently, a protein-protein interaction network of the intersection genes was constructed using the STRING database. Then, GO and KEGG analyses were conducted on the intersection genes. In addition, mendelian randomization was employed to identify core targets. Finally, molecular docking techniques were used to perform molecular docking of the core active pharmaceutical ingredients and core targets for Jie-gu capsules in the treatment of fractures. In this study, a total of 65 intersection genes involved in Jie-gu capsule treatment of fractures were identified. GO and KEGG results indicated that these 65 intersection genes were primarily associated with biological processes such as response to tumor necrosis factor and are involved in signaling pathways, especially the regulation of the MAPK signaling pathway. We identified 5 core active ingredients of Jie-gu capsules (quercetin, baicalein, kaempferol, luteolin, and succinic acid). Mendelian randomization confirmed 2 core targets (ALOX12 and EGF). Molecular docking results demonstrated that the core active pharmaceutical ingredients (quercetin, baicalein, kaempferol, luteolin, and succinic acid) exhibit high affinities with the core targets (ALOX12 and EGF). This study has unveiled the core active pharmaceutical ingredients and potential action targets of the Jie-gu capsules in treating fractures, offering valuable insights for subsequent foundational research and the development of new medications.

Probiotic Mixture Attenuates Colorectal Tumorigenesis in Murine AOM/DSS Model by Suppressing STAT3, Inducing Apoptotic p53 and Modulating Gut Microbiota.

Colorectal cancer (CRC) is one of the most common cancers worldwide. The standard CRC chemo drug, 5-Fluorouracil (5-FU), has a poor response rate and chemoresistance, prompting the need for a more effective and affordable treatment. In this study, we aimed to evaluate whether Prohep, a novel probiotic mixture, would alleviate azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colorectal tumorigenesis and enhance 5-FU efficacy and its mechanism. Our results suggested that Prohep showed stronger anti-tumorigenesis effects than 5-FU alone or when combined in the AOM/DSS model. Prohep significantly reduced the total tumor count, total tumor size, caecum weight, colonic crypt depth, colonic inflammation, and collagen fibrosis. Prohep downregulated pro-inflammatory TNF-α and proliferative p-STAT3 and upregulated apoptotic p53. Metagenomics analysis indicated that Prohep-enriched Helicobacter ganmani, Desulfovibrio porci, Helicobacter hepaticus, and Candidatus Borkfalkia ceftriaxoniphila were inversely correlated to the total tumor count. In addition, Prohep-enriched Prevotella sp. PTAC and Desulfovibrio porci were negatively correlated to AOM/DSS enriched bacteria, while forming a co-existing community with other beneficial bacteria. From KEGG analysis, Prohep downregulated CRC-related pathways and enhanced pathways related to metabolites suppressing CRC like menaquinone, tetrapyrrole, aminolevulinic acid, and tetrahydrofolate. From Metacyc analysis, Prohep downregulated CRC-related peptidoglycan, LPS, and uric acid biosynthesis, and conversion. Prohep elevated the biosynthesis of the beneficial L-lysine, lipoic acid, pyrimidine, and palmitate. Prohep also elevated metabolic pathways related to energy utilization of lactic acid-producing bacteria (LAB) and acetate producers. Similarly, fecal acetate concentration was upregulated by Prohep. To sum up, Prohep demonstrated exceptional anti-tumorigenesis effects in the AOM/DSS model, which revealed its potential to develop into a novel CRC therapeutic in the future.

The therapeutic effects of Paeoniae Radix Rubra on chronic hepatitis through network pharmacology and molecular docking.

Chronic hepatitis (CH) refers to liver inflammation lasting at least 6 months caused by various factors, significantly impacting patients' daily lives. Paeoniae Radix Rubra (CS) is a classic blood-activating and stasis-dissolving herb known for its protective effects on the liver. This research seeks to investigate the underlying mechanisms by which CS treat CH, employing network pharmacology and molecular docking. The active constituents of CS for CH treatment were identified through the TCMSP database. Targets associated with CH were gathered from GeneCards, the Therapeutic Target Database, and OMIM databases. The intersecting genes between these targets and the components of CS were considered potential therapeutic targets. Protein-protein interaction analysis was performed with the use of the STRING database and Cytoscape software, leading to the identification of core targets. These core targets underwent KEGG and GO enrichment analysis, and the top 10 pathways were chosen for building a drug-compound-target-pathway-disease' network. Finally, molecular docking was utilized to evaluate the binding affinities between the compounds and the core targets. From the TCMSP database, 29 compounds were screened, and 101 potential intersection targets of CS for treating CH were identified. The protein-protein interaction network analysis revealed that the core targets included EGFR, HSP90AA1, SRC, TNF, ALB, ESR1, CASP3, PTGS2, ERBB2, and FGF2. Pathway analysis indicated that CS's treatment of CH is mainly associated with the pathway in cancer. Molecular docking results indicated that Paeoniflorin and Baicalin exhibited strong binding affinity with EGFR and HSP90AA1. This research uncovers the possible mechanisms of CS in CH treatment, offering new avenues for future studies.

Effects of PGK1 on immunoinfiltration by integrated single-cell and bulk RNA-sequencing analysis in sepsis

BackgroundSepsis, a life-threatening organ dysfunction caused by a dysregulated immune response to infection, remains a significant global health challenge. Phosphoglycerate kinase 1 (PGK1) has been implicated in regulating inflammation and immune cell infiltration in inflammatory conditions. However, the role of PGK1 in sepsis remains largely unexplored.MethodsFour microarray datasets and a high throughput sequencing dataset were acquired from GEO database to reveal the PGK1 expression in patients of sepsis. Quantitative real-time PCR and western blotting was then used to validate the PGK1 level. Additionally, microarray and single-cell RNA sequencing data integration, including gene set enrichment analysis (GSEA), KEGG and GO functional enrichment analysis, immune infiltration analysis, and single-cell sequencing analysis, were performed to elucidate the role of PGK1 in sepsis.ResultsOur results revealed a significant upregulation of PGK1 in sepsis patients, with the area under the ROC curve (AUC) exceeding 0.9 across multiple datasets, indicating PGK1’s strong potential as a diagnostic biomarker. Notably, PGK1 was enriched in key immune-related pathways, including the TNF signaling pathways, and leukocyte transendothelial migration, suggesting its involvement in immune regulation. Furthermore, PGK1 expression showed a positive correlation with the levels of inflammatory mediators CXCL1, CXCL16, and the chemokine receptor CCR1. In terms of immune cell infiltration, PGK1 was positively correlated with naive B cells, resting memory CD4 T cell, gamma delta T cells, M0 macrophages, eosinophils and negatively correlated with plasma cells, CD8 T cells, activated memory CD4 T cell, Tregs, activated dendritic cells.ConclusionsThis study concluded that PGK1 served as a novel diagnostic biomarker for sepsis, with potential implications for prognosis and immune regulation. The significant upregulation of PGK1 in sepsis patients and its association with immune-related pathways and cell types highlight its potential role in the pathogenesis of sepsis.

Proteomic Analysis Reveals Differentially Expressed Proteins in Cordyceps militaris Cultured with Different Media.

Cordyceps militaris is rich in high quality protein, which is an excellent protein supplement. In this study, proteins were extracted from C. militaris cultured with tussah pupa and C. militaris cultured with wheat and analyzed by liquid chromatography coupled with mass spectrometer. Results showed that a total of 83 differentially expressed proteins (DEPs) were identified. KEGG analysis showed that the number of DEPs involved in amino sugar and nucleotide sugar metabolism and metabolic pathways was the largest. The expression levels of chitinase, tubulin alpha chain and heat shock 70 kDa protein were upregulated in C. militaris cultured with tussah pupa, and these key DEPs were mainly related to immune modulation and disease resistance. The results revealed the nutritional and functional differences in the fruiting bodies of C. militaris cultured with tussah pupa and wheat, respectively. The findings provide a theoretical basis for further studies on the biological function of proteins in C. militaris.

A Metabolomic Analysis of Tomato Fruits in Response to Salt Stress

Salt stress affects all stages of tomato growth and development, reducing tomato yield, but moderate salt stress improves tomato quality. To gain a deeper understanding of the effect of salt stress on tomato fruits, a widely targeted metabolomic method based on ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) was used to analyze tomato fruits under three different soil salt contents (CK: 0.05 g·kg−1; MS: 3 g·kg−1; and HS: 6 g·kg−1). A total of 847 metabolites were detected in tomato fruit under salt stress, including six primary metabolites such as lipids, amino acids and their derivatives, sugars, nucleotides and their derivatives, and organic acids, and nine secondary metabolites such as phenolic acids, alkaloids, and flavonoids. There were 54 different metabolites in the three treatments, mainly flavonols and phenolamines. Dopamine, galactotol, and mannitol were not detected in the control group, but their contents were higher in the salt treatment. KEGG analysis showed that the differential metabolites were mainly concentrated in flavonoid biosynthesis, betaine metabolism, sulfur metabolism, and galactose metabolism. This study provides a theoretical basis for the regulation of tomato quality through salt stress.

Identification of potential biomarkers from amino acid transporter in the activation of hepatic stellate cells via bioinformatics.

The etiopathogenesis of hepatic stellate cells (HSC) activation has yet to be completely comprehended, and there has been broad concern about the interplay between amino acid transporter and cell proliferation. This study proposed exploring the molecular mechanism from amino acid transport-related genes in HSC activation by bioinformatic methods, seeking to identify the potentially crucial biomarkers. GSE68000, the mRNA expression profile dataset of activated HSC, was applied as the training dataset, and GSE67664 as the validation dataset. Differently expressed amino acid transport-related genes (DEAATGs), GO, DO, and KEGG analyses were utilized. We applied the protein-protein interaction analysis and machine learning of LASSO and random forests to identify the target genes. Moreover, single-gene GESA was executed to investigate the potential functions of target genes via the KEGG pathway terms. Then, a ceRNA network and a drug-gene interaction network were constructed. Ultimately, correlation analysis was explored between target genes and collagen alpha I (COL1A), alpha-smooth muscle actin (α-SMA), and immune checkpoints. We identified 15 DEAATGs, whose enrichment analyses indicated that they were primarily enriched in the transport and metabolic process of amino acids. Moreover, two target genes (SLC7A5 and SLC1A5) were recognized from the PPI network and machine learning, confirmed through the validation dataset. Then single-gene GESA analysis revealed that SLC7A5 and SLC1A5 had a significant positive correlation to ECM-receptor interaction, cell cycle, and TGF-β signaling pathway and negative association with retinol metabolism conversely. Furthermore, the mRNA expression of target genes was closely correlated with the COL1A and α-SMA, as well as immune checkpoints. Additionally, 12 potential therapeutic drugs were in the drug-gene interaction network, and the ceRNA network was constructed and visualized. SLC7A5 and SLC1A5, with their relevant molecules, could be potentially vital biomarkers for the activation of HSC.

Homocysteine affects macrophage polarization by altering m6A methylation of scavenger receptors CD209 and CD163L1

ABSTRACT Atherosclerosis is a chronic inflammatory disease characterized by fatty plaque deposits on artery walls. Elevated plasma homocysteine (Hcy) levels are an independent risk factor for atherosclerosis. Research on the mechanism by which Hcy promotes atherosclerosis has gradually turned to epigenetic inheritance, but the correlation between Hcy and m6A (N6-methyladenosine) modification has not been reported. In this study, MeRIP-seq was performed on macrophages and Hcy-treated macrophages. GO and KEGG analyses were used to perform functional analysis of differentially methylated genes. qRT-PCR and western blot were taken to determine the expression of CD209, CD163L1, proinflammatory, and anti-inflammatory factors. Flow cytometry was used to detect the proportion of M2 macrophages. The results showed that after Hcy treatment, the overall m6A methylation of macrophages was down-regulated, and 856 differential methylation peaks were annotated to 781 genes. These included CD209 and CD163L1, whose m6A methylation was inhibited after treatment with Hcy. In addition, mRNA and protein expressions of CD209 and CD163L1 were also inhibited after Hcy treatment. Overexpression of CD209 or CD163L1 prevents the Hcy-induced decrease in the proportion of M2 macrophages. This article identified changes in the modification level of m6A in macrophages by Hcy and revealed the possible mechanism by which Hcy induces macrophage polarization.

Non-submerged attached growth process for low-concentration methane emission treatment using downflow hanging sponge

The gas-liquid mass transfer issue has always been a challenge in the biological oxidation of methane waste gas treatment. Therefore, this study aims to apply the Downflow Hanging Sponge (DHS) that widely used in wastewater treatment, to mitigate the gas-liquid mass transfer obstacles on methane waste gas treatment. The comprehensive experimental results indicate that among the three sponge carriers, the Melamine Foam (MF) exhibits the strongest wettability, characterized by smaller pore size and a uniformly arranged pore structure. And it demonstrates excellent performance in methane degradation. (maintaining methane degradation efficiency above 5 mol·h−1m−3 in the third phase.) Furthermore, the combined analysis of microbial QPCR and KEGG reveals that the MF sponge possesses a more diverse microbial population and superior methane oxidation capability compared to the other two sponges. This study confirms the superiority of the MF sponge as a biological carrier, capable of enhancing the efficiency of DHS treatment of methane waste gas and providing valuable suggestions for carrier selection and modification.

Mechanisms Underlying the Attenuating Effects of Bugantang on Liver Fibrosis based on Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.

Liver fibrosis, a chronic liver disease, threatens people's health, increases the burden of healthcare, and currently lacks effective treatment measures. Bugantang (BGT) is a traditional Chinese herbal prescription from Jin Kui Yi with promising potential for treating liver fibrosis. Despite this potential, the efficacy and mechanism for treating liver fibrosis remain unclear. To primarily prove the efficacy, predict the active components of BGT, and explore the mechanism of BGT on liver fibrosis. The liver condition of CCL4-induced mice was examined using hematoxylin and eosin staining. The targets and active compounds of BGT were sourced from HERB and TCMSP databases, while the targets related to liver fibrosis were acquired from DisGeNET, Gene Expression Omnibus, and GeneCards databases. The core targets were identified, and the network of protein-protein interactions was established. KEGG and GO analyses were performed on DAVID. Molecular docking and molecular dynamics simulations assessed the active components' interactions with potential targets. A total of 215 targets and 152 active compounds were identified for BGT. The network analysis identified kaempferol, quercetin, 2-(2,4-dihydroxyphenyl)-7-hydroxy-4Hchromen- 4-one, sitosterol, naringenin, adenosine, plo, and beta-sitosterol as potential key compounds, and AKT1, MMP9, SRC, TNF, ESR1, NF-κB, and PPARG as potential key targets. KEGG and GO analyses revealed that the therapeutic effect of BGT on liver fibrosis may be associated with the PI3K-AKT and MAPK signaling pathways, as well as cell apoptosis, protein phosphorylation, and inflammation. Molecular docking demonstrated high-affinity binding of the identified targets to the active compounds. Additionally, molecular dynamics simulation further confirmed that the bindings of AKT1-beta-sitosterol and MMP9-quercetin exhibited good stability. The potential of BGT in alleviating liver fibrosis may be attributed to a combination of various active compounds, targets, and pathways. These results could support the use of BGT in treating liver fibrosis and facilitate the development of new drug candidates for this condition.

Xuebijing Exerts Protective Effects on Myocardial Cells by Upregulating TRIM16 and Inhibiting Oxidative Stress and Apoptosis.

This study utilized transcriptomic sequencing combined with cellular and animal models to explore the potential mechanisms of Xuebijing in treating sepsis-induced myocardial dysfunction, also known as sepsis-induced myocardial injury. We investigated potential targets and regulatory mechanisms of XBJ injection using network pharmacology and RNA sequencing. The effects of XBJ on oxidative stress and apoptosis levels in human cardiac myocytes (AC16) and C57BL/6 mice exposed to lipopolysaccharide (LPS) were evaluated by Enzyme-Linked Immunosorbent Assay (ELISA), fluorescent probe, Fluorescent Quantitative Polymerase Chain Reaction (qPCR), Western Blot, Transmission Electron Microscopy, oxidative stress-related indicators detection kit, flow cytometry, and Immunohistochemistry (IHC). First, it was verified that XBJ can reduce the deformation of AC16 cardiomyocytes induced by LPS and the production and secretion of ROS (P <0.01). The transcriptome sequencing results showed that the TRIM16 gene was significantly increased after XBJ treatment, and the data of KEGG and GO analyses demonstrated that XBJ could inhibit the pathway expression of oxidative stress damage in AC16 cells, and PCR verified that XBJ could indeed increase the expression level of TRIM16 gene in AC16 cells (P <0.01). Basic animal and cell experiments showed that LPS could inhibit the expression of TRIM16 and NRF2 in cardiomyocytes (P <0.05) and promote the expression of Keap1 (P <0.01), while XBJ could significantly upregulate the expression levels of TRIM16 and NRF2 (P <0.01) and inhibit the expression of Keap1 (P <0.01), thereby affecting the expression levels of downstream proinflammatory cytokines and alleviating LPS-induced oxidative stress damage. In addition, XBJ also inhibited the expression of the pro-apoptotic proteins Bax and c-caspase3 (P <0.01), promoted the expression of the anti-apoptotic protein Bcl2 (P <0.01), and reduced LPS-induced apoptosis by upregulating TRIM16. Our comprehensive data demonstrated that TRIM16 is a key gene in the therapeutic action of Xuebijing in sepsis-induced myocardial dysfunction, protecting myocardial cells from injury through antioxidative stress and anti-apoptotic mechanisms.

Prognostic and diagnostic value of SPINK mRNAs expression in head and neck squamous cell carcinoma based on genome-wide analysis

Aim: Head and neck squamous cell carcinoma (HNSC) is a major contributor to the global cancer burden. The serine protease inhibitor Kazal-type (SPINK) gene family has been linked to various cancers. This study explores the prognostic value of SPINK genes in predicting overall survival (OS) in HNSC patients. Methods: We analyzed RNA sequencing and clinical data from 504 cancer and 44 non-cancer samples from the TCGA database. Differential expression and functional enrichment analyses gene ontology and Kyoto encyclopedia of genes and genomes (GO and KEGG) were performed using clusterProfiler. Protein-protein interaction (PPI) networks were built with STRING and visualized. Immune infiltration was evaluated using single-sample Gene Set Enrichment Analysis (ssGSEA). Survival analysis utilized Kaplan-Meier curves and Cox regression models. Results: Our results showed that SPINK5, SPINK7, SPINK8, SPINK9, and SPINK14 were significantly overexpressed in normal tissues compared to carcinoma tissues, whereas SPINK1, SPINK4, and SPINK6 showed higher expression in carcinoma tissues. Correlation analysis revealed significant relationships among SPINK family members. GO and KEGG analyses highlighted their involvement in processes such as negative regulation of peptidase activity and serine-type endopeptidase inhibitor activity. PPI network analysis indicated close interactions between several SPINK proteins and other relevant proteins. Immune infiltration analysis showed that NK cells and Th2 cells were negatively correlated with SPINK genes, while mast cells and neutrophils were positively correlated. Survival analysis revealed that high mRNA expression levels of SPINK1, SPINK5, and SPINK6 were significantly associated with OS in HNSC patients. Receiver operating characteristic (ROC) curve analysis indicated that these genes have diagnostic value. We developed a nomogram model that combines tumor stage and SPINK gene expression providing a predictive tool for patient prognosis. Conclusions: This study elucidates the multifaceted roles of the SPINK gene family in HNSC. These findings offer valuable insights into their potential as diagnostic biomarkers and therapeutic targets.

ITGB4 is a prognostic biomarker and correlated with lung adenocarcinoma brain metastasis.

The aim of this study is to explore the prognostic value and immune signature of ITGB4 expression in lung adenocarcinoma (LUAD) brain metastasis. We comprehensively screened genes associated with LUAD brain metastasis by integrating datasets from the GEO database and TMT-based quantitative proteomics profiles. Univariable survival and Multivariate Cox analysis was used to compare several clinical characteristics with survival, and a risk model was constructed. The biological functions were explored via GO and KEGG analysis. Gene set enrichment analysis (GSEA) was performed using the TCGA dataset. In addition, we use TIMER to explore the collection of ITGB4 Expression and Immune Infiltration Level in LUAD. The ability of ITGB4 to regulate tumor metastasis was further assessed by migration, invasion assay and Western-blot in H1975-BrM4 cells. We found that ITGB4 was the only gene with high clinical diagnostic and prognostic value in LUAD. Enrichment analysis indicated that ITGB4 is associated with brain metastasis, infiltration of immune cells, and the response to immunotherapy. ITGB4 expression can effectively predict the outcomes of patients with LUAD who are receiving anti-PD-1 therapy. ITGB4 knockdown inhibited the invasion, migration of H1975-BrM4 brain metastasis cells, as well as epithelial-mesenchymal transition (EMT) abilities. The heightened expression of ITGB4 protein was shown to promote EMT and enhance the metastatic potential. ITGB4 promotes the progression in H1975-BrM4 cells via MEK/ERK signaling pathway. Our findings indicate that the expression of ITGB4 is linked to the occurrence of brain metastasis and infiltration of immune cells, suggesting that ITGB4 might be a clinical treatment target for LUAD.

Identification of PANoptosis-Related Genes in Community-Acquired Pneumonia Diagnosis.

This study aimed to identify and characterize novel PANoptosis biomarkers for community-acquired pneumonia (CAP) diagnosis. Transcriptomic data from training set GSE196399 and validation sets GSE94916 and GSE202947 were utilized. A PANoptosis gene set was identified by intersecting DEGs linked to CAP, WGCNA hub genes, and PANoptosis-related genes. GO and KEGG analyses were conducted for enrichment analysis. PANoptosis scores were calculated via ssGSEA. Feature genes were identified using SVM-RFE, LASSO regression, and RF methods. Diagnostic performance was assessed via ROC analysis. Immune cell infiltration was evaluated using CIBERSORT. A PPI network was constructed, and a nomogram was developed for CAP prediction. Drug-gene interactions were investigated. qRT-PCR was conducted to confirm feature gene alterations in clinical samples. We identified 7555 DEGs associated with CAP from the GSE196399 dataset. Through WGCNA, a PANoptosis gene set of 39 genes was found, showing significant enrichment in pathways related to apoptosis and inflammation. CAP patients exhibited significantly reduced PANoptosis scores compared to healthy controls, with a marked upregulation in the majority of the PANoptosis gene set in high-score individuals. Four feature genes (ZNF304, AKT3, MAPK8, and ARHGAP10) were identified as potential biomarkers, exhibiting high diagnostic accuracy with AUCs generally above 0.8. These genes also showed significant correlations with M0 macrophages and neutrophils. Drug-gene interaction analysis revealed potential therapeutic agents targeting MAPK8 and AKT3. Validation in clinical samples confirmed gene expression alterations in CAP patients. The identified PANoptosis feature genes demonstrate high diagnostic accuracy for CAP, serving as potential biomarkers and therapeutic targets for CAP.