Regulation Of Inflammatory Mediators Research Articles

Whole transcriptome analysis revealed the regulatory network and related pathways of non-coding RNA regulating ovarian atrophy in broody hens.

Poultry broodiness can cause ovarian atresia, which has a detrimental impact on egg production. Non-coding RNAs (ncRNAs) have become one of the most talked-about topics in life sciences because of the increasing evidence of their novel biological roles in regulatory systems. However, the molecular mechanisms of ncRNAs functions and processes in chicken ovarian development remain largely unknown. Whole-transcriptome RNA sequencing of the ovaries of broodiness and laying chickens was thus performed to identify the ncRNA regulatory mechanisms associated with ovarian atresia in chickens. Subsequent analysis revealed that the ovaries of laying chickens and those with broodiness had 40 differentially expressed MicroRNA (miRNAs) (15 up-regulated and 25 down-regulated), 379 differentially expressed Long Noncoding RNA (lncRNAs) (213 up-regulated and 166 down-regulated), and 129 differentially expressed circular RNA (circRNAs) (63 up-regulated and 66 down-regulated). The competing endogenous RNAs (ceRNA) network analysis further revealed the involvement of ECM-receptor interaction, AGE-RAGE signaling pathway, focal adhesion, cytokine-cytokine receptor interaction, inflammatory mediator regulation of TRP channels, renin secretion, gap junction, insulin secretion, serotonergic synapse, and IL-17 signaling pathways in broodiness. Upon further analysis, it became evident that THBS1 and MYLK are significant candidate genes implicated in the regulation of broodiness. The expression of these genes is linked to miR-155-x, miR-211-z, miR-1682-z, gga-miR-155, and gga-miR-1682, as well as to the competitive binding of novel_circ_014674 and MSTRG.3306.4. The findings of this study reveal the existence of a regulatory link between non-coding RNAs and their competing mRNAs, which provide a better comprehension of the ncRNA function and processes in chicken ovarian development.

Poly (ADP-ribose) Polymerase-1 modulations in the genesis of thrombosis.

Thrombosis, a coagulation disorder, occurs due to altered levels of coagulation, fibrinolytic and immune factors, which are otherwise known to maintain hemostasis in normal physiological conditions. Here, we review the direct and indirect participation of a multifunctional nuclear enzyme poly (ADP-ribose) polymerase-1 (PARP1) in the expression of key genes and cellular processes involved in thrombotic pathogenesis. PARP1 biological activities range from maintenance of genomic integrity, chromatin remodeling, base excision DNA repair, stress responses to cell death, angiogenesis and cell cycle pathways. However, under homeostatic imbalances, PARP1 activities are linked with the pathogenesis of diseases, including cancer, aging, neurological disorders, and cardiovascular diseases. Disease-associated distressed cells employ a variety of PARP-1 functions such as oxidative damage exacerbations, cellular energetics and apoptosis pathways, regulation of inflammatory mediators, promotion of endothelial dysfunction, and ERK-mediated signaling in pathogenesis. Thrombosis is one such pathogenesis that comprises exacerbation of coagulation cascade due to biochemical alterations in endothelial cells, platelet activation, overexpression of adhesion molecules, cytokines release, and leukocyte adherence. Thus, the activation of endothelial and inflammatory cells in thrombosis implicates a potential role of PARP1 activation in thrombogenesis. This review article explores the direct impact of PARP1 activation in the etiology of thrombosis and discusses PARP1-mediated endothelial dysfunction, inflammation, and epigenetic regulations in the disease manifestation. Understanding PARP1 functions associated with thrombosis may elucidate novel pathogenetic mechanisms and help in better disease management through newer therapeutic interventions targeting PARP1 activity.

Exploring the mechanisms underlying effects of bisphenol a on cardiovascular disease by network toxicology and molecular docking

BackgroundGlobally, cardiovascular disease (CVD) has emerged as a leading cause of mortality. Bisphenol A (BPA), recognized as one of the most prevalent and widely distributed endocrine-disrupting chemicals (EDCs), has been consistently linked to the progression of CVD. This research centers on unraveling the molecular mechanisms responsible for the toxic effects of BPA exposure on CVD. Key targets and pathways involved in action of BPA on CVD were investigated by network toxicology. Binding abilities of BPA to core targets were evaluated by molecular docking. Methods and resultsBased on information retrieved from ChEMBL, DrugBank, and OMIM databases, a total of 27 potential targets were found to be associated with the influence of BPA on CVD. Furthermore, the STRING and Cytoscape software were employed to identify three central genes—ESR1, PPARG, and PTGS2—and to construct both the protein-protein interaction network and an interaction diagram of potential targets. Gene ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes, KEGG) pathway enrichment analyses via WebGestalt revealed key biological processes (BP), cellular components (CC), molecular functions (MF), and pathways, such as the calcium signaling pathway, inflammatory mediator regulation of TRP channels, gap junction, adrenergic signaling in cardiomyocytes, cGMP-PKG signaling pathway, and cAMP signaling pathway, predominantly involved in BPA-induced CVD toxicity. By using molecular docking investigations, it proved that BPA binds to ESR1, PPARG, and PTGS2 steadily and strongly. ConclusionThis study not only establishes a theoretical framework for understanding the molecular toxicity mechanism of BPA in cardiovascular disease (CVD) but also introduces an innovative network toxicology approach to methodically investigate the influence of environmental contaminants on CVD. This methodology sets the stage for drug discovery efforts targeting CVD linked to exposure to endocrine-disrupting chemicals (EDCs).

Mechanism of Microwave Radiation-Induced Learning and Memory Impairment Based on Hippocampal Metabolomics.

The brain is complex and metabolically active, and the detection of metabolites plays an important role in brain development and diseases. Currently, there is a lack of research on the metabolic spectrum changes in learning and memory impairment, and hippocampal damage induced by microwave radiation from the metabolic perspective. Aiming to provide sensitive indicators for microwave radiation-induced brain damage and establish a foundation for understanding its injury mechanisms, this study employed non-targeted metabolomics to investigate metabolic fluctuations and key metabolic pathway alterations in rats' hippocampal tissue after microwave radiation. The memory and spatial exploration abilities of rats decreased after radiation. The postsynaptic densities were thickened in the MW group. The cholesterol sulfate, SM(d16:1/24:1(15Z)), and linoelaidylcarnitine were significantly increased after radiation, whereas etrahydrocorticosterone, L-phenylalanine, and histamine were significantly decreased after radiation. These metabolites were enriched in signaling pathways related to the inflammatory mediator regulation of transient receptor potential (TRP) channels, neuroactive ligand-receptor interaction, steroid hormone biosynthesis, and phenylalanine, tyrosine, and tryptophan biosynthesis. These findings indicate that microwave radiation causes spatial learning and memory dysfunction in rats and structural damage to hippocampal tissue.

Identification of Age-Related Characteristic Genes Involved in Severe COVID-19 Infection Among Elderly Patients Using Machine Learning and Immune Cell Infiltration Analysis.

Elderly patients infected with severe acute respiratory syndrome coronavirus 2 are at higher risk of severe clinical manifestation, extended hospitalization, and increased mortality. Those patients are more likely to experience persistent symptoms and exacerbate the condition of basic diseases with long COVID-19 syndrome. However, the molecular mechanisms underlying severe COVID-19 in the elderly patients remain unclear. Our study aims to investigate the function of the interaction between disease-characteristic genes and immune cell infiltration in patients with severe COVID-19 infection. COVID-19 datasets (GSE164805 and GSE180594) and aging dataset (GSE69832) were obtained from the Gene Expression Omnibus database. The combined different expression genes (DEGs) were subjected to Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Diseases Ontology functional enrichment analysis, Gene Set Enrichment Analysis, machine learning, and immune cell infiltration analysis. GO and KEGG enrichment analyses revealed that the eight DEGs (IL23A, PTGER4, PLCB1, IL1B, CXCR1, C1QB, MX2, ALOX12) were mainly involved in inflammatory mediator regulation of TRP channels, coronavirus disease-COVID-19, and cytokine activity signaling pathways. Three-degree algorithm (LASSO, SVM-RFE, KNN) and correlation analysis showed that the five DEGs up-regulated the immune cells of macrophages M0/M1, memory B cells, gamma delta T cell, dendritic cell resting, and master cell resisting. Our study identified five hallmark genes that can serve as disease-characteristic genes and target immune cells infiltrated in severe COVID-19 patients among the elderly population, which may contribute to the study of pathogenesis and the evaluation of diagnosis and prognosis in aging patients infected with severe COVID-19.

Elevated interleukin 8 and matrix metalloproteinase 9 levels are associated with myocardial pathology in users of Anabolic-Androgenic Steroids.

In the current paper, we aim to explore the effect of both current and former long-term anabolic-androgenic steroid (AAS) use on regulation of systemic inflammatory markers and mediators of extracellular matrix (ECM) remodeling and their association with hormones and echocardiographic myocardial pathology in weightlifters. In a cross-sectional study, 93 weightlifting AAS-users, of which 62 were current and 31 were past users, with at least one-year cumulative AAS-use (mean 11±7 accumulated years of AAS-use), were compared to 54 non-using weightlifting controls (WLC) using clinical interview, blood pressure measurements, and echocardiography. Serum levels of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF), interferon (IFN)γ, growth differentiation factor (GDF)-15 and matrix metalloproteinase (MMP-9), sex hormones and lipids were analyzed. Serum levels of IL-8, GDF-15 and MMP-9 were significantly increased in current AAS users compared to former users and WLC. MMP-9, but not IL-8, correlated consistently with sex-hormone levels, and sex-hormone levels correlated consistently with mean wall thickness, in current users. Moreover, HDL cholesterol was significantly lower in current versus former AAS users, in significantly inversely correlated with MMP-9 in current users. Further, in current users, MMP-9 and IL-8 correlated with markers of myocardial strain, and MMP9 also with indices of cardiac mass, which was not seen in former users. Mediation analyses suggested that MMP-9 could partly explain hormone-induced alterations in markers of myocardial damage in current users. In conclusion, long-term AAS is associated with increased levels of markers of inflammation and extracellular matrix remodeling, which seems to have a hormone-dependent (MMP-9) and hormone-independent (IL-8) association with markers of myocardial dysfunction.

Transcriptomic sequencing analysis of key long noncoding RNAs and mRNAs expression profiles in postoperative recurrence of hepatocellular carcinoma.

Recurrence is the main cause of death in hepatocellular carcinoma (HCC) patients after liver resection. The long non-coding RNAs (lncRNAs) have been reported participated in progression and prognosis of HCC, however, the vital role of lncRNA in postoperative recurrence of HCC has rarely been systematically identified. RNA-sequencing (RNA-seq) was performed between orthotopic model of HCC and hepatoma postoperative recurrent model to comprehensively analyze the integrated transcriptome expression profiles of lncRNA and mRNA. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) was then conducted to quantify the expression levels of DElncRNAs and their target mRNAs. In our study, 211 lncRNAs (P-value < 0.05) and 1125 mRNAs (P-adjust < 0.05) were significantly differentially expressed (DE) between two groups. Moreover, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that DElncRNAs and DEmRNAs were mainly enriched in lipid metabolism, including Arachidonic acid metabolism, PPAR signaling pathway, Steroid hormone biosynthesis, Linoleic acid metabolism, Inflammatory mediator regulation of TRP channels, and Fatty acid degradation. Furthermore, we constructed lncRNA-mRNA interaction networks and protein-protein interaction (PPI) network, and verified by qRT-PCR, suggesting that increased DEIncRNAs (XLOC_063499 and XLOC_042016) may prevent HCC recurrence after surgery by upregulating on targeted cytochrome P450 (CYP) family genes in the lipid metabolism pathway, such as cyp3a16, cyp3a44, cyp2c39, cyp2c40 and cyp2c68. Overall, Our findings provided new insights for further investigation of biological function in lncRNA related HCC recurrence.

Unlocking the Uterine Code: Microbiota, Immune Cells, and Therapy for Recurrent Reproductive Failure.

The uterine microbiota has been the subject of increasing study, but its interaction with the local immune system remains unclear. Successful embryo implantation relies on endometrial receptivity, which is pivotal for immunological tolerance to fetal antigens and precise regulation of inflammatory mediators. Emerging data suggest a dynamic interplay between endometrial microflora and the immune system, making dysbiosis a potential determinant of pregnancy outcomes. Imbalances in the regulation of immune cells in the endometrium and decidua have been associated with infertility, miscarriage, and obstetric complications. A thorough comprehension of the immune system in the female reproductive tract shows potential for improving women's health and pregnancy outcomes. The objective of this study was to evaluate the patterns of endometrial microbiota in patients with recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL) and to explore their implications for endometrial immune cells and chronic endometritis (CE). Immune cells in biopsies from 107 RIF and 93 RPL patients were examined using flow cytometry. The endometrial microbial composition was analyzed using real-time polymerase chain reaction (RT-PCR). The research uncovered disrupted endometrial microbiota in most women with RIF and RPL, which was often associated with significant effects on lymphocytes, T cells, and uNK cells.

A Modern Interpretation of Cold-Heat Pattern in Traditional Medicine with a Focus on Thermo-Regulation

Cold-heat patterns (C-HPs) in Traditional East Asian Medicine are essential for individually diagnosing and treating patients. However, the concept of C-HPs and their biological mechanisms (thermoregulation) remains unclear. C-HPs studies published between January 2000 and May 2023 were retrieved from 5 databases (PubMed, Google Scholar, OASIS, Korean studies Information Service System, and Research Information Sharing Service). Among the 8,373 articles screened, 132 were included in the review and categorized. Nineteen articles were clinical studies related to traditional concept of C-HP identification, 14 studies investigated diseases affecting thermosensation or thermoregulation, and 99 studies identified candidate genes as potential markers for C-HP identification. Further analysis, including gene ontology, and gene set enrichment analysis of the candidate genes, revealed 3 primary biological processes closely associated with thermoregulation-related genes, including localization, responses to stimuli, and homeostatic processes. Notably there was a significant association between the candidate genes and inflammatory mediator regulation of transient receptor potential channels (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). A significant association between C-HPs and inflammation-related pathways across thermosensation-related and thermoregulation-related clinical and preclinical studies was observed, suggesting that the traditional concept of C-HPs should be studied further from an immunological perspective.

Bacterial diversity and metabolites: Exploring correlations with preservative properties in soybean pastes.

Soybean paste, a traditional fermented condiment, exhibits distinct quality attributes by its microbial communities. This study employed Illumina sequencing and LC-MS to scrutinize the bacterial biota and metabolome of highly preserved (HP) and easily spoiled (ES) soybean pastes. Firmicutes were prevalent in both pastes, with HP showcasing greater microbial α-diversity compared to ES pastes. Bacillus predominated in HP pastes, whereas Lactobacillus was most abundant in ES pastes. Significant metabolic differences were observed between HP and ES samples in lipids, peptides, nucleic acids, secondary metabolite biosynthesis, protein digestion, amino acid metabolism, inflammatory mediator regulation, and neomycin, kanamycin, and gentamicin biosynthesis. Lactobacillus exhibited positive associations with daidzein and 3,4,5-trihydroxypentanoylcarnitine, whereas Bacillus showed negative correlations with 1,n6-ethenoadenosine, 2-deoxy-2,3-dehydro-n-acetyl-neuraminic acid, 3,4,5-trihydroxypentanoyl carnitine, and fructosyl valine. These findings highlight the collaborative impact of bacterial communities and metabolites on soybean paste quality attributes. This research enhances our comprehension of preservation mechanisms in fermented foods, particularly soybean pastes. PRACTICAL APPLICATION: The investigation would provide insights into the soybean pastes fermentation, safe and quality control methods, bio-preservative development strategies, and so on of soybean pastes for related studies and the consumers. Bacteria and their metabolites could be used to optimize the fermentation processes for the preservative and safe regulations.

Integrating transcriptomics and metabolomics to elucidate the mechanism by which taurine protects against DOX-induced depression.

Doxorubicin (DOX) is an effective anticancer drug with potent antitumour activity. However, the application of DOX is limited by its adverse reactions, such as depression. Taurine can alleviate depression induced by multiple factors. However, it is still unclear whether and how taurine improves DOX-induced depression. To address this question, the aim of this study was to explore the potential mechanism by which taurine protects against DOX-induced depression. Mice were randomly divided into three groups (n = 8): (1) the control group, (2) the DOX group, and (3) the DOX + taurine group. The open field test (OFT), elevated plus maze test, and forced swim test (FST) were first performed to assess the effects of DOX and taurine on the behaviour of mice. Next, a combined transcriptomic and metabolomic analysis was performed to analyse the possible antidepressive effect of taurine. Taurine pretreatment increased the total distance travelled and speed of mice in the OFT, increased the number of entries into the open arm and the time spent in the open arm, and reduced the immobility time in the FST. In addition, 179 differential genes and 51 differentially abundant metabolites were detected in the DOX + taurine group compared to the DOX group. Furthermore, differential genes and differentially abundant metabolites were found to be jointly involved in 21 pathways, which may be closely related to the antidepressant effect of taurine. Taurine alleviated DOX-induced depressive behaviour. The various pathways identified in this study, such as the serotonergic synapse and the inflammatory mediator regulation of TRP channels, may be key regulatory pathways related to depression and antidepressant effects.

Exploration the mechanism of Shenling Baizhu San in the treatment of chronic obstructive pulmonary disease based on UPLC-Q-TOF-MS/MS, network pharmacology and in vitro experimental verification

Ethnopharmacological relevanceShenling Baizhu San (SLBZS) is a formula of traditional Chinese medicine (TCM) that enhances the functions of the qi, spleen, and lung. According to the theory of TCM, chronic obstructive pulmonary disease (COPD) is often caused by lung qi deficiency, and SLBZS is often used in the treatment of COPD and has achieved remarkable results. However, the active components of SLBZS absorbed in serum and the underlying mechanism of SLBZS in treating COPD remain unclear and require further studies. Aim of the studyThe objective of this study is to investigate the active components of SLBZS in rat serum, as well as the crucial targets and signaling pathways involved in the therapeutic effects of SLBZS for COPD. Materials and methodsFirst, the absorption components and metabolites of SLBZS in rat serum were identified using ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Second, potential targets of SLBZS for the treatment of COPD were acquired from publicly accessible online sources. Cytoscape (v3.7.0) software was used to construct a component-target-pathway network and a protein-protein interaction (PPI) network. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of potential targets was performed using the Metascape database. The binding status of the active components in SLBZS to the potential targets was assessed with molecular docking technology. Finally, a cell model of COPD was successfully developed for experimental validation In vitro. ResultsA total of 108 active components were identified, including 30 prototype components and 78 metabolites. A total of 292 potential targets for the treatment of COPD were identified, including TNF, IL-6, TLR9, RELA, and others. The KEGG pathway included inflammatory mediator regulation of TRP channels, necroptosis, and the NF-κB signaling pathway, among others. The In vitro experiments showed that SLBZS-containing serum had the ability to decrease the levels of inflammatory factors and cell death. Additionally, it was observed that SLBZS-containing serum could control the expression levels of TLR9, MyD88, TRAF6, NF-κB, and IκBα at the mRNA and protein levels. These findings suggested that SLBZS-containing serum was likely to be involved in the regulation of the TLR9/NF-κB pathway. ConclusionsThe mechanism of action of SLBZS on COPD was preliminarily elucidated using UPLC-Q-TOF-MS/MS, network pharmacology, and In vitro experiments. The primary active components and potential targets of SLBZS were identified, providing a scientific foundation for further research.

Effects of chronic triclosan exposure on nephrotoxicity and gut microbiota dysbiosis in adult mice

Triclosan (TCS), a broad-spectrum, lipophilic, and antibacterial agent, has been commonly used in cosmetics, medical devices, and household products. The toxicity of TCS has recently become a research hotspot. Emerging evidence has shown that TCS can easily migrate to humans and animals and cause adverse effects on various target organs. However, the effects of TCS exposure on nephrotoxicity and underlying mechanisms remain unknown. The aim of the present study was to explore TCS-induced nephrotoxicity. Therefore, we establish a mouse model based on adult male mice to explore the effects of 10-week TCS exposure (50 mg/kg) on kidney. After mice were sacrificed, their blood, feces, and renal tissues were harvested for further analysis. We found that TCS treatment dramatically caused kidney structural damage, and increased blood urea nitrogen (BUN) and creatinine (Cr) expression levels, which indicated renal dysfunction. In addition, TCS exposure increased the malondialdehyde (MDA) and decreased superoxide dismutase (SOD) and total cholesterol (TCHO) expression levels, which indicated oxidative stress and lipid metabolism changes. The RNA sequencing (RNA-seq) of kidney tissue identified 221 differentially expressed genes (DEGs) enriched in 50 pathways, including drug metabolism-other enzymes, oxidative phosphorylation, glutathione metabolism, and inflammatory mediator regulation of TRP channels signaling pathways. The full-length 16S rRNA gene sequencing results showed that TCS exposure altered the community of gut microbiota, which was closely related to renal function damage. The above findings provide new insights into the mechanism of TCS-induced nephrotoxicity.

Blood Transcriptome Analysis Provides Responsive Changes in Gene Expression between Ex Situ and Captive Yangtze Finless Porpoises (Neophocaena asiaeorientalis asiaeorientalis)

The Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis, YFP) is an endangered species endemic to the Yangtze River in China, and it is the only freshwater whale in the genus Neophocaena. In terms of protection, three effective conservation strategies exist: in situ conservation, ex situ conservation, and artificial breeding, all of which have been implemented by the Chinese government. Of these, ex situ conservation involves the relocation of Yangtze finless porpoises to semi-natural waters with less human interference, and artificial breeding involves the relocation of Yangtze finless porpoises to a controlled environment that is more strictly managed. To compare and analyze the responsive changes in gene expression of the YFPs between the ex situ and controlled environments, we performed the RNA sequencing of blood tissues from these YFPs. A total of 1201 differentially expressed genes (DEGs) were identified, of which 423 were up-regulated in the ex situ population and 778 were up-regulated in the controlled-environment population. Gene enrichment analysis showed that 1201 DEGs between the ex situ and controlled-environment populations were generally enriched for vision-, digestion- and immune-system-related pathways. Further analysis revealed that several key immune system pathways, such as the chemokine signaling pathway and B cell receptor signal pathway, were activated in the ex situ population. In addition, the key pathways related to vision, including phototransduction and the inflammatory mediator regulation of TRP channels, as well as the pathways related to the digestive system, such as protein digestion and absorption and salivary secretion, were activated in the controlled-environment population. These results suggest that the ex situ populations may respond to complex environmental conditions in semi-natural waters by enhancing their immune function through the increased expression of immune-related genes and that the visual function and protein digestion of the YFPs were improved compared to those of the ex situ population based on the conditions of artificial feeding, such as the higher transparency of the water and regular feeding. This study provides clues for evaluating the adaptability of YFPs to different environments and is a useful reference for future ex situ conservation and artificial breeding.

Network Analysis and Experimental Verification of the Mechanisms of Hydroxysafflor Yellow A in Ischemic Stroke Following Atherosclerosis

Hydroxysafflor yellow A (HSYA) is derived from Carthamus tinctorius L. (Honghua in Chinese) and is used to treat cardiovascular and cerebrovascular disease. However, the mechanism by which HSYA treats ischemic stroke following atherosclerosis (ISFA) remains unclear. The targets and pathways of HSYA against ISFA were obtained using network analysis. A total of 3335 potential IFSA-related targets were predicted using the GenCards and Drugbank databases, and a total of 88 potential HSYA-related targets were predicted using the Swiss Target Prediction database. A total of 62 HSYA-related targets against IFSA were obtained. The network was composed of HSYA, 62 targets, and 20 pathways. The top 20 targets were constructed via the protein–protein interaction (PPI) network. Gene Ontology analysis revealed that the targets were involved in signal transduction, protein phosphorylation, the cytoplasm, the plasma membrane, the cytosol, zinc ion binding, ATP binding, protein kinase binding/activity, and enzyme binding. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the pathways were associated with cancer, inflammatory mediator regulation of the transient receptor potential channels, and microRNA in cancer. Additionally, molecular docking indicated that HSYA mainly interacts with five targets, namely interleukin 1 beta (IL-1β), signal transducer and activator of transcription 3 (STAT3), E1A-binding protein p300 (EP300), protein kinase C alpha (PRKCA), and inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB). In animal experiments, HSYA administration ameliorated the infarct size, neurological deficit score, histopathological changes, carotid intima-media thickness (IMT), and blood lipid level (total cholesterol and triglycerides). Immunochemistry and quantitative PCR showed that HSYA intervention downregulated the expression of STAT3, EP300, PRKCA, and IKBKB, and the enzyme-linked immunoassay showed reduced IL-1β levels. The findings of this study provide a reference for the development of anti-ISFA drugs.

In-depth analyses of lncRNA and circRNA expression in the hippocampus of LPS-induced AD mice by Byu d Mar 25.

Byu d Mar 25 (BM25) has been verified to have neuroprotective effects in Alzheimer's disease (AD) mice. However, the molecular mechanism remains unclear. We aimed to investigate the expression profiling of lncRNAs and circRNAs by microarray analysis. Six hippocampus from LPS-mediated AD mice model treated with (normal saline (NS) (n = 3) and AD mice model treated with BM25 (n = 3) were selected. Microarray analysis was performed to detect the expression profiles of lncRNAs and circRNAs in hippocampus. Differentially expressed (DE) lncRNAs, mRNAs and circRNAs were identified through scatter plot and volcano plot filtering with a threshold of fold-change ≥2 and P ≤ 0.05. Co-expression network is analyzed by Circos software. Cis - and Trans - regulation were analyzed using RIsearch-2.0 and FEELNC softwares. LncRNA-transcription factors (TFs) and LncRNA-Target-TFs network were analyzed by Clusterprofiler software. The prediction of miRNAs bind to circRNAs were performed with miRNAbase. A total of 113 DElncRNAs, 117 DEmRNAs, and 4 DEcircRNAs were detected. The pathway analysis showed the mRNAs that correlated with lncRNAs were involved in apoptosis, inflammatory mediator regulation of TRP channels, NF-kappa B and PI3K-Akt signaling pathway. The lncRNA-TFs network analysis suggested the lncRNAs were mostly regulated by Ncoa1, Phf5a, Klf6, Lmx1b, and Pax3. Additionally, lncRNA-target-TFs network analysis indicated the GATA6, Junb, Smad1, Twist1, and Mafb mostly regulate the same lncRNAs: XR_001783430.1 and NR_051982.1. Furthermore, 480 miRNAs were predicted binding to 4 identified circRNAs. The BM25 may affect AD by regulating the expression of lncRNAs and circRNAs, which could regulate the expressions of mRNAs or miRNAs by LncRNA-Target-TFs network.

Targeted screening of inflammatory mediators in spontaneous degenerative disc disease in dogs reveals an upregulation of the tumor necrosis superfamily.

The regulation of inflammatory mediators in the degenerating intervertebral disc (IVD) and corresponding ligamentum flavum (LF) is a topic of emerging interest. The study aimed to investigate the expression of a broad array of inflammatory mediators in the degenerated LF and IVD using a dog model of spontaneous degenerative disc disease (DDD) to determine potential treatment targets. LF and IVD tissues were collected from 22 normal dogs (Pfirrmann grades I and II) and 18 dogs affected by DDD (Pfirrmann grades III and IV). A qPCR gene array was used to investigate the expression of 80 inflammatory genes for LF and IVD tissues, whereafter targets of interest were investigated in additional tissue samples using qPCR, western blot (WB), and immunohistochemistry. Tumor necrosis factor superfamily (TNFSF) signaling was identified as a regulated pathway in DDD, based on the significant regulation (n-fold ± SD) of various TNFSF members in the degenerated IVD, including nerve growth factor (NGF; -8 ± 10), CD40LG (464 ± 442), CD70 (341 ± 336), TNFSF Ligand 10 (9 ± 8), and RANKL/TNFSF Ligand 11 (85 ± 74). In contrast, TNFSF genes were not significantly affected in the degenerated LF compared to the control LF. Protein expression of NGF (WB) was significantly upregulated in both the degenerated LF (4.4 ± 0.5) and IVD (11.3 ± 5.6) compared to the control group. RANKL immunopositivity was significantly upregulated in advanced stages of degeneration (Thompson grades IV and V) in the nucleus pulposus and annulus fibrosus of the IVD, but not in the LF. DDD involves a significant upregulation of various TNFSF members, with tissue-specific expression profiles in LF and IVD tissues. The differential involvement of TNFSF members within multiple spinal tissues from the same individual provides new insights into the inflammatory processes involved in DDD and may provide a basis to formulate hypotheses for the determination of potential treatment targets.

A Network Pharmacology Prediction and Molecular Docking-Based Strategy to Explore the Potential Pharmacological Mechanism of Astragalus membranaceus for Glioma.

Glioma treatment in traditional Chinese medicine has a lengthy history. Astragalus membranaceus, a traditional Chinese herb that is frequently utilized in therapeutic practice, is a component of many Traditional Chinese Medicine formulas that have been documented to have anti-glioma properties. Uncertainty persists regarding the molecular mechanism behind the therapeutic effects. Based on results from network pharmacology and molecular docking, we thoroughly identified the molecular pathways of Astragalus membranaceus' anti-glioma activities in this study. According to the findings of the enrichment analysis, 14 active compounds and 343 targets were eliminated from the screening process. These targets were mainly found in the pathways in cancer, neuroactive ligand-receptor interaction, protein phosphorylation, inflammatory response, positive regulation of phosphorylation, and inflammatory mediator regulation of Transient Receptor Potential (TRP) channels. The results of molecular docking showed that the active substances isoflavanone and 1,7-Dihydroxy-3,9-dimethoxy pterocarpene have strong binding affinities for the respective targets ESR2 and PTGS2. In accordance with the findings of our investigation, Astragalus membranaceus active compounds exhibit a multicomponent and multitarget synergistic therapeutic impact on glioma by actively targeting several targets in various pathways. Additionally, we propose that 1,7-Dihydroxy-3,9-dimethoxy pterocarpene and isoflavanone may be the main active ingredients in the therapy of glioma.

Hong Kong Guangdong Rheumatology Meeting

Rheumatoid arthritis (RA) is an autoimmune disorder that has been associated with the gut microbiota. However, whether and how the gut microbiota plays a pathogenic role in RA remains unexplored. Here, we observed that Fusobacterium nucleatum is enriched in RA patients and positively associated with RA severity. F. nucleatum similarly aggravates arthritis in a mouse model of collagen-induced arthritis (CIA). F. nucleatum outer membrane vesicles (OMVs) containing the virulence determinant FadA translocate into the joints, triggering local inflammatory responses. Specifically, FadA acts on synovial macrophages, resulting in the activation of the Rab5a GTPase involved in vesicle trafficking and inflammatory pathways and YB-1, a key regulator of inflammatory mediators. OMVs containing FadA and heightened Rab5a-YB-1 expression were observed in RA patients compared with controls. These findings suggest causal role of F. nucleatum in aggravating RA and provide promising therapeutic targets for clinically ameliorating RA.

Interaction between Rumen Epithelial miRNAs-Microbiota-Metabolites in Response to Cold-Season Nutritional Stress in Tibetan Sheep.

Tibetan sheep are already well adapted to cold season nutrient stress on the Tibetan Plateau. Rumen, an important nutrient for metabolism and as an absorption organ in ruminants, plays a vital role in the cold stress adaptations of Tibetan sheep. Ruminal microbiota also plays an indispensable role in rumen function. In this study, combined multiomics data were utilized to comprehensively analyze the interaction mechanism between rumen epithelial miRNAs and microbiota and their metabolites in Tibetan sheep under nutrient stress in the cold season. A total of 949 miRNAs were identified in the rumen epithelium of both cold and warm seasons. A total of 62 differentially expressed (DE) miRNAs were screened using FC > 1.5 and p value < 0.01, and a total of 20,206 targeted genes were predicted by DE miRNAs. KEGG enrichment analysis revealed that DE miRNA-targeted genes were mainly enriched in axon guidance(ko04360), tight junction(ko04530), inflammatory mediator regulation of TRP channels(ko04750) and metabolism-related pathways. Correlation analysis revealed that rumen microbiota, rumen VFAs and DE miRNAs were all correlated. Further study revealed that the targeted genes of cold and warm season rumen epithelial DE miRNAs were coenriched with differential metabolites of microbiota in glycerophospholipid metabolism (ko00564), apoptosis (ko04210), inflammatory mediator regulation of TRP channels (ko04750), small cell lung cancer (ko05222), and choline metabolism in cancer (ko05231) pathways. There are several interactions between Tibetan sheep rumen epithelial miRNAs, rumen microbiota, and microbial metabolites, mainly through maintaining rumen epithelial barrier function and host homeostasis of choline and cholesterol, improving host immunity, and promoting energy metabolism pathways, thus enabling Tibetan sheep to effectively respond to cold season nutrient stress. The results also suggest that rumen microbiota have coevolved with their hosts to improve the adaptive capacity of Tibetan sheep to cold season nutrient stress, providing a new perspective for the study of cold season nutritional stress adaptation in Tibetan sheep.