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关键词： Porphyromonas gingivalis(P.gingivalis)   Benign prostatic hyperplasia(BPH)   Periodontitis   Oral pathogens   Inflammation  

摘要： Background:Benign prostatic hyperplasia(BPH)is the most common disease in elderly *** is increasing evidence that periodontitis increases the risk of BPH,but the specific mechanism remains *** study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis(***)in the development of ***:The subgingival plaque(Sp)and prostatic fluid(Pf)of patients with BPH concurrent periodontitis were extracted and cultured for 16S r DNA ***-induced periodontitis,testosterone-induced BPH and the composite models in rats were *** *** and its toxic factor *** lipopolysaccharide(***)were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate.P.g-LPS was used to construct the prostate cell infection model for mechanism ***:***,Streptococcus oralis,Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Sp and Pf of patients with BPH concurrent periodontitis,and the average relative abundance of *** was found to be the *** was detected in both Sp and Pf in 62.5%of *** periodontitis and BPH synergistically aggravated prostate histological *** and *** infection could induce obvious hyperplasia of the prostate epithelium and stroma(epithelial thickness was 2.97-fold and 3.08-fold that of control group,respectively),and increase of collagen fibrosis(3.81-fold and 5.02-fold that of control group,respectively).*** infection promoted prostate cell proliferation,inhibited apoptosis,and upregulated the expression of inflammatory cytokines interleukin-6(IL-6;4.47-fold),interleukin-6 receptor-α(IL-6Rα;5.74-fold)and glycoprotein 130(gp130;4.47-fold)in prostatic tissue.P.g-LPS could significantly inhibit cell apoptosis,promote mitosis and proliferation of cells.P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 co

关键词： Endothelial cells   Monocytes   Anthocyanins   Phenolic metabolites   Inflammation  

摘要： PurposeIn this study we investigated how anthocyanins and their metabolites exert protection on the vasculature by reducing the inflammation-induced monocyte adhesion to endothelial cells, a fundamental stage in endothelial dysfunction (ED) and *** umbilical vein endothelial cells (HUVECs) were pre-treated with varying concentrations (1,5 and 10 mu M) of cyanidin-3-glucoside or phenolic metabolites, protocatechuic acid (PCA) and vanillic acid (VA), for 24 h, followed by TNF-alpha stimulation for 24 h, with or without the presence of THP-1 monocytes for 1 *** the co-culture model, the adhesion of fluorescent monocytes attached to HUVECs was quantified, as well as pro-inflammatory cytokine IL-6 and MCP-1 in cell supernatant. Expression levels of transcription factors Nrf2 and NF-kappa B-p65, as well as vascular cell adhesion molecule-1 (VCAM-1), intracellular cell adhesion molecule (ICAM-1) and heme oxygenase 1 (HO-1) were measured in HUVECs. All treatments prevented the adhesion of monocytes to endothelial cells, which was associated with reductions in IL-6 and MCP-1. Additionally, phenolic metabolites suppressed adhesion molecules, potentially by their ability to upregulate Nrf2 expression and suppress NF-kappa B p65 phosphorylation. Furthermore, VA caused an upregulation of HO-1 *** findings suggest that pre-exposed physiologically relevant concentrations of phenolic metabolites may hinder ED and inflammation by reducing the adhesion of monocytes to endothelial cells and the inflammatory response via the modulation of NF-kappa B and Nrf2 pathway.

关键词： ROR gamma t   Tc17   Immunotherapy   HCC   CD8+T cells  

摘要： While interferon-alpha (IFN-alpha) demonstrates potent antineoplastic activity against hepatocellular carcinoma (HCC), but many patients have a low response rate and may even develop resistance to it. It is necessary to find new strategies to reduce IFN-alpha resistance and improve its efficacy. RAR-related orphan receptor gamma t (ROR gamma t) agonists exhibit dual immunomodulatory functions, demonstrating both immunosuppression-reducing and immune-activating properties. In this study, we demonstrated that the combination of the ROR gamma t agonist-LYC-55716 and IFN-alpha significantly promoted cytotoxic T cell 17 (Tc17 cell) differentiation and interleukin-17a (I1-17a) expression through activation of the Akt/Stat3 signal pathway. The combination therapy markedly enhanced the tumoricidal activity of differentiated Tc17 cells against hepatoma carcinoma cells. Moreover, this therapeutic strategy showed superior antitumor efficacy in multiple HCC models while maintaining a favorable safety profile compared to single-agent treatment. Importantly, our findings revealed that the combination treatment significantly enhanced CD8+ T cells infiltration into tumor tissues. Moreover, our mechanistic studies revealed that the observed synergistic antitumor effect was mediated by enhanced CD8+ T cell tumor infiltration, which was facilitated by the C-X-C motif chemokine ligand 10 (Cxcl10)-C-X-C motif chemokine receptor 3 (Cxcr3) interaction. Collectively, these findings support a novel immunoregulatory strategy that leverages ROR gamma t agonists to enhance the efficacy of IFN-alpha in HCC therapy.

关键词： Human leukocyte antigen (HLA)   Genetic polymorphisms   Magnetic resonance imaging (MRI)   Brain imaging   Multiple sclerosis (MS)  

摘要： This systematic review and meta-analysis synthesizes current evidence on associations between genetic polymorphisms of human leukocyte antigen (HLA) class I and II molecules, which play key roles in antigen presentation and immune response regulation, and brain imaging phenotypes across various neurological and psychiatric conditions. The strongest associations were observed in multiple sclerosis (MS), where HLADRB1*15:01 was linked to increased lesion volume and disease progression. Meta-analyses revealed significant pooled effect sizes for both T1 and T2 lesion volumes. Emerging evidence also suggests that variants in HLA class I and II genes contribute to brain structural changes associated with age-related cognitive decline, schizophrenia, and Gulf War illness. Our findings revealed stronger patterns of association between HLA class II polymorphisms with brain imaging implications as compared to class I in neurodegenerative conditions. Considering HLA class II roles in exogenous protein/peptide presentation, this highlights the potential importance of neuroimmune-environmental interactions as contributing factors to disease pathogenesis and progression. Population-based studies from the UK Biobank highlight the potential influence of HLA class I and II genetic polymorphisms on brain structure beyond disease-specific contexts, suggesting broader implications for neurodevelopment and neurodegeneration. Despite these emerging insights, the limited availability of studies using imaging modalities beyond structural MRI, along with inconsistent findings within specific diseases and across conditions, underscores the need for further investigation into the mechanistic contributions of specific genetic variants on impacting brain structural and functional outcomes. Future research should include larger, more diverse study cohorts and employ advanced genotyping technologies to provide a more comprehensive investigations of HLA's role on brain health across the lifespan.

关键词： Subarachnoid hemorrhage   G -protein-coupled receptor 40   NLRP3 inflammasome   Neuroinflammation   IL-1 beta   Exosome  

摘要： Subarachnoid hemorrhage is one type of strokes with high mortality and disability and there exists several mechanisms in SAH pathology. G-protein-coupled receptor 40 (GPR40) is proven to exert anti-inflammatory effects in several central nervous system (CNS) diseases. However, the precise role of GPR40 in SAH pathogenesis remains largely unknown. In this study, both in vivo and in vitro SAH models were used to investigate the mechanism of GPR40 attenuating neuroinflammation after SAH onset. We found that GPR40 expression in microglia decreased, which promoted IL-1 beta secretion and aggravated neuronal death after SAH onset. The GPR40 agonist GW9508 attenuated neuronal damage and ameliorated neurological deficits in SAH-model mice. Mechanistically, GPR40 in microglia inhibited pyroptosis, and cytokine production via inhibiting NLRP3/caspase-1/IL-1 beta pathway. Then the level of IL-1 beta secreted by microglia and transported to neurons via exosome were decreased, which down-regulated glutaminase, counteracted glutamate accumulation, and facilitated neuronal survival. These results revealed that GPR40 is a novel regulator that inhibits microglia-mediated neuroinflammation and is a potential therapeutic target in SAH therapy.

关键词： Pelteobagrus fulvidraco   Interleukin 21   Interleukin 21 receptor   Molecular cloning   Gene expression   Intestinal immunity  

摘要： Interleukin 21 (IL-21) is a member of the IL-2 family and a pleiotropic cytokine that exerts its effects by binding to its receptor complex (IL-21R alpha and gamma chain). Due to the critical role and multifunctionality of IL-21, its functions have been extensively studied in mammals;however, there has been limited research on IL-21 in teleosts. In this study, the cDNA sequences of Pf_IL-21, Pf_IL-21R alpha.1, Pf_IL-21R alpha.2, Pf_gamma c1 and Pf_gamma c2 genes were cloned from yellow catfish (Pelteobagrus fulvidraco). Four alpha-helices and two q-helices were found in Pf_IL-21, one alpha-helices and three q-helices were found in Pf_IL-21R alpha.1/2, and four alpha-helices and three q-helices were found in Pf_gamma c1/2. Quantitative real-time PCR analysis revealed high levels of mRNA expressions of Pf_IL-21 and its four receptors in mucosal and immune-related tissues of healthy yellow catfish. The mRNA expressions of these five genes in peripheral blood leukocytes (PBLs) were found to be regulated after stimulation with lipopolysaccharides (LPS), phytohaemagglutinin (PHA) and polyinosinic-polycytidylic acid (Poly I:C). Following Edwardsiella ictaluri infection, the mRNA expressions of these genes were significantly up-regulated in peripheral blood, hindgut, swim bladder, and other mucosal or immune-related tissues. In addition, the impact of recombinant (r) Pf_IL-21 protein on the intestinal microbiota and histological structure following E. ictaluri infection was examined. The results showed that E. ictaluri infection resulted in a decline in intestinal microbiota richness and diversity, while Fusobacteriota and Cetobacterium abnormally increased, and hindgut exhibited significant pathological alterations. However, the injection of rPf_IL-21 led to a restoration of intestinal microbiota richness and diversity, accompanied by an increase in certain beneficial bacteria and a better recovery of the hindgut structure. These findings suggest that Pf_IL-21 and its four

关键词： SVM classifier   Biosensor   IL-10 protein detection   LPFG   Mach-Zehnder interferometer  

摘要： Currently, techniques such as machine learning (ML), derived from great technological progress, play a fundamental role in different areas, from finance, marketing, security, education, transportation to science and health. The latter, with the growth in the development of sensors and biosensors, technological tools such as ML allow systems to learn, extract, analyze and classify useful information from the signals they receive. Biosensors, being devices that convert biological signals into quantifiable data, generate a large volume of information, which becomes difficult to interpret manually, but can be processed more efficiently through ML. Support vector machine (SVM), is a supervised machine learning technique, used for classification, regression and even outliers detection, especially useful in the context of biosensors to classify them into different biological states forming a discriminant analysis. This work focuses on the study of SVM as a classifying technique, applied to optical fiber biosensors for the detection of Interleukin 10 (IL-10) due to its role as a neuroprotector protein. Serum samples from ischemic, and ischemic treated with estradiol benzoate (EB) male rats were evaluated at 2 h post-ischemia. In this work we show the performance of SVM on the measured responses of three optical fiber biosensor that are based on a tapered, long period grating and Mach-Zehnder interferometer. The results demonstrate that SVM technique is a good alternative to determine the IL-10 expression on serum sample of a murine model.

关键词： Peanut hypersensitivity   food hypersensitivity   anaphy-   laxis   genetic association study   HLA antigens   MHC   racial groups  

摘要： Background: Peanut is a major cause of food allergy. HLA genes have been consistently associated with peanut allergy in association studies. To date, however, there have been very few genetic studies of peanut allergy in non-Hispanic Black (Black) individuals, a group disproportionately affected by food allergy. Objective: Our aim was to study the relationship between HLA alleles and peanut allergy among Black individuals. Methods: The analysis consisted of Black participants from the Study of Asthma-Related Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity (SAPPHIRE), a large cohort of individuals from metropolitan Detroit. At the time of enrollment, participants provided detailed food allergy histories, including symptoms. Four-digit resolution HLA allele calls were made using whole genome sequence data. Results: The cases consisted of 119 individuals with reported peanut allergy and 59 individuals with peanut-related anaphylaxis;the comparison group consisted of 2640 individuals without reported food allergy. HLA-DRB1*13:02 was the most significant allele associated with peanut allergy (adjusted odds ratio = 1.94 [95% CI = 1.28-2.93]), and HLA-DQA1*01:02 was the top association with peanut-related anaphylaxis (aOR = 1.67 [95% CI = 1.14-2.44]). Amino acid polymorphisms at position 71 in the binding groove of HLADRB1 were associated with peanut allergy and estimated to affect peanut allergen binding affinity. Conclusions: In a cohort of Black individuals, this study independently identified the same associations of peanut allergy and HLA that were previously observed in non-Hispanic White individuals. Our findings suggest that specific HLA binding groove amino acid polymorphisms may confer similar peanut allergy risk across population groups and HLA alleles. Allergy Clin Immunol Global 2025;4:100485.)

关键词： TGEV   IFN   IFIT3   TBK1   STAT1  

摘要： TGEV mainly infects pig small intestinal epithelium, resulting in vomiting, diarrhea, dehydration, and death. IFIT3 is involved in resisting viral infection and is an innate immune regulator. In this study, we determined that TGEV infection could induce IFIT3 expression. The overexpression of IFIT3 inhibited TGEV infection, promoted the phosphorylation of TBK1 and STAT1, and upregulated the transcription of IFN-beta and interferon-stimulated genes (ISGs). Conversely, knockdown of IFIT3 decreased the activation of the interferon immune response. Blocking the JAK-STAT1 pathway inhibited the transmission of interferon signals and reversed the restriction of IFIT3 to TGEV infection. Immunoprecipitation revealed that IFIT3 interacted with TBK1 and STAT1, indicating that TBK1 and STAT1 are key molecules through which IFIT3 regulates the interferon immune response and inhibits TGEV infection. This study preliminarily revealed that IFIT3 regulated the innate immune response to inhibit TGEV infection, enriching the theoretical understanding of the interaction between TGEV and the host.

关键词： Nanomaterials   Green synthesis   In-silico analysis   Rheumatoid arthritis   TNF-a  

摘要： Nanotechnology is widely recognised as one of the most important advances in science from the last decades. Its numerous applications and rapidly expanding demand have led the way for innovative approaches to the synthesis of nanomaterials of higher quality. Green synthesis of silver nanoparticles (AgNPs) using the Dimorphocalyx glabellus (Sny. Tritaxis glabella Thwaites *** & Welzen var. glabella) which has many medicinal properties including treatment of psoriasis and it also has anti-diabetic, anti-diuretic and anti-rheumatic property. The present study assessed with methanolic extract leaves of D. glabellus and its characterization through GC-MS analysis to identify the phyto-constituents. Moreover, AgNPs were synthesized using the leaf extract of D. glabellus and subsequently characterized using UV-Vis Spectrophotometer, Scanning Electron Microscope (SEM), and Fourier Transform Infrared Spectroscopy (FTIR) techniques to verify the formation of AgNPs within the plant extract. The analysis of FTIR spectra revealed the presence of various functional groups such as carboxyl, amine, and phenolic compounds which play a vital role in the reduction of silver ions in the leaf extract of D. glabellus. Furthermore, the phyto-constituents compounds in the plant extract were studied in-silico for possible interaction with TNF-alpha, vital for rheumatoid arthritis and other diseases. This suggests the potential use of these phyto-constituents of D. glabellus as a natural remedy for the treatment of Rheumatoid Arthritis, offering a promising alternative to traditional medications. (c) 2025 SAAB. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.