Immune Processes Research Articles

Critical Role of S100A9 in Sepsis-associated Acute Kidney Injury: Mechanistic Insights through Pyroptosis Pathway Modulation.

This study investigates the role of S100A9 in sepsis-associated AKI (SA-AKI) through the lens of pyroptosis, a controlled form of cell death mediated by the gasdermin protein family. Using C57BL/6 mice and S100A9 knockout mice subjected to cecal ligation and puncture (CLP), RNA sequencing and bioinformatics analyses revealed differentially expressed genes (DEGs) related to inflammation and immune responses, with notable upregulation of S100A9. Functional enrichment analyses (GO and KEGG) indicated these DEGs are involved in interferon-beta response, immune processes, and cell adhesion. Protein-protein interaction (PPI) network analyses further emphasized S100A9's pivotal role in SA-AKI.Clinical validation measured S100A9 levels in serum and urine samples from SA-AKI patients and healthy volunteers, finding elevated S100A9 levels in the former. In vivo experiments showed that S100A9 knockout mice exhibited reduced kidney injury and inflammation, indicated by lower serum creatinine, urea nitrogen, and inflammatory markers (IL-1β and IL-18). Histopathological analyses and immunohistochemistry confirmed less renal damage and reduced expression of cleaved IL-1β and GSDMD-N in S100A9-deficient mice. Electron microscopy and Western blotting validated that S100A9 deficiency mitigates caspase-1-dependent pyroptosis.Cellular experiments with HK-2 cells demonstrated that S100A9 knockdown alleviated LPS-induced cell damage and reduced pyroptosis markers. These findings illuminate S100A9's involvement in NLRP3 inflammasome activation and pyroptosis, suggesting potential therapeutic targets for SA-AKI. Targeting S100A9 may offer new therapeutic avenues, improving outcomes for sepsis-related kidney injury patients. Future research should aim to validate these findings in larger clinical settings.

Deoxynivalenol-Induced Spleen Toxicity in Mice: Inflammation, Endoplasmic Reticulum Stress, Macrophage Polarization, and the Dysregulation of LncRNA Expression.

The spleen is a primary target of deoxynivalenol (DON) toxicity, but its underlying molecular mechanisms remain unclear. This study investigates the effects of DON on inflammation, splenic macrophage polarization, endoplasmic reticulum (ER) stress, and transcriptome changes (mRNA and lncRNAs) in mouse spleen. We found that DON exposure at doses of 2.5 or 5 mg/kg BW significantly induced inflammation and polarized splenic macrophages towards the M1 phenotype. Additionally, DON activated PERK-eIF2α-ATF4-mediated ER stress and upregulated apoptosis-related proteins (caspase-12, caspase-3). The ER stress inhibitor, 4-Phenylbutyric acid, significantly alleviated DON-induced ER stress, apoptosis, and the M1 polarization of splenic macrophages. Transcriptome analysis identified 1968 differentially expressed (DE) lncRNAs and 2664 DE mRNAs in mouse spleen following DON exposure. Functional enrichment analysis indicated that the upregulated genes were involved in pathways associated with immunity, including Th17 cell differentiation, TNF signaling, and IL-17 signaling, while downregulated mRNAs were linked to cell survival and growth pathways. Furthermore, 370 DE lncRNAs were predicted to target 255 DE target genes associated with immune processes, including the innate immune response, interferon-beta response, cytokine production regulation, leukocyte apoptosis, and NF-κB signaling genes. This study provides new insights into the mechanisms underlying DON toxicity and its effects on the immune system.

Gut Microbiota and Its Connection to Neurological Disorders - summary of current knowledge

Introduction and Purpose: The gut microbiota plays a crucial role not only in absorption, metabolic, and immune processes but also increasingly in shaping behavior and is strongly linked to the gut-brain axis. Different sections of the digestive system, due to varying environmental conditions and physiological functions, have a unique microbiota composition, both quantitatively and qualitatively, including bacteria, fungi, and archaea. This study aims to review current scientific research on the impact of the gut microbiome on the gut-brain axis and to explore how this influence may affect neurological disorders. Brief Description of the State of Knowledge: Dysbiosis in the digestive system leads to changes in the composition of the gut microbiome, which can significantly impact the development and progression of various mental health conditions, as indicated by numerous clinical studies examining the gut-brain axis correlation. The main challenge is the insufficient understanding of which microorganisms within the human microbiota have positive or negative effects on mental health. Therefore, further research is needed to better elucidate these mechanisms. Summary: Neurological disorders are a common challenge in clinical practice. Evaluating gut microbiota and metabolic states may provide valuable diagnostic and therapeutic insights, potentially improving patients' quality of life. Materials and Evidence: A literature review was conducted using the PubMed database.

Causal relationship between oral microbiota and epilepsy risk: Evidence from Mendelian randomization analysis in East Asians.

Gut microbiota can traverse into the brain, activate the vagus nerve, and modulate immune responses and inflammatory processes, thereby influencing the onset of epileptic seizures. However, research on oral microbiota and epilepsy remains limited, and observational studies have been inconsistent. We aim to estimate the potential links between oral microbiota and epilepsy and elucidate which specific oral microbes may directly influence the pathogenesis of epilepsy. A two-sample MR analysis was conducted using genome-wide association study (GWAS) data specific to OM and epilepsy in East Asian individuals. Single nucleotide polymorphisms (SNPs) independent of confounders served as instrumental variables (IVs) to deduce causality. MR methodologies, including inverse variance weighted (IVW), MR-Egger, weighted median, and weighed mode methods, were utilized. Sensitivity analysis, including Cochrane's Q test, MR-Egger intercept test, and leave-one-out analysis, was applied to confirm the robustness of results. Among the 3117 bacterial taxa examined, we observed that 14 OM, like s_Streptococcus_mitis, s_Streptococcus_pneumoniae, and s_Haemophilus, were positively associated with epilepsy, while 7 OM, like g_Fusobacterium and g_Aggregatibacter, were negatively related to epilepsy. The MR-Egger intercept suggested that no evidence of horizontal pleiotropy was observed (p > 0.05). The leave-one-out analysis validated the robustness of the results. This study underscores the effect of OM on epilepsy, suggesting potential mechanisms between the OM and epilepsy. Further investigation into the potential role of the OM is needed to enhance our in-depth understanding of the pathogenesis of epilepsy. Previous research has demonstrated that the microbiota may influence the onset of epileptic seizures. We applied 3117 oral microbiota from the newest publicly available database of East Asian populations. Mendelian randomization analysis was utilized to estimate the causal relationship between oral microbiota and epilepsy. Our results showed that a causal effect exists between 21 oral microbiota and epilepsy. We provided genetic evidence for risk assessment and early intervention in epilepsy.

Gut microbiota-related modulation of immune mechanisms in post-infarction remodelling and heart failure.

The immune system has long been recognized as a key driver in the progression of heart failure (HF). However, clinical trials targeting immune effectors have consistently failed to improve patient outcome across different HF aetiologies. The activation of the immune system in HF is complex, involving a broad network of pro-inflammatory and immune-modulating components, which complicates the identification of specific immune pathways suitable for therapeutic targeting. Increasing attention has been devoted to identifying gut microbial pathways that affect cardiac remodelling and metabolism and, thereby impacting the development of HF. In particular, gut microbiota-derived metabolites, absorbed by the host and transported to the peripheral circulation, can act as signalling molecules, influencing metabolism and immune homeostasis. Recent reports suggest that the gut microbiota plays a crucial role in modulating immune processes involved in HF. Here, we summarize recent advances in understanding the contributory role of gut microbiota in (auto-)immune pathways that critically determine the progression or alleviation of HF. We also thoroughly discuss potential gut microbiota-based intervention strategies to treat or decelerate HF progression.

Immunologic aspects of asthma: from molecular mechanisms to disease pathophysiology and clinical translation.

In the present review, we focused on recent translational and clinical discoveries in asthma immunology, facilitating phenotyping and stratified or personalized interventions for patients with this condition. The immune processes behind chronic inflammation in asthma exhibit marked heterogeneity, with diverse phenotypes defining discernible features and endotypes illuminating the underlying molecular mechanisms. In particular, two primary endotypes of asthma have been identified: "type 2-high," characterized by increased eosinophil levels in the airways and sputum of patients, and "type 2-low," distinguished by increased neutrophils or a pauci-granulocytic profile. Our review encompasses significant advances in both innate and adaptive immunities, with emphasis on the key cellular and molecular mediators, and delves into innovative biological and targeted therapies for all the asthma endotypes. Recognizing that the immunopathology of asthma is dynamic and continuous, exhibiting spatial and temporal variabilities, is the central theme of this review. This complexity is underscored through the innumerable interactions involved, rather than being driven by a single predominant factor. Integrated efforts to improve our understanding of the pathophysiological characteristics of asthma indicate a trend toward an approach based on disease biology, encompassing the combined examination of the clinical, cellular, and molecular dimensions of the disease to more accurately correlate clinical traits with specific disease mechanisms.

Effect of Moniezia Benedeni infection on ileal transcriptome profile characteristics of sheep

BackgroundThe intestinal mucosal immune system, renowned for its precise and sensitive regulation, can provide comprehensive and effective protection for the body, among which the ileum is a critical induction site for regulating mucosal immune homeostasis. Moniezia benedeni parasitizes the small intestine of sheep and can cause serious pathological damage or even death to the host when the infection is severe. In this study, 5 sheep infected with Moniezia benedeni were selected as the infected group, and 5 uninfected sheep were selected as the control group. The ileal transcriptome profile characteristics of Moniezia benedeni infection were analyzed based on RNA-seq sequencing technology, aiming to lay a foundation for further exploring the perception mechanism of sheep intestines to Moniezia benedeni infection and formulating effective prevention and control strategies.ResultsThe results showed that a total of 3,891 differentially expressed genes (DEGs) were detected in the ileum tissues of sheep between the infected and control groups with 2,429 up-regulated genes and 1,462 down-regulated genes. GO and KEGG pathway enrichment analysis of differential genes, as well as Clue GO analysis showed that differential genes were significantly enriched in immune and metabolic-related biological processes and signaling pathways. Particularly, in immune-related signaling pathways, the B cell receptor signaling pathway was significantly down-regulated, while in metabolic regulation related signaling pathways, Bile secretion, Fat digestion and absorption and Vitamin digestion and absorption were notably up-regulated. On this basis, the differential core genes related to immune metabolism were verified by qRT-PCR method. The results showed that OVAR, CD3E, CD8A, CD4 and CD28 were significantly up-regulated (P < 0.05), while CIITA, BLNK, BCL6 and CD79A were significantly down-regulated (P < 0.05), which were consistent with transcriptome sequencing data.ConclusionsThe results demonstrated that Moniezia benedeni infection significantly affected the immune and metabolic processes in sheep ileum, particularly, it significantly inhibited the activation process of host B cells, and also led to an overactive function of bile acid metabolism. This finding provides a solid foundation for further elucidating the response mechanism of Peyer's patches in sheep ileum to Moniezia tapeworm infection.

Ion-Engineered Clay Nanozyme via Tumor Microenvironment Remodeling for Enhanced Tumor Therapy.

Metal ions show tremendous promise for tumor therapy due to their critical roles in many important catalytic circulations and immune processes. However, the valence state variability and systemic side-effects of metal ions cause ineffective ion enrichment in tumor cells, which limit their further application. Here, a Mn3+ ion delivery system (Mn-HNT) is constructed based on halloysite nanotubes (HNT) via an ion-engineered strategy. Due to the stabilizing effect of HNT on Mn3+ ions, Mn-HNT not only maintained the valence state of Mn3+ ions, but also presented strong catalase (CAT)- and glutathione oxidase (GSHOx)-like catalytic activity to catalyze O2 generation and GSH consumption to relieve the inhibition of tumor microenvironment on photodynamic therapy (PDT). After further coordination with the photosensitizer porphyrin (TCPP), obtained TCPP-Mn-HNT not only inherited the catalytic properties of Mn-HNT to produce oxygen and consume GSH, but acted as photosensitizer for ROS accumulation to effectively destroy tumor cells. Moreover, TCPP-Mn-HNT can promote the maturation of dendritic cells (≈2.8 times), and present the tumor antigen triggered by PDT to T cells to strengthen high-efficient tumor therapy. The study provides new opportunities for designing metal ion delivery system with versatile biofunctions and offers a paradigm of synergistic metal-ion-mediated tumor therapy.

Decoding the intricacies: a comprehensive analysis of microRNAs in the pathogenesis, diagnosis, prognosis and therapeutic strategies for COVID-19.

The pandemic of coronavirus disease-19 (COVID-19), provoked by the appearance of a novel coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), required a worldwide healthcare emergency. This has elicited an immediate need for accelerated research into its mechanisms of disease, criteria for diagnosis, methods for forecasting outcomes, and treatment approaches. microRNAs (miRNAs), are diminutive RNA molecules, that are non-coding and participate in gene expression regulation post-transcriptionally, having an important participation in regulating immune processes. miRNAs have granted substantial interest in their impact on viral replication, cell proliferation, and modulation of how the host's immune system responds. This narrative review delves into host miRNAs' multifaceted roles within the COVID-19 context, highlighting their involvement in disease progression, diagnostics, and prognostics aspects, given their stability in biological fluids and varied expression profiles when responding to an infection. Additionally, we discuss complicated interactions between SARS-CoV-2 and host cellular machinery facilitated by host miRNAs revealing how dysregulation of host miRNA expression profiles advances viral replication, immune evasion, and inflammatory responses. Furthermore, it investigates the potential of host miRNAs as therapeutic agents, whether synthetic or naturally occurring, which could be harnessed to either mitigate harmful inflammation or enhance antiviral responses. However, searching more deeply is needed to clarify how host's miRNAs are involved in pathogenesis of COVID-19, its diagnosis processes, prognostic assessments, and treatment approaches for patients.

Exercise-Induced Proteomic Profile Changes in Patients with Advanced Heart Failure.

The pathophysiological background of the processes activated by physical activity in patients with heart failure (HF) is not fully understood. Proteomic studies can help to preliminarily identify new protein markers for unknown or poorly defined physiological processes. We aimed to analyse the changes in the plasma proteomic profile of HF patients after a cardiopulmonary exercise test (CPET) to define pathways involved in the response to exercise. The study prospectively enrolled 20 male patients with advanced HF (aged 53.3 ± 8.3 years). Blood samples were taken from the patients before and immediately after the CPET to obtain plasma proteomic profiles. Two-sample t-tests (paired or non-paired) were performed with and without false discovery rate (FDR) correction for multiple testing. Enrichment analysis was performed to associate biological processes and pathways with the study results. A total of 968 plasma proteins were identified, of which 722 underwent further statistical analysis. Of these, 236 proteins showed differential expression when comparing all plasma samples collected before and after CPT (p < 0.05), and for 86 of these the difference remained statistically significant after FDR correction. Proteins whose expression changed after exercise are mostly involved in immune response and inflammatory processes, coagulation, cell adhesion, regulation of cellular response to stimulus and regulation of programmed cell death. There were no differences in resting proteomics according to HF etiology (ischemic vs. non-ischemic). Changes in the proteomic profile revealed a complexity of exercise-induced processes in patients with HF, suggesting that few major physiological pathways are involved. Further studies focusing on specific pathways are needed.

Tracing troubles: Unveiling the hidden impact of inorganic contamination on juvenile green sea turtle

Human activities and climate change have negatively affected the world's oceans, leading to a decline of 30 to 60 % in coastal ecosystems' biodiversity and habitats. The projected increase in the human population to 9.7 billion by 2050 raises concerns about the sustainability of marine ecosystem conservation and exploitation. Marine turtles, as sentinel species, accumulate contaminants, including trace elements, due to their extensive migration and long-life span. However, there is a lack of data on the degree of contamination and their effects on marine turtles' health. This study focuses on assessing in-situ inorganic contamination in juvenile green sea turtles from La Réunion Island and its short-term impact on individual health, using conventional biomarkers and proteomics. The goals include examining contamination patterns in different tissues and identifying potential new biomarkers for long-term monitoring and conservation efforts. The study identified differential metal contamination between blood and scute samples, which could help illuminate temporal exposure to trace elements in turtle individuals. We also found that some conventional biomarkers were related to trace element exposure, while the proteome responded differently to various contaminant mixtures. Immune processes, cellular organization, and metabolism were impacted, indicating that contaminant mixtures in the wild would have an effect on turtle's health. Fifteen biomarker candidates associated with strong molecular responses of sea turtle to trace element contamination are proposed for future long-term monitoring. The findings emphasize the importance of using proteomic approaches to detect subtle physiological responses to contaminants in the wild and support the need for non-targeted analysis of trace elements in the biomonitoring of sea turtle health.

Proteomic analysis of plasma-derived extracellular vesicles: pre- and postprandial comparisons

Extracellular vesicles (EVs) are key in intercellular communication, carrying biomolecules like nucleic acids, lipids, and proteins. This study investigated postprandial characteristics and proteomic profiles of blood-derived EVs in healthy individuals. Twelve participants fasted overnight before baseline assessments. After consuming a controlled isocaloric meal, EVs were isolated for proteomic and flow cytometric analysis. Plasma triacylglyceride levels confirmed fasting completion, while protein concentrations in plasma and EVs were monitored for postprandial stability. Proteomic analysis identified upregulated proteins related to transport mechanisms and epithelial/endothelial functions postprandially, indicating potential roles in physiological responses to nutritional intake. Enrichment analyses revealed vesicle-related pathways and immune system processes. Flow cytometry showed increased expression of CD324 on CD9+CD63+CD81+ large extracellular vesicles postprandially, suggesting an epithelial origin. These findings offer valuable insights into postprandial EV dynamics and their potential physiological significance, highlighting the need for stringent fasting guidelines in EV studies to account for postprandial effects on EV composition and function.

The indispensability of methyltransferase-like 3 in the immune system: from maintaining homeostasis to driving function.

Methyltransferase-like 3(METTL3), recognized as the primary N6-methyladenosine methyltransferase, influences cellular functions such as proliferation, migration, invasion, differentiation, and fate determination by regulating gene expression post-transcriptionally. Recent studies have highlighted the indispensability of METTL3 in various immune cells such as hematopoietic stem/progenitor cells, innate immune cells (monocytes, macrophages, dendritic cells), and adaptive immune cells (thymic epithelial cell, T cells, natural killer cells). However, a comprehensive summary and analysis of these findings to elucidate the relationship between METTL3 and the immune system is yet to be undertaken. Therefore, in this review, we systematically collate reports detailing the mechanism underlying the role of METTL3 in regulating various immune processes and examine the modification of METTL3 and its potential implications. This review suggests that METTL3 plays an essential role in the immune system, ranging from maintaining homeostasis to regulating functions. Collectively, this review provides a comprehensive analysis of the relationship between METTL3 and the immune system, serving convenient researchers to understand the frontiers of immunological research and facilitate future clinical applications.

MICROBIOLOGICAL CHARACTERISTICS OF THE ORAL MUCOSAIN PATIENTS WITH LICHEN PLANUS ERYTHEMATOSUS

Lichen planus is a multifactorial disease that involves immune, neuroendocrine, microbiological, and other metabolic processes associated with skin and mucosal damage. The microflora of the oral cavity in CPL SOPR was studied by E. S. Leontieva etal., 2014, the microbiocenosis of various biotopes of the oral cavity in patients with CPL SOPR was studied. The study involved 95 patients with CPL SOPR, who underwent hygienic, periodontal and microbiological research methods. The results of the degree of bacterial contamination indicate a more pronounced colonization of foci of CPL lesion by representatives of the coccoid flora: Streptococcus salivares and Streptococcus mutans, but there is no correlation between them. Isolated Streptococcus Sanguis colonies were observed in 55% of patients. In addition, fungi of the genus Candida albicans were detected in 50%, the average level of adhesion of Candida albicans strains in patients with CPL was 16.78±1.64%. The frequency of detection of fungi of the genus Candida albicans in foci of CPL lesion correlates (r=0.79) with the activity of the disease course. The significance of Candida albicans contamination is determined not so much by the degree of contamination of the lesion foci, but by such pathogenic properties of Candida albicansas the level of adhesion and the activity of germination tubes formation [1,2,3,6,11,2,3,6,11]. Authors Chuikin S. V., Akmalova G. M., Chernysheva N. D., 2014, analyzed the qualitative and quantitative microbiocenosis of the oral cavity in patients with CPL. The study included 145 patients with CPL aged 21 to 76 years, of whom 5% were men and 95% were women. The predominant form of CPL was erosive-ulcerative form (33.1%), the lowest frequency was observed in 2% of patients with bullous form. The results of the study showed that dysbiotic changes were observed with a predominance of candida infection and were found in 57.2% of the examined patients, which are observed more often in erosive-ulcerative and bullous forms of CPL. The results of the study showed that all the examined patients had microbiocenosis disorders of varying severity from dysbiotic shift to IYgrade IY dysbiosis and high sensitivity to bacteriophages was revealed. It should be noted that high sensitivity of pathogenic and opportunistic microorganisms sown in дисбактериозахoral dysbiosis was detected to цефалоспориногоcephalosporin antibiotics (100%), oxacillin (79%), gentamicin (76%), lincomycin (73%). [5,7,9,12]. A number of foreign authors Villa (TG, Sá ncheznchez-Pérez rez Á, Sieiro C., 2021) believe that microbial infection triggers an autoimmune response. Withdysbiosisof the intestinal microbiota , there is a violationof the integrity of the intestinal barrier, followed by an increase in intestinal permeability, and the penetration микроорганизмof microorganisms and their toxinов into the circulatory system. Current knowledge about this disease requires the inclusion of this disease in the list of autoimmune diseases, since the progression of CPL involves colonization of locally affected areas by bacteria, fungi or viruses that occur after damage to the oral mucosa and skin. The process of healing the disease should include eliminating microbial dysbiosis and restoring the normal microbiota of the oral mucosa, skin, and intestines. [4,6,8,10,13,14].

Integrative Analysis of Acupuncture Targets and Immune Genes in Diabetes, Diabetic Peripheral Neuropathy, and Adjunct Therapy of Cancer.

Acupuncture may help treat diabetes mellitus (DM), diabetic peripheral neuropathy (DPN), and adjunct therapy for cancer, but the biological mechanisms and immune-related genes involved are unclear; this study aims to clarify these aspects. Comprehensive gene expression analysis revealed differentially expressed genes (DEGs) among DM, DPN, and control samples. Key genes from WGCNA were intersected with DEGs and acupuncture targets. Inflammatory responses, immune processes, signaling pathways, immune cell infiltration, and microRNA-gene interactions were studied. Hub immune-related genes' dysregulation was analyzed for copy number variation and gene methylation. A pan-cancer nomogram model was created to predict survival based on various factors, linking hub genes to cancer properties. Our analysis found 3,217 and 2,191 DEGs in DM/control and DPN/DM comparisons, respectively, and identified 1,830 potential acupuncture targets. We pinpointed 21 key genes in DM and 43 in DPN, involved in inflammatory responses, immune processes, CAMKK2, and cAMP signaling pathways. Distinct immune cell infiltration patterns, including M0 and M2 macrophages, neutrophils, and follicular helper T cells, were noted. Further analysis revealed microRNAs and TF genes interacting with immune hub genes in both conditions. Dysregulation of eight hub immune-related genes was linked to copy number variation and gene methylation, correlating with cancer prognosis. Co-occurrence of single nucleotide variations and oncogenic mutations was observed in these genes. The pan-cancer nomogram model showed strong prognostic capabilities, and a significant association was found between the eight genes and cancer properties like angiogenesis, EMT, and cell cycle progression. Our findings underscore the pivotal roles of MAPK3, IL1RN, SOD2, CTSD, ESR1, SLC1A1, NPY, and CCR2 in the immune response mediated by acupuncture in the context of DM, DPN, and adjunct therapy for cancer.

Unraveling the Molecular Mechanisms of OSA-Related Cardiovascular Event Recurrence: A Post Hoc Analysis From the ISAACC Study

RationaleAlthough obstructive sleep apnea (OSA) is a prevalent condition among patients with acute coronary syndrome (ACS), the impact of OSA on cardiovascular event (CVE) recurrence is not homogeneous. We previously defined a specific phenotype of first-ACS patients without previous cardiovascular disease who are at increased risk of OSA-related CVE recurrence. However, the pathobiological mechanisms whereby OSA leads to adverse cardiovascular outcomes in this singular ACS phenotype remain to be investigated. ObjectiveTo characterize the molecular pathways that relate OSA with CVE recurrence. MethodsThis post hoc analysis of the ISAACC study (NCT01335087) included subjects without previous cardiovascular disease who were hospitalized for a first ACS and developed a recurrent CVE during the follow-up. Patients underwent respiratory polygraphy and fasting blood extraction during hospitalization. Two study groups were established on the basis of the apnea–hypopnea index (AHI): untreated severe OSA (AHI≥30events/h) and non-OSA (AHI<15events/h) groups. Proteomic profiling analysis included 276 cardiovascular and inflammatory-related plasma proteins via Olink® technology. ResultsProteomics was performed in 58 patients (77.6% male, median [p25;p75] age 58.0 [51.2;65.8] years, and median BMI 28.6 [25.8;31.2]kg/m2). Thirty patients had severe OSA, and 28 subjects were considered non-OSA controls. A total of 24 plasma proteins were differentially expressed between the groups. Among these proteins, 18 were significantly associated with OSA severity parameters derived from respiratory polygraphy. Further bioinformatic analyses of OSA-related proteins revealed their involvement in several molecular pathways, mostly related to immune function, cell signaling, and inflammatory processes. ConclusionA specific proteomic profile related to OSA presence and severity was identified in the plasma of ACS patients who developed recurrent CVEs. This analysis suggests the activation of key OSA-mediated molecular pathways with potential implications for cardiovascular prognosis.

Yi-Fei-San-Jie Chinese medicine formula reverses immune escape by regulating deoxycholic acid metabolism to inhibit TGR5/STAT3/PD-L1 axis in lung cancer

BackgroundYi-Fei-San-Jie Formula (YFSJF), a proprietary medicine of the First Affiliated Hospital of Guangzhou University of Chinese Medicine, has been widely used in clinical practice for several years and is currently being tested in randomized controlled trials for early-stage lung cancer in China. However, the mechanisms by which YFSJF affects lung cancer biology, particularly the immune microenvironment and metabolic processes, remain poorly understood. PurposeThis study aims to explore how YFSJF modulates the immune microenvironment and metabolism in lung cancer, specifically its unique role in inhibiting immune evasion by targeting the TGR5/STAT3/PD-L1 pathway, which has not previously been reported. MethodsComputed Tomography (CT) scan was used to assess YFSJF efficacy in patients with lung cancer and a mouse model of urethane-induced lung cancer. Histopathological evaluation, flow cytometry, and metabolomic analysis were used to assess lung tissue structure, immune cell subset changes, and metabolism modulation, respectively. Western blotting and immunohistochemistry were used to detect Ki67, TTF-1, TGR5, STAT3, p-STAT3, and PD-L1 protein expression. Serum cytokines were detected by ELISA. ResultsYFSJF effectively reduced the size of human lung cancer lesions and decreased the tumor burden and improved survival rates in mice. Lung tissue structure was also improved after YFSJF treatment. YFSJF regulated T-cell subsets, particularly by downregulating cells with PD-1-positive expression of CD3+, CD4+, and CD8+, and elevated serum TNF-α, IFN-γ, and GzmB levels. In addition, YFSJF modulated bile acid metabolism, particularly by inhibiting deoxycholic acid metabolism, which participates in immune regulation in lung cancer by acting on the G protein-coupled bile acid receptor TGR5. ConclusionFinally, YFSJF inhibited immune evasion by blocking the TGR5-mediated STAT3/PD-L1 pathway, weakening PD-L1 and PD-1 binding and reviving T-cell immune activity, thereby countering lung cancer immune evasion and exerting anti-tumor effects.

The genetic composition of Anopheles mosquitoes and the diverse population of gut-microbiota within the Anopheles subpictus and Anopheles vagus mosquitoes in Tamil Nadu, India

In recent days, in tropical and subtropical regions, secondary vectors of Anopheles mosquitoes are becoming more important in transmitting diseases to humans as primary vectors. Various molecular techniques have separated closely related Anopheles subpictus and Anopheles vagus mosquitoes based on their diversity with other mosquito species. Despite their widespread distribution, the An. subpictus and An. vagus mosquitoes, which carry Plasmodium in their salivary glands, were not considered primary malaria vectors in India. An. vagus mosquitoes are zoophilic and physically similar to An. subpictus. We intend to identify An. subpictus and An. vagus mosquito's sister species based on their Interspaced Transcribed Region-2 (ITS2). We isolated the midgut gDNA from each mosquito and used ITS2-PCR and Sanger sequencing to characterize the mosquito species. BioEdit software aligned the sequences, and MEGA7 built a phylogenetic tree from them. According to this study, the information gathered from these mosquito samples fits the An. subpictus species A form and the An. vagus Indian form. Furthermore, gut microbiome plays an important role in providing nutrients, immunity, and food processing, whereas mosquitoes' midgut microbiota changes their hosts and spreads illnesses. So, we used the Illumina sequencer to look at the gut microbiome diversity of An. subpictus and An. vagus mosquitoes using 16S rRNA-based metagenomic sequencing. Both mosquito species had an abundant phylum of Pseudomonadota (Proteobacteria), Bacillota, Bacteroidota, and Actinomycetota in their gut microbiomes. Notably, both mosquito species had the genus Serratia in their gut. In the subpictus midgut, the genus of Haematosprillum bacteria was dominant, whereas in the vagus mosquito, the genus of Salmonella was dominant. Notably, current research has observed the Sodalis spp. Bacterial genus for the first time.

ZBP1 as a prognostic biomarker correlated with cell proliferation in clear cell renal cell carcinoma

BackgroundZ-DNA-binding protein 1 (ZBP1) is a critical Z-DNA- and Z-RNA-binding protein. However, its diagnostic and prognostic significance, as well as its functions in clear cell renal cell carcinoma (ccRCC), are not well understood. Materials and methodsPaired and unpaired differential expression analyses of ZBP1 were performed in pan-cancer cells. Receiver operating characteristic (ROC) curves and survival analyses were used to evaluate the clinical significance of ZBP1. Functional enrichment and immune infiltration analyses were used to explore the mechanisms underlying ZBP1 expression. Western blotting, qRT-PCR, CCK-8, and colony formation assays were used to investigate the potential function of ZBP1 in ccRCC cells. Molecular docking was utilized to identify drugs targeting ZBP1. ResultsZBP1 was highly expressed in ccRCC, demonstrating significant diagnostic and prognostic value. ZBP1 mRNA expression correlated with TNM stage, pathologic stage, and histologic grade. Functional enrichment analyses indicated that ZBP1 is involved in multiple immune processes. Moreover, ZBP1 mRNA expression was positively correlated with the infiltrating levels of T cells and cytotoxic cells, and negatively correlated with the infiltrating levels of mast cells and Th17 cells in ccRCC. Biological experiments confirmed that ZBP1 promotes ccRCC cell proliferation. Molecular docking studies identified rucaparib as a potential drug targeting ZBP1. ConclusionOur research findings suggest that targeting ZBP1 could represent a novel therapeutic approach to inhibit the progression of ccRCC.

Multilevel and geographically weighted regression analysis of factors associated with full immunization among children aged 12–23 months in Ethiopia

Immunization is the process of building immunity or resistance to an infectious disease, typically through administering a vaccine. It is one of the most effective strategies for lowering child morbidity and death. It protects against more than 20 potentially fatal diseases, increasing longevity and health. Despite progress, Ethiopia failed to meet its vaccination coverage target. The magnitude of full immunization is different across areas. Therefore, conducting geographically weighted regression to identify the local factors and multilevel analysis to investigate and identify factors associated with full immunization coverage among children aged 12–23 months is necessary. The study was conducted using the 2019 Ethiopian Mini Demographic Health Survey dataset. A sample of 1028 weighted children aged 12–23 months were included in the analysis. Descriptive statistics were used to describe variables. For the spatial analysis, Arc-GIS version 10.8 statistical software was used. Spatial regression (geographically weighted regression) was done to identify factors associated with the proportion of full immunization, and model comparison was based on adjusted R2 and Akaike Information Criteria (AICc). Multilevel mixed-effect binary logistic regression models were fitted to identify factors associated with full immunization. The fitted models were compared based on log-likelihood, deviance, median odds ratio, and Proportional Change in Variance. Finally, statistically significant factors were reported using an adjusted odd ratio (AOR) with a 95% Confidence Interval for fixed effect. All variables with a p-value less than 0.05 in the final model were considered statistically significant factors. In Ethiopia, the overall full immunization coverage among children aged 12–23 months was 40.58%, with spatial variation across regions in Ethiopia. The significant spatial distribution of full immunization coverage among children aged 12–23 months was detected in northern Tigray, Addis Ababa, central Oromia, and southeastern Amhara regions. The proportion of rural residents,the proportion of women aged 35–44 years, the proportion of women who had ANC 4 and above andthe proportion of women who had PNC were local factors associated with the proportion of full immunization among children aged 12–23 months. Rural residence [AOR 0.27 (95% CI 0.10, 0.70)], family size 4 and above[AOR 0.41 (95% CI 0.17, 0.96)], never breastfeed [AOR 0.026(95% CI 0.003, 0.21)], 1–3 times ANC visit [AOR 0.45 (95% CI 0.23, 0.86)], being from Oromia region [AOR 0.23 (95% CI 0.05, 0.97)], Eastern pastoralist region [AOR 0.09 (95% CI 0.023, 0.35)], age 35–44 years [(AOR 6 (95% CI 1.57, 22.9)], and PNC [AOR 2.40 (95% CI 1.24, 4.8)] were significant factors associated with fully immunization in multilevel mixed effect analysis. Full immunization coverage in Ethiopia is below the global target with significant geographical variation. The high proportion of rural residents, the high proportion of women who had ANC 4 and above, mothers who had a high proportion of PNC, and the high proportion women age 35-44 years were local geographical factors for the proportion of full immunization among children age 12–23 months in Ethiopia. Women who had PNC, ANC visits four or more times, and increased maternal age were positively associated, whereas larger family size, no breastfeeding, rural residence, and being from Oromia and eastern pastoralist region were negatively associated with full immunization. Strengthening maternal and child health services, focusing on rural areas and low-coverage regions, is essential to increase immunization coverage in Ethiopia.