Immune-related Conditions Research Articles

Interactions of human milk oligosaccharides with the immune system

Human milk oligosaccharides (HMOs) are abundant, diverse and complex sugars present in human breast milk. HMOs are well-characterized barriers to microbial infection and by modulating the human microbiome they are also thought to be nutritionally beneficial to the infant. The structural variety of over 200 HMOs, including neutral, fucosylated and sialylated forms, allows them to interact with the immune system in various ways. Clinically, HMOs impact allergic diseases, reducing autoimmune and inflammatory responses, and offer beneficial support to the preterm infant immune health. This review examines the HMO composition and associated immunomodulatory effects, including interactions with immune cell receptors and gut-associated immune responses. These immunomodulatory properties highlight the potential for HMO use in early stage immune development and for use as novel immunotherapeutics. HMO research is rapidly evolving and promises innovative treatments for immune-related conditions and improved health outcomes.

The detection, function, and therapeutic potential of RNA 2'-O-methylation

<p>RNA modifications play crucial roles in shaping RNA structure, function, and metabolism. Their dysregulation has been associated with many diseases, including cancer, developmental disorders, cardiovascular diseases, as well as neurological and immune-related conditions. A particular type of RNA modification, 2'-O-methylation (Nm) stands out due to its widespread occurrence on all four types of nucleotides (A, U, G, C) and in most RNA categories, e.g., mRNA, rRNA, tRNA, miRNA, snRNA, snoRNA, and viral RNA. Nm is the addition of a methyl group to the 2' hydroxyl of the ribose moiety of a nucleoside. Given its great biological significance and reported association with many diseases, we first reviewed the occurrences and functional implications of Nm in various RNA species. We then summarized the reported Nm detection methods, ranging from biochemical techniques in the 70’s and 80’s to recent methods based on Illumina RNA sequencing, artificial intelligence (AI) models for computational prediction, and the latest nanopore sequencing methods currently under active development. Moreover, we discussed the applications of Nm in the realm of RNA medicine, highlighting its therapeutic potential. At last, we present perspectives on potential research directions, aiming to offer insights for future investigations on Nm modification.</p>

Revolutionizing the Potential of Probiotics an Evidence-Based Review

Background Probiotics, which are live microorganisms beneficial to human health, have garnered significant attention in recent years due to their potential therapeutic and preventive effects on various health conditions. The human gut microbiota, comprising trillions of microorganisms, plays a crucial role in digestion, metabolism, immune function, and overall health. Disruptions in the gut microbiota have been associated with various diseases, including gastrointestinal disorders, metabolic syndrome, immune-related conditions, and even mental health disorders. Objective The objective of conducting an evidence-based review on the potential of probiotics is to assess their efficacy, safety, and mechanisms of action in various health conditions. Methods A literature search was conducted in PubMed, Scopus, along EBSCO databases. The topics include " Probiotics", " History", " Composition", " Clinical significance, Prevention ", or " Recent advancements,". Results This involves gathering and analyzing scientific research, clinical trials, and meta-analyses to evaluate the effects of probiotics on specific health outcomes. The review aims to provide an unbiased synthesis of available evidence to inform healthcare professionals, researchers, and policymakers about the role of probiotics in disease prevention, treatment, and maintenance of overall health. Key objectives may include: Conclusion In conclusion, an evidence-based review on probiotics aims to assess their efficacy, safety, and mechanisms of action across various health conditions. By synthesizing scientific research and clinical trials, such reviews provide valuable insights into the role of probiotics in disease management, overall health promotion, and potential adverse effects. Through rigorous analysis, these reviews inform healthcare professionals, researchers, and policymakers about the appropriate use of probiotics to optimize health outcomes.

Glycan analysis probes inspired by human lectins for investigating host-microbe crosstalk.

Human lectins are critical carbohydrate-binding proteins that recognize diverse glycoconjugates from microorganisms and can play a key role in host-microbe interactions. Despite their importance in immune recognition and pathogen binding, the specific glycan ligands and functions of many human lectins remain poorly understood. Using previous proof-of-concept studies on selected lectins as the foundation for this work, we present ten additional glycan analysis probes (GAPs) from a diverse set of human soluble lectins, offering robust tools to investigate glycan-mediated interactions. We describe a protein engineering platform that enables scalable production of GAPs that maintain native-like conformations and oligomerization states, equipped with functional reporter tags for targeted glycan profiling. We demonstrate that the soluble GAP reagents can be used in various applications, including glycan array analysis, mucin-binding assays, tissue staining, and microbe binding in complex populations. These capabilities make GAPs valuable for dissecting interactions relevant to understanding host responses to microbes. The tools can be used to distinguish microbial from mammalian glycans, which is crucial for understanding the cross-target interactions of lectins in a physiological environment where both glycan types exist. GAPs have potential as diagnostic and prognostic tools for detecting glycan alterations in chronic diseases, microbial dysbiosis, and immune-related conditions.

Perceiving immunity, predicting somatic symptoms: Validation of the'Perceived Immunity' scale and its association with daily health.

While ample research links health beliefs to physical health in both healthy and clinical populations, the specific health beliefs that drive this effect remain underexplored. Addressing this gap is critical for mechanistic examinations and targeted intervention development. Building on previous work, this study aimed to assess subjective beliefs about immune system efficacy and develop a novel Perceived Immunity scale. Across three studies (total N = 378; Study 1: N = 206 healthy; Study 2: N = 132 healthy and N = 40 with immune-related diseases; and Study 3: subset of N = 87 from Study 2), we examine Perceived Immunity scale's validity, reliability, and association with everyday physical health. Perceived immunity demonstrated excellent internal consistency (Cronbach alpha = 0.9), strong construct validity (all items were loaded onto one factor) and structural validity, including convergence validity with scales assessing subjective health perceptions, and discriminant validity from scales measuring external health control. These findings were replicated across different cohorts. Furthermore, regression analyses revealed significant correlations with daily physical health measures, specifically somatic symptoms, across cohorts (all β > -0.347, all p < .001) and sick leave days (all β = -0.174, all p < .045). These associations were stronger in individuals with immune-related conditions. Finally, Perceived Immunity exhibited good test-retest reliability (interclass correlation coefficient = 0.74) and prospectively predicted somatic symptoms over time (β = -0.324, p = .002), with significant results observed up to 1 year. The Perceived Immunity scale offers a valuable tool for researchers and health care providers, providing insights into the interplay between specific health beliefs and daily health. Furthermore, its validation lays the groundwork for targeted interventions that explore how health perceptions may directly influence actual physical experiences.

MOSES: a methylation-based gene association approach for unveiling environmentally regulated genes linked to a trait or disease

BackgroundDNA methylation is a critical regulatory mechanism of gene expression, influencing various human diseases and traits. While traditional expression quantitative trait loci (eQTL) studies have helped elucidate the genetic regulation of gene expression, there is a growing need to explore environmental influences on gene expression. Existing methods such as PrediXcan and FUSION focus on genotype-based associations but overlook the impact of environmental factors. To address this gap, we present MOSES (methylation-based gene association), a novel approach that utilizes DNA methylation to identify environmentally regulated genes associated with traits or diseases without relying on measured gene expression.ResultsMOSES involves training, imputation, and association testing. It employs elastic-net penalized regression models to estimate the influence of CpGs and SNPs (if available) on gene expression. We developed and compared four MOSES versions incorporating different methylation and genetic data: (1) cis-DNA methylation within 1 Mb of promoter regions, (2) both cis-SNPs and cis-CpGs, 3) both cis- and a part of trans- CpGs (±5Mb away) from promoter regions), and 4) long-range DNA methylation (±10 Mb away) from promoter regions. Our analysis using nasal epithelium and white blood cell data from the Epigenetic Variation and Childhood Asthma in Puerto Ricans (EVA-PR) study demonstrated that MOSES, particularly the version incorporating long-range CpGs (MOSES-DNAm 10 M), significantly outperformed existing methods like PrediXcan, MethylXcan, and Biomethyl in predicting gene expression. MOSES-DNAm 10 M identified more differentially expressed genes (DEGs) associated with atopic asthma, particularly those involved in immune pathways, highlighting its superior performance in uncovering environmentally regulated genes. Further application of MOSES to lung tissue data from idiopathic pulmonary fibrosis (IPF) patients confirmed its robustness and versatility across different diseases and tissues.ConclusionMOSES represents an innovative advancement in gene association studies, leveraging DNA methylation to capture the influence of environmental factors on gene expression. By incorporating long-range CpGs, MOSES-DNAm 10 M provides superior predictive accuracy and gene association capabilities compared to traditional genotype-based methods. This novel approach offers valuable insights into the complex interplay between genetics and the environment, enhancing our understanding of disease mechanisms and potentially guiding therapeutic strategies. The user-friendly MOSES R package is publicly available to advance studies in various diseases, including immune-related conditions like asthma.

Dihydroberberine alleviates Th17/Treg imbalance in premature ovarian insufficiency mice via inhibiting Rheb/mTOR signaling

BackgroundPremature ovarian insufficiency (POI) is an immune-related condition. Dihydroberberine (dhBBR) plays a regulatory role in maintaining the T-helper 17 (Th17)/regulatory T (Treg) cell balance. This study aimed to explore the action mechanisms of dhBBR on POI.MethodsIn vivo, female BALB/c mice were used as POI models, treated with dhBBR, or injected with recombinant interleukin (rIL)-17 and anti-CD25 monoclonal antibody. Hematoxylin and eosin staining was used to validate the model and assess the therapeutic effects of dhBBR. mRNA expression levels of cytochrome P450 (Cyp)-17a1, Cyp19a1, Cyp11a1, steroidogenic acute regulatory protein, and luteinizing hormone receptor in mouse ovaries were quantified via quantitative polymerase chain reaction (qPCR). Enzyme-linked immunosorbent assay was used to determine the cytokine and sex hormone levels. Immunohistochemical staining for cleaved-caspase 3 and Ki-67 were performed to assess ovarian cell apoptosis and proliferation. Flow cytometry was used to analyze the Th17/Treg cell balance in the ovary and spleen. In vitro cytotoxicity of dhBBR was measured using the cell counting kit-8 assay. GTP-Ras homolog enriched in brain (Rheb) activity was determined via immunofluorescence assay. Co-immunoprecipitation was performed to assess Rheb activity, Th17 or Treg induction, and binding between Rheb and mammalian target of rapamycin (mTOR) after dhBBR treatment. Flow cytometry and qPCR assays were used to verify the effect of dhBBR on CD4 + cell differentiation. Finally, Rheb/mTOR pathway activation was confirmed via western blotting of proteins, including mTOR, p-mTOR, p70S6K, p-p70S6K, 4E-BP1, and p-4E-BP1.ResultsdhBBR improved the ovarian function in a dose-dependent manner. It also decreased ovarian cell apoptosis and increased cell proliferation. It decreased Th1 and Th17 cell proportions but increased Treg cell proportions in the ovaries and spleens of POI model mice. Cell experiments revealed that dhBBR promoted CD4 + cell differentiation into Treg cells. Co-immunoprecipitation revealed Rheb as the dhBBR target that bound to mTOR. However, MHY1485 restored dhBBR-induced changes in forkhead box P3, IL-10, transforming growth factor-β1, IL-17, IL-22, retinoic acid-related orphan receptor-γt and p-mTOR levels in Th17- and Treg-induced CD4 + cells.ConclusionOverall, dhBBR targeted the Rheb/mTOR pathway to promote CD4 + cell differentiation into Treg cells and alleviate POI.

Unveiling the Immunomodulatory Potential of Finger Millet Components: A High-Resolution Mass Spectrometry Analysis.

Finger millet/ragi (Eleusine coracana) is recognized for its nutritional benefits and health-promoting properties, but detailed molecular insights into its bioactive components remain limited. This study employs high-resolution mass spectroscopy (HRMS) to profile the complex biochemical constituents of finger millet, focusing on identifying compounds with potential immunomodulatory effects. Through comprehensive analysis of finger millet extracts, we identified a range of bioactive molecules belonging to different classes of drugs. The data reveal five compounds with significant immunomodulatory activity, suggesting that finger millet may enhance immune system regulation and offer therapeutic potential for immune-related conditions. This research not only deepens our understanding of the molecular makeup of finger millet but also highlights its potential as a functional food with beneficial effects on immune health.

Modulation of M1/M2 Cytokines and Inflammatory Enzymes by Persicaria Species Leaf Extracts in Lipopolysaccharide-stimulated RAW 264.7 Cell Macrophages.

Investigating the impacts of plant-based substances on the regulation of pro-inflammatory M1 and anti-inflammatory M2 cytokines could have significant implications for immune-related health conditions. Seven Persicaria plant species from sub-Saharan Africa were specifically selected for analysis, based on their traditional use in treating inflammation. To investigate the inhibitory effects of methanol leaf extracts from selected plants on enzymes involved in chronic inflammation. The inhibition of nitric oxide production, acetylcholinesterase activity, and 15-lipoxygenase activity was assessed using the Griess reagent method, Ellman's colorimetric method, and the ferrous oxidation-xylenol orange assay. The quantity of M1/M2 cytokines released was quantified using a flow cytometer. At a concentration of 50 µg/mL, the methanol extracts of P. limbata exhibited the highest NO inhibition (97.67%), followed by P. nepalensis (93.06%) and P. setosula (92.78%). The NO inhibition caused by the plant extracts was correlated directly with the decrease in NO release by the LPS-stimulated macrophages. Furthermore, the pro-inflammatory enzyme assays indicated that the methanol extracts of P. setosula exhibited the highest enzyme inhibitory activity (LOX 89.59%, AChE 72.12 %). This was followed by P. limbata (with 92.76% for LOX and 56.93% for AChE) and P. nepalensis (with 88.16% for LOX and 47.17% for AChE). Cytokine assays revealed that the extracts of P. limbata had significant dose-dependent suppressive effects on IFN-γ and TNF-α expression while promoting the secretion of IL-2, IL-4, IL-6, and IL-10. Extracts of P. limbata contain immunomodulatory compounds that could be further explored as potential remedies to target the molecular drivers of chronic inflammation.

CD71 + erythroid cells promote intestinal symbiotic microbial communities in pregnancy and neonatal period

BackgroundThe establishment of microbial communities in neonatal mammals plays a pivotal role in shaping their immune responses to infections and other immune-related conditions. This process is influenced by a combination of endogenous and exogenous factors. Previously, we reported that depletion of CD71 + erythroid cells (CECs) results in an inflammatory response to microbial communities in newborn mice.ResultsHere, we systemically tested this hypothesis and observed that the small intestinal lamina propria of neonatal mice had the highest frequency of CECs during the early days of life. This high abundance of CECs was attributed to erythropoiesis niches within the small intestinal tissues. Notably, the removal of CECs from the intestinal tissues by the anti-CD71 antibody disrupted immune homeostasis. This disruption was evident by alteration in the expression of antimicrobial peptides (AMPs), toll-like receptors (TLRs), inflammatory cytokines/chemokines, and resulting in microbial dysbiosis. Intriguingly, these alterations in microbial communities persisted when tested 5 weeks post-treatment, with a more notable effect observed in female mice. This illustrates a sex-dependent association between CECs and neonatal microbiome modulation. Moreover, we extended our studies on pregnant mice, observing that modulating CECs substantially alters the frequency and diversity of their microbial communities. Finally, we found a significantly lower proportion of CECs in the cord blood of pre-term human newborns, suggesting a potential role in dysregulated immune responses to microbial communities in the gut.ConclusionsOur findings provide novel insights into pivotal role of CECs in immune homeostasis and swift adaptation of microbial communities in newborns. Despite the complexity of the cellular biology of the gut, our findings shed light on the previously unappreciated role of CECs in the dialogue between the microbiota and immune system. These findings have significant implications for human health.9S5HPFpJwLA9vyqyoAGSTRVideo

Fast Targeted Metabolomics for Analyzing Metabolic Diversity of Bacterial Indole Derivatives in ME/CFS Gut Microbiome.

Disruptions in microbial metabolite interactions due to gut microbiome dysbiosis and metabolomic shifts may contribute to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and other immune-related conditions. The aryl hydrocarbon receptor (AhR), activated upon binding various tryptophan metabolites, modulates host immune responses. This study investigates whether the metabolic diversity-the concentration distribution-of bacterial indole pathway metabolites can differentiate bacterial strains and classify ME/CFS samples. A fast targeted liquid chromatography-parallel reaction monitoring method at a rate of 4 minutes per sample was developed for large-scale analysis. This method revealed significant metabolic differences in indole derivatives among B. uniformis strains cultured from human isolates. Principal component analysis identified two major components (PC1, 68.9%; PC2, 18.7%), accounting for 87.6% of the variance and distinguishing two distinct B. uniformis clusters. The metabolic difference between clusters was particularly evident in the relative contributions of indole-3-acrylate and indole-3-aldehyde. We further measured concentration distributions of indole derivatives in ME/CFS by analyzing fecal samples from 10 patients and 10 healthy controls using the fast targeted metabolomics method. An AdaBoost-LOOCV model achieved moderate classification success with a mean LOOCV accuracy of 0.65 (Control: precision of 0.67, recall of 0.60, F1-score of 0.63; ME/CFS: precision of 0.64, recall of 0.7000, F1-score of 0.67). These results suggest that the metabolic diversity of indole derivatives from tryptophan degradation, facilitated by the fast targeted metabolomics and machine learning, is a potential biomarker for differentiating bacterial strains and classifying ME/CFS samples. Mass spectrometry datasets are accessible at the National Metabolomics Data Repository (ST002308, DOI: 10.21228/M8G13Q; ST003344, DOI: 10.21228/M8RJ9N; ST003346, DOI: 10.21228/M8RJ9N).

Psychiatric morbidity across the life course and provoked vulvodynia: is it dependent upon the presence of non-stress-related immune dysfunction?

Vulvodynia impacts up to 8% of women by age 40, and these women may have a more compromised immune system than women with no vulvar pain history. Given that psychiatric morbidity is associated with vulvodynia and is known to activate immune inflammatory pathways in the brain and systemically, we sought to determine whether the association between psychiatric morbidity and vulvar pain was independent of or dependent upon the presence of immune-related conditions. Women born in Sweden between 1973 and 1996 with localized provoked vulvodynia (N76.3) and/or vaginismus (N94.2 or F52.5) diagnosed between 2001 and 2018 were matched to two women from the same birth year with no vulvar pain. International Statistical Classification of Diseases and Related Health Problems (ICD-9 or -10 codes) were used to identify women with a history of depression, anxiety, attempted suicide, neurotic disorders, stress-related disorders, behavioral syndromes, personality disorders, psychotic disorders, or chemical dependencies, as well as a spectrum of immune-related conditions. The Swedish National Prescribed Drug Register was used to identify women with filled prescriptions of antidepressants or anxiolytics. Vulvodynia, vaginismus, or both were outcomes assessed in relation to psychiatric morbidity. Women with vulvodynia, vaginismus, or both, relative to those without vulvar pain, had adjusted odds ratios between 1.4 and 2.3, with CIs highly compatible with harmful effects. When we assessed women with and those without a lifetime history of immune-related conditions separately, we also observed elevated odds ratios in both groups for mood, anxiety, and neurotic and stress disorders. Documenting psychiatric impairment as a cause or consequence of vulvodynia is critical in clinical practice because psychiatric conditions may impact treatment efficacy. Strengths of this study include a data source that represents the entire population of women in Sweden that is known to be highly accurate because Sweden provides universal healthcare. Limitations include difficulty in making an accurate assessment of temporality between psychiatric morbidity and the first onset of vulvar pain. In addition, because Swedish registry data have limited information on lifestyle, behavioral, and anthropomorphic factors such as smoking, diet, physical activity, and obesity, these conditions could not be assessed as confounders of psychiatric morbidity and vulvar pain. Immune pathways by which women with psychiatric conditions increase their risk of vulvar pain could be independent from other immune pathways.

Changing the location of proteins on the cell surface is a promising strategy for modulating T cell functions.

Targeting immune receptors on T cells is a common strategy to treat cancer and autoimmunity. Frequently, this is accomplished through monoclonal antibodies targeting the ligand binding sites of stimulatory or inhibitory co-receptors. Blocking ligand binding prevents downstream signalling and modulates specific T cell functions. Since 1985, the FDA has approved over 100 monoclonal antibodies against immune receptors. This therapeutic approach significantly improved the care of patients with numerous immune-related conditions; however, many patients are unresponsive, and some develop immune-related adverse events. One reason for that is the lack of consideration for the localization of these receptors on the cell surface of the immune cells in the context of the immune synapse. In addition to blocking ligand binding, changing the location of these receptors on the cell surface within the different compartments of the immunological synapse could serve as an alternative, efficient, and safer approach to treating these patients. This review discusses the potential therapeutic advantages of altering proteins' localization within the immune synapse and summarizes published work in this field. It also discusses the novel use of bispecific antibodies to induce the clustering of receptors on the cell surface. It presents the rationale for developing novel antibodies, targeting the organization of signalling receptor complexes on the cell surface. This approach offers an innovative and emerging technology to treat cancer patients resistant to current immunotherapies.

Comparison of FOXP3 methylation status using three different methods

Abstract The FOXP3 gene is an X chromosome encoded transcription factor that is critical for the function of regulatory T (Treg) cells that maintain immunological self-tolerance and homeostasis. FOXP3 expression is primarily controlled by DNA methylation and the necessary development of Treg cells requires the establishment of Treg-specific DNA methylation patterns. FOXP3 and its epigenetic control genes have been associated with several immune-related conditions such as auto-immunity, asthma, food allergies and cancer. Here, we have conducted a study comparing the sensitivity to methylation status within our assays that cover FOXP3 using pyrosequencing, targeted bisulfite NGS (tbNGS), and methylation-sensitive high-resolution melting (MS-HRM) using a variety of different starting materials in both human and mice. As we transition away from pyrosequencing, we ensure that both tbNGS and MS-HRM result in methylation profiles which do not exhibit significant differences in sensitivity and accuracy to pyrosequencing, while also reducing the cost to the end user.

Macrophage GPR18 signaling activation by Resolvin D2 mediates metabolic switch and cardiac repair after myocardial infarction.

Abstract Higher inflammatory response is a major cause of heart failure and mortality post myocardial infarction (MI), a major health problem worldwide. Resolution of inflammation, well established as an actively orchestrated programmed response, is mediated by specialized pro-resolving lipid mediators (SPM) and cellular processes like efferocytosis. Resolvin D2 (RvD2), one such potent SPM, is expressed in leukocytes and stimulates the resolution of inflammation through signaling by its receptor GPR18. RvD2 signaling attenuates inflammation in immune-related conditions through macrophage (Mφ) cell-intrinsic and extrinsic mechanisms. The therapeutic potential of SPM has been demonstrated in treatment of sepsis and arthritis. However, the role of Mφ RvD2-GPR18 signaling in heart post-MI has not been elucidated. Here, we demonstrate (i) induction of GPR18 receptor on cardiac Mφ, (ii) &amp;gt;50% reduction in survival of myeloid- and Mφ-specific GPR18-/- mice, (iii) reduced heart function in GPR18-/- mice post-MI, (iv) a GPR18-dependent suppression of TLR4 signaling cytokines, and (v) suppression of TLR4-induced glycolytic metabolism by RvD2-GPR18 signaling in vitro in Mφ from human GPR18 chimeric adult mice. To summarize, our data suggest GPR18-dependent metabolic and phenotype switch to anti-inflammatory Mφ and cardiac repair post-MI. Further interrogation will delineate the intracellular pathways downstream of GPR18 and demonstrate the potential of RvD2 in reducing mortality post-MI.

Predicting FFAR4 agonists using structure-based machine learning approach based on molecular fingerprints

Free Fatty Acid Receptor 4 (FFAR4), a G-protein-coupled receptor, is responsible for triggering intracellular signaling pathways that regulate various physiological processes. FFAR4 agonists are associated with enhancing insulin release and mitigating the atherogenic, obesogenic, pro-carcinogenic, and pro-diabetogenic effects, normally associated with the free fatty acids bound to FFAR4. In this research, molecular structure-based machine-learning techniques were employed to evaluate compounds as potential agonists for FFAR4. Molecular structures were encoded into bit arrays, serving as molecular fingerprints, which were subsequently analyzed using the Bayesian network algorithm to identify patterns for screening the data. The shortlisted hits obtained via machine learning protocols were further validated by Molecular Docking and via ADME and Toxicity predictions. The shortlisted compounds were then subjected to MD Simulations of the membrane-bound FFAR4-ligand complexes for 100 ns each. Molecular analyses, encompassing binding interactions, RMSD, RMSF, RoG, PCA, and FEL, were conducted to scrutinize the protein–ligand complexes at the inter-atomic level. The analyses revealed significant interactions of the shortlisted compounds with the crucial residues of FFAR4 previously documented. FFAR4 as part of the complexes demonstrated consistent RMSDs, ranging from 3.57 to 3.64, with minimal residue fluctuations 5.27 to 6.03 nm, suggesting stable complexes. The gyration values fluctuated between 22.8 to 23.5 nm, indicating structural compactness and orderliness across the studied systems. Additionally, distinct conformational motions were observed in each complex, with energy contours shifting to broader energy basins throughout the simulation, suggesting thermodynamically stable protein–ligand complexes. The two compounds CHEMBL2012662 and CHEMBL64616 are presented as potential FFAR4 agonists, based on these insights and in-depth analyses. Collectively, these findings advance our comprehension of FFAR4’s functions and mechanisms, highlighting these compounds as potential FFAR4 agonists worthy of further exploration as innovative treatments for metabolic and immune-related conditions.

Chronic Hepatitis C Virus Infection, Extrahepatic Disease and the Impact of New Direct-Acting Antivirals.

Chronic hepatitis C virus infection is an important cause of liver cirrhosis, hepatocellular carcinoma and death. Furthermore, it is estimated that about 40-70% of patients develop non-hepatic alterations in the course of chronic infection. Such manifestations can be immune-related conditions, lymphoproliferative disorders and metabolic alterations with serious adverse events in the short and long term. The introduction of new Direct-Acting Antivirals has shown promising results, with current evidence indicating an improvement and remission of these conditions after a sustained virological response.

Plant-derived bioactive compounds as key players in the modulation of immune-related conditions

AbstractThe immune system is a complex and fundamental network for organism protection. A minimal unbalance in the host defense system homeostasis can originate severe repercussions in human health. Fundamentally, immune-related diseases can arise from its compromise (immunodeficiency diseases), overactivation against itself (autoimmune diseases) or harmless substances (allergies), and failure of eliminating the harmful agent (chronic inflammation). The notable advances and achievements in the immune system diseases pathophysiology have been allowing for a dramatic improvement of the available treatments. Nevertheless, they present some drawbacks, including the inappropriate benefit/risk ratio. Therefore, there is a strong and urgent need to develop effective therapeutic strategies. Nature is a valuable source of bioactive compounds that can be explored for the development of new drugs. Particularly, plants produce a broad spectrum of secondary metabolites that can be potential prototypes for innovative therapeutic agents. This review describes the immune system and the inflammatory response and examines the current knowledge of eight plants traditionally used as immunomodulatory medicines (Boswellia serrata, Echinacea purpurea, Laurus nobilis, Lavandula angustifolia, Olea europaea, Salvia officinalis, Salvia rosmarinus, and Taraxacum officinale). Moreover, the issues responsible for possible biologic readout inconsistencies (plant species, age, selected organ, developmental stage, growth conditions, geographical location, drying methods, storage conditions, solvent of extraction, and extraction method) will also be discussed. Furthermore, a detailed list of the chemical composition and the immunomodulatory mechanism of action of the bioactive compounds of the selected plant extracts are presented. This review also includes future perspectives and proposes potential new avenues for further investigation.

Optimization for Parameter Estimation in Mathematical Model to Predict the Behaviour of Immune System

This paper surveys and compares various optimization functions related to diabetes to study the various parameter affecting on diabetes. The most important stage in improving the precision and predictive ability of mathematical models is parameter estimation. Mathematical models for immunity are used to describe and predict the behaviour of the immune system in response to infections, vaccinations, and various other immunological processes. These models are quite complex, involved differential equations and various parameters. Ongoing research aims to better understand these immune-related conditions and develop targeted treatments to modulate immune responses appropriately related to diabetes disease.

Study of vitamin D levels in patients with allergic rhinitis

Allergic rhinitis (AR) is the most common type of chronic rhinitis, affecting 10-20% of the population. Severe allergic rhinitis has been associated with significant impairments in quality of life, sleep, and work performance. Vitamin D and its role in regulation of immune function was first proposed after the identification of vitamin D receptors in lymphocytes. There are recent researches linking vitamin D to various immune-related conditions, including allergy, although the pattern of this relationship is still yet to establish. Methods and materials: an observational descriptive study conducted in the Outpatient Department of ENT of Sri Siddhartha Medical College, Tumkur, Karnataka, over a period of 1 year comprising of around 40 patients from 18-65 years of age suffering from allergic rhinitis patients were scored using Total nasal symptoms scoring system (TNSS) based on nasal symptoms. Also, Vitamin D levels are measured and based on these levels patients are graded. Results: Among 40 patients, male predominance with 23(57.5%) cases with mean age of 38.4 +/- 6.8. Majority of patients were in 7-10 TNSS with 15 patients accounting for 37.5%. Patients with severe allergic symptoms had mean vitamin D level about 19.6 +/- 4.2 ng/dl, patients with moderate symptoms were seen with mean vitamin D level 28.6 +/- 3.6 ng/dl and with mild symptoms 34.4+/- 2.8 ng/dl and the p value was significant (&lt;0.04) in our study. Conclusion: Vitamin D could improve allergy symptoms directly or indirectly by potentiating the anti-inflammatory effects of the medications used to treat allergy.