Search Results (1,056)

Next-generation sequencing has overturned the dogma of biliary sterility, revealing low-biomass microbiota along the gut–biliary axis with metabolic and immunologic effects. This review synthesizes evidence on composition, function, and routes of colonization across benign and malignant disease. In cholelithiasis, Proteobacteria- and Firmicutes-rich consortia provide β-glucuronidase, phospholipase A₂, and bile salt hydrolase, driving bile supersaturation, nucleation, and recurrence. In primary sclerosing cholangitis, primary biliary cholangitis, and autoimmune hepatitis, intestinal dysbiosis and disturbed bile acid pools modulate pattern recognition receptors and bile acid signaling (FXR, TGR5), promote Th17 skewing, and injure cholangiocytes; bile frequently shows Enterococcus expansion linked to taurolithocholic acid. Distinct oncobiomes characterize cholangiocarcinoma subtypes; colibactin-positive Escherichia coli and intratumoral Gammaproteobacteria contribute to DNA damage and chemoresistance. In hepatocellular carcinoma, intratumoral microbial signatures correlate with tumor biology and prognosis. We critically appraise key methodological constraints—sampling route and post-sphincterotomy contamination, antibiotic prophylaxis, low biomass, and heterogeneous analytical pipelines—and outline a translational agenda: validated microbial/metabolomic biomarkers from bile, tissue, and stent biofilms; targeted modulation with selective antibiotics, engineered probiotics, fecal microbiota transplantation, and bile acid receptor modulators. Standardized protocols and spatial, multi-omic prospective studies are required to enable risk stratification and microbiota-informed therapeutics. Full article

Background/Objectives: Opportunistic fungal infections are common among people living with HIV (PLHIV) and contribute substantially to morbidity, mortality, and hospitalization rates in this population. This study aimed to determine the prevalence of dermatological manifestations of fungal infections in HIV-positive patients and examine their association with demographic, clinical, and immunological characteristics. Methods: A retrospective review of medical records from 2500 PLHIV treated at the Infectious Diseases Unit of “Andreas Syggros” Hospital for Skin and Venereal Diseases between 1988 and 2017. Data from patients diagnosed with opportunistic fungal infections were analyzed. Participants were classified as either antiretroviral therapy (ART)-naïve or already receiving treatment. Recorded fungal infections were correlated with epidemiological variables and CD4+ T-cell counts. Results: Opportunistic fungal infections were identified in 859 patients (34.36%), with a marked male predominance. Candidiasis was the most frequently reported condition, with a higher prevalence among female patients. Lower CD4+ counts were significantly associated with an increased risk of cryptococcal meningitis, esophageal candidiasis, Pneumocystis jirovecii pneumonia (PJP), and oral candidiasis, whereas higher CD4+ counts were more common in patients with dermatophytosis, onychomycosis, and pityriasis/tinea versicolor. Conclusions: Opportunistic fungal infections remain highly prevalent in PLHIV, particularly among those with advanced immunosuppression. CD4+ T-cell counts are key diagnostic and prognostic markers, reinforcing their importance in monitoring disease progression and guiding clinical management. Full article

Oral squamous cell carcinoma (OSCC) is a malignant neoplasm of the oral epithelium that constitutes majority of oral cancers and is strongly associated with risk factors such as tobacco use and genetic alterations. Mortality rates for OSCC are high because many cases are misdiagnosed or identified at later stages, and treatment options are limited with high recurrence. Therefore, there is an urgent need for improved diagnostic and therapeutic strategies. OSCC tumor cells, like those in other solid malignancies, exhibit significant alterations in metabolic pathways and the immune microenvironment. These changes can serve as valuable biomarkers for early detection and as targets for innovative treatment strategies. This review summarizes the current understanding of metabolic and immunological biomarkers that are either currently in use for OSCC or are in different phases of clinical trials. Full article

Inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC) are chronic immune-mediated inflammatory diseases (IMIDs) that affect the gastrointestinal and hepatobiliary systems. They are characterized by persistent inflammation, potentially progressive fibrosis, and an elevated risk of developing cholangiocarcinoma and colorectal cancer. IBD and PSC share phenotypical, genetic, and immunological features, largely due to the central role of immune cell dysregulation. Despite their increasing global prevalence, the underlying drivers remain poorly understood, and effective treatment options are still lacking. Efforts towards an improved comprehension of their pathogenic mechanisms are therefore pivotal. Emerging evidence highlights the role of canonical ASC-dependent inflammasomes—multiprotein bioactive Interleukin (IL)-1-producing complexes of the innate immune system—and serum amyloid A (SAA) as key structures of gastrointestinal and hepatobiliary inflammation, tissue remodeling, stromal crosstalk, and fibrosis. In this review, we explore immunological connections and analogies between IBD and PSC, highlighting the converging roles of canonical ASC-dependent inflammasomes, the IL-1 superfamily, SAA, and sustained gut microbiota-driven chronic inflammation in disease pathology and their surging potential as therapeutic targets across the gut–liver axis. Full article

Helicobacter pylori (H. pylori) and intestinal helminthes are common in low- and middle-income countries, where co-infection is endemic due to similar modes of transmission and poor sanitation. Whereas H. pylori are recognized gastric pathogens that induce gastritis, ulcers, and gastric carcinoma, helminths possess systemic immunomodulatory functions. The immunological, epidemiological, and clinical features of H. pylori and helminth co-infections will be discussed in this review. Key findings include that helminths induce a Th2-biased and regulatory immune response, potentially counteracting the Th1/Th17 H. pylori-induced inflammation and therefore limiting gastric tissue damage and cancer risk. Certain human studies and animal models concluded that co-infection would be protective against extreme gastric pathology by modulating immunity, altering gut microbiota, and by helminth-secreted extracellular vesicles. Epidemiologic data show large regional heterogeneity in co-infection prevalence with higher rates in children and rural socioeconomically disadvantaged populations. Much of the research mechanisms, however, are limited to models in the lab, and few human studies exist. Lastly, helminth co-infection is also potentially immunoprotective against H. pylori-associated illnesses, but greater translational research and human clinical trials are necessary. Public health policy in endemic regions must consider the complex relationships between co-infecting parasites when developing control. Full article

Obesity is strongly associated with an increased risk of heart failure. Recent studies indicate that epicardial adipose tissue plays a critical role in the development of obesity-related cardiomyopathy. This distinct visceral fat depot, located between the myocardium and the visceral pericardium, is involved in direct cross-talk with the adjacent myocardium, influencing both its structural integrity and electrophysiological function. This review aims to provide an up-to-date overview of the morphological, metabolic, immunological, and functional alterations of this adipose compartment in the context of obesity, and to explore its contribution to the pathogenesis of heart failure. Moreover, the article synthesizes current evidence on the potential cardioprotective effects of emerging anti-obesity pharmacotherapies—particularly GLP-1 and dual GLP-1/GIP receptor agonists—on metabolic pathways associated with epicardial fat that are implicated in obesity-induced cardiomyopathy. Further clinical trials are required to clarify the impact of these therapies on the course and prognosis of heart failure, as well as on the epidemiology and societal burden of the disease. Full article

Ischemic stroke triggers a dynamic immune response that influences both acute damage and long-term recovery. This review synthesizes a decade of evidence on immunological and inflammatory biomarkers in ischemic stroke, emphasizing their prognostic and therapeutic significance. Following ischemic insult, levels of pro-inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and chemokines like interleukin-8 (IL-8) rapidly rise, promoting blood–brain barrier disruption, leukocyte infiltration, and neuronal death. Conversely, anti-inflammatory mediators such as interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) facilitate repair, neurogenesis, and immune regulation in later phases. The balance between these pathways determines outcomes and is reflected in circulating biomarkers. Composite hematological indices including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) offer accessible and cost-effective prognostic tools. Several biomarkers correlate with infarct size, neurological deterioration, and mortality, and may predict complications like hemorrhagic transformation or infection. Therapeutic strategies targeting cytokines, especially IL-1 and IL-6, have shown promise in modulating inflammation and improving outcomes. Future directions include personalized immune profiling, real-time cytokine monitoring, and combining immunotherapy with neurorestorative approaches. By integrating immune biomarkers into stroke care, clinicians may enhance risk stratification, optimize treatment timing, and identify candidates for novel interventions. This review underscores inflammation’s dual role and evolving therapeutic and prognostic relevance in ischemic stroke. Full article

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy by providing durable responses and a favorable safety profile, ushering in a new era of tumor immunotherapy. However, immune-related adverse events (irAEs) remain a significant clinical challenge. Among these, gastrointestinal irAEs, especially immune-related colitis (ir-colitis), can lead to serious complications if not promptly recognized and managed. Here, we present a case of grade 3 ir-colitis induced by the programmed cell death protein 1 (PD-1) inhibitor sintilimab in a 68-year-old woman with endometrial cancer. The patient developed severe acute diarrhea following ICI administration, which progressed despite initial antidiarrheal and antimicrobial treatments. A multidisciplinary team (MDT) involving gastroenterologists, oncologists, a pathologist, and a clinical pharmacist confirmed the diagnosis and implemented high-dose corticosteroid therapy, yielding significant clinical improvement. Importantly, this report highlights the mechanistic link between PD-1 blockade and ir-colitis pathogenesis, focusing on the dysregulation of the mucosal immune environment and its role in triggering colonic injury. In addition to the case description, we provide a comprehensive review of the literature and clinical guidelines, discussing risk factors, diagnostic approaches, therapeutic strategies, and long-term monitoring. By integrating insights from pharmacology, immunology, and clinical practice, this work emphasizes the importance of early detection, patient education, and MDT collaboration for optimizing therapeutic outcomes and advancing the understanding of ir-colitis in the context of ICI therapy. Full article

Background/Objectives: Natural products with claimed adaptogenic and/or immunomodulatory effects are widely used in traditional medicine systems across Eurasia. These include herbal remedies (e.g., Panax ginseng), fungi (e.g., Ganoderma lucidum), and animal-derived substances (e.g., propolis from Apis mellifera). Despite their popularity, the safety profiles of these products—particularly concerning adverse events (AEs) and serious adverse events (SAEs)—remain insufficiently understood. This study aimed to assess the safety profiles of adaptogenic and immunomodulatory natural products through a scoping review of published human studies and an analysis of individual case safety reports (ICSRs) from the WHO-UMC VigiBase database. Methods: A scoping review was conducted using PubMed (1980–2024) in line with PRISMA-ScR guidelines. Eligible studies included randomized and non-randomized clinical trials and case reports in humans focused on safety outcomes. Data extraction followed the Joanna Briggs Institute (JBI) standardized template. ICSRs from VigiBase were analyzed by product type, AE type and seriousness, and demographic characteristics. The data were further organized to highlight the 15 most frequently reported products and their top five System Organ Classes (SOCs) and Preferred Terms (PTs). Results: The scoping review identified 51 natural products with reported adaptogenic and/or immunomodulatory properties. This included 285 clinical trials and 119 case studies on single-ingredient products and 54 clinical trials and 21 case studies on multi-ingredient preparations. Common AEs included gastrointestinal, dermatological, hepatic, cardiovascular, and immunological reactions. SAEs were rare but reported for Echinacea purpurea, Silybum marianum, and Camellia sinensis. From Vigibase, 45,042 ICSRs were retrieved for 49 natural products: 10,702 for single-ingredient and 34,340 for multi-ingredient products. Among 7856 reports listing a single-ingredient product as the sole suspect, 15.8% were SAEs, including eight fatal cases. However, the causality remained unclear due to insufficient data. Ganoderma lucidum, Viscum album, and Silybum marianum were most frequently associated with SAEs. In multi-ingredient products, propolis was frequently linked to hypersensitivity and skin reactions. Conclusions: This study provides a comprehensive overview of the safety profiles of adaptogenic and immunomodulatory natural products. Variability in product composition, lack of standardization, incomplete reporting in clinical studies, and underreporting in pharmacovigilance databases complicate accurate risk assessment. For multi-ingredient products, attributing specific AEs to specific components remains difficult. Further high-quality clinical research and improved pharmacovigilance are needed, along with clear safety warnings to reduce risks for consumers. Full article

Lung cancer (LC), with non-small-cell lung cancer (NSCLC) as its predominant subtype, remains the leading cause of cancer-related mortality worldwide. While immune checkpoint inhibitors (ICIs) have redefined the therapeutic paradigm in advanced NSCLC, durable responses are confined to a limited subset of patients. A major clinical challenge persists: the inability to accurately predict which patients will derive meaningful benefit, which will exhibit primary resistance, and which are at risk for severe immune-related toxicities. The imperative to individualize ICI therapy necessitates robust, dynamic, and accessible biomarkers. Liquid biopsy has emerged as a transformative, minimally invasive tool that enables real-time molecular and immunologic profiling. Through analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, and peripheral blood immune components, liquid biopsy offers a window into both tumor intrinsic and host-related determinants of ICI response. These biomarkers not only hold promise for identifying predictive signatures—such as tumor mutational burden, neoantigen landscape, or immune activation states—but also for uncovering mechanisms of acquired resistance and guiding treatment adaptation. Beyond immunotherapy, liquid biopsy plays an increasingly central role in the landscape of targeted therapies, allowing early detection of actionable driver mutations and resistance mechanisms (e.g., EGFR T790M, MET amplification, and ALK fusion variants). Importantly, serial sampling via liquid biopsy facilitates longitudinal disease monitoring and timely therapeutic intervention without the need for repeated tissue biopsies. By guiding therapy selection, monitoring response, and detecting resistance early, liquid biopsy has the potential to significantly improve outcomes in NSCLC. Full article

Dental caries is now recognised as a multifactorial disease shaped by complex interactions among genetic, epigenetic, microbiological, environmental, and social factors. This narrative review synthesises recent findings on the influence of genetic and epigenetic factors on caries susceptibility, exploring implications for personalised prevention strategies, including novel vaccine approaches. Numerous gene polymorphisms in pathways related to enamel formation, saliva composition, immune response, and taste perception have been linked to increased caries risk, with some effects modulated by sex and tooth-specific factors. Early-life environmental exposures (diet, tobacco, and antibiotic use) have been demonstrated to further alter risk through epigenetic modifications such as DNA methylation, microRNA regulation, and histone changes. The recognition of this landscape of inherited and acquired vulnerabilities has given rise to interest in innovative preventive measures. In particular, anti-caries vaccines targeting Streptococcus mutans are being developed using protein subunits, DNA constructs, and even plant-based antigen production. Notwithstanding the challenges that still need to be overcome—chiefly the achievement of robust mucosal immunity, the assurance of safety, and the enhancement of production—these vaccines are proving to be a promising addition to traditional oral hygiene and fluoride measures. The integration of genetic and epigenetic insights with immunological advances has the potential to facilitate the development of more effective, personalised interventions to prevent dental caries. Full article

Tuberculosis remains a serious infectious disease that causes over 1.3 million deaths annually. Following the COVID-19 pandemic, the global incidence of tuberculosis has increased to 10.8 million cases. Pregnant women represent a particularly vulnerable population requiring tailored approaches to the prevention, diagnosis, and treatment of tuberculosis. SARS-CoV-2 infection may have impacted existing clinical protocols. Implementing updated methods of tuberculosis prevention, diagnosis, and treatment in pregnant women could help reduce adverse maternal and fetal outcomes. The aim of this review was to explore potential modifications in tuberculosis management among pregnant women in the post-COVID-19 era, including co-infection with SARS-CoV-2. Methods: A review was conducted, incorporating a systematic literature search across major international databases, including Medline, PubMed, Web of Science, Scopus, and Google Scholar. The search covered publications released between December 2019 and September 2024 and used targeted keywords such as “COVID-19” OR “SARS-CoV-2”, “tuberculosis” OR “TB” OR “latent tuberculosis infection” OR “pulmonary tuberculosis”, and “pregnancy” OR “pregnant women”. Results: Pregnant women living with HIV are at increased risk of developing tuberculosis, which can negatively affect both maternal and perinatal outcomes. Screening for tuberculosis is recommended for all HIV-positive pregnant women, even in the absence of clinical symptoms. Notably, immunological testing before and during pregnancy facilitates the timely and safe detection of tuberculosis infection, enabling preventive and therapeutic interventions during any stage of gestation and the early postpartum period, for the benefit of both mother and child. Drug–drug interactions play a significant role in tuberculosis management, both among anti-tuberculosis agents and with medications for comorbid conditions. Current knowledge of the pharmacokinetics and pharmacodynamics of antituberculosis agents, coupled with therapeutic drug monitoring, supports the development of individualized and effective treatment regimens, which are particularly critical for pregnant patients. Recommendations for managing tuberculosis in pregnant women after COVID-19 infection include measuring D-dimer levels, performing echocardiography, and consulting cardiologists to prevent treatment-related complications. Conclusions: Pregnant women represent a distinct subgroup of tuberculosis patients requiring individualized management. Changes observed in tuberculosis progression and treatment responses in pregnant women before and after SARS-CoV-2 infection should inform therapeutic choices, especially in cases of drug-resistant tuberculosis treated with bedaquiline. COVID-19 has been associated with increased cardiovascular risk, which may heighten the likelihood of adverse drug reactions in this population, especially given the limited therapeutic options. Further research is required to assess the long-term outcomes of latent tuberculosis infection in pregnant women and to evaluate the safety and efficacy of novel regimens for drug-resistant TB during pregnancy. Full article

Research is required to determine whether the coinfections by Fasciola spp. and other parasite species result from poor rural hygiene or reflect underlying epidemiological patterns and causes. Therefore, the role of fascioliasis is analyzed concerning coinfection complexity, risk of multiparasitism, parasite associations, pathogenic implications and their multifactorial causes. Helminth and protozoan coinfections are studied in 2575 previously untreated individuals from four rural hyperendemic areas (Northern Bolivian Altiplano, Peruvian Altiplano and Cajamarca valley, and the Egyptian Nile Delta). This cross-sectional study was conducted from January 2011 to December 2023. Coinfections were coprologically assessed by the merthiolate–iodine–formalin and formol–ether concentration techniques. Infection intensity was measured as eggs/gram of feces (epg) with the Kato–Katz technique. Parasite and coinfection prevalences were stratified by age, sex and geographical location. High mixed infections, fascioliasis prevalences and very low non-coinfected Fasciola-infected subjects were associated with the following regions: Bolivian Altiplano, 96.5%, 16.8% and 3.5%; Peruvian Altiplano, 100%, 24.6% and 0%; Cajamarca valley, 98.7%, 21.4% and 1.8%; Nile Delta, 84.1%, 13.0% and 15.9%. Transmission routes and human infection sources underlie fascioliasis associations with protozoan and other helminth infections. Prevalence pattern of protozoan–helminth coinfections differed between Fasciola-infected individuals and individuals not infected with Fasciola, presenting higher prevalences in individuals with fascioliasis. Multiparasitism diagnosed in Fasciola-infected subjects included coinfections by up to nine parasite species, eight protozoan species, and five helminth species. The most prevalent pathogenic protozoan was Giardia intestinalis. The most prevalent helminth species differ according to environmental conditions. Several parasites indicate fecal environmental contamination. When the fascioliasis burden increases, the total number of parasite species also increases. The fascioliasis risk increases when the total helminth species number/host increases. Fasciola-infected subjects may present a modification in the clinical phenotypes of coinfecting parasitic diseases. Fascioliasis coinfection factors include transmission ways and immunological, environmental and social aspects. Coinfections must be considered when assessing the health impact of fascioliasis, including the analysis of the fascioliasis effects on malnutrition and physical/intellectual child development. Fascioliasis-control schemes should, therefore, integrate control measures mainly against other helminthiases. Full article

Background/Objectives: Periodontitis is a chronic infectious inflammatory disorder that affects the supporting structures of the teeth. The gingival epithelium plays a crucial role as a physical and immunological barrier, producing pro-inflammatory cytokines in response to microbial pathogens. Modulation of gingival epithelial function has been proposed as a therapeutic strategy to prevent the progression of periodontal disease. Houttuynia cordata, a perennial herb traditionally used in Asian medicine, is recognized for its anti-inflammatory properties, with documented benefits in the cardiovascular, respiratory, and gastrointestinal systems. However, its potential therapeutic role in oral pathologies, such as periodontitis, remains underexplored. This study aimed to investigate the anti-inflammatory effects of H. cordata extract on interleukin (IL)-1β-stimulated primary gingival keratinocytes (PGKs) subjected to IL-1β-induced inflammatory stress, simulating the conditions encountered during orthodontic treatment. Methods: Inflammation was induced in PGKs using IL-1β, and the impact of H. cordata extract pretreatment was assessed using quantitative real-time reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunoblotting. Results: H. cordata extract significantly downregulated the mRNA and protein expression levels of tumor necrosis factor-alpha, IL-8, and intercellular adhesion molecule-1 in IL-1β-stimulated PGKs without inducing cytotoxicity. Conclusions: These findings suggest that H. cordata holds promise as a preventive agent against periodontitis by attenuating inflammatory responses in gingival epithelial tissues. We believe that our findings will inform the development of prophylactic interventions to reduce periodontitis risk in patients undergoing orthodontic therapy. Full article

This study examined the distribution and disease associations of non-HLA-B*27 HLA-B alleles in Romanian spondyloarthritis (SpA) patients, aiming to address the underrepresentation of Eastern European populations in immunogenetic research. Methods: We analyzed 263 HLA-B*27-negative patients from Northeastern Romania fulfilling ASAS criteria. HLA-B genotyping was performed at two-digit resolution, and allele distributions were compared with two Romanian HLA-B*27-negative control groups (n = 335 and n = 1705 cases), using chi-square testing and logistic regression. Compared to controls, HLA-B*47 (p = 0.0007) and HLA-B*54 (p = 0.0013) were significantly enriched, while HLA-B*40 was underrepresented (p = 0.0287). Notably, HLA-B*54 was observed exclusively in axial SpA. Within the cohort, both HLA-B*13 and HLA-B*57 alleles were associated with psoriasis, while HLA-B*37 and HLA-B*41 alleles were clustered within the reactive arthritis group. The HLA-B*35 and HLA-B*18 alleles were the most frequently observed alleles across most clinical phenotypes. When comparing the frequency of HLA-B associations, the most common genotypes among SpA patients were B*08-B*18, B*13-B*35, and B*35-B*51. Notably, B*08-B*18 was more frequent in patients with radiographic sacroiliitis grade ≥ 2, while B*35-B*51 was more frequent in those with confirmed systemic inflammation, as indicated by elevated CRP or ESR levels. Analysis of peptide-binding patterns revealed a cluster of risk alleles, HLA-B*08, B*18, B*35, B*40, and B*54, sharing similar features, distinct from the canonical profile of B*27. These findings highlight the contribution of non-B*27 HLA-B alleles to SpA susceptibility in an Eastern European population and support the notion that HLA-B*27-negative SpA may represent a distinct clinical and immunological entity, driven by alternative pathogenic mechanisms. They also emphasize the importance of population-specific immunogenetic profiling and support expanding genetic characterization in HLA-B*27-negative patients. Full article