Search Results (3,514)

Morbid obesity is a chronic condition characterized by metabolic disorders and low-grade chronic inflammation, both of which are closely linked to insulin resistance and adipokine dysregulation. In addition to its systemic effects, obesity also leads to structural and functional changes in the skin, supporting its role as an active metabolic and immunological organ. This study analyzed skin lesions occurring in individuals with morbid obesity and explored their potential relevance in the context of metabolic risk and treatment response rather than establishing clinically validated tools. The focus was on how excess adipose tissue affects the skin through metabolic, hormonal and mechanical mechanisms. Although this review focuses on morbid obesity, many of the included studies examine general obesity without separating its severity. Therefore, the findings may not fully reflect patients with BMI ≥ 40 kg/m² and should be interpreted with caution. Three main areas were considered: the pathophysiological mechanisms underlying obesity-related skin lesions, selected dermatological manifestations as potential markers associated with metabolic risk, and changes in these manifestations during pharmacological, surgical, and lifestyle interventions. Available studies show that acanthosis nigricans and multiple acrochordons are consistently associated with insulin resistance, metabolic syndrome, and metabolic dysfunction-associated steatotic liver disease. An increase in BMI is also associated with impairment of the epidermal barrier, changes in the composition of skin lipids, and modifications of the skin microbiome, while biomechanical factors promote the development of chronic inflammation in the intertriginous areas. It has been shown that normalization of metabolic parameters achieved through GLP-1-based pharmacotherapy, bariatric surgery, or lifestyle changes can improve some skin manifestations, especially acanthosis nigricans. However, it should be emphasized that most available data are based on cross-sectional or observational studies, and validated composite dermatological indices are still unavailable. Skin changes in patients with morbid obesity often reflect underlying metabolic and hormonal disturbances. They may have potential as additional, non-invasive clinical clues, but they should not be treated as independent tools for risk assessment or treatment monitoring. At present, most evidence shows associations only, and it is unclear whether these findings add meaningful predictive value beyond standard metabolic markers. More prospective studies are needed to confirm their clinical usefulness and to define their role in assessing metabolic risk and monitoring treatment over time. Full article

Allergic anisakiasis (AA), caused by the ingestion of fish contaminated with Anisakis larvae, has emerged as a growing global health concern due to the increasing consumption of raw or undercooked seafood. Anisakis simplex is identified as the primary etiologic species, responsible for gastrointestinal symptoms, IgE-mediated (Type I) or cell-mediated (Type IV) manifestations, and gastro-allergic anisakiasis (GAA), a unique clinical overlap between parasitic infection and acute IgE-mediated food allergy. In this review, we analyzed the epidemiology of Anisakis simplex allergy, the main diagnostic methods to confirm a diagnosis of food allergy, its clinical manifestations, and how these differ in different countries around the world. This multidisciplinary synthesis provides, for the first time, an integrated understanding of Anisakis-induced disease mechanisms across human, animal, and cellular levels. The persistence of allergenic proteins despite standard food processing underscores the need for improved diagnostic tools, public health surveillance, and preventive strategies—particularly in populations with high seafood consumption or occupational exposure. A comprehensive approach combining clinical, molecular, and immunological perspectives is essential to address the expanding global burden of allergic anisakiasis. Full article

Background/Objectives: Whole-cell vaccines have demonstrated clinical potential in cancer treatment and recurrence prevention, yet their immunogenicity and dendritic cell (DC) activation remain suboptimal. This study aimed to evaluate whether a needle-free injector (NFI) could enhance the immunogenicity and antitumor efficacy of whole-cell tumor vaccines. Methods: Adaptive immune responses induced by NFI and traditional syringe injection (SYI) were compared following whole-cell vaccine administration. The morphology of vaccine fluid ejected by NFI and SYI was examined, and the effects on DC antigen uptake and activation were assessed. Antitumor efficacy was further evaluated in MC38 colon adenocarcinoma challenge models. Results: NFI administration elicited stronger antigen-specific adaptive immune responses than SYI. The high-velocity pressure generated by NFI resulted in fragmentation of whole-cell vaccine material, and this morphological alteration was associated with enhanced DC antigen uptake and activation. These immunological improvements corresponded with superior tumor suppression in MC38 models following NFI-delivered vaccination. Conclusions: NFI delivery enhances the immunogenicity and antitumor efficacy of whole-cell tumor vaccines. These findings suggest that needle-free injectors may serve as a simple and effective strategy to improve the performance of whole-cell cancer vaccines. Full article

Immune dysregulation is being increasingly recognized as a prominent feature of a wide range inborn errors of immunity (IEIs) with different molecular backgrounds. Among the manifestations of immune dysregulation, inflammatory arthritis has emerged as an important yet underrecognized complication that may occur across multiple IEI categories, including humoral immunodeficiencies (such as X-linked agammaglobulinemia, hyper-IgM syndrome, common variable immunodeficiency, and others), complement deficiencies, disorders of immune dysregulation (STAT3 gain of function mutation, CTLA4 and LRBA haploinsufficiency), and combined immunodeficiencies. In some patients, arthritis may represent the first or predominant clinical manifestation, resulting in a diagnostic challenge in the rheumatologic setting. The pathogenesis of arthritis in IEIs reflects different immunological mechanisms, including the defective clearance of immune complexes, dysregulated B- and T-cell responses, impaired regulatory T-cell function, and aberrant cytokine signaling. Clinically, IEI-associated arthritis may mimic classical rheumatologic conditions such as juvenile idiopathic arthritis, rheumatoid arthritis, or other connective tissue diseases, although distinctive immunological and histopathological features are often present. Recognizing arthritis as a potential manifestation of IEIs has important clinical implications. The presence of specific “red flags”, including treatment refractoriness, recurrent infections, or additional signs of immune dysregulation (other autoimmune diseases, atopy, lymphoproliferation, enteropathy), should prompt targeted immunological evaluation. While management often relies on conventional immunosuppressive therapies, advances in the molecular characterization of IEIs are increasingly enabling the use of targeted treatments directed at the underlying pathogenic mechanisms. This paper provides an overview of the current knowledge of arthritis associated with IEIs, highlighting diagnostic challenges, underlying immunopathogenic mechanisms, and emerging therapeutic perspectives. Full article

Despite prolonged viral inhibition with combination antiretroviral therapy (ART), HIV-1 survives as genetically intact, replication-capable proviruses within durable CD4+ T-cell fractions, involving central memory, transitional memory, and stem cell-like memory populations, as well as within tissue-resident compartments including lymphoid follicles and gut-associated lymphoid tissue. Reservoir stability is preserved via clonal growth of infected cells and epigenetic processes that impose proviral transcriptional silencing. As a result, current therapeutic approaches seek to either directly alter proviral survival or to improve immune-driven elimination of infected cells. At the molecular level, investigational strategies such as CRISPR–Cas9 and CRISPR–Cas12 gene-editing systems are intended to remove or induce inactivating mutations inside embedded proviral DNA, as well as alter host entrance co-receptors such as CCR5 to provide cellular resistance to infection. In addition, pharmacologic latency regulation is being studied via histone deacetylase inhibitors, protein kinase C agonists, and bromodomain inhibitors to reverse latency, along with Tat inhibitors and other transcriptional repressors aimed to persistently silence proviral expression. Moreover, immunological techniques aim to counteract inefficient endogenous antiviral defenses. Broadly neutralizing antibodies with tailored Fc-driven effector functions are under examination for both neutralization and antibody-dependent cellular cytotoxicity. Therapeutic vaccine approaches seek to elevate polyfunctional HIV-specific CD8+ T-cell responses, while adoptive cellular approaches, involving CAR-T cells aiming HIV envelope epitopes, remain in early clinical research. Immune checkpoint blockade is also being investigated to reverse T-cell depletion inside reservoir-rich tissues. Nevertheless, the key obstacles continue to be the diverse reservoir composition, restricted tissue penetration, viral escape, and safety limitations. The molecular and translational obstacles that characterize attempts toward an HIV cure must be addressed through ongoing multidisciplinary research. Full article

Over the past several decades, the gut microbiome (GM) has been the focus of extensive investigation. In recent years, major discoveries such as the role of maternal breastfeeding in infant GM development and mode of delivery on infant GM health have expanded scientific knowledge on this topic. As this is a rapidly expanding field of research, substantial work remains to further elucidate and integrate the existing evidence on its role in allergic response and immunological development. This comprehensive review will examine the latest discoveries in GM research and its role in the development of food allergies across the lifespan. Examining the existing literature may identify knowledge gaps regarding precise mechanisms through which the development of GM influences the maturation of the immune system. Given the abundance of the literature, we conducted a database search for articles published within the past 10 years. A total of 56 original research articles were retrieved, analyzed, and included in our review. This review article aims to integrate the current evidence on understanding how the development of GM impacts the immune system and food allergy response throughout the lifespan. We aim to uncover microbial mechanisms of allergy response, host and microbe interactions, and opportunities for therapeutic intervention. Additionally, we aim to reveal gaps in the current knowledge of the GM’s influence on allergy development, offering directions for future research. Full article

Pertussis is a highly contagious respiratory infection caused by Bordetella pertussis and remains a persistent global health challenge despite widespread vaccination. This review aims to analyze the immune pathogenesis of B. pertussis infection and to identify key immunological limitations of current acellular pertussis vaccines that contribute to ongoing transmission. A narrative review of the literature was conducted, focusing on mechanisms of host–pathogen interaction, immune evasion, and vaccine-induced immunity. Evidence indicates that although acellular vaccines effectively reduce disease severity, they fail to prevent nasopharyngeal colonization and transmission, largely due to insufficient induction of mucosal immunity, T helper 1 (Th1) and T helper 17 (Th17) responses, and airway tissue-resident memory T cells. In contrast, natural infection induces broader immune responses, including secretory IgA production and robust cellular immunity, which are associated with improved bacterial clearance. Emerging next-generation vaccine strategies, including mucosal, outer membrane vesicle-based, and live-attenuated platforms, demonstrate enhanced ability to reduce bacterial colonization in preclinical and clinical models. In conclusion, effective control of pertussis transmission will require vaccine approaches that replicate infection-induced immunity at the respiratory mucosa, emphasizing the need for redesigned immunization strategies. Full article

Background/Objective: Apart from the attributes such as cost, yields and consistency that define the feasibility of a manufacturing process, physicochemical and immunological quality traits equally signify the functionality of a biological product. The present study investigates one such promising Meningococcal B vaccine candidate, a chimeric fHbp-PorA protein in Escherichia coli. Methods: The chimeric fHbp–PorA protein, expressed with an N-terminal tag of HIS-MBP-TEV was produced in a 10 L fermenter under two different media and induction strategies: chemically defined (CD) media with lactose induction and complex media (CM) with galactose-mediated autoinduction. Comparative analysis was carried out between the two approaches for cell growth, protein expression, and purification, and the final chimeric proteins were characterized to evaluate for their biochemical, structural, in vitro and in vivo immunochemical properties. Results: Growth in the CD media resulted in several-fold-higher biomass compared to that in CM media in a short cultivation time; however, more than a third of the expressed protein remained in an insoluble state. Meanwhile, almost all of the expressed protein with CM media was recovered in soluble form. Moreover, purification of the unprocessed tagged protein and recovery of chimeric protein (tag removed) resulted in 75% greater yield in CM media when compared to CD media. The final chimeric proteins obtained from each medium varied significantly in their physicochemical characteristics, including their epitope projection and CD spectra. The results of in vivo animal immunogenicity response also showed higher serum bactericidal activity associated with chimeric protein obtained from CM media compared to CD media. Conclusions: The outcomes demonstrate that complex media with galactose-induced expression not only show higher productivity but also exhibit superior quality attributes, qualifying their reliable use in the manufacturing process of this promising vaccine candidate. Full article

Sjögren’s disease (SjD) is a chronic autoimmune disorder characterized by progressive dysfunction of the exocrine glands, driven primarily by aberrant T- and B-cell activation. Current therapeutic strategies remain largely symptomatic and are frequently limited by off-target effects and long-term toxicity, underscoring an urgent need for safer, mechanism-based adjunctive approaches. In recent years, nutritional interventions and medicinal herbs have emerged as promising complementary strategies, owing to their capacity to modulate immune–metabolic pathways and restore immune homeostasis. Nutrients such as n-3 polyunsaturated fatty acids (PUFAs) and short-chain fatty acids (SCFAs) exert well-documented anti-inflammatory effects and influence immune cell differentiation via immunometabolic reprogramming. Concurrently, bioactive constituents derived from medicinal herbs offer multi-target regulation of inflammatory signaling and lymphocyte function. This review synthesizes current advances in the immunomodulatory roles of dietary components and edible herbs in the context of SjD, focusing on their mechanistic convergence on T-cell subsets, B-cell responses, and the gut–immune axis. By integrating traditional knowledge with contemporary immunological insights, this article aims to provide a conceptual framework for the rational integration of nutritional and herbal strategies into the clinical management of SjD. Full article

Treatment-resistant schizophrenia (TRS) remains a significant clinical challenge due to limited therapeutic options and a poor understanding of its underlying biology. Recent findings suggest that immune system dysregulation may play a critical role in the pathophysiology of TRS. This systematic review aimed to synthesize current evidence on immunological abnormalities associated with TRS, with a focus on inflammatory markers, immune cell profiles, and the role of autoantibodies, and to explore their potential utility in diagnosis and treatment. A systematic review of the literature was conducted in accordance with PRISMA guidelines, incorporating clinical, molecular, and translational studies on immunological markers in patients with TRS. Included studies assessed cytokine levels, immune cell phenotypes, autoantibodies, genetic factors, and the effects of immunomodulatory therapies. Emphasis was placed on findings differentiating TRS from treatment-responsive schizophrenia. TRS is associated with distinct immune profiles, including elevated IL-6, IL-8, TNF-α, and sCD25 levels, overexpression of CD33 on monocytes and expansion of CD123+ plasmacytoid dendritic cells. Autoantibodies, particularly those targeting glutamatergic receptors, are more prevalent in TRS and decrease with clozapine treatment. Predictive models using IgM autoantibodies and genetic variants show promise for early identification of at-risk individuals. Emerging immunomodulatory treatments such as rituximab, levamisole, and senolytics are under investigation, offering potential for personalized strategies. Immunological dysfunction represents a reproducible and biologically relevant feature of TRS. Integration of immune biomarkers into clinical practice may enhance diagnostic precision and inform personalized therapeutic approaches. Future research should prioritize standardized biomarker protocols and longitudinal studies to validate causal associations and optimize treatment algorithms. Full article

Trained immunity refers to the enduring functional reprogramming of innate immune cells after particular stimuli, driven by epigenetic and metabolic alterations that augment non-specific responses upon subsequent exposure. Neutrophils and monocytes/macrophages, as essential innate effectors, are crucial for the induction and control of trained immunity, which is the primary emphasis of this review. Neutrophils, the predominant circulating leukocytes, were historically considered incapable of memory owing to their brief lifespan. Emerging evidence indicates that trained immunity functions at the bone marrow progenitor level, influencing granulopoiesis to produce neutrophils with lasting functional modifications. This research offers new insights into neutrophil functions in infection, cancer, and inflammation. Monocytes and macrophages, characterized by phenotypic plasticity and tissue residence, function as conventional models of trained immunity. They experience direct peripheral reprogramming or emerge as primed descendants of trained bone marrow precursors, performing pro-inflammatory or reparative roles in malignancies, infections, and ischemia lesions. This study comprehensively outlines the regulatory mechanisms of trained immunity in these cells, clarifies their functions in various clinical situations, and examines therapeutic applications. Comprehending these pathways is crucial for elucidating the cellular foundation of innate immunological memory, uncovering its multiple functions in disease, and guiding innovative therapeutics aimed at granulopoiesis and monocyte-macrophage polarization. Full article

Air pollution represents a critical yet modifiable factor influencing the recurrence and progression of upper-airway infections. This review explores the molecular, immunological, and environmental mechanisms linking airborne pollutants to recurrent sinus and respiratory tract inflammation. Particular focus is placed on pollutant-induced oxidative stress, epithelial barrier disruption, alterations in the microbiome, and immune dysregulation, which collectively heighten disease susceptibility. Integrating recent advances in exposomics, multi-omics, and artificial intelligence, the discussion highlights new approaches to unravel exposure–response pathways and identify predictive biomarkers. Future directions emphasize precision exposure assessment, interventional strategies to improve air quality, and the emerging framework of “clean-air medicine” to guide prevention and policy. Overall, this synthesis underscores the urgent need for multidisciplinary collaboration across environmental science, molecular biology, and clinical research to mitigate the growing burden of pollution-related airway disease and promote sustainable respiratory health. Full article

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease in which B-cell dysregulation plays a central pathogenic role beyond autoantibody production. Advances in B-cell biology have led to the development of targeted therapies, including inhibition of the B-cell activating factor (BAFF) pathway. Belimumab, a monoclonal antibody that neutralizes soluble BAFF, modulates B-cell survival signals upstream, promoting progressive immunologic remodeling rather than rapid depletion. This review integrates current knowledge on BAFF-dependent B-cell biology with mechanistic, pharmacokinetic, and clinical data to provide a comprehensive framework for understanding belimumab’s effects in SLE and lupus nephritis (LN). Belimumab preferentially reduces transitional and naïve B cells, while memory B cells show a relative transient increase followed by a gradual return to baseline levels, reflecting redistribution rather than expansion, and long-lived plasma cells are largely unaffected. These effects result in progressive remodeling of B-cell compartment dynamics and contribute to broader modulation of adaptive immune amplification pathways. Pharmacokinetic data support a threshold-based model of BAFF neutralization, with exposure influenced by disease-related factors such as proteinuria in LN. Clinical response is primarily determined by baseline disease biology, with greater benefit observed in patients with serologically active disease and less established organ involvement. Across clinical trials and real-world studies, belimumab reduces disease activity and flares, enables glucocorticoid tapering, and slows organ damage accrual. In LN, it improves renal outcomes and reduces the risk of kidney-related events. Collectively, these findings support belimumab as a disease-modifying therapy in SLE. Further research is needed to refine patient selection and optimize treatment sequencing and combination strategies. Full article

Antimicrobial resistance (AMR) is an ever-growing threat to global healthcare. It is largely driven by delayed or inadequate pathogen identification and antimicrobial susceptibility testing in routine clinical workflows. By the time the clinician receives results to guide treatment from traditional culture-based diagnostics, several days may have elapsed, leading to the use and potential over-prescription of broad-spectrum antibiotics and the development of resistant pathogens. A rapid and clinically actionable diagnostic approach at the clinical point of care (POC) may help address this gap. This review examines current and emerging POC diagnostic technologies for AMR and outlines the fundamental principles and mechanistic classifications of POC diagnostic technologies. These include phenotypic, genotypic, immunological, and biosensor-based approaches. A critical overview of key technological platforms, including rapid phenotypic antimicrobial susceptibility testing (AST), microfluidics and isothermal nucleic acid amplification (e.g., LAMP and RPA), CRISPR-based diagnostics, nanomaterial-enhanced biosensors, and mobile-integrated systems is provided. The impact of POC diagnostics on antimicrobial stewardship, time to appropriate therapy, and patient outcomes in primary care settings, hospitals, intensive care units, and resource-limited settings is presented and discussed. In addition to clinical implementation challenges, this review considers the issues of analytical performance, workflow, regulatory pathways, cost, and implementation readiness. In addition, it outlines key trends regarding digital integration, surveillance, workforce training, and policy frameworks. Overall, the review outlines the role of POC diagnostics in enhancing antimicrobial response surveillance and the global fight against AMR. Among emerging platforms, rapid phenotypic AST, microfluidic and isothermal-based assays, CRISPR-based diagnostics, and integrated biosensor systems show the greatest potential for near-term clinical impact; however, widespread implementation remains constrained by challenges related to clinical validation, cost, workflow integration, and alignment with antimicrobial stewardship frameworks. Full article

Invasive pulmonary aspergillosis (IPA) poses a serious threat to immunocompromised hosts, with limited therapeutic options highlighting the need for novel strategies. Coptis chinensis Franch. (CCF), a traditional Chinese herb containing antimicrobial alkaloids like berberine, was investigated for its therapeutic efficacy and immunological effects in a murine IPA model. Immunosuppressed female KM mice infected with Aspergillus fumigatus AF293 were treated with CCF or amphotericin B (AmB). CCF significantly improved survival, reduced fungal burden, and alleviated lung pathology, without inducing hepatotoxicity or nephrotoxicity. Transcriptomic profiling revealed a time-dependent immune response. Complement-related pathways were enriched at 2 days post-infection, whereas neutrophil recruitment and NET-related pathways became more prominent by day 4. Hub gene analysis identified Syk, Rac2, Ncf1, and Cybb as key nodes associated with the NADPH oxidase complex. Western blot and inhibitor experiments further supported the involvement of this pathway in CCF-mediated protection. Additionally, 16S rDNA sequencing indicated enrichment of Clostridium species in the gut microbiota of CCF-treated mice, which was positively correlated with the expression of NADPH oxidase-related genes, suggesting a potential gut–lung association. In conclusion, these findings support the antifungal efficacy of CCF in IPA and suggest that its protective effects may involve coordinated changes in complement-related responses, NADPH oxidase-associated neutrophil activity, and gut microbiota composition. Full article