Interleukin-35 (IL-35), consisting of two subunits - Ebi3 and p35, is a pleiotropic anti-inflammatory cytokine implicated in fetal tolerance and pregnancy maintenance. Reduced IL-35 levels in abortion-prone mice and women with recurrent miscarriage suggest its deficiency contributes to pregnancy failure. In abortion-prone mice, IL-35 administration during mid-term gestation rescued pregnancy. However, it is unclear whether IL-35 administration before implantation (during the time of the first recognition of paternal antigens) can expand regulatory lymphocyte pools and restore maternal tolerance. Therefore, this study aimed to investigate the influence of intraperitoneal administration of recombinant IL-35 (rIL-35) and anti-Ebi3 antibody shortly after mating on successful pregnancy, fetal blood flow, and the profiles of several types of regulatory cells in a murine abortion-prone model.

Tumor necrosis factor alpha (TNF-α) is an important cytokine that frequently contributes to the pathogenicity of autoimmune diseases. Therefore, TNF inhibitors (TNFi) are used to treat autoimmune diseases. However, around 40% of the patients do not respond to TNFi, with genetic variants being a contributor to this variance. The prevalence of genetic variants affecting TNFi response in Middle Eastern populations is still not understood.

Oligocentric Castleman Disease (OCD), a distinct subtype of Castleman Disease (CD) intermediate between Unicentric (UCD) and idiopathic Multicentric (iMCD) forms, remains poorly characterised.

Adhesion to host cells is the first and essential step in () infection. Among adhesion molecules, the PGRS domain of PE_PGRS33 plays a critical role in invasion but is dominated by B cell epitopes and lacks sufficient T cell epitopes, restricting its capacity to induce a balanced immune response.

India, has a rich ethnomedicinal tradition where numerous herbs are used in cancer care. However, scientific validation of these practices remains limited. This narrative review explores the phytochemical mechanisms underlying their anti-cancer effects of 32 herbs identified by herbal activists, including physicians and traditional healers from Tamil Nadu, India, for their purported anticancer properties.

Osteosarcoma is a highly aggressive bone malignancy characterized by frequent metastasis and therapy resistance. Although mitophagy and pyruvate metabolism are increasingly recognized as critical metabolic regulators, their interaction in osteosarcoma remains poorly understood. The autophagy-related protein GABARAP, central to mitochondrial quality control, has not been systematically evaluated in osteosarcoma.

Tislelizumab, a programmed cell death-1 inhibitor approved for multiple malignancies, may induce Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)-a rare but potentially fatal severe drug eruption-and early effective intervention is pivotal for reducing SJS/TEN-related mortality. We describe an elderly male with hepatic malignancy who developed progressive SJS/TEN, involving over 80% of his total body surface area, after his first tislelizumab infusion. Conventional treatment with systemic corticosteroids combined with intravenous immunoglobulin was ineffective in halting disease progression. Subsequently, adjunctive therapy with a tumor necrosis factor-α (TNF-α) inhibitor and hemoperfusion was initiated, leading to the patient's eventual recovery. Managing SJS/TEN in patients with advanced malignancies poses substantial challenges, given the life-threatening nature of both entities. To our knowledge, this is the first reported case of using a TNF-α inhibitor for treating tislelizumab-induced SJS/TEN. This case highlights a novel, cost-effective, and well-tolerated therapeutic strategy that yielded favorable outcomes.

This study aims to explore the prognostic significance of necroptosis-related genes in pancreatic cancer.

Neutralizing antibodies (NAbs) are critical for protection against SARS-CoV-2, but there is limited information on their role in pregnancy, especially among Cameroonian women. Here, we aimed to determine the prevalence of pan-coronavirus reactive antibodies from pregnant women sampled before and during the COVID-19 pandemic.

Over 6 million people worldwide are affected by primary immunodeficiencies (PIDs), which often remain undiagnosed, and the diagnostic process is complex and challenging. Dysfunction of the immune system can lead to permanent damage to body systems and organs; moreover, Ig replacement therapy carries the risk of anaphylactic shock following the administration of the immunoglobulin preparation. The present study proposes an alternative testing method for IgA deficiency, using the BSA-peptide conjugate with the RYDERY sequence, which may serve as a simpler alternative to complex diagnostic schemes.

Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment (TME) which promote drug resistance by remodeling the extracellular matrix, generating an immunosuppressive microenvironment, and activating metabolic signaling pathways. Nanomaterials provide an effective method for specifically targeting CAF-mediated drug resistance because of their unique targeted delivery capabilities, responsive release characteristics, and multifunctional integration. Here, we describe the mechanisms underlying the role of CAFs in drug resistance. The types of materials used and design principles are described, and examples of the application of nanomaterials for targeting CAFs are provided. Current challenges and future directions of nanomaterials targeting CAFs for reversing tumor drug resistance are also discussed to provide theoretical support for the development of effective nanotherapies aimed at reversing drug resistance in cancer.

While local immune responses in periprosthetic joint infection (PJI) are increasingly studied, systemic immune alterations remain poorly characterized. Therefore, this study aimed to investigate the change in peripheral lymphocyte subsets and immune-related protein profiles in patients with PJI, and explore the potential value of these indicators for the diagnosis of PJI.

Microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer (CRC) is characterized by high tumor mutational burden and strong immunogenicity, making it responsive to immune checkpoint inhibitors. Hepatoid adenocarcinoma (HAC) of the colon is an exceptionally rare and aggressive subtype, often resistant to conventional chemotherapy. We report a 77-year-old woman who presented with progressive anemia and a right-sided colonic mass. She underwent laparoscopic radical right hemicolectomy, and pathology revealed hepatoid features with vascular and neural invasion. Immunohistochemistry showed loss of MLH1, PMS2, and MSH6, confirming dMMR status, and MSI testing indicated MSI-H. BRAF V600E mutation was identified, and germline testing excluded Lynch syndrome. Given her age and potential chemotherapy toxicity, she received eight cycles of adjuvant envafolimab (200 mg every 3 weeks). Over 38 months of follow-up, she remained disease-free without experiencing any grade ≥2 immune-related adverse events.

Human metapneumovirus (HMPV) is a major cause of acute respiratory disease in children, the elderly, and immunocompromised individuals. While pro-inflammatory cytokines and type I interferons (IFNs) are important for antiviral defense, excessive tumor necrosis factor (TNF) is associated with severe disease in HMPV and other respiratory infections. Hence, defining regulatory mechanisms by which HMPV induces TNF and IFN-β is important for therapeutic strategies in airway disease. The immunoregulatory receptors Toll-like receptor (TLR)4 and signaling lymphocytic activation molecule family 1 (SLAMF1) mediate TNF and IFN-β expression in response to LPS and Gram-negative bacteria, but their involvement in HMPV-stimulated cytokine expression is unclear.

Yeasts have contributed to human and animal health through functional antigen production for vaccine formulations. Some yeast-made vaccines have become a reality for humankind because they have reached commercialization (hepatitis B, HPV, and tick parasitosis). Many other vaccine prototypes are under preclinical and clinical evaluations, hoping for their usage soon. Currently, genomes, genetic modification techniques, and industrial vaccine manufacturing have been successfully developed for , , and . Moreover, several yeast species are under research as prospects for vaccine production systems, such as , and . This review was mainly focused on commercial human and animal vaccines, describing and discussing genetic engineering tools, downstream antigen purification processes, GMP according to regulatory issues, and identifying challenges and future directions on the use of yeast as a vaccine production platform to fight against infectious diseases.

The increasing prevalence of multidrug-resistant (MDR) bacteria has reduced the effectiveness of standard antibiotics, prompting renewed interest in bacteriophage (phage) therapy as an alternative or adjunctive treatment. Phage therapy offers high specificity, self-amplification at infection sites, and minimal disruption to the gut microbiota. However, clinical implementation is challenging, due to the risk of phage resistance and uncertainties regarding optimal dosing and immune interactions.

Rheumatoid arthritis (RA) is a persistent autoimmune condition marked by systemic inflammation, primarily impacting multiple joints and causing irreversible structural and functional damage. While pathophysiology remains complex, immune cells and cytokines are crucial to the disease's initiation and progression. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are routinely used to assess disease activity. However, in recent years, the pan-immune inflammatory value (PIV) has emerged as a focal point of inquiry. As a new, single biomarker calculated from various routine blood parameters, PIV accurately reflects the patient's comprehensive systemic immune-inflammatory condition and offers a more integrated perspective than traditional markers. This article provides a focused analysis of the potential role and clinical significance of PIV in assessing the activity and advancement of RA.

Heart failure is a complex clinical syndrome caused by structural and/or functional cardiac abnormalities. Ventricular remodeling contributes to its progression. Cardiac macrophages regulate inflammation, fibrosis, and tissue repair that drive this process. In this Review, we describe the origins and phenotypic diversity of cardiac macrophages, including both resident and monocyte-derived subsets. In the left ventricle, macrophages respond to ischemia, pressure overload, and metabolic stress. In the right ventricle, they display distinct immune features under pulmonary hypertension and other stress conditions. We further discuss the interactions between macrophages and other cardiac cell types, such as fibroblasts, cardiomyocytes, endothelial cells, and lymphocytes. These interactions shape the immune environment and structural integrity of the myocardium. We also highlight recent advances in single-cell and spatial technologies that reveal chamber-specific macrophage signatures. Finally, we summarize emerging therapeutic strategies targeting macrophages, including pharmacological agents, engineered cell therapies, and nanoparticle-based delivery systems. Together, these insights provide a framework for understanding macrophage-mediated remodeling and for guiding precision immunotherapies in heart failure.

Foxp3 regulatory T (Treg) cells exhibit remarkable plasticity, enabling them to phenotypically and functionally adapt to diverse immune responses across tissues. However, this plasticity comes with the risk of lineage instability, including downregulation of Foxp3 and acquisition of pro-inflammatory effector programs. Although Treg transdifferentiation has been implicated in autoimmunity, its precise contribution to disease pathogenesis has remained incompletely understood. Recent advances in single-cell RNA and TCR sequencing provide evidence that, in visceral adipose tissue (VAT), the loss of Treg cells during obesity is driven by the selective transdifferentiation of thymus-derived Treg cells in response to local inflammatory stress. We propose that this process fuels chronic inflammation and may represent one pathway linking Treg instability to chronic VAT inflammation and metabolic dysfunction. Here, we summarize emerging evidence for Treg destabilization in VAT and discuss how local inflammatory and systemic metabolic cues may interact to drive this process, drawing conceptual parallels with autoimmune diseases, particularly type 1 diabetes.

This study identifies and characterizes previously unrecognized medullary B cell niches within murine mucosa-draining lymph nodes (LNs), challenging the conventional understanding of LN architecture. Utilizing advanced imaging techniques, including synchrotron radiation-based phase-contrast micro-computed tomography (SRµCT), correlated high-resolution electron microscopy and immunohistochemistry (IHC), we revealed spherical to ovoid structures termed , being distinct lymphoid compartments consistently localized in the medullary region of mandibular and other mucosa-draining LNs. These nodules were primarily composed of unswitched, non-proliferative CD45R B cells expressing IgD and IgM, lacking germinal center features or typical activation markers. They were seamlessly integrated into the medullary architecture, surrounded by LYVE-1 lymphatic endothelial cells, and situated in close proximity to medullary high endothelial venules (HEVs), revealed by PNAd staining. Under steady-state conditions, this has not been previously observed in the medullary compartment of LNs but is likely facilitating nodule-like B cell aggregation in mucosa-draining LNs due to sustained low level antigenic stimulation common in mucosal environments and is underpinned by proteomics. Additionally, the nodules displayed a capillary network that closely resembles the vascularization seen in conventional B cell follicles revealed by SRµCT. Nodule formation occured between two and four weeks postnatally, thus emerging later than B cell follicles, and their abundance showed a tendency to increase with age. Functionally, these nodules appear to represent a quiescent B cell niche, potentially supporting B cell homeostasis, tolerance, or memory-like readiness, and are distinct from pathological hyperplasias. Their preservation in aged LNs, coupled with the absence of lipomatosis, suggests a role in maintaining structural integrity and immune readiness through persistent B cell-stromal interactions. This research challenges the established paradigm of LN microarchitecture and suggests specialized niches for B cell function and lymphocyte trafficking in regions subject to constant antigenic exposure.