Integrative multi-omics analysis identifies coronin 1C as a potential mediator linking circadian rhythm disruption to neuroimmune dysregulation in ischemic stroke.

The Notch1 signalling pathway promotes Silicotic fibrosis by modulating macrophage polarization in response to crystalline silica.

Induction of regulatory T cells by an aluminum-CpG combination adjuvant for therapeutic and preventive vaccination against pollen allergy.

Organic acidemias (OAs) are a group of inherited disorders, most commonly caused by defects in mitochondrial enzymes involved in amino acid and fatty acid metabolism. While they characteristically present with metabolic and neurological crises, growing evidence reveals a significant burden of chronic immune dysregulation in some disorders and patients. This review provides a synthesis of clinical and mechanistic evidence discussing immune dysregulation in OAs. Cytopenia can occur in OAs and predispose patients to recurrent and severe infections. Adaptive immune deficits, such as hypogammaglobulinemia, reduced B and T cell populations, and impaired vaccine-specific antibody responses, including to diphtheria and tetanus in MSUD and to the inactivated COVID-19 vaccine in propionic acidemia, have also been reported. Additionally, some case series note hyperinflammatory conditions, such as hemophagocytic lymphohistiocytosis. Mechanistic studies indicate that accumulated metabolites disrupt innate and adaptive hematopoietic progenitor function, mitochondrial homeostasis, and inflammatory signaling. Emerging therapeutic avenues, such as gene and mRNA-based therapies, hold the potential to improve or normalize the biochemical phenotype in OAs. While their impact on immune abnormalities remains largely unexplored, future clinical trials offer an opportunity to systematically assess potential effects on immune parameters. OAs are increasingly recognized as disorders with intrinsic immune dysregulation, extending beyond their well-characterized metabolic and neurological manifestations. Future clinical trials will benefit from including immunological endpoints to evaluate immunological recovery for novel therapies.

Smart multifunctional ROS-responsive supramolecular hydrogel for simultaneously regulating oxidative stress, immune dysregulation, and bacterial infection in diabetic wound healing.

Leptin, an adipokine predominantly secreted by adipose tissue, has exhibited a wide range of biological functions, including regulation of energy balance, appetite, and metabolism. Accumulating evidence has demonstrated that leptin also plays a role in obesity-associated tumor progression. Elevated circulating leptin levels in obese individuals, together with the close association between obesity and increased cancer risk, have led to growing interest in leptin as a potential mediator linking adiposity to tumor growth and immune dysregulation. Recent studies have shown that leptin can directly interact with immune cells within the tumor microenvironment and promote dysfunction or exhaustion in various immune cell populations, thereby impairing anti-tumor immunity. These findings suggest that tumor-promoting effects of leptin may be mediated, at least in part, through modulation of anti-tumor immune responses. Notably, metabolic reprogramming of both immune cells and cancer cells appears to be a critical mechanism underlying leptin-mediated tumor progression and immune dysfunction. Since obesity is characterized by altered adipokine production, chronic low-grade inflammation, and immune dysregulation, leptin may serve as a critical mediator linking excess adiposity to impaired immune surveillance and cancer progression. However, the biological effects of leptin are highly context-dependent. Although leptin predominantly supports tumor progression and immune suppression in many obesity-associated cancers, it may also exert immune-stimulatory or anti-tumor effects under specific conditions. This review summarizes current mechanistic insights into the role of leptin in tumor progression and immune regulation. We also highlight therapeutic strategies that integrate leptin-targeted approaches with immunotherapy.

Smoldering multiple myeloma (SMM) represents a heterogeneous precursor stage between monoclonal gammopathy of undetermined significance and symptomatic multiple myeloma (MM). Advances in diagnostic criteria, particularly the adoption of the SLiM-CRAB framework, have improved the distinction between SMM and MM and reduced the risk of misclassification. Contemporary risk stratification models, such as the Mayo 20/2/20 criteria and International Myeloma Working Group refinements, integrate both static and dynamic biomarkers to provide more accurate predictions of progression. Genomic and immunological studies have further revealed key drivers of disease evolution, patterns of clonal evolution, and immune dysregulation, which may guide therapeutic decisions. Clinical trials have demonstrated that early intervention with lenalidomide or daratumumab can delay progression. In contrast, intensive multi-agent regimens, such as those used in the GEM-CESAR and ASCENT trials, have achieved high rates of minimal residual disease negativity and suggest curative potential. Nevertheless, the long-term survival benefits of these strategies remain uncertain, and the risks of toxicity in asymptomatic patients require careful consideration. Ongoing studies, including CAR-PRISM and ImmunoPRISM, are evaluating cellular and antibody-based therapies for high-risk SMM. Collectively, these advances highlight the need for refined, individualized approaches that balance the benefits and risks in the management of SMM.

Targeted dermal delivery of phloretin via thermoresponsive nanoparticles potently suppresses STAT3/NF-κB-driven psoriatic inflammation.

Berberine pretreatment enhances the homing and anti-inflammatory efficacy of dental pulp mesenchymal stem cells in TNBS-induced inflammatory bowel disease via activating the CXCR4/SDF-1 signaling pathway.

Topical ionic liquid-mediated GLUT1 gene editing ameliorates psoriasis and prevents recurrence.

Estrogen receptor-positive (ER+) breast cancer accounts for the majority of breast cancer cases worldwide, yet the long-term efficacy of endocrine therapy is limited by resistance and recurrence. While tumor-intrinsic mechanisms of endocrine resistance are well established, growing evidence highlights the contributions of innate immune cells and the tumor microenvironment (TME) in shaping therapeutic outcomes. This review synthesizes recent advances into how tumor-associated macrophages (TAMs), natural killer (NK) cells, myeloid-derived suppressor cells (MDSCs), and tumor-associated neutrophils (TANs) collectively foster an immunosuppressive TME that undermines endocrine responsiveness. Central to this crosstalk is the STAT3 signaling pathway, which integrates inflammatory and metabolic stress signals to drive immune reprogramming, promotes tumor progression, and facilitates therapy resistance. By activating tolerogenic pathways and inhibiting anti-tumor immunity, STAT3 provides a mechanistic link between innate immune dysregulation and endocrine resistance. Preclinical studies demonstrate that STAT3 inhibition can restore tamoxifen sensitivity in resistant ER+ breast cancer models, highlighting its therapeutic potential. These insights reveal the immunological complexity of endocrine resistance and provide rationale for combinatorial strategies integrating endocrine therapy with immunomodulation. Future approaches that incorporate STAT3 inhibitor, immune checkpoint blockade, and biomarker-guided patient selection may transform the management of ER+ breast cancer, offering more durable and clinically meaningful outcomes by acknowledging the emerging interactions between immune dysregulation and metabolic stress in resistant ER+ breast cancer.

Systemic modulation of toll-like receptors, cytokine polarization and inflammasome signaling in dogs with generalized demodicosis.

Dimethyl fumarate alleviated DSS-induced colitis by regulating Th17/Treg balance via suppressing JAK2/STAT3 and NF-κB signaling.

Immunomodulatory therapies and emerging drug associations with microscopic colitis: A global pharmacovigilance analysis.

Idiopathic pulmonary fibrosis is a progressive and fatal lung disease characterized by irreversible tissue scarring, structural distortion, and declining respiratory function. Although currently approved antifibrotic therapies can slow disease progression, they do not stop or reverse fibrosis, highlighting the need to better understand upstream disease mechanisms. Increasing evidence identifies cellular senescence as a central biological process linking aging, epithelial cell vulnerability, mitochondrial dysfunction, and abnormal tissue repair in pulmonary fibrosis. Senescent epithelial and mesenchymal cells remain metabolically active and release a broad array of secreted factors that promote fibroblast activation, persistence of contractile cells, and excessive matrix deposition. Recent advances using single-cell and three-dimensional culture approaches further reveal the accumulation of transitional epithelial cell states that fail to complete normal differentiation and instead perpetuate fibrotic remodeling. These findings suggest that senescence represents not merely a consequence of tissue injury, but a self-sustaining driver of disease progression. This review integrates current mechanistic insights into how cellular senescence coordinates epithelial injury, immune dysregulation, and biomechanical feedback to drive lung fibrosis. We also discuss emerging therapeutic strategies that target senescent cells or their downstream signaling pathways, highlighting their potential to complement existing antifibrotic treatments and enable more effective disease modification.

Iron, autoimmunity, and thrombosis: Exploring sex-specific interactions.

Social determinants of health (SDoHs) are increasingly recognized as important contributors to the development, course, and outcomes of psychiatric disorders. However, their integration into clinical psychiatry and mechanistic models remains limited. This overview synthesizes emerging evidence on the biopsychosocial mechanisms through which SDoHs influence mental health. There is a need to distinguish between individual-level, clinically actionable health-related social needs and family-, community-, and society-level structural SDoHs, and to consider both adverse and protective social factors. Converging research demonstrates that social experiences are biologically embedded through interacting pathways, including exposomics, epigenetics, allostatic load, accelerated inflammaging, immune dysregulation, and gut-brain-microbiome signaling. These mechanisms influence neural circuitry underlying stress regulation, reward processing, and social cognition. Psychological processes-including individual differences in resilience, wisdom, compassion, and purpose in life-shape responses to SDoHs and are supported by identifiable neurobiological substrates. Social connection has emerged as a central, potentially modifiable SDoH that is strongly associated with whole health and longevity. Loneliness and social isolation have become major global public health challenges. The authors propose a biopsychosocial framework that integrates social exposures, biological mechanisms, neural systems, and psychological processes to better understand the risk, course, and prevention of mental illnesses. Clinical and public health implications include the need for routine assessment of SDoHs, incorporation of protective factors at individual and societal levels, and development of pragmatic, multidomain interventions. Finally, rapidly evolving digital technologies, including artificial intelligence, offer new opportunities but also require careful governance. Advancing toward human-centered "artificial wisdom" may enhance the capacity of technology to promote whole health in individuals with mental illnesses globally.

Dopaminergic modulation of NK cell maturation and immune-associated social behavior in a 15q dup mouse model.

Tear fluid multi-omics and biosensor integration for diagnosis and personalized therapeutics in dry eye disease.

The oral-systemic interface of micro- and nanoplastics.