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Cardiovascular diseases (CVDs) are a leading cause of global morbidity and mortality, significantly driven by chronic inflammation. Interleukin-6 (IL-6) and interleukin-1β (IL-1β) are critical inflammatory cytokines implicated in CVD progression. This systematic review evaluates the roles of IL-6 and IL-1β in CVDs by synthesizing data from relevant studies to understand their impact on cardiovascular outcomes and identify potential therapeutic interventions. A comprehensive literature search was conducted using PubMed and Embase, covering studies from January 2014 to December 2024. Inclusion criteria encompassed studies investigating IL-6 and/or IL-1β in CVDs, including human and relevant animal models, and reporting clinical outcomes, molecular mechanisms, or therapeutic interventions. Data extraction and quality assessment were performed independently by two reviewers. Our review included 12 studies focusing on the roles of IL-6 and IL-1β in various CVDs. Elevated IL-6 levels were significantly associated with peripheral artery disease, myocardial infarction, and heart failure, while IL-1β levels were linked to worse outcomes in coronary artery disease and heart failure. Meta-analyses indicated a significant association between higher IL-6 and IL-1β levels and increased risk of adverse cardiovascular events. These findings suggest that targeting IL-6 and IL-1β could offer promising therapeutic strategies for reducing inflammation and improving cardiovascular outcomes.

Pulmonary fibrosis is a chronic, progressive, irreversible lung disease characterized by fibrotic scarring in the lung parenchyma. This condition involves the excessive accumulation of extracellular matrix (ECM) due to the aberrant activation of myofibroblasts in the alveolar environment. Transforming growth factor beta (TGF-β) signaling is a crucial driver of fibrogenesis because it promotes excessive ECM deposition, thereby leading to scar formation and lung damage. A primary target of TGF-β signaling in fibrosis is Collagen Triple Helix Repeat Containing 1 (CTHRC1), a secreted glycoprotein that plays a pivotal role in ECM deposition and wound repair. TGF-β transcriptionally regulates CTHRC1 in response to tissue injury and controls the wound healing response through functional activity. CTHRC1 may also play an essential role in re-establishing and maintaining tissue homeostasis after wound closure by modulating both the TGF-β and canonical Wnt signaling pathways. This dual function suggests that CTHRC1 regulates tissue remodeling and homeostasis. However, deregulated CTHRC1 expression in pathogenic fibroblasts has recently emerged as a hallmark of fibrosis in multiple organs and tissues. This review highlights recent studies suggesting that CTHRC1 can serve as a diagnostic and prognostic biomarker for fibrosis in idiopathic pulmonary fibrosis, systemic sclerosis, and post-COVID-19 lung fibrosis. Notably, CTHRC1 expression is responsive to antifibrotic drugs that target the TGF-β pathway, such as pirfenidone and bexotegrast, indicating its potential as a biomarker of treatment success. These findings suggest that CTHRC1 may present new opportunities for diagnosing and treating patients with lung fibrosis.

Hashimoto’s thyroiditis (HT) and alopecia areata (AA) are organ-specific autoimmune diseases that frequently co-occur, suggesting shared immunological and microbial pathways. The gut microbiome has emerged as a key modulator of immune function, yet disease-specific microbial signatures remain poorly defined. Fecal samples from 51 participants (HT: n = 16, AA: n = 17, healthy controls: n = 18) aged 18–65 years were analyzed using shotgun metagenomic sequencing followed by multivariate statistical analyses. While alpha and beta diversity did not differ significantly across groups, taxonomic profiling revealed disease-specific microbial patterns. Bacteroides fragilis was significantly enriched in HT, suggesting a potential role in immune modulation; although mechanisms such as polysaccharide A production and molecular mimicry have been proposed in previous studies, their involvement in HT remains to be confirmed. Microbacterium sp. T32 was elevated in both HT and AA, indicating its potential as a shared autoimmune marker. Functional analysis showed increased fermentation and amino acid biosynthesis in AA, contrasting with reduced metabolic activity and elevated carbohydrate biosynthesis in HT. HT and AA exhibit distinct gut microbial and metabolic signatures. Bacteroides fragilis and Microbacterium sp. T32 may serve as potential microbial correlates for autoimmune activity, offering new insights into disease pathogenesis and targets for microbiome-based interventions.

Vitiligo is an autoimmune skin disease characterized by melanocyte destruction. Regulatory T cells (Tregs) are greatly reduced in vitiligo skin, and replenishing peripheral skin Tregs can provide protection against depigmentation. Ganglioside D3 (GD3) is overexpressed by perilesional epidermal cells, including melanocytes, which prompted us to generate GD3-reactive chimeric antigen receptor (CAR) Tregs to treat vitiligo. Mice received either untransduced Tregs or GD3-specific Tregs to test the hypothesis that antigen specificity contributes to reduced autoimmune reactivity in vitro and in vivo . CAR Tregs displayed increased IL-10 secretion in response to antigen, provided superior control of cytotoxicity towards melanocytes, and supported a significant delay in depigmentation compared to untransduced Tregs and vehicle control recipients in a TCR transgenic mouse model of spontaneous vitiligo. The latter findings were associated with a greater abundance of Tregs and melanocytes in treated mice versus both control groups. Our data support the concept that antigen-specific Tregs can be prepared, used, and stored for long-term control of progressive depigmentation.

Heart failure (HF) represents a global health burden with distinct phenotypes characterized by varying left ventricular ejection fraction (LVEF). Despite shared endothelial dysfunction, heart failure with reduced (HFrEF) and preserved ejection fraction (HFpEF) exhibit fundamentally different pathophysiological mechanisms, comorbidity profiles, and treatment responses. This systematic review and meta-analysis examine inflammatory, cardiac remodelling and congestion, and myocardial injury biomarkers across HF phenotypes, integrating data from 78 studies encompassing 58,076 subjects. Our analysis reveals a significant elevation of IL-6, TNF-alpha, and hs-CRP in HF compared to controls, with distinct biomarker profiles emerging between phenotypes. While inflammatory markers universally increase with disease severity, their utility in phenotypic differentiation remains limited due to substantial overlap. Comorbidity burden significantly influences inflammatory profiles, creating diagnostic challenges that multi-biomarker approaches may address. NT-proBNP, sST2, GDF-15, and cardiac troponins demonstrate complementary value when combined with inflammatory markers, potentially enabling more precise phenotypic classification. Our findings highlight the central role of inflammation in HF pathophysiology while identifying critical knowledge gaps, particularly regarding HFpEF-specific inflammatory signatures. This comprehensive analysis provides a foundation for developing targeted immunomodulatory therapies and personalized diagnostic approaches in heart failure management. https://www.crd.york.ac.uk/PROSPERO/view/CRD42025639405, PROSPERO CRD42025639405.

In Kazakhstan, the number of people living with HIV (PLHIV) has increased steadily by 39% since 2010. Development of antiretroviral therapy (ART) resistance mutations (ARTRM) is a major hurdle in achieving effective treatment and prevention against HIV. Using HIV pol sequences from 602 PLHIV from Kazakhstan, we analyzed ARTRMs for their association with factors that may promote development of ARTRMs. 56% PLHIV were infected with HIV subtype A6 and 42% with CRF02_AG. The ARTRM Q174K was associated with increased viral load and decreased CD4+ cell count, while infection with CRF02_AG was associated with a lower likelihood of Q174K. Interestingly, CRF02_AG was positively associated with the ARTRM L10V that, in turn, was observed frequently with darunavir administration. Infection with CRF02_AG was positively associated with the ARTRM S162A that, in turn, was frequently observed with the administration of nevirapine, also associated with lower CD4 counts. Zidovudine or Nevirapine receipt was associated with the development of the ARTRM E138A, that, in turn, was associated with lower CD4 counts. Determination of a patient’s HIV variant can help guide ART choice in Kazakhstan. For example, PLHIV infected with CRF02_AG will benefit less from darunavir and nevirapine, and emtricitabine should replace zidovudine.

Background Heart failure poses a significant health concern globally, and despite advancements in treatment, the search for additional, supportive therapeutic options remains crucial. This systematic review and meta-analysis studied the impact of probiotics and polyphenols on heart failure biomarkers, focusing on potential improvements in heart function and inflammation. Methods We analyzed studies published in Embase, PubMed and Cochrane library from 2012 to 2024, focusing on randomized controlled trials. Our findings are drawn from 5 studies on probiotics, involving 401 participants, and 3 studies on polyphenols with a total of 140 participants. The analysis included assessments of LVEF, hs-CRP, creatinine and NT-proBNP levels in intervention and control groups. Results The probiotics or polyphenols from the included studies did not demonstrate significant changes in the health indicators analyzed for heart failure patients compared to placebo. Conclusions The systematic review suggested that while the concept of dietary management for heart failure is promising, further research is necessary to validate the efficacy of probiotics and polyphenols as supplementary therapies in heart failure care, by analyzing more diverse health outcomes and patient populations.

The SARS-CoV-2 pandemic has created a public health crisis worldwide. Although vaccines against the virus are efficiently being rolled out, they are proving to be ineffective against certain emerging SARS-CoV-2 variants. The high degree of sequence similarity between SARS-CoV-2 and other human coronaviruses (HCoV) presents the opportunity for designing vaccines that may offer protection against SARS-CoV-2 and its emerging variants, with cross-protection against other HCoVs. In this study, we performed bioinformatics analyses to identify T and B cell epitopes originating from spike, membrane, nucleocapsid, and envelope protein sequences found to be evolutionarily conserved among seven major HCoVs. Evolutionary conservation of these epitopes indicates that they may have critical roles in viral fitness and are, therefore, unlikely to mutate during viral replication thus making such epitopes attractive candidates for a vaccine. Our designed vaccine construct comprises of twelve T and six B cell epitopes that are conserved among HCoVs. The vaccine is predicted to be soluble in water, stable, have a relatively long half-life, and exhibit low allergenicity and toxicity. Our docking results showed that the vaccine forms stable complex with toll-like receptor 4, while the immune simulations predicted that the vaccine may elicit strong IgG, IgM, and cytotoxic T cell responses. Therefore, from multiple perspectives, our multi-subunit vaccine design shows the potential to elicit a strong immune-protective response against SARS-CoV-2 and its emerging variants while carrying minimal risk for causing adverse effects.

Mutations underlying disease in tuberous sclerosis complex (TSC) give rise to tumors with biallelic mutations in TSC1 or TSC2 and hyperactive mammalian target of rapamycin complex 1 (mTORC1). Benign tumors might exhibit de novo expression of immunogens, targetable by immunotherapy. As tumors may rely on ganglioside D3 (GD3) expression for mTORC1 activation and growth, we compared GD3 expression in tissues from patients with TSC and controls. GD3 was overexpressed in affected tissues from patients with TSC and also in aging Tsc2+/ – mice. As GD3 overexpression was not accompanied by marked natural immune responses to the target molecule, we performed preclinical studies with GD3 chimeric antigen receptor (CAR) T cells. Polyfunctional CAR T cells were cytotoxic toward GD3-overexpressing targets. In mice challenged with Tsc2 –/– tumor cells, CAR T cells substantially and durably reduced the tumor burden, correlating with increased T cell infiltration. We also treated aged Tsc2+/ – heterozygous (>60 weeks) mice that carry spontaneous Tsc2 –/– tumors with GD3 CAR or untransduced T cells and evaluated them at endpoint. Following CAR T cell treatment, the majority of mice were tumor free while all control animals carried tumors. The outcomes demonstrate a strong treatment effect and suggest that targeting GD3 can be successful in TSC.

Background. The objective of this systematic review and meta-analysis was to estimate the proportions of individuals infected with Campylobacter, Escherichia, Salmonella, Shigella, or Yersinia who develop reactive arthritis. Methods. A systematic review was conducted, encompassing English-language articles published before January 2024, sourced from the Embase, PubMed, Scopus, and Web of Science databases. This review included observational studies that reported the occurrence of reactive arthritis (ReA) among patients with Campylobacter, Escherichia, Salmonella, Shigella, or Yersinia infections. Data extraction was carried out independently by two reviewers. Subsequently, a random-effects meta-analysis was performed, with heterogeneity assessed using the I2 value. Additionally, meta-regression was employed to investigate the potential influence of study-level variables on the observed heterogeneity. Results. A total of 87 studies were identified; 23 reported on ReA development after Campylobacter infection, 7 reported on ReA after Escherichia infection, 30 reported ReA onset after salmonellosis, 14 reported ReA after shigellosis, and 13 reported ReA after Yersinia infection. The proportion of Campylobacter patients who developed ReA was 0.03 (95% CI [0.01, 0.06], I2 = 97.62%); the proportion of Escherichia patients who developed ReA was 0.01 (95% CI [0.00, 0.06], I2 = 92.78%); the proportion of Salmonella patients was 0.04 (95% CI [0.02, 0.08], I2 = 97.67%); the proportion of Shigella patients was 0.01 (95% CI [0.01, 0.03], I2 = 90.64%); and the proportion of Yersinia patients who developed ReA was 0.05 (95% CI [0.02, 0.13], I2 = 96%). Conclusion. A significant proportion of Salmonella, Shigella, and Yersinia cases resulted in ReA. Nonetheless, it is important to interpret the findings cautiously due to the substantial heterogeneity observed between studies.