BACKGROUND: Vitiligo is a common depigmentation disorder characterized by defined white patches on the skin and affecting around 0.5% to 2% of the general population. Genetic association studies have identified several pre-disposing genes and single nucleotide polymorphisms (SNPs) for vitiligo pathogenesis; nonetheless, the reports are often conflicting and rarely conclusive. This comprehensive meta-analysis study was designed to evaluate the effect of the risk variants on vitiligo aetiology and covariate stratified vitiligo risk in the Asian population, considering all the studies published so far.
METHODS: We followed a systematic and comprehensive search to identify the relevant vitiligo-related candidate gene association studies in PubMed using specific keywords. After data extraction, we calculated, for the variants involved, the study-level unadjusted odds ratio, standard errors, and 95% confidence intervals by using logistic regression with additive, dominant effect, and recessive models using R software package (R, 3.4.2) \"metafor.\" Subgroup analysis was performed using logistic regression (generalized linear model; \"glm\") of disease status on subgroup-specific genotype counts. For a better understanding of the likely biological function of vitiligo-associated variant obtained through the meta-analysis, in silico functional analyses, through standard publicly available web tools, were also conducted.
RESULTS: Thirty-one vitiligo-associated case-control studies on eleven SNPs were analysed in our study. In the fixed-effect meta-analysis, one variant upstream of TNF-α gene: rs1800629 was found to be associated with vitiligo risk in the additive (p = 4.26E-06), dominant (p = 1.65E-7), and recessive (p = 0.000453) models. After Benjamini-Hochberg false discovery rate (FDR) correction, rs1800629/TNF-α was found to be significant at 5% FDR in the dominant (padj = 1.82E-6) and recessive models (padj = 0.0049). In silico characterization revealed the prioritized variant to be regulatory in nature and thus having potential to contribute towards vitiligo pathogenesis.
CONCLUSIONS: Our study constitutes the first comprehensive meta-analysis of candidate gene-based association studies reported in the whole of the Asian population, followed by an in silico analysis of the vitiligo-associated variant. According to the findings of our study, TNF-α single nucleotide variant rs1800629G>A has a risk association, potentially contributing to vitiligo pathogenesis in the Asian population.

BACKGROUND: Despite the important role of inflammation-related factors on the occurrence of chronic diseases, there is still conflicting evidence about the effects of the ketogenic diet (KD) on these factors.
OBJECTIVE: In order to obtain a better viewpoint, this study aimed to comprehensively investigate the effects of a KD on inflammation-related markers.
METHODS: To find pertinent randomized controlled trials up to August 2023, databases including PubMed/Medline, Web of Science, Scopus, Cochrane Library, and Embase were searched.
METHODS: This study included all randomized controlled trials investigating the effects of a KD on C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-8, and IL-10 levels. Pooled weighted mean difference (WMD) and 95% confidence intervals (CIs) were achieved by random-effects model analysis for the best estimation of outcomes.
METHODS: Forty-four studies were included in this article. The pooled findings showed that a KD has an effect on lowering TNF-α (WMD: -0.32 pg/mL; 95% CI: -0.55, -0.09; P = 0.007) and IL-6 (WMD: -0.27 pg/mL; 95% CI: -0.52, -0.02; P = 0.036) compared with control groups. However, no significant effect was reported for others inflammation marker-related levels. The results of the subgroup analysis showed that, in trials following the KD for ≤8 weeks and in people aged ≤50 years, the reduction in TNF-α levels was significantly higher than in other groups. In addition, in people with a body mass index greater than 30 kg/m2 compared to a body mass index ≤30 kg/m2, IL-6 levels decreased to a greater extent after receiving the KD.
CONCLUSIONS: Consequently, adherence to a KD appears to improve some markers associated with inflammation, including TNF-α and IL-6.

Inflammation is a major component of heart failure (HF), causing peripheral vasculopathy and cardiac remodeling. High levels of circulating inflammatory cytokines in HF patients have been well recognized. The hallmark of the inflammatory imbalance is the insufficient production of anti-inflammatory mediators, a condition that leads to dysregulated cytokine activity. The condition progresses because of the pathogenic consequences of the cytokine imbalance, including the impact of endothelial dysfunction and adrenergic responsiveness deterioration, and unfavorable inotropic effects on the myocardium. Hence, to develop possible anti-inflammatory treatment options that will enhance the outcomes of HF patients, it is essential to identify the potential pathophysiological mechanisms of inflammation in HF. Inflammatory mediators, such as cytokines, adhesion molecules, and acute-phase proteins, are elevated during this process, highlighting the complex association between inflammation and HF. Therefore, these inflammatory markers can be used in predicting prognosis of the syndrome. Various immune cells impact on myocardial remodeling and recovery. They lead to stimulation, release of alarmins and risk-related molecule patterns. Targeting key inflammatory mechanisms seems a quite promising therapy strategy in HF. Cytokine modulation is only one of several possible targets in the fight against inflammation, as the potential molecular targets for therapy in HF include immune activation, inflammation, oxidative stress, alterations in mitochondrial bioenergetics, and autophagy.

This review analyzes the role of TNF-α and its increase in biological fluids in mild cognitive impairment, and Alzheimer\'s disease (AD). The potential inhibition of TNF-α with pharmacological strategies paves the way for preventing AD and improving cognitive function in people at risk for dementia. We conducted a narrative review to characterize the evidence in relation to the involvement of TNF-α in AD and its possible therapeutic inhibition. Several studies report that patients with RA and systemic inflammatory diseases treated with TNF-α blocking agents reduce the probability of emerging dementia compared with the general population. Animal model studies also showed interesting results and are discussed. An increasing amount of basic scientific data and clinical studies underscore the importance of inflammatory processes and subsequent glial activation in the pathogenesis of AD. TNF-α targeted therapy is a biologically plausible approach for cognition preservation and further trials are necessary to investigate the potential benefits of therapy in populations at risk of developing AD.

The review presents data from the literature on the role of Tumor necrosis factor-α (TNF-α) and ionizing radiation (IR) in the pathogenesis and treatment of plasma cell myeloma (PCM). There was analyzed disturbance of regulation of functioning of this cytokine, which affects the interaction of the immune system with substrate plasma cells under the influence of negative external factors, including ionizing radiation IR. Modern directions of therapy of this disease using the latest technologies are presented, in particular CAR T-cell therapy, which will allow to optimize in the future treatment of this disease and, thus, improve the quality and life expectancy of PCM patients.
В огляді представлені дані літератури стосовно ролі фактора некрозу пухлин-α (TNF-α) та іонізуючого випромінювання в патогенезі і лікуванні плазмоклітинної мієломи. Проаналізовано порушення функціонуваннярегуляції даного цитокіну, що впливає на взаємодію імунної системи з субстратними плазматичними клітинами за умов впливу негативних зовнішніх чинників, у тому числі – іонізуючого випромінювання. Представлено сучасні напрямки терапії даного захворювання з використанням новітніх технологій, зокрема CAR Т-клітинної терапії, що дозволять в перспективі оптимізувати лікування цього захворювання і, таким чином, покращити якістьта тривалість життя хворих на плазмоклітинну мієлому.

Psoriasis is an immune-mediated disease with a strong genetic component that brings many challenges to sick individuals, such as chronic illness, and which has multiple associated comorbidities like cardiovascular disease, metabolic syndrome, inflammatory bowel disease, and psychological disorders. Understanding the interplay between the innate and adaptative immune system has led to the discovery of specific cytokine circuits (Tumor Necrosis Factor-alpha (TNF-α), IL-23, IL-17), which has allowed scientists to discover new biomarkers that can be used as predictors of treatment response and pave the way for personalized treatments. In this review, we describe the footprint psoriasis leaves on the skin and beyond, key pathophysiological mechanisms, current available therapeutic options, and drawbacks faced by existing therapies, and we anticipate potential future perspectives that may improve the quality of life of affected individuals.

Kawasaki disease (KD), an autoinflammatory disease primarily affecting young children, characterized by consisting of acute systemic vasculitis and coronary artery involvement in severe cases. Intravenous immunoglobulin gamma (IVIG) combined with aspirin therapy is the first-line regimen for the prevention of coronary aneurysms in the acute phase of KD. The etiology and pathogenesis of KD are unclear, but its incidence is increasing gradually, especially in the cases of IVIG-naïve KD and refractory KD. Conventional therapies for refractory KD have unsatisfactory results. At present, infliximab (IFX), a human-murine chimeric monoclonal antibody that specifically blocks tumor necrosis factor-α (TNF-α), has made great progress in the treatment of KD. This review revealed that IFX infusion (5 mg/kg) could effectively modulate fever, reduce inflammation, improve arthritis, diminish the number of plasma exchange, decrease hospitalizations, and prevent the progression of coronary artery lesions. The adverse effects of IFX administration included skin rash, arthritis, respiratory disease, infusion reaction, hepatomegaly, and vaccination-associated complications. But the incidence of these adverse effects is low. The clear optimal application protocol of the application of IFX for either initial combination therapy or salvage therapy in KD is still under investigation. In addition, there are no effective biomarkers to predict IFX resistance. Further multicenter trials with large sample size and long-term follow-up are still needed to validate the clinical efficacy and safety of IFX for IVIG-resistant KD or refractory KD.

Tumor Necrosis Factor-alpha (TNF-α) is ubiquitous in the human body and plays a significant role in various physiological and pathological processes. However, TNF-α-induced diseases remain poorly understood with limited efficacy due to the intricate nature of their mechanisms. N6-methyladenosine (m6A) methylation, a prevalent type of epigenetic modification of mRNA, primarily occurs at the post-transcriptional level and is involved in intranuclear and extranuclear mRNA metabolism. Evidence suggests that m6A methylation participates in TNF-α-induced diseases and signaling pathways associated with TNF-α. This review summarizes the involvement of TNF-α and m6A methylation regulators in various diseases, investigates the impact of m6A methylation on TNF-α-induced diseases, and puts forth potential therapeutic targets for treating TNF-α-induced diseases.

Inflammatory biomarkers; C-reactive protein (CRP), Interleukin 6 (IL-6), and tumor necrosis factor- alpha (TNF-α) play a very crucial role in disease pathogenesis. Studies conducted earlier showed the associativity of these biomarkers with malaria severity. Meta-analysis of individual biomarkers was done in many studies, while in a few others, all these candidates were estimated, but the findings were inconclusive. Therefore, a systematic review and meta-analyses were performed to evaluate differences in biomarkers mentioned above in complicated and uncomplicated malaria patients. Studies focussed on CRP, IL-6, and TNF-α with quantitative data on complicated and uncomplicated malaria patients were searched on PubMed, Scopus, and Google Scholar. The quality of the studies selected for this review was checked following Newcastle-Ottawa Scale guidelines. The standard mean difference and confidence interval of biomarkers in the targeted groups were calculated using the random effects model. Egger\'s test and funnel plot asymmetry were performed to assess the publication bias. Thirteen studies that qualified the inclusion criteria were considered for this meta-analysis. CRP levels were higher in complicated malaria patients than uncomplicated ones (P < 0.00001, pooled SMD: 0.90 mg/L, 95 % CI: 0.51 to 1.30 mg/L, I2: 80 %, six studies). IL-6 levels were elevated in complicated cases (P < 0.00001, pooled SMD: 0.89 pg/ml, 95 % CI: 0.66 to 1.12, I2: 99 %, four studies) and TNF-α also showed an increase in severe complicated patients (P < 0.00001, pooled SMD: 1.18 pg/ml, 95 % CI: 1 to 1.36, I2: 99 %, six studies). In most of the included studies, CRP, IL-6, and TNF-α were higher in complicated malaria patients. Nevertheless, the results of a few studies were not convincing. Due to the lack of specificity in all individual biomarkers, none had adequate diagnostic accuracy. Considering the role of pro-inflammatory cytokines in the CRP activation pathway in malaria progression, the combination of these biomarkers should be used in monitoring the disease severity.

BACKGROUND: Both acute exercise and environmental hypoxia may elevate inflammatory cytokines, but the inflammatory response in the hypoxic exercise is remaining unknown.
OBJECTIVE: We performed this systematic review and meta-analysis to examine the effect of exercise in hypoxia on inflammatory cytokines, including IL-6, TNF-α and IL-10.
METHODS: PubMed, Scopus and Web of Science were searched to identify the original articles that compared the effect of exercise in hypoxia with normoxia on IL-6, TNF-α and IL-10 changes, published up to March 2023. Standardized mean differences and 95% confidence intervals (CIs) were calculated using a random effect model to (1) determine the effect of exercise in hypoxia, (2) determine the effect of exercise in normoxia and (3) compare the effect of exercise in hypoxia with normoxia on IL-6, TNF-α and IL-10 responses.
RESULTS: Twenty-three studies involving 243 healthy, trained and athlete subjects with a mean age range from 19.8 to 41.0 years were included in our meta-analysis. On comparing exercise in hypoxia with normoxia, no differences were found in the response of IL-6 [0.17 (95% CI - 0.08 to 0.43), p = 0.17] and TNF-α [0.17 (95% CI - 0.10 to 0.46), p = 0.21] between the conditions. Exercise in hypoxia significantly increased IL-10 concentration [0.60 (95% CI 0.17 to 1.03), p = 0.006] compared with normoxia. In addition, exercise during both hypoxia and normoxia increased IL-6 and IL-10, whereas TNF-α was increased only in hypoxic exercise condition.
CONCLUSIONS: Overall, exercise in both hypoxia and normoxia increased inflammatory cytokines; however, hypoxic exercise may lead to a greater inflammatory response in adults.