Search Results (285)

Background/Objectives: This 8-week randomized pilot intervention trial examined the effects of Greek yogurt (GY) supplementation on markers of bone turnover and inflammation in older adult exercisers. Methods: A total of 48 participants aged 55+ completed this 8-week intervention: 33 exercisers randomized to exercisers receiving GY (GYEX, n = 18, 12 females) and exercisers without GY (NYEX, n = 15, 12 females), and a group of 15 age-matched, community-dwelling, non-exercisers also receiving GY (GYNE, n = 15, 10 females). Exercisers were enrolled in a moderate-intensity community-based exercise program. GYEX and GYNE supplemented their diet with two daily servings of 175 g of GY (17 g protein, 225 mg calcium per serving). Assessments at baseline and week 8 included dietary intake, body composition, and fasting blood samples for bone markers and pro-inflammatory cytokines. Results: Body mass increased modestly across groups (time effect, p = 0.033), with no changes in body fat. C-terminal telopeptide of type I collagen (bone resorption marker) increased 14% in GYEX (time × group interaction, p = 0.022). Osteoprotegerin (bone formation regulator) decreased overall by 4% (time effect, p = 0.002). Dickkopf-1 (bone formation inhibitor) increased by 13% (p = 0.008) in GYNE but not in exercisers (time × group interaction, p = 0.018). Interleukin 1β and interleukin 6 showed significant interactions (p = 0.043 and p = 0.023), where interleukin 1β increased by 80% (p = 0.007) and interleukin 6 decreased by 89% (p < 0.001) in GYNE, but remained stable in exercisers. Tumor necrosis factor alpha remained unchanged. Conclusions: Although the observed effects of GY on the assessed biomarkers were limited and should be interpreted cautiously due to pilot design and statistical constraints, they highlight the need for longer interventions to determine whether whole-food dairy proteins can meaningfully support skeletal and immune health in older adults. Full article

Background: Sarcoidosis is a systemic granulomatous disease of unknown etiology. Pulmonary sarcoidosis with extrapulmonary lesions (EPL) confers poor prognoses. The transcriptomic features of peripheral blood mononuclear cells (PBMCs) could be crucial in sarcoidosis pathogenesis. However, the gene expression characteristics associated with EPL development remain unknown. Methods: Bulk PBMCs were collected from 26 healthy controls and 14 patients with pulmonary sarcoidosis stratified into those with (n = 9) or without (n = 5) EPL. None of the participants were receiving immunosuppressive agents. PBMC transcriptomic analysis was conducted using RNA sequencing. Results: Principal component analysis (PCA) revealed a clear distinction between pulmonary sarcoidosis and healthy control groups, with 227 differentially expressed genes (88 upregulated, 139 downregulated), including upregulated (CLEC7A, GBP5, JAK2, IL15, IL1B, CXCL8, and CXCL10) and downregulated (TNFRSF13C, CD40LG, CD28, and ID3) genes in pulmonary sarcoidosis group. Enrichment analysis revealed upregulated immunological pathways related to granuloma formation in pulmonary sarcoidosis PBMCs, including T helper 17 and tumor necrosis factor-alpha signaling pathways, IL-1B, IL-6, and IL-17 production, and response to external stimuli. Furthermore, patients with and without EPL showed 206 differentially expressed genes (131 upregulated, 75 downregulated), including upregulated (IFNG and IFNLR1) and downregulated (SOCS3, MMP9, and CXCL10) genes. Gene ontology (GO) analysis revealed that interleukin 6 (IL-6) and IL-23 production were upregulated in patients with EPL. Conclusions: These findings elucidate the mechanisms underlying granuloma formation in sarcoidosis and demonstrate the differential transcriptomic features of PBMCs in patients with and without EPL. The upregulation of IFNG and IFNLR1 may be related to EPL development and could serve as potential therapeutic targets for sarcoidosis. Full article

The absent in melanoma 2 (AIM2) inflammasome is a cytosolic DNA sensor that links genomic instability, mitochondrial dysfunction, and chronic inflammation. Unlike the nucleotide-binding domain, leucine-rich repeat (NLR) family pyrin domain-containing protein 3 (NLRP3) inflammasome, AIM2 is activated directly by double-stranded Deoxyribonucleic Acid (dsDNA), including mitochondrial DNA (mtDNA) released under stress conditions. This positions AIM2 at the intersection of oxidative stress, impaired mitophagy, and innate immune dysregulation. Current therapies for ankylosis spondylitis (AS), such as anti-tumor necrosis factor (TNF), anti-interleukin 17 (IL-17), and Janus kinase (JAK) inhibitors, improve clinical outcomes; however, they do not address upstream mitochondrial dysfunction or DNA-driven inflammasome activation. By contrast, other inflammasomes, such as AIM2, remain comparatively less studied. Since autoimmune diseases, including AS, are frequently accompanied by uncontrolled innate immune responses to self-DNA, these findings provide a framework for comprehending the mechanisms of AIM2 activation and its interaction with inflammation, mitophagy, and oxidative stress. Here, we review the current evidence on AIM2 inflammasome involvement in AS pathogenesis and its potential as a therapeutic target. This approach offers new insight into disease control through re-establishing the balance between mitochondrial dysfunction and autoimmunity. Full article

Interleukin 17 (IL-17) is a crucial mediator at the interface of periodontal dysbiosis and host immunity. This review synthesizes current evidence on IL-17 in periodontitis (PD), its systemic connections, and the role of IL-17 gene variants. Clinical and experimental studies show that IL-17 rises in periodontal disease and is associated with the severity of PD via action on epithelial, stromal and osteoblastic cells to promote chemokine release, neutrophil recruitment, cyclooxygenase 2 and prostaglandin E2 synthesis, RANKL expression, osteoclastogenesis, and matrix metalloproteinase activity. Periodontopathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans pre-activate the local inflammation-maintaining Th17 response. There is converging evidence linking IL-17-centered signaling with rheumatoid arthritis, diabetes mellitus, and psoriasis in favor of a shared inflammatory network in barrier tissues and synovium. Despite these associations, IL-17 biology is contextually determined with mucosal defense and bone homeostatic roles that caution against unidimensional explanations. Evidence on IL-17A and IL-17F polymorphisms is still heterogeneous across populations with modest and variable risk associations with PD. Clinically, IL-17 in gingival crevicular fluid, saliva, or serum is a potential monitoring biomarker when utilized along with conventional indices. Therapeutically, periodontal therapy that reduces microbial burden may inhibit IL-17 function, and IL-17-targeted therapy has to balance potential benefit to inflammation and bone resorption against safety in oral tissues. The following research must utilize harmonized case definitions, standardized sampling, and multiethnic cohorts, and it must include multiomics to be able to differentiate between causal and compensatory IL-17 signals. Full article

In recent years, monoclonal antibodies targeting key cytokines underlying the occurrence of psoriatic skin lesions and joint involvement, i.e., Tumor Necrosis Factor-alpha (TNF-α), Interleukin 17 (IL-17), Interleukin 12 (IL-12), and Interleukin 23 (IL-23), have become more commonly used in the therapy of psoriasis. Due to the high effectiveness, a favorable safety profile, and growing availability of biological treatment methods, the number of patients receiving chronic monoclonal antibody therapy is increasing each year. However, the factors affecting the effectiveness of biological drugs are not fully recognized. The study aimed at analyzing the clinical profile of patients and non-specific inflammatory markers in terms of the response to the psoriasis treatment with IL-17, IL-23, IL-12/23, and TNF-α inhibitors. The analysis involved 185 patients receiving biological therapy in the Department of Dermatology and Venereology at the Medical University of Lodz, which resulted in a total of 222 treatment cycles (TC). The super-response was defined as 100% reduction in the Psoriasis Area and Severity Index (PASI 100), at week 16 (±4 weeks) of therapy. Our study indicates that the chance of achieving a super-response was higher among younger patients with no psoriatic lesions on palms and soles, not suffering from non-alcoholic fatty liver disease, previously treated with methotrexate, and characterized by a higher level of derived Neutrophil-to-Lymphocyte Ratio (dNLR) at the beginning of treatment. Full article

Background/Objectives: The association between plasma metabolites derived from dietary substrates and inflammatory processes remains underexplored, despite its potential relevance in the prevention of non-communicable diseases. This systematic review aimed to examine the relationship between blood metabolites and the modulation of inflammatory biomarkers. Methods: A total of 25 randomized controlled trials, published between 2019 and 2024, were included from an initial pool of 111 records. These studies investigated the effects of dietary patterns, specific food groups, or nutritional supplements on the human metabolome and their potential links to inflammation. Results: Metabolomic analyses were predominantly performed using mass spectrometry (MS)-based platforms (17 out of 25), with liquid chromatography–mass spectrometry as the most frequently employed method. Both targeted (n = 14) and untargeted (n = 11) approaches were represented, and samples were drawn from plasma, urine, and feces. Across the interventions, 64 metabolites were modulated, including fatty acyls, glycerolipids, benzenoids, and organic acids, reflecting potential changes in pathways related to oxidative stress, lipid and carbohydrate metabolism, and inflammatory signaling. Several studies also assessed classical inflammatory biomarkers such as C-reactive protein (CRP), tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). Interventions involving healthy traditional dietary patterns, improvements in dietary fat quality, or the use of specific probiotic strains were often associated with favorable immunometabolic outcomes. In contrast, some interventions, such as Mohana Choorna, elicited upregulation of immune-related gene expression in adipose tissue without improvements in glucose or lipid metabolism. Conclusions: While metabolomic responses varied across studies, the evidence highlights the value of dietary interventions in modulating systemic metabolism and inflammation. These findings support the integration of metabolomics into clinical nutrition to define more personalized and effective dietary strategies for inflammation-related chronic disease prevention. Full article

Alcohol-associated liver disease is a global health burden with high morbidity and mortality, and the fungal microbiome is important for its progression. In particular, Candida albicans and C. albicans-reactive T helper 17 (Th17) cells contribute to alcohol-associated liver disease. Specific C. albicans antigens that activate Th17 cells during this disease are unknown. The C. albicans 65 kDa mannoprotein (CaMp65p) is one of the most abundant and immunodominant proteins of C. albicans, and is capable of eliciting robust T cell and interleukin (IL)-17A responses. The aim of this study was to measure levels of CaMp65p in serum of patients with alcohol use disorder and liver disease. Serum CaMp65p levels were measured in the serum of 60 patients with alcohol use disorder using an indirect competitive Enzyme-Linked Immunoabsorbent Assay (ELISA). Serum CaMp65p levels were correlated with liver disease severity. Serum CaMp65p levels positively correlated with several clinical and biochemical markers of liver injury and disease within the patient group with alcohol use disorder, including serum aspartate aminotransferase (AST; R = 0.33, p = 0.0092), alanine aminotransferase (ALT; R = 0.27, p = 0.037), gamma-glutamyl transferase (GGT; R = 0.35, p = 0.0055) and alkaline phosphatase (R = 0.36, p = 0.0052), and with the circulating M65 fragment of cytokeratin 18 (CK18-M65; R = 0.51, p = 0.0012), a marker of hepatocyte death. In addition, patients with alcohol use disorder in the upper quartile had significantly higher liver stiffness (p = 0.0022). Serum CaMp65p was significantly higher in patients with fibrosis stage F2–F4 as compared with patients with no or minimal fibrosis F0–F1 (p = 0.0082). The area under the curve (AUC) for detecting F2–F4 fibrosis was 0.70. Elevated serum CaMp65p levels are associated not only with more severe hepatic injury, but also with liver fibrosis in patients with alcohol use disorder. Therefore, CaMp65p may serve as a non-invasive biomarker for fibrosis assessment in patients with alcohol use disorder. Full article

Major depressive disorder (MDD) is a severe mental disorder associated with significant functional impairment and decreased quality of life. Growing evidence suggests that immune-inflammatory mechanisms, particularly cytokine dysregulation, take part in its development and course. This systematic review and meta-analysis aimed to evaluate whether cytokine alterations are present in early stages of MDD, specifically in first-episode (FE) and drug-naïve (DN) patients. Following PRISMA guidelines a comprehensive search of PubMed, Scopus, and Web of Science was conducted in March 2025. Studies were eligible if they compared levels of inflammatory cytokines between adult FE or DN MDD patients and healthy controls (HCs). Meta-analyses using random-effects models were performed, including subanalyses depending on the source of the sample and the quality of the studies. In total, 17 eligible studies involving 1371 MDD patients were included. The meta-analysis showed significantly elevated levels of interleukin 6 (IL-6), interleukin 2 (IL-2), and tumor necrosis factor alfa (TNF-α) in FE patients compared to HCs. DN patients’ quantitative analysis showed increased levels of IL-6, IL-2, interleukin 4 (IL-4), interleukin 10 (IL-10), TNF-α, and interferon gamma (IFN-γ) compared to healthy individuals. Moreover, in the case of TNF-α, IL-2, interleukin 1 beta (IL-1β), and IL-4, there was a difference in results depending on the sample source (plasma/serum). Cytokine dysregulation is present in first-episode and drug-naïve MDD individuals. These findings highlight that the immune–inflammatory response exists in the early stages of this disorder. Moreover, since more cytokines were elevated in DN patients, pharmacological antidepressant treatment might be a significant factor involved in inflammatory regulation in MDD. Nonetheless, future prospective studies with standardized protocols and division by clinical subtypes are needed to better understand the dynamics and clinical relevance of cytokine alterations in depression. Full article

Background: Psoriasis is a chronic inflammatory disease that frequently affects difficult-to-treat areas such as the scalp, nails, genitalia, and palms/soles, with significant physical and psychological burden. Bimekizumab, a monoclonal antibody targeting both interleukin (IL)-17A and IL-17F, has shown rapid and durable efficacy in clinical trials, but real-world data in these subgroups remain limited. Methods: We performed a 52-week, single-center retrospective study including patients with psoriasis involving at least one difficult-to-treat area. Effectiveness was assessed using site-specific Physician’s Global Assessment (sc-PGA, f-PGA, sPGA-G, pp-PGA). The primary endpoint was the proportion of patients achieving a PGA 0/1 (clear or almost clear). Safety data were collected at each visit. Results: Eighty-five patients were included (61.8% male; mean age 48.1 years; mean Body Mass Index (BMI, 26.9 kg/m²). Difficult-to-treat areas involved were the scalp (70.6%), nails (41.2%), genitalia (27.1%), and palms/soles (24.7%). At week 52, sc-PGA 0/1 was achieved in 90.6% of patients, sPGA-G 0/1 in 81.3%, f-PGA 0/1 in 66.7%, and pp-PGA 0/1 in 87.5%. Mean PGA values progressively decreased across all sites. The most common adverse event was oral candidiasis (11.8%). Conclusions: Bimekizumab showed rapid, sustained, and clinically meaningful improvement across all difficult-to-treat areas with a favorable safety profile. Full article

Background: Early childhood caries (ECC) is a common chronic disease in young children, influenced by multiple factors, including the activity of bacteria and other microorganisms, diet, and immune response. Pro-inflammatory cytokines like interleukin-8 (IL-8) and anti-inflammatory cytokines like interleukin-10 (IL-10) play crucial roles in the inflammatory process of caries. However, their relationship with ECC severity remains unclear. This study aimed to compare salivary IL-8 and IL-10 levels in children with and without ECC and analyze their association with caries severity using the International Caries Detection and Assessment System (ICDAS). Children with and without central obesity were included to evaluate the potential influence of nutritional status on cytokine expression. Methods: A cross-sectional study was conducted from March 2022 to December 2023 in San Luis Potosí, México, including 76 children aged 3 to 5 years (40 with ECC and 36 caries-free). Anthropometric measurements were taken to classify children as centrally obese or non-centrally obese. Unstimulated saliva samples were collected, and IL-8 and IL-10 levels were measured using ELISA. Statistical analysis included the Mann–Whitney U test, Spearman’s rank correlation coefficient, and binary logistic regression analysis, considering p < 0.05 as statistically significant. Results: IL-8 levels were higher in the ECC group (85 ± 119 pg/mL) than in the control group (45 ± 74 pg/mL), but this difference was not significant (p = 0.3613). IL-10 levels were lower in the ECC group (3 ± 2 pg/mL) than in the control group (11 ± 44 pg/mL; p = 0.6481). The difference between IL-8 and IL-10 levels was greater in the ECC group (27 ± 41 pg/mL) than in the control group (17 ± 33 pg/mL; p = 0.1709). No significant correlation was found between cytokine levels and ICDAS scores (p > 0.05), and binary logistic regression did not show an association between IL-8, IL-10, WHtR, and cavitated caries lesions. Conclusions: Although IL-8 tended to be elevated and IL-10 reduced in children with ECC, the differences were not statistically significant. The observed trend suggests a possible local immunological imbalance in children with caries, which may contribute to disease progression independently of bacterial activity or behavioral influences. Full article

Background: Artificial sweeteners, widely used as non-nutritive sugar substitutes, are increasingly prevalent in ultra-processed products. Although promoted for weight management due to their minimal caloric content, their impact on systemic inflammation remains uncertain. This systematic review of animal studies aims to evaluate the association between artificial sweetener consumption and inflammatory biomarkers. Methods: A systematic literature search was conducted up to May 2025 across PubMed, Web of Science, and Scopus, following PRISMA guidelines and registered in PROSPERO (CRD420251084004). Risk of bias was assessed using the ARRIVE guidelines and SCYRCLE’s risk of bias tool. Results: Thirty-seven animal studies were included: aspartame (n = 17), sucralose (n = 16), acesulfame potassium (n = 5), and saccharin (n = 4). Protocols varied in terms of dosage, exposure duration, animal models, and assessment of inflammatory outcomes, including C-reactive protein, interleukins (IL-6 and IL-1β), and tumor necrosis factor alpha. Aspartame and sucralose could elevate inflammatory markers, with sucralose also disrupting gut integrity and microbiota. Acesulfame K and saccharin showed variable, dose-dependent effects. Conclusions: This systematic review of animal studies suggests a possible mechanistic association between the consumption of certain artificial sweeteners and systemic inflammation. However, this relationship remains to be clarified and warrants exploration through well-designed, large-scale randomized controlled trials. Full article

Background/Objectives: Psoriasis is currently treated with biologics targeting the IL-17A signaling, which plays a major role in immune response and keratinocyte hyperproliferation. These include inhibitors of IL-17A and/or its heterodimer with IL-17F (Secukinumab, Ixekinumab and Bimekizumab) and the receptor IL17-RA (Brodalumab). Although these drugs are safe and highly effective, there is significant variability in response among patients. This can be partly attributed to the patients’ genetic background, thus pointing to the need to identify pharmacogenetic markers for treatment response. Methods: The study involved 88 Greek patients who were treated with inhibitors of the IL-17A signaling for at least 6 months. Patients were classified as responders and non-responders according to the change in Psoriasis Area Severity Index. A total of 730,000 variants were genotyped and analyzed for association with the 3-month and 6-month responses to treatment. Results: The analysis identified 21 variants which were associated with the response, showing statistical significance after Bonferroni correction. These include variants located in protein coding genes (TP63, NRG1, SCN8A, TAF9, TMEM9, SMIM36, SYT14, BPIFC, SEZ6L2, PCARE), as well as intergenic and long non-coding RNA intronic variants. The functional significance of the variants was assessed using in silico analysis and for several variants, a link with immune processes was proposed. Notably, rs11649499 status, which was associated with complete clinical remission at 3 months, may influence key lipid mediators involved in psoriasis. Conclusions: This GWAS identified novel variants that could be utilized upon validation in larger populations as predictive markers regarding patient response to drugs targeting the IL-17A pathway. Full article

Background/Objectives: Eosinophilic myocarditis (EM) is a rare, life-threatening inflammatory cardiomyopathy driven by eosinophil cytotoxicity and extracellular trap formation. Interleukin-5 (IL-5) inhibition may disrupt this pathogenic cascade. We reviewed contemporary evidence on IL-5 blockade in EM and contextualized it with an illustrative case. Methods: We searched PubMed through May 2025 for reports of EM treated with mepolizumab or benralizumab. Inclusion criteria were consistent with prior cohorts: acute cardiac symptoms with biomarker elevation plus abnormalities on transthoracic echocardiography and/or cardiac magnetic resonance imaging (CMR), along with documented IL-5-targeted therapy. We extracted clinical, imaging, biopsy, treatment-timing, and outcome data and included one institutional case. Results: Twenty-one episodes were analyzed (median age, 45 years; 10 men). Underlying conditions included eosinophilic granulomatosis with polyangiitis (10 cases; 48%), hypereosinophilic syndrome (5 cases; 24%), drug reaction with eosinophilia and systemic symptoms (DRESS, 3 cases; 14%), and eosinophilic asthma (3 cases; 14%). Treatments involved mepolizumab in 17 cases (81%) and benralizumab in 4 (19%); 4 patients received “early-start” therapy within 14 days of EM diagnosis. Among the 11 episodes with reported left ventricular ejection fraction (LVEF) at baseline and follow-up, the median baseline LVEF was 40% (range, 30–62), with 10 of 11 (91%) <50%. On follow-up, all 11 patients improved: 4 normalized (≥50%) and 7 improved to 40–49%. CMR (n = 18) demonstrated late gadolinium enhancement in 14 cases (78%), edema in 9 (50%), and intracardiac thrombus in 4 (22%). Endomyocardial biopsy confirmed eosinophilic infiltration in 13 of 15 cases (87%). Outcomes included one death (fulminant DRESS), one recovery following veno-arterial extracorporeal membrane oxygenation, and one successful heart transplantation. Illustrative case: A 24-year-old man on a steroid taper received mepolizumab 300 mg on Day 4. His LVEF improved from 47% to 59% by Day 15, accompanied by biomarker decline and successful steroid tapering. Conclusions: Across published cases and our institutional experience, IL-5–targeted therapy appears safe, steroid-sparing, and associated with rapid ventricular recovery, particularly when initiated early. Although limited, these findings support the need for prospective trials to define the optimal agent, dosing, timing, and integration with standard immunosuppression and anticoagulation. Full article

Ischemic stroke is a leading cause of mortality and disability in adults. The inflammatory cascade is driven by various inflammatory molecules, such as interleukin-1β (IL-1β), and counteracted by its antagonist, interleukin-1 receptor antagonist (IL-1Ra). Eicosanoids are inflammatory derivatives of free fatty acids. Arachidonic acid (AA) derivatives exhibit pro-inflammatory activity, while eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derivatives, known as specialized pro-resolving mediators, have anti-inflammatory properties. This study aimed to analyze potential associations between eicosanoids and key inflammatory molecules, including IL-1β and its antagonist IL-1Ra. In this prospective study, we investigated inflammatory molecules in 73 ischemic stroke patients. We analyzed interactions between IL-1β, IL-1Ra, and eicosanoids as follows: resolvin E1, prostaglandin E2, resolvin D1, lipoxin A4 (5S, 6R, 15R), protectin DX, maresin 1, leukotriene B4, 18RS-HEPE, 13S-HODE, 9S-HODE, 15S-HETE, 17 HDHA, 12S-HETE, 5-oxo-ETE, and 5-HETE. In 73 ischemic stroke patients, mean IL-1β was 1.31 ± 1.54 pg/mL and IL-1Ra 810.8 ± 691.0 pg/mL. Spearman correlations showed positive associations between IL-1β and protectin DX (ρ = 0.56, p < 0.001), and 17 HDHA (ρ = 0.26, p < 0.05) and 5-oxo-ETE (ρ = 0.27, p < 0.05). IL-1Ra correlated negatively with protectin DX (ρ = −0.58, p < 0.001) and 17 HDHA (ρ = −0.29, p < 0.05), and positively with leukotriene B4 (ρ = 0.34, p < 0.005). After multivariable adjustment, associations with IL-1β lost statistical significance, whereas the inverse relationships between IL-1Ra and protectin DX/17 HDHA remained significant (p < 0.005). Despite the known anti-inflammatory roles of protectin DX and 17 HDHA, and the pro-inflammatory role of leukotriene B4, their activity in the early subacute phase of ischemic stroke appears to be influenced by complex interplays, possibly mediated by IL-1β and IL-1Ra. The activity of protectin DX, 17 HDHA, and leukotriene B4 is correlated with IL-1β and IL-1Ra levels in the early subacute phase of stroke. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a significant global public health issue, affecting approximately 25% of the population and currently offering limited treatment options. Trimetazidine (TMZ) serves as a metabolic modulator that shifts cellular energy metabolism from fatty acid oxidation to glucose oxidation, thereby providing a novel therapeutic strategy aimed at addressing the underlying metabolic dysfunctions that contribute to the pathogenesis of MASLD. Our study aims to assess the efficacy of trimetazidine in improving hepatic steatosis, inflammation, and various metabolic parameters. Methods: In this double-masked, randomized controlled trial, 60 patients with confirmed MASLD diagnoses were randomly assigned in a 1:1 ratio to receive either trimetazidine 20 mg three times daily or a placebo, alongside lifestyle modifications, for 24 weeks. The trial was conducted in accordance with the Declaration of Helsinki and approved by the ethics committees of both participating institutions. We measured changes in hepatic steatosis, non-invasive fibrosis scores, inflammatory markers (including interleukin-6, tumor necrosis factor-alpha, and highly sensitive C-reactive protein), liver enzymes, and lipid profiles at baseline and at the end of the 24 weeks. Results: Hepatic steatosis decreased significantly, with controlled attenuation parameter scores from 352.5 to 302 dB/m in the TMZ group compared to the control (p < 0.001). TNF-α was reduced significantly in the TMZ group compared to the control group (p = 0.001). Fibrosis to AST score decreased from 0.49 to 0.25 in the TMZ group (p < 0.001). Aspartate aminotransferase decreased significantly compared to the control group (p 0.032). Notably, TMZ also imparted cardioprotective benefits, reducing total cholesterol by 14%, LDL by 17% (both p < 0.05), and triglycerides by 16% (p = 0.176). Conclusions: This groundbreaking trial supports the potential of trimetazidine as a promising therapeutic agent for MASLD, indicating substantial improvements in hepatic steatosis, inflammation, and metabolic disturbances. These findings underscore the urgency and importance of further multicenter trials to validate trimetazidine’s efficacy as a disease-modifying therapy for MASLD. Full article