Search Results (642)

Liver fibrosis, the progressive accumulation of scar tissue resulting from chronic liver disease, is increasingly recognized as a multi-system condition, the effects of which extend beyond the liver, affecting brain health. Dementia, characterized by progressively impaired cognition sufficient to impede daily functioning, is a major global health issue with incompletely defined risk factors and pathogenic precursors. To examine the relationship between liver fibrosis and cognitive outcomes, we conducted a comprehensive PubMed literature search, and human studies published in English were included. Evidence is synthesized on the pathophysiology and clinical significance of liver fibrosis, types of dementia, and studies supporting the association between liver fibrosis and cognitive impairment. Meta-analytic data indicate that liver fibrosis is associated with an approximately 30% increased risk of incident dementia (pooled hazard ratio ~1.3), with progressively higher risks across more advanced fibrosis stages. Putative pathomechanisms, potentially modulated by age and sex, include chronic systemic and neuro-inflammation, insulin resistance, vascular dysfunction, and a perturbed intestinal microbiota–liver–brain axis. Non-invasive liver fibrosis diagnostics, advanced neuroimaging, and biomarkers represent key tools for assessing risk. In conclusion, liver fibrosis is a systemic condition that can affect brain health. Early detection, thorough risk assessment and interventions, such as lifestyle changes, metabolic therapies, and antifibrotic treatments, may help protect neural function. Key research gaps are identified, with suggestions for improving understanding of liver fibrosis’s connection to dementia or cognitive impairment. Full article

Background/Objectives: Postoperative pulmonary complications (PPCs) remain frequent and increase morbidity, mortality, and resource use. Preoperative risk scores (ARISCAT, NSQIP-derived calculators) use mostly static variables and may miss the dynamic perioperative host response preceding respiratory deterioration or infection. We address the gap in clinically interpretable syntheses of perioperative blood biomarker trajectories that distinguish infectious from non-infectious PPCs and clarify bedside-ready versus exploratory markers. Methods: We conducted a narrative review with a structured Medline search (inception to 1 November 2025) plus reference screening. We included English-language adult surgical studies (observational or interventional) evaluating perioperative blood biomarkers in relation to PPCs or postoperative pulmonary infection; case reports, editorials, and reviews were excluded. No formal risk-of-bias assessment or quantitative meta-analysis was performed. Results: Across 298 cited publications, serial patterns of routinely available biomarkers (C-reactive protein, procalcitonin, lactate, albumin, and leukocyte-derived indices) were most consistently associated with PPC risk and helped separate expected postoperative inflammation from evolving infection when interpreted longitudinally rather than as single values. Mechanistic biomarkers (cytokines/immune-function assays, endothelial injury and coagulation/fibrinolysis markers, oxidative stress indicators) add biological insight but are limited by assay availability, heterogeneous sampling windows, and absent standardized cut-offs. Omics signatures and machine learning models combining biomarker kinetics with clinical variables are promising but require prospective, transportable validation. Conclusions: Key barriers to implementation include biological variability, non-specificity across postoperative syndromes, heterogeneous sampling windows, and lack of standardized cut-offs. Integrating multimarker panels into validated, dynamic predictive frameworks represents a promising direction for perioperative precision medicine. Full article

Background: Peri-implantitis, a condition characterized by inflammation and progressive bone loss around dental implants, presents a significant challenge in contemporary dentistry. Conventional non-surgical treatments often fail to fully eliminate bacterial biofilms, particularly on complex implant surfaces. Laser therapies have emerged as potential adjuncts due to their antimicrobial and bio-modulatory properties. However, their microbiological effectiveness and suitability for individualized patient treatment planning remain unclear. Objective: Τhis study aims to systematically assess and synthesize the microbiological effects of various laser-assisted non-surgical treatments for peri-implantitis compared to conventional mechanical debridement. Methods: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD420251035354). Randomized controlled trials (RCTs) evaluating microbiological changes following laser-assisted non-surgical treatment of peri-implantitis, with a minimum follow-up of one month, were identified through searches in multiple databases and registries up to February 2025. The ncluded studies used lasers such as diode, Er: YAG, and photodynamic therapy (PDT) either alone or as adjuncts to mechanical debridement. Outcomes of interest included bacterial counts. Risk of bias was assessed using the RoB2 tool, and certainty of evidence was evaluated via GRADE. Quantitative synthesis used random-effects meta-analysis, with standardized mean differences (SMDs) calculated. Results: Eight RCTs involving 266 patients and 335 implants were included in the systematic review. Quantitative synthesis of three pathogens (counts of Fusobacterium nucleatum, P. gingivalis, T. denticola) across three studies displayed no statistically significant differences between laser and control groups at 3 and 6 months (p > 0.05 for all comparisons). When examining individual study findings, PDT, particularly in patients with diabetes or acute abscess, showed short-term reductions in red complex bacteria (e.g., Porphyromonas gingivalis and Treponema denticola). In contrast, diode and Er: YAG lasers demonstrated inconsistent or transient effects. The quality of evidence was rated as very low according to GRADE. Conclusions: Laser-assisted therapies, especially PDT, may provide targeted microbiological benefit in selected patient groups, supporting their adjunctive use within personalized treatment planning rather than as replacements for mechanical debridement, which remains the gold standard. Further high-quality RCTs incorporating well-defined patient risk profiles, such as systemic conditions and behavioral factors, and precision treatment algorithms are needed. Full article

Background: Atherosclerosis (AS) is the primary pathological basis for cardiovascular and cerebrovascular events, with its development closely linked to dyslipidemia and chronic inflammation. The gut–liver axis, serving as a core bridge connecting gut microbiota, hepatic metabolism, and systemic inflammation, has gained increasing prominence in AS pathogenesis. Phytochemicals exhibit multifaceted biological activities, yet their mechanisms for preventing and treating AS via the gut–liver axis remain to be systematically summarized. This review aims to summarize the potential mechanisms of phytochemicals interventions in AS from an intestinal–hepatic axis perspective. Methods: A systematic literature search was conducted using PubMed, Web of Science, and Embase, focusing on previously published articles, reviews, and meta-analyses. Keywords included “phytochemicals”, “flavonoids”, “atherosclerosis”, “AS”, “gut–liver axis”, “gut axis”, “intestinal axis”, “gut microbiota” and “TMAO”. This narrative review synthesizes current research evidence on the interactions among phytochemicals, the gut–liver axis, and atherosclerosis, summarizing their action pathways and molecular mechanisms. Results: Phytochemicals (such as polyphenols, carotenoids, saponins, etc.) have low bioavailability but can be metabolized and transformed by gut microbiota. Through multiple mechanisms—including modulating gut microbiota composition, enhancing intestinal barrier function, regulating bile acid metabolism, and exerting anti-inflammatory and antioxidant effects—they positively influence gut–liver axis function. This alleviates lipid metabolism disorders, suppresses systemic inflammation, and thereby combats the onset and progression of atherosclerosis at multiple stages. Conclusions: Phytochemicals can intervene in the progression of atherosclerosis through the gut–liver axis. Future studies should further investigate dose–response relationships and conduct clinical validation to determine optimal usage strategies. Full article

Background: China is currently developing standards for Food for Special Medical Purposes (FSMP) targeting for oncology patients. However, substantial challenges remain in defining optimal fortification levels of omega-3 polyunsaturated fatty acids (ω-3 PUFAs). Accumulating evidence suggests that ω-3 PUFA intake improves postoperative prognosis by modulating oncological parameters in colorectal cancer (CRC) patients. This meta-analysis aimed to evaluate the therapeutic efficacy of ω-3 PUFA supplementation in enhancing postoperative safety and recovery stability following CRC surgery, to address critical gaps in nutritional interventions for optimizing clinical outcomes. These findings are expected to FSMP standard development, clinical nutrition protocols and product innovation. Methods: A systematic literature search was conducted, in accordance with PRISMA guidelines, across major databases until June 16, 2025. Data were analyzed using RevMan v5.4 (Cochrane Collaboration). Results: Thirty-four randomized controlled trials (RCTs) (n = 2889) were included. Compared to controls, the ω-3 PUFAs group showed significantly increased levels of nutritional markers: total protein (p < 0.00001), albumin (p = 0.001); immunological parameters: CD3⁺/CD4⁺/CD8⁺ T-cells, CD4⁺/CD8⁺ ratio (all p < 0.0001); Karnofsky Performance Status (KPS) scores (p = 0.04); and serum ω-3 PUFA concentrations (p = 0.0004). Significant reductions were observed in inflammatory markers, such as procalcitonin, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) (p = 0.004 to < 0.00001); and clinical outcomes, such as hospitalization duration (p < 0.00001), infectious complications (p < 0.00001), anastomotic leakage (p = 0.0005), surgical site infections (p = 0.03). No significant intergroup differences were detected for white blood cells, transcription factor activity, mortality, or crypt cell proliferation indices (p = 0.06–0.55). Conclusions: Overall, ω-3 PUFA supplementation significantly attenuates postoperative inflammation, enhances immune function, shortens hospitalization, and improves the quality of life in CRC patients, though without mortality benefit. Notably, post hoc dose–response analysis identified a supplementation range of 0.16–0.30 g/kg/day as a potentially optimal supplementation range for Chinese CRC populations, providing foundational evidence for clinical practice and FSMP standardization. Full article

Type 2 diabetes mellitus (T2DM) is a global health burden characterized by hyperglycemia, oxidative stress, and systemic inflammation, which leads to complications that remain insufficiently managed by standard therapies. Photobiomodulation therapy (PBMT) has been proposed to be a complementary approach, but its effects in T2DM are unclear. We conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the effects of PBMT on metabolic, inflammatory, and neurological outcomes in adults with T2DM. Five databases were searched until June 2025 (PROSPERO CRD420251083550) for relevant studies. Metabolic, inflammatory, and neurological outcomes were defined a priori as primary outcomes and were synthesized narratively due to substantial heterogeneity and incomplete reporting that precluded valid quantitative pooling. Although periodontal outcomes were not predefined as primary outcomes, they were reported in multiple trials; thus, these were analyzed quantitatively as secondary outcomes where sufficient homogeneity enabled meta-analysis. The narrative synthesis of primary outcomes showed inconsistent and largely short-term effects on glycemic control, systemic inflammation, and neurological function. In contrast, meta-analysis of secondary periodontal outcomes demonstrated modest but statistically significant improvements in clinical attachment level (−0.21 mm) and probing depth (−0.25 mm), with no effect on plaque index. Overall, the certainty of the evidence was low. PBMT may offer statistically significant but small adjunctive periodontal effects in adults with T2DM. However, the certainty of evidence is low, and these effects are unlikely to be clinically meaningful in isolation. Evidence for systemic metabolic, inflammatory, and neurological outcomes is preliminary and requires confirmation in larger, standardized RCTs. Full article

This systematic review and meta-analysis aimed to evaluate the efficacy and safety of carbocisteine in reducing chronic obstructive pulmonary disease (COPD) exacerbations based on evidence from randomized controlled trials (RCTs). A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. RCTs comparing carbocisteine (1500 mg/day) with placebo in COPD patients, with a minimum follow-up of six months, were included. Data on exacerbation rates and adverse events were extracted and analyzed using a random-effects model. Four RCTs involving 1746 patients met inclusion criteria. Pooled analysis showed that carbocisteine significantly reduced the annual rate of acute exacerbations compared to placebo (WMD = −0.40; 95% CI: −0.69 to −0.11), with no significant increase in adverse events (OR = 1.02; 95% CI: 0.76 to 1.37). Mechanistically, carbocisteine improves mucociliary clearance, suppresses airway inflammation, reduces oxidative stress, and may hinder bacterial colonization. Carbocisteine is associated with a significant reduction in COPD exacerbations and demonstrates a favorable safety profile. It may serve as an effective adjunctive therapy in patients with frequent exacerbations and mucus hypersecretion. Full article

Chronic diseases, characterized by their high prevalence and protracted course, represent a paramount challenge to global public health, necessitating effective, evidence-based preventive strategies. While functional foods are widely recognized for their potential, a comprehensive synthesis elucidating their multitargeted mechanisms within a “food-medicine homology” framework and a clear trajectory from broad-spectrum health promotion to targeted intervention remains lacking. This review bridges this critical gap by systematically evaluating the scientific evidence and application potential of functional foods, with a specific focus on key bioactive compounds—β-glucan, omega-3 polyunsaturated fatty acids (PUFAs), dietary fiber, and catechins. We provide a critical analysis of how these components orchestrate synergistic effects at molecular, cellular, and systemic levels to counteract core pathological processes, including oxidative stress, chronic inflammation, metabolic dysregulation, and gut microbiota imbalance. Our unique contribution lies in integrating the ancient wisdom of food-medicine homology with modern multi-omics and evidence-based research, thereby proposing a refined nutritional intervention paradigm. The review offers critical insights into the convergent actions of these bioactives, their dose-response relationships substantiated by clinical meta-analyses, and the emerging role of gut microbiota-derived metabolites. Furthermore, this review also explores the emerging evidence for synergistic interactions among these key bioactives, proposing that their combined use may yield amplified and more network-based protective effects against chronic diseases through complementary mechanisms, aims to develop integrated prevention strategies targeting both cardiometabolic and neurodegenerative diseases. The integrated prevention strategies systematically connect mechanistic insights into bioactive compounds, evaluates the strength of clinical evidence, and examines the implications for regulatory standards and societal acceptance, thereby bridging the gap between basic science, clinical application, and public health policy. The “mechanism-to-evidence-to-regulation” framework in this review links molecular insights with clinical validation and regulatory implications, offering a holistic perspective rarely addressed in existing literature. Full article

Metabolic syndrome (MetS) and its associated conditions, namely, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), obesity, and polycystic ovary syndrome (PCOS) are characterized by insulin resistance, dyslipidemia, and low-grade inflammation. Curcumin, a polyphenolic compound derived from Curcuma longa Linn., exhibits pleiotropic metabolic and anti-inflammatory properties and has thus been evaluated as a nutraceutical intervention for these conditions, but findings remain inconsistent. This systematic review and meta-analysis evaluated the clinical efficacy of Curcuma longa supplementation on anthropometric, glycemic, lipid, inflammatory, and oxidative stress parameters in adults with MetS or related disorders. A comprehensive search of databases (PubMed, Scopus, AMED, LILACS, and Google Scholar) identified 104 eligible randomized controlled trials (RCTs). The included trials primarily assessed standardized oral turmeric/curcumin supplements and bioavailability-enhanced formulations rather than whole culinary turmeric. Pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs) were computed using random-effects models. Subgroup analyses were conducted by disease category, dose, and formulation. Risk of bias was assessed using the Cochrane RoB 2 tool. Curcumin supplementation significantly reduced fasting blood sugar (SMD = −0.54, 95% CI −0.72 to −0.36) and HbA1c (SMD = −0.41, 95% CI −0.60 to −0.23) in T2DM; decreased triglycerides (SMD = −0.48; 95% CI: −0.70 to −0.25), and LDL cholesterol (SMD = −0.39; 95% CI: −0.59 to −0.18) while elevating HDL cholesterol (SMD = 0.45; 95% CI: 0.25 to 0.65) and total antioxidant capacity (SMD = 0.73; 95% CI: 0.51 to 0.94). Curcuma longa also attenuated systemic inflammation, lowering C-reactive protein (SMD = −0.62; 95% CI: −0.81 to −0.43), TNF-α (SMD = −0.57; 95% CI: −0.80 to −0.34), and IL-6 (SMD = −0.50; 95% CI: −0.70 to −0.29). Heterogeneity was moderate-to-high, reflecting some differences in the formulation, dosage, and duration. Collectively, these findings affirm that Curcuma longa exerts measurable, clinically relevant improvements on glycemic regulation, lipid metabolism, and inflammatory−oxidative balance, supporting its role as a nutraceutical adjunct in metabolic health management, while its bioavailability-enhanced formulations show superior efficacy. Larger, long-term, multicenter RCTs are warranted to confirm durability, optimal dosing, and safety. Full article

Background: Pentraxin 3 (PTX3) is a key biomarker of innate immunity and inflammation, associated with muscle mass, metabolic syndrome, and obesity-related indicators. However, its role in training adaptations remains unclear, with studies reporting inconsistent PTX3 responses to acute and chronic exercise. This study aimed to compare the effects of aerobic exercise, resistance training, high-intensity interval training (HIIT), and acute exercise on PTX3 levels. Methods: A systematic search using Boolean logic was conducted in Web of Science, PubMed, and Google Scholar to identify randomized controlled trials examining the effects of exercise training and acute exercise on PTX3 levels. Results: Out of 3434 records published from 1992 to July 2025, 19 studies met the eligibility criteria. Meta-analysis revealed that aerobic training significantly increased PTX3 levels (SMD = 0.71; 95% CI, 0.173 to 1.252; p = 0.01; I² = 83.14%), whereas resistance training significantly reduced them (SMD = −0.69; 95% CI, −1.025 to −0.370; p = 0.0001; I² = 17.52%). HIIT did not elicit a significant change (SMD = 0.086; 95% CI, −0.364 to 0.535; p = 0.70; I² = 0.00%). Notably, exercise training significantly elevated PTX3 in individuals over 50 years old (SMD = 1.124; 95% CI, 0.231 to 2.017; p = 0.014; I² = 87.97%) but not in younger participants (SMD = −0.156; 95% CI, −0.640 to 0.327; p = 0.526; I² = 78.80%). Conclusion: Aerobic and resistance exercise exert opposing effects on PTX3, suggesting distinct mechanisms through which different training modalities modulate inflammatory pathways relevant to muscle metabolism and repair. Acute exercise may also transiently elevate PTX3 to manage exercise-induced inflammation. Full article

Background: This study aimed to assess the efficacy, optimal dosing, and timing of colchicine therapy in reducing major adverse cardiovascular events (MACE), its impact on inflammatory markers, and safety concerns in patients following acute coronary syndrome (ACS) through a systematic review and meta-analysis of randomized controlled trials (RCTs). Methods: A comprehensive search of PubMed, Embase, and the Cochrane Library was conducted in accordance with PRISMA guidelines to identify RCTs comparing colchicine versus placebo or standard treatment in ACS patients. The primary outcome was MACE and secondary outcomes included all-cause and cardiovascular mortality, non-fatal MI, stroke, revascularization, heart failure, CRP/hs-CRP changes, and adverse effects. Fifteen RCTs involving 19,131 patients were analyzed. Results: The benefit of colchicine in reducing MACE risk was marginally significant (RR = 0.79, 95% CI: 0.63–0.99, p = 0.04, I² = 59%). No significant reduction was observed for all-cause mortality, cardiovascular mortality, other cardiovascular outcomes, early initiation of colchicine (≤3 days), or choice of dosage (≤0.5 mg/day vs. >0.5 mg/day). The findings pertaining to the delayed time-to-initiation (>3 days) and changes in CRP or hs-CRP levels were inconclusive. Gastrointestinal side effects, especially diarrhea (RR = 1.76, 95% CI: 1.16–2.66, p = 0.001), were most common. No increase in hematologic events or infections was observed. Conclusions: Colchicine potentially reduces MACE in ACS patients, without evidence of benefit in improving all-cause mortality or other cardiovascular outcomes. Gastrointestinal intolerance is the most common side effect. This result is consistent with current clinical guidelines: a Class IIb recommendation for colchicine use in ACS. There is a need for further high-quality trials to refine patient selection and optimize treatment regimens. Full article

Vascular endothelium balances antithrombotic and anti-inflammatory activity to control blood vessel tone under physiological conditions. However, endothelial dysfunction impairs these processes, causing a state that promotes clotting and inflammation. Eicosanoids are a major class of bioactive lipid mediators crucial for modulating endothelial and platelet function. Research has highlighted the roles of eicosanoids in vascular diseases, showing pro-inflammatory, prothrombotic, and protective activities. Specifically, prostaglandin E₂ (PGE₂) is crucial because of its major role in atherosclerosis development and progression, acting via EP receptors involved in forming, maintaining, and stabilizing atherosclerotic lesions, thereby making PGE₂-EP signalling a specific target for treating cardiovascular diseases. This review will explore the evidence on eicosanoids and the role of their receptor modulation in platelet and vascular dysfunction in atherothrombosis. The studies included in this scoping review were retrieved from PubMed, Web of Science, Cochrane, and Scopus in accordance with the Preferred Reporting Items for Scoping Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) statement and the Population Intervention Comparison Outcome Population (PICO) framework. Eight clinical studies were found, which highlighted the crucial role of eicosanoids, like prostaglandins and their receptors, in endothelial and platelet dysfunction, and also how pharmacological mechanisms affect atherothrombosis. A new therapeutic approach for cardiovascular dysfunction is indicated by the recent findings, specifically against atherothrombosis, focusing on eicosanoids, their receptors, and processes like oxidative stress. Despite this evidence, there is a lack of comprehensive research results from scientific databases; therefore, further in vitro, in vivo, and clinical studies should be promoted to validate the preliminary results. Full article

Cardiovascular–kidney–metabolic syndrome (CKMS) represents the intricate interconnection of cardiovascular, kidney, and metabolic disorders, with systemic inflammation now recognized as a key driver of both pathogenesis and prognosis. This systematic review aimed to synthesize current evidence on the prognostic value of inflammatory biomarkers in individuals with CKMS. A systematic search of PubMed, Embase, CINAHL, Web of Science, and Scopus were conducted to identify studies published between 1 January 2024 and 30 June 2025, following the recognition of CKMS as a distinct syndrome in December 2023. Eligible studies included adults (aged ≥ 18 years) with CKMS, that assesses one or more inflammatory markers and reported prognostic outcomes such as mortality or disease progression. Data extracted included study characteristics, biomarker types, outcome measures, and key findings. In addition to longitudinal cohorts, we included a small number of cross-sectional studies and treated them as association (non-prognostic) evidence analyzed in a separate stream from prognostic cohorts. Risk of bias was evaluated using the Quality in Prognostic Studies (QUIPS) tool. Due to considerable variability in prognostic outcomes, follow-up durations, and inflammatory indices, a meta-analysis was not feasible. Instead, a narrative synthesis was undertaken to summarize the evidence, identify consistent associations, and emphasize the need for standardized approaches and biomarker validation in future CKMS research. Analysis was conducted in line with the SWiM guidelines. Thirteen studies (n = 13) comprising 282,016 participants (100,590 males; 97,295 females) were included from 1404 initial records. Five of the studies were cross-sectional, providing information on associations rather than prognostic outcomes. Most were large-scale cohort studies conducted in the USA and China. Frequently assessed biomarkers included systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), high-sensitivity C-reactive protein to high-density lipoprotein cholesterol ratio (hs-CRP/HDL-C), dietary inflammatory index (DII), and triglyceride–glucose (TyG) index. Elevated levels of these biomarkers were consistently associated with higher risk of all-cause and cardiovascular mortality, CKMS progression, and adverse metabolic outcomes. This review highlights systemic inflammation as a critical and associated marker of CKMS prognosis. Inflammatory biomarkers may assist in hypothesis generation, but clinical utility remains to be established pending standardized adjustment and external validation. Because CKMS has only recently been operationalized, we limited inclusion to studies published from 1 January 2024 onward, enhancing definitional comparability but narrowing the evidence base and potentially emphasizing early-adopter regions (predominantly the U.S. and China). Accordingly, these findings should be interpreted as early signals that require replication in diverse settings and confirmation through longitudinal and interventional studies to inform integrative CKMS management strategies. Across observational studies, the certainty of evidence is low to moderate due to indirectness and imprecision; findings should be treated as associational signals pending external validation. Full article

Major depressive disorder is increasingly recognized as a metabolic–immune disorder in which chronic inflammation diverts tryptophan (Trp) metabolism toward the kynurenine pathway (KP), reducing serotonin synthesis and producing neurotoxic metabolites such as quinolinic acid (QA). Elevated kynurenine (KYN)/Trp ratios and an altered QA/kynurenic acid (KYNA) balance have been consistently reported in depressed individuals, implicating the KP as a key therapeutic target. Exercise provides a unique, translationally relevant intervention: unlike pharmacological agents acting directly on neurotransmission, contracting skeletal muscle acts as a “kynurenine sink” by inducing kynurenine aminotransferases that convert circulating KYN into neuroprotective KYNA, thereby reducing brain KYN uptake and mitigating excitotoxicity. Clinical studies and meta-analyses confirm that aerobic, resistance, and high-intensity training produce antidepressant effects comparable to pharmacotherapy, while also improving cognition, fatigue tolerance, and cardiometabolic function. Beyond KP remodeling, exercise-induced myokines (irisin, IL-6, BDNF, apelin, FGF21) and adipokines (adiponectin, leptin modulators) coordinate systemic anti-inflammatory and neurotrophic adaptations that enhance resilience and brain plasticity. Furthermore, pharmacological “exercise mimetics” and metabolic modulators, such as PPAR agonists, AMPK activators, NAD⁺ boosters, meldonium, trimetazidine, and adiponectin receptor agonists, may be promising adjuncts for patients with low exercise capacity or metabolic comorbidities. This review provides a novel concept, positioning exercise as a systemic antidepressant that breaks the kynurenine lock of depression. Through proper interpretation of skeletal muscle as an endocrine organ of resilience, we integrate molecular, clinical, and translational findings to show how exercise remodels Trp–KYN metabolism and inflammatory signaling and how pharmacological mimetics may extend these benefits. This perspective consolidates scattered mechanistic and clinical data and outlines a forward-looking therapeutic framework that links exercise and lifestyle, metabolism, and drug discovery. We highlight that re-consideration of our understanding of depression, as a whole-body disorder, should provide new opportunities for precision interventions. Full article

Background and Objectives: Preterm prelabor rupture of membranes (PPROM) is a significant obstetric complication associated with increased maternal and neonatal morbidity and mortality. Inflammation plays a central role in its pathophysiology, and maternal inflammatory biomarkers have gained increasing attention as potential predictors of disease onset and adverse outcomes. Materials and Methods: This systematic review and meta-analysis synthesized evidence from PubMed, Scopus and Web of Science databases evaluating maternal inflammatory biomarkers—particularly interleukin-6 (IL-6)—in women with PPROM compared with controls. Eligible studies assessed biomarker levels in serum, plasma, or amniotic fluid and reported quantitative outcomes. Data were pooled using random-effects models, and heterogeneity was quantified using the I² statistic. Results: A total of 23 studies involving 2841 participants were included. Maternal IL-6 concentrations were significantly elevated in PPROM compared with controls in both maternal serum (pooled SMD = 1.72; 95% CI: 1.15–2.29; p < 0.001) and amniotic fluid (SMD = 2.84; 95% CI: 2.01–3.67; p < 0.001). CRP showed a moderate association (SMD = 0.98; 95% CI: 0.61–1.36; p < 0.001), whereas IL-8 and TNF-α displayed inconsistent relationships. Conclusions: Elevated maternal IL-6 concentrations, particularly in amniotic fluid, are strongly associated with PPROM and adverse perinatal outcomes. IL-6 demonstrated superior diagnostic and prognostic value compared with other inflammatory markers. These findings support IL-6 as a promising biomarker for early risk identification and individualized the management of high-risk pregnancies. Full article