Search Results (7,682)

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear transcription factors comprising three isoforms—PPARα, PPARγ, and PPARβ/δ—that regulate hepatic lipid metabolism, glucose homeostasis, inflammation, bile acid synthesis, and fibrogenesis. Because liver diseases involve overlapping metabolic, inflammatory, cholestatic, and fibrotic pathways, PPAR agonists have emerged as a versatile therapeutic class across a spectrum of hepatic conditions. PPARα agonists (e.g., fenofibrate) promote fatty acid β-oxidation and suppress de novo lipogenesis; PPARγ agonists (e.g., pioglitazone) improve insulin sensitivity and exert anti-inflammatory and antifibrotic effects; and PPARδ agonists (e.g., seladelpar) regulate bile acid and cholesterol metabolism. Dual agonists (elafibranor [PPARα/δ] and saroglitazar [PPARα/γ]) and pan-PPAR agonists (lanifibranor [PPARα/γ/δ] and bezafibrate) aim to simultaneously address multiple pathogenic mechanisms. In primary biliary cholangitis (PBC), elafibranor and seladelpar received accelerated FDA approval in 2024 based on phase 3 trials (ELATIVE and RESPONSE, respectively), demonstrating significant biochemical response rates of 51% and 62% versus 4% and 20% with the placebo. Long-term open-label extension data from the ELATIVE trial have demonstrated sustained improvements in cholestatic biomarkers and stabilization of fibrosis markers over three years, with durable benefits on fatigue and pruritus. The ASSURE open-label study has confirmed the durability of seladelpar’s effects on biochemical response and pruritus through up to two years of treatment. Saroglitazar, a dual PPARα/γ agonist, has shown positive topline phase 3 results in the EPICS-III trial and received an FDA priority review designation. Bezafibrate has shown a survival benefit in large retrospective analyses and is used as a second-line therapy in Europe and Japan; notably, bezafibrate functions as a dual PPAR/pregnane X receptor (PXR) agonist, inducing CYP3A4 and efflux transporters that contribute to bile acid detoxification. In metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH), pioglitazone remains the most extensively studied PPAR agonist, with meta-analytic evidence supporting MASH resolution and fibrosis reduction regardless of diabetes status. Lanifibranor demonstrated histological improvement in the phase 2b NATIVE trial and is currently in phase 3 development (NATiV3). PPAR agonists have also demonstrated therapeutic effects on liver fibrosis inhibition through direct modulation of hepatic stellate cell activation and suppression of fibrogenic signaling. This narrative review synthesizes the molecular pharmacology of PPAR isoforms; the available clinical and preclinical evidence for mono-, dual-, and pan-PPAR agonists; and their therapeutic applications across MASLD/MASH, alcohol-associated liver disease (ALD), PBC, primary sclerosing cholangitis (PSC), intestinal failure-associated liver disease (IFALD), and advanced chronic liver disease (ACLD). The evolution from single-isoform to multi-isoform PPAR agonism reflects the recognition that overlapping pathogenic mechanisms in liver diseases may require broader receptor coverage for optimal therapeutic efficacy. Full article

Resting myokine abundance cannot distinguish adaptive signaling from compensation, tissue injury, altered receptor availability, or non-muscle contribution. We conducted a targeted narrative review of PubMed/MEDLINE, Embase, Web of Science Core Collection, and Scopus through 30 June 2026 to examine ciliary neurotrophic factor (CNTF), cardiotrophin-like cytokine factor 1 (CLCF1), and muscle metabolism across basal, insulin-stimulated, exercise, recovery, and training states. CNTF has the better-established CNTFR$\alpha$–LIFR–gp130 receptor model, and pharmacological studies link it to AMPK activation, glucose uptake, ceramide handling, and insulin responsiveness. CLCF1 depends partly on CRLF1-associated extracellular availability, whereas its receptor usage and tissue source in skeletal muscle remain incompletely resolved. One recent study provides important preclinical and exploratory human evidence for exercise-responsive CLCF1, but direct human studies pairing CNTF/CLCF1 kinetics with muscle metabolomics or isotope-resolved flux are lacking. We, therefore, present neurotrophic secretory flexibility as a testable, hypothesis-generating construct rather than a validated biological system or biomarker. Its minimum evaluation requires synchronized measurements of extracellular ligand, receptor-proximal signaling, and metabolic output within the same physiological challenge. Targeted and untargeted metabolomics, lipidomics, quality-controlled annotation, paired tissue and plasma sampling, and stable isotope tracing can determine whether putative coupling is reproducible, muscle-relevant, and altered by aging. Full article

Prostate cancer (PCa) is one of the most prevalent malignancies in men worldwide. Established clinicopathological parameters do not fully describe the biological heterogeneity of PCa or consistently predict its clinical course after radical prostatectomy, supporting the investigation of additional prognostic markers. Stroma AReactive Invasion Front Areas (SARIFA) is a recently described histomorphological pattern characterized by direct contact between tumor cells and adipocytes without intervening desmoplastic or inflammatory stroma at the invasion front. Limited retrospective evidence from prostatectomy specimens indicates that SARIFA positivity is associated with adverse pathological features. However, its independent prognostic value and clinical utility remain to be established. Because SARIFA can potentially be assessed on routinely prepared hematoxylin and eosin-stained sections without additional molecular assays or immunohistochemical staining, it represents a potentially accessible candidate marker, although its reproducibility, standardization, and cost-effectiveness require formal evaluation. This review summarizes current evidence concerning lipid metabolic remodeling and tumor–adipocyte interactions that may contribute to the SARIFA phenotype in PCa. Androgen receptor-regulated lipid metabolism, uptake of adipocyte-derived fatty acids, adipokine signaling, and extracellular vesicle-mediated communication provide a plausible mechanistic framework. Nevertheless, direct experimental evidence linking several of these processes specifically to SARIFA in PCa remains limited, and some proposed relationships are based on indirect evidence or findings from other tumor types. Further studies should establish standardized scoring criteria, intra- and interobserver reproducibility, external validation, and incremental prognostic value before the clinical implementation of SARIFA can be considered. Full article

Background: Non-proliferative diabetic retinopathy (NPDR) is a common microvascular complication of type 2 diabetes mellitus (T2DM) associated with chronic inflammation, metabolic dysregulation, and multiple interacting systemic factors. This study evaluated the associations of inflammatory biomarkers, serum 25-hydroxyvitamin D [25(OH)D], electrolyte homeostasis, and lipid-derived indices with NPDR. Methods: In this cross-sectional study with prospective recruitment, 98 patients with T2DM were classified into NPDR (n = 55) and non-DR (n = 43) groups. Clinical characteristics, hematological inflammatory indices, serum interleukin-6 (IL-6), C-reactive protein (CRP), 25(OH)D, electrolyte concentrations, lipid profile, and derived biomarkers—including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune–inflammation index (SII), LDL-C/HDL-C ratio, and calculated serum osmolarity—were compared. Receiver operating characteristic (ROC) analysis and multivariable logistic regression were performed to assess discriminatory performance and independent associations with NPDR. Results: Patients with NPDR had significantly lower serum 25(OH)D concentrations than the non-DR group (16.6 ± 7.5 vs. 21.0 ± 5.2 ng/mL, p < 0.001). Serum IL-6 levels (4.2 ± 3.1 vs. 2.8 ± 1.4 pg/mL, p = 0.047), NLR (p = 0.043), LDL-C/HDL-C ratio (p = 0.031), and calculated serum osmolarity (p = 0.033) were significantly higher, whereas lymphocyte count and the lymphocyte-to-monocyte ratio were significantly lower. Among individual biomarkers, serum 25(OH)D showed the best discriminatory performance (AUC = 0.712). A multivariable model including insulin therapy, IL-6, serum 25(OH)D, and the LDL-C/HDL-C ratio demonstrated good discrimination (AUC = 0.813), with 81.8% sensitivity and 81.4% specificity. Bootstrap validation supported the stability of the model. Conclusions: NPDR was associated with lower serum 25(OH)D concentrations, systemic inflammation, and a less favorable LDL-C/HDL-C ratio. A multivariable model integrating inflammatory, metabolic, and nutritional biomarkers showed better discriminatory performance than individual biomarkers. The association between insulin therapy and NPDR likely reflects greater diabetes severity rather than a direct effect of insulin. These findings are exploratory, and prospective studies in larger independent cohorts are needed to determine whether these biomarkers improve risk stratification beyond established clinical factors. Full article

Background and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with substantial morbidity, and hepatic fibrosis stage is the strongest predictor of long-term outcomes. Although liver biopsy remains the reference standard for fibrosis assessment, its invasiveness has driven the development of noninvasive diagnostic tools, including transient elastography (TE) and serum-based fibrosis scores. To evaluate and compare the diagnostic performance of TE and commonly used serum-based fibrosis scores for detecting clinically significant fibrosis (≥F2) in patients with biopsy-proven MASLD. Materials and Methods: This retrospective cross-sectional exploratory diagnostic accuracy study included 30 adults with biopsy-confirmed MASLD. Patients were classified into clinically significant fibrosis (CSF, ≥F2; n = 9) and no/mild fibrosis (NMF, F0–F1; n = 21) groups. Among the nine patients with CSF, six had stage F2 fibrosis and three had stage F3 fibrosis. TE, FIB-4, APRI, NAFLD Fibrosis Score (NFS), BARD score, and HOMA-IR were evaluated. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis, optimal cutoff values, dual-cutoff strategies, and confusion matrix analysis. Results: TE, FIB-4, and APRI demonstrated the highest diagnostic performance (AUROC: 0.93 for each). TE showed the most balanced diagnostic accuracy (sensitivity 88.9%, specificity 90.5%), whereas APRI provided the highest specificity (95.2%) and the strongest positive likelihood ratio (+LR: 18.67). FIB-4 achieved 100% sensitivity with lower specificity (76.2%). NFS demonstrated moderate diagnostic performance (AUROC: 0.83) with a relatively wide gray zone (56.7%), whereas BARD and HOMA-IR showed limited discriminative ability. When fibrosis categories automatically assigned by the TE device were evaluated, the overall diagnostic accuracy was 93.3%. Conclusions: TE, FIB-4, and APRI demonstrated promising diagnostic performance as noninvasive tools for identifying clinically significant fibrosis in biopsy-proven MASLD. These findings generate the hypothesis that a sequential diagnostic strategy using serum-based fibrosis scores for initial risk stratification followed by TE for confirmation may reduce the need for liver biopsy. However, this hypothesis requires confirmation in larger prospective validation studies. Full article

Obesity is an increasingly important and modifiable driver of chronic kidney disease (CKD), with effects that extend well beyond its associations with type 2 diabetes, hypertension, and dyslipidemia. To synthesize the evidence that excess adiposity is a causal and modifiable determinant of kidney disease, and to examine how specific adipose depots injure the glomerulus and the tubulointerstitium, and then map these mechanisms onto established and emerging therapies. Throughout, obesity-related kidney disease (ORKD) denotes the full spectrum of diposity-driven renal injury, whereas obesity-related glomerulopathy (ORG) is reserved for the biopsy-defined glomerular lesion. Central, visceral, perirenal and renal-sinus adiposity act first through structural and haemodynamic mechanisms, promoting glomerular hyperfiltration, mechanical renal compression and activation of the adipose-derived renin–angiotensin–aldosterone system (RAAS). In parallel, these depots drive cellular and metabolic injury through lipotoxicity, adipokine imbalance, sterile inflammation, oxidative stress, gut dysbiosis, mitochondrial dysfunction, epigenetic remodelling and cellular senescence. Ectopic lipid accumulation within the renal parenchyma—fatty kidney—offers a unifying description of these changes and is most marked in type 2 diabetes mellitus. These interacting processes converge on podocyte stress, tubular metabolic failure, endothelial dysfunction and interstitial fibrosis, producing a phenotypic continuum that ranges from early albuminuria to obesity-related glomerulopathy and progressive CKD. Within the RAAS limb we highlight two comparatively underappreciated, adiposity-linked routes to injury: adipocyte-derived leptin directly upregulates adrenal aldosterone synthase (CYP11B2), and mast-cell chymase generates angiotensin II independently of angiotensin-converting enzyme, together reinforcing aldosterone- and angiotensin II–mediated damage that conventional RAAS blockade only partially interrupts. We further consider the counter-regulatory ghrelin–leptin axis, in which the suppression of ghrelin that accompanies obesity may withdraw an antioxidant, anti-inflammatory and podocyte-protective signal precisely as leptin-driven glomerular injury intensifies, positioning ghrelin as a plausible modulator and candidate biomarker of obesity-related kidney injury. We also examine how obesity complicates renal risk assessment, drug dosing, dialysis delivery and transplant access. Emerging, mechanism-matched therapies—SGLT2 inhibitors, GLP-1 receptor agonists, finerenone, structured lifestyle intervention, metabolic-bariatric surgery and, most recently, aldosterone synthase inhibitors that suppress the chymase- and leptin-driven aldosterone escaping receptor blockade—now enable a precision cardiovascular-kidney-metabolic framework that aligns adipose-depot biology, biomarkers, histology and treatment response to guide mechanism-based care in ORKD. Full article

Schizophrenia is a heterogeneous neurodevelopmental disorder in which genetic liability, developmental exposures, illness stage, treatment, and metabolic or inflammatory comorbidity may shape redox biology. This narrative review evaluates the human and mechanistic evidence for impaired redox adaptation as a convergence mechanism linking glutathione (GSH) regulation, N-methyl-D-aspartate receptor hypofunction, parvalbumin-interneuron and perineuronal-net vulnerability, mitochondrial–glial dysfunction, and neuroimmune signalling. The findings do not support a uniform oxidative abnormality across all patients or compartments: the peripheral biomarkers are heterogeneous, the group-level brain GSH magnetic resonance spectroscopy findings are largely null, and treatment-related changes vary by marker and illness phase. Beyond the established GSH–NMDA–redox–immune models, we integrate iron–lipid redox regulation as a conditional, hypothesis-generating extension and apply a deliberately conservative evidence hierarchy. Human studies more often report a lower peripheral iron and reduced or redistributed brain iron than a uniform iron excess; the plasma signals for predominantly intracellular proteins remain analytically unvalidated, and ferroptotic neuronal death has not been demonstrated. Longitudinal, sex-aware, multi-compartment, and challenge-based studies are needed to define meaningful redox subgroups; no redox- or ferroptosis-related biomarker is currently validated to guide treatment selection. Full article

Ovarian cancer (OC) remains the most lethal gynecological malignancy, mostly due to its frequent diagnosis at advanced stages, early peritoneal dissemination, ascites formation, and limited sensitivity of currently available approaches for early detection. Extracellular vesicles (EVs), particularly exosomes, mediate intercellular communication through the transfer of proteins, lipids, metabolites, and nucleic acids. In OC, EV-associated protein profiles reflect both tumor-cell-intrinsic programs and the complex interactions between malignant cells and the peritoneal microenvironment. This review summarizes current evidence regarding the involvement of exosomal proteins in OC progression, with particular emphasis on epithelial–mesenchymal transition, mesothelial reprogramming, extracellular matrix remodeling, angiogenesis, immune suppression, peritoneal dissemination, and platinum resistance. Mechanistic studies indicate that exosomal proteins, including CD44, the integrin α5β1/asparaginyl endopeptidase complex, annexin A2, low-density lipoprotein receptor-related protein 1, and programmed death-ligand 1, can directly contribute to metastatic niche formation and tumor progression. In parallel, proteomic studies of plasma-, serum-, ascites-, peritoneal-fluid-, and uterine-lavage-derived EVs have identified candidate liquid-biopsy biomarkers, including MUC1, EpCAM, FOLR1, integrins, complement- and coagulation-related proteins, and proteins associated with treatment resistance. To integrate the biological significance of proteins reported in OC-associated exosomes, we additionally performed protein–protein interaction and functional enrichment analyses. These analyses revealed interconnected protein groups associated with cell adhesion, oxidative stress adaptation, secretory remodeling, lipid metabolism, extracellular matrix organization, and inflammatory signaling. Taken together, the available evidence supports exosomal proteome profiling as a promising approach for investigating OC dissemination and developing minimally invasive diagnostic and prognostic tools. However, standardized EV isolation, quantitative proteomics, functional validation, and independent clinical cohorts remain essential for translation into clinical practice. Full article

High-sensitivity cardiac troponin has made the diagnosis of myocardial infarction (MI) faster and more precise, but it does not measure the broader biological vulnerability that often determines the outcome after an acute coronary syndrome (ACS). Growth differentiation factor-15 (GDF-15) is induced by ischemic stress, inflammation, oxidative injury, renal dysfunction, metabolic disease, and ageing. This biology explains its appeal in ACS, but also its diagnostic limitation: GDF-15 is not cardiac-specific and should not be used as an alternative to electrocardiography and high-sensitivity troponin algorithms for early MI diagnosis. Its better supported role is prognostic. Across emergency department chest pain cohorts, non-ST elevation MI, ST elevation MI, post-ACS trial populations, and serial biomarker studies, higher GDF-15 concentrations are most consistently associated with all-cause mortality, cardiovascular mortality, heart failure, and major bleeding, while associations with recurrent ischemic events alone are less specific. The key unresolved issue is incremental clinical value. GDF-15 may improve discrimination and reclassification beyond clinical predictors, troponin, natriuretic peptides, renal function and GRACE or GRACE 2.0 in selected settings, but statistical association is not equivalent to clinical utility. Its possible role in bleeding risk estimation and antithrombotic benefit–risk assessment is clinically important, especially after the PLATO biomarker analyses, yet routine GDF-15-guided dual antiplatelet therapy decisions remain unsupported. Future implementation requires validated thresholds, calibration, decision curve evidence, health economic evaluation, and trials in which GDF-15-guided management changes care and improves outcomes. Full article

Background/Objectives: Obesity is a major global health challenge characterized by adipose tissue dysfunction, insulin resistance, chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, and increased cardiometabolic risk. Despite substantial therapeutic advances, limitations related to cost, adverse effects, and long-term adherence have stimulated interest in complementary nutritional approaches. Sulforaphane, a bioactive isothiocyanate derived primarily from broccoli and other cruciferous vegetables, has attracted considerable attention because of its antioxidant, anti-inflammatory, and metabolic regulatory properties. This narrative review critically evaluates the current evidence regarding the role of sulforaphane and broccoli-derived preparations in obesity and obesity-associated metabolic dysfunction. Methods: A narrative review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Eligible publications included in vitro, animal, clinical, observational, and relevant review studies investigating sulforaphane, glucoraphanin, or broccoli-derived preparations in relation to obesity, adiposity, insulin resistance, metabolic syndrome, inflammation, oxidative stress, energy metabolism, and related metabolic abnormalities. Results: In vitro studies consistently demonstrate inhibition of adipocyte differentiation and lipid accumulation, attenuation of oxidative stress and inflammatory signaling, and enhancement of cellular energy metabolism. Animal studies further report reductions in adiposity, insulin resistance, hepatic steatosis, oxidative stress, and chronic inflammation, together with improvements in energy expenditure, metabolic flexibility, and obesity-associated metabolic abnormalities. Mechanistic evidence indicates that sulforaphane exerts pleiotropic metabolic effects through activation of the Nrf2 and AMPK pathways, suppression of NF-κB-mediated inflammation, improvement of mitochondrial function, promotion of thermogenesis and adipose tissue browning, regulation of lipid metabolism, and modulation of gut microbiota composition. Human studies, although limited and heterogeneous, suggest possible improvements in glycemic control, insulin sensitivity, endothelial function, and other surrogate metabolic biomarkers associated with obesity. However, evidence demonstrating clinically meaningful reductions in body weight, adiposity, or body composition remains limited and inconsistent, and improvements in these surrogate biomarkers should not be interpreted as evidence of reduced obesity-related morbidity or clinically meaningful adiposity reduction. Bioavailability, myrosinase activity, food processing, gut microbiota composition, and interindividual variability remain important determinants of efficacy and key translational challenges. Conclusions: Current evidence provides strong mechanistic and preclinical support for sulforaphane as a promising candidate adjunctive nutritional intervention for improving obesity-associated metabolic dysfunction. Nevertheless, current human evidence suggests possible metabolic benefits but does not establish sulforaphane as an effective weight-loss intervention or an evidence-based treatment for obesity. Large, long-term randomized controlled trials employing standardized sulforaphane preparations and comprehensive assessments of body weight, adiposity, body composition, metabolic health, pharmacokinetics, and gut microbiota composition are required to establish its clinical efficacy and define its role within precision nutrition strategies for obesity and obesity-associated metabolic dysfunction. Full article

Carbon nanotube (CNT)-based biosensors have emerged as promising platforms for non-invasive biofluid analysis because of their high electrical conductivity, large surface area, tunable optical properties, and versatile surface chemistry, enabling miniaturized, flexible sensing devices. Sweat, saliva, tears, and urine are increasingly recognized as attractive alternatives to blood for point-of-care diagnostics because they enable repeated, non-invasive sampling while containing clinically relevant metabolites, electrolytes, proteins, hormones, nucleic acids, pathogens, and other biomarkers. However, the low abundance of many analytes, matrix complexity, biofouling, and biofluid-specific variability present significant analytical challenges. This review critically examines the different CNT-based sensor architectures, and their recent advances in non-invasive analysis of sweat, saliva, tears, and urine. It integrates sensor architecture, biofluid-specific analytical challenges, sample-validation level, and translational readiness within a single comparative framework. Representative applications are discussed for metabolic monitoring, renal health assessment, infectious disease testing, and other clinically relevant uses. Beyond clinical diagnostics, emerging non-clinical applications, including drug-of-abuse detection, forensic body-fluid identification, and occupational or environmental exposure assessment, are also highlighted. Finally, we discuss key barriers limiting real-world translation of CNT biosensors, including material reproducibility issues, biofouling, physiological interpretation of biofluid biomarkers, scalable manufacturing, and long-term operational stability, and outline future strategies to advance these platforms toward robust, reliable, and widely deployable biosensing technologies. Full article

Coronavirus disease 2019 (COVID-19) is increasingly recognized as a multisystem disorder associated with persistent metabolic complications extending beyond the acute phase of infection. Accumulating evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may disrupt glucose homeostasis through mechanisms involving pancreatic β-cell dysfunction, insulin resistance, chronic inflammation, oxidative stress, mitochondrial dysfunction, and hypoxia-related signalling. This review summarizes current evidence regarding the molecular and cellular mechanisms linking SARS-CoV-2 infection to impaired insulin secretion and post-COVID metabolic disturbances. Particular emphasis is placed on the regulation of insulin secretion, β-cell compensation and failure, oxidative stress, inflammatory signalling, mitochondrial dysfunction, and the development of the post-COVID metabolic phenotype. Emerging evidence indicates that persistent metabolic abnormalities after COVID-19 may range from transient dysglycaemia to new-onset diabetes mellitus and metabolic syndrome. The review also discusses clinical implications, biomarkers, therapeutic perspectives, and unresolved questions regarding the reversibility of post-COVID β-cell dysfunction. A better understanding of the mechanisms underlying post-COVID metabolic dysfunction may improve risk stratification, facilitate early intervention, and support development of targeted therapeutic strategies aimed at preserving β-cell function and long-term metabolic health. Full article

Microbiota has emerged as a potential regulator of female reproductive health through immunological, metabolic, and endocrine networks. Growing evidence suggests that the composition and stability of the vaginal, uterine, and gut microbiota are associated with fertility outcomes. Disruptions in reproductive tract homeostasis have been linked to infertility, implantation failure, pregnancy loss, and diminished success in assisted reproductive technologies. Beyond local interactions, maternal gut microbiota may influence systemic immunity and metabolic pathways related to vaginal and endometrial microbiota. While these findings highlight the microbiome-based signatures’ potential as predictive and prognostic biomarkers, their clinical applicability remains unconfirmed. Evidence is limited by small cohort sizes, methodological and analytical heterogeneity, and lack of standardization, limiting clinical translation. This narrative review summarizes the current knowledge regarding the microbiome’s role in female reproductive health, highlighting its potential impact on pathophysiology, diagnostics, and therapeutic strategies. While this approach allows for a broad conceptual overview, we explicitly note that it is not systematic. As a result, this review is limited by the absence of a standardized search protocol, which may introduce selection bias. Finally, we review advances in microbial engineering and synthetic biology, highlighting engineered living biotherapeutics as promising strategies to improve microbiome-based reproductive medicine. Full article

Acute kidney injury (AKI), chronic kidney disease (CKD), and diabetic kidney disease (DKD) are interconnected disorders linked by shared mechanisms involving redox imbalance and mitochondrial dysfunction. This review summarizes current evidence on the role of excessive reactive oxygen species (ROS) production, impaired oxidized nicotinamide adenine dinucleotide (NAD⁺) metabolism, altered mitochondrial bioenergetics, disrupted mitochondrial dynamics, and defective mitochondrial quality control pathways, including mitophagy and the mitochondrial unfolded protein response (UPR^mt), in kidney disease progression. Experimental and clinical studies indicate that these mechanisms contribute to inflammation, fibrosis, apoptosis, and maladaptive repair, promoting progression from AKI to CKD and worsening DKD. The review also discusses emerging biomarkers and therapeutic strategies targeting oxidative stress and mitochondrial dysfunction. Overall, redox-mediated mitochondrial injury represents a shared pathogenic axis and a potential therapeutic target across kidney diseases. Full article

Background/Objectives: The physiological adaptations required to sustain elite football performance are influenced by both genetic background and dynamic biochemical responses, although their interaction across a full competitive season remains insufficiently characterized. This study aimed to examine the association between polygenic profiles and longitudinal biochemical adaptations in professional football players. Methods: Forty male professional football players competing in the Spanish league were monitored across two consecutive seasons. Blood samples were collected at six time points representing different phases of the competitive cycle. Biomarkers related to muscle metabolism, iron status, and hepatic function were analyzed. Polygenic profiles were calculated using Total Genotype Scores (TGS) for muscle performance, hepatic resilience, and metabolic efficiency. Associations were initially explored using Pearson correlations and subsequently evaluated using linear mixed-effects models accounting for repeated measurements within subjects. Results: Exploratory correlation analyses identified several associations between polygenic profiles and biochemical markers. Muscle performance TGS was inversely associated with serum iron (r = −0.36, p = 0.017) and positively associated with CK (r = 0.32, p = 0.041), Hb (r = 0.29, p = 0.046), and Hct (r = 0.33, p = 0.024). Hepatic resilience TGS showed inverse associations with ALT (r = −0.39, p = 0.012), urea (r = −0.51, p = 0.011), and BUN (r = −0.51, p = 0.011). Metabolic efficiency TGS was negatively associated with AST (r = −0.43, p = 0.044), ALT (r = −0.33, p = 0.025), and GGT across multiple time points (p = 0.001–0.013). However, although several nominal associations emerged in linear mixed-effects models accounting for repeated measurements, none remained statistically significant after false discovery rate correction. These findings should therefore be interpreted as exploratory and hypothesis-generating. Conclusions: Polygenic profiles may be associated with inter-individual variability in biochemical adaptations throughout a competitive season. These findings suggest the integration of genomic and biochemical data in precision athlete monitoring, while highlighting causal relationships and predictive applications require further investigation. Full article