Search Results (889)

This protocol details an optimized step-by-step procedure for performing the Seahorse XF Cell Mito Stress Test on human umbilical vein endothelial cells (HUVECs) using the Agilent Seahorse XF Pro Analyzer. Designed to address practical challenges often overlooked in standard manuals, the method preserves the native adherent state of HUVECs—a key in vitro model in vascular aging (VA) research—enabling real-time, label-free measurement of mitochondrial respiration and glycolytic function without cell detachment. The workflow is presented chronologically, covering instrument preparation, cell seeding, compound loading, assay execution, and post-assay normalization, with integrated notes and troubleshooting tips refined through hands-on experience based on the official manuals. This protocol aims to set up a detailed, rearranged standard workflow to improve experimental efficiency, reduce operator error, and support reproducible and well-organized metabolic profiling of HUVECs in aging and cardiovascular studies. Full article

Dilated cardiomyopathy (DCM) is a major contributor to heart failure and cardiac transplantation. This study investigated the metabolic potential of human myocardium-derived mesenchymal stem/stromal cells (hmMSCs) and subsequently cardiac sphere-derived cells (SDCs) obtained from healthy (non-dilated) and pathological (dilated) myocardial tissues. hmMSCs were isolated using the explant outgrowth method and expanded in monolayer culture. Small round cells loosely attached on hmMSCs were harvested and cultivated as cardiac spheroids for 1–3 days, subsequently obtaining SDCs. The cell morphology, proliferation rate, mitochondrial activity, and intracellular calcium levels were analyzed using flow cytometry, Seahorse metabolic assays, and spectrophotometry, while expression of cell progenitor and cardiac commitment genes were analyzed by quantitative PCR. Both healthy and pathological SDCs demonstrated significantly enhanced mitochondrial function—reflected by increased maximal respiration, ATP production, and coupling efficiency—along with reduced steady-state intracellular calcium levels compared with hmMSCs. SDCs from both healthy and dilated myocardium showed marked upregulation of several cardiac progenitor and lineage-commitment genes relative to hmMSCs. SDCs derived from both healthy and dilated myocardiums possess a more favorable metabolic, progenitor and cardiac commitment profile than conventional hmMSCs. hmMSCs and SDCs from dilated myocardium retain residual metabolic potential, which may be further enhanced under 3D culture conditions. Full article

Background/Objectives: Breast cancer cells rely on both mitochondrial metabolism and proteostatic mechanisms for cell fitness. The mitochondrial enzyme IDH2 supports redox balance and biosynthesis, while the ubiquitin-proteasome system (UPS) preserves protein quality. This study aimed to determine whether inhibiting IDH2 enhances sensitivity to proteasome-targeting agents across breast cancer subtypes. Methods: A panel of human and murine breast cancer cell lines was treated with the IDH2 inhibitor AGI-6780, alone or in combination with the proteasome inhibitor carfilzomib (CFZ) or the E1 ubiquitin-activating enzyme inhibitor TAK-243. Synergy was evaluated using Bliss scoring. Apoptosis, clonogenicity, and pathway modulation were assessed through Western blotting, colony-formation assays, and reverse-phase protein array (RPPA) profiling. Results: We observed that co-targeting IDH2 and the UPS produced strong synergistic cytotoxicity in multiple breast cancer models, including in triple-negative MDA-MB-231 and 4T1 cells (Bliss > 25). Combination treatments led to pronounced apoptosis, evidenced by cleaved PARP-1 and Caspase-3 cleavage, and a marked loss of clonogenic potential. RPPA analysis revealed significant alterations in key survival and stress-response pathways, including NF-κB, PI3K-p85, Src, and p38-MAPK. Conclusions: Inhibition of IDH2 markedly enhances the cytotoxic effects of proteasome-targeting by disrupting metabolic–proteostatic balance and promoting apoptotic cell death. These findings identify a growth-inhibitory effect that may be leveraged to improve functional dependency in breast cancer, particularly in triple-negative breast cancer, which currently lacks efficient drug treatments. Full article

Mitochondria are highly dynamic organelles that integrate metabolic regulation, signal transduction, and programmed cell death with their canonical role in adenosine triphosphate (ATP) production. Their ability to undergo continuous remodeling through the opposing processes of fusion and fission is essential for maintaining cellular homeostasis, preserving organelle quality control, and enabling adaptive responses to metabolic and oxidative stress. Among the core regulators of mitochondrial dynamics, the dynamin-related guanosine triphosphatase (GTPase) OPA1 plays a central role in inner membrane fusion, cristae architecture maintenance, bioenergetic efficiency, and the modulation of redox balance and apoptotic signaling. Accumulating evidence indicates that dysregulation of OPA1 expression or activity contributes to the initiation and progression of multiple malignancies, underscoring its importance in tumor cell survival, proliferation, metabolic adaptation, and resistance to stress. Here, we summarize current knowledge on OPA1 dysregulation in cancer and, based on preliminary, unpublished in silico analyses, we highlight the growing relevance of OPA1 as a therapeutic target, particularly through its GTPase domain and the still understudied Interface 7. Overall, these findings outline how integrated computational approaches could potentially guide the identification of novel OPA1 modulators, offering a conceptual framework that highlights OPA1 as a promising, yet still largely underexplored, target in oncology. Full article

Oxidative stress, caused by an imbalance between the production of reactive oxygen species and endogenous antioxidant capacity, is a key etiological factor in numerous pathologies, including neurodegenerative and cardiovascular diseases. The limited clinical efficacy of conventional antioxidants is primarily due to their insufficient accumulation within the mitochondria, the main site of intracellular ROS generation. This article reviews the design and application of Mitochondria-Targeted Antioxidants, which represent a major advance in precision medicine. The design of these compounds involves linking an antioxidant “payload” to a lipophilic cation, such as the triphenylphosphonium group. This positive charge leverages the negative electrochemical gradient across the inner mitochondrial membrane to drive the antioxidant into the organelle. This mechanism allows the drug to reach concentrations over 100 times higher than non-targeted alternatives. The discussion encompasses the structure-activity analysis of the carrier, the payload (e.g., quinone derivatives), and the linker, which determine optimal subcellular partitioning and scavenging efficiency. Preclinical data highlight the therapeutic potential of this approach, showing strong neuroprotection in models of Parkinson’s and Alzheimer’s diseases, as well as improved outcomes in cardiovascular and ocular health. By restoring redox balance specifically within the mitochondria, these targeted therapies offer a more effective way to treat chronic oxidative damage. Full article

We present a simplified phenomenological computational framework that integrates the GABA shunt into established metabolic mechanisms underlying pancreatic beta cell insulin secretion. The GABA shunt introduces carbon into the tricarboxylic acid (TCA) cycle via succinate, thereby functioning as an anaplerotic pathway. This anaplerotic input is coupled to oscillatory cataplerotic fluxes, primarily involving α-ketoglutarate, whose effective extrusion requires coordinated counter-fluxes of malate and aspartate. Within the model, these cataplerotic exchanges are facilitated by UCP2-mediated transport processes and necessitate complementary anaplerotic replenishment through pyruvate carboxylase (PC). Based on this functional interdependence, we introduce the Dual Anaplerotic Model (DAM), which conceptually links two anaplerotic routes—the GABA shunt-mediated pathway and the glucose-dependent PC pathway—into a unified metabolic response module. DAM describes a coordinated, breathing-like redistribution of carbon between mitochondrial and cytosolic metabolite pools, while efficient oxidative metabolism of glucose-derived carbon entering the TCA cycle via pyruvate dehydrogenase is maintained. The model is driven by experimentally observed ATP/ADP and Ca²⁺ dynamics and is not intended to generate autonomous oscillations. Instead, it enables qualitative, phase-dependent visualization of how dual anaplerotic fluxes constrain and shape oscillatory metabolic states in beta cells. DAM provides an integrative conceptual scaffold for interpreting experimental observations and for motivating future quantitative modeling and experimental studies addressing metabolic regulation in physiological and pathophysiological contexts. Full article

Pine wilt disease (PWD), caused by Bursaphelenchus xylophilus, is driven by a tri-component system involving the pinewood nematode, Monochamus spp. beetle vectors, and susceptible pine hosts. Chemical control remains a scenario-dependent option for emergency suppression and high-value protection, but its deployment is constrained by strong regional regulatory and practical differences. In Europe (e.g., Portugal and Spain), field chemical control is generally not practiced; post-harvest phytosanitary treatments for wood and wood packaging rely mainly on heat treatment, and among ISPMs only sulfuryl fluoride is listed for wood treatment with limited use. This review focuses on recent progress in PWD chemical control, summarizing advances in nematicide discovery and modes of action, greener formulations and delivery technologies, and evidence-based, scenario-oriented applications (standing-tree protection, vector suppression, and infested-wood/inoculum management). Recent studies highlight accelerated development of target-oriented nematicides acting on key pathways such as neural transmission and mitochondrial energy metabolism, with structure–activity relationship (SAR) efforts enabling lead optimization. Formulation innovations (water-based and low-solvent products, microemulsions and suspensions) improve stability and operational safety, while controlled-release delivery systems (e.g., micro/nanocapsules) enhance penetration and persistence. Application technologies such as trunk injection, aerial/Unmanned aerial vehicle (UAV) operations, and fumigation/treatment approaches further strengthen scenario compatibility and operational efficiency. Future research should prioritize robust target–mechanism evidence, resistance risk management and rotation strategies, greener formulations with smart delivery, and scenario-based exposure and compliance evaluation to support precise, green, and sustainable integrated control together with biological and other sustainable approaches. Full article

Thrips are cosmopolitan agricultural pests and important vectors of plant viruses, and the increasing coexistence of multiple morphologically similar species has intensified the demand for species-specific molecular identification. However, traditional morphological identification and PCR assays using universal primers are often inadequate for mixed-species samples and field-adaptable application. In this study, we developed a species-specific molecular identification framework targeting a polymorphism-rich region of the mitochondrial cytochrome c oxidase subunit I (COI) gene, which is more time-efficient than sequencing-based COI DNA barcoding, for four economically important thrips species in southern China, including the globally invasive Frankliniella occidentalis. By aligning COI sequences, polymorphism-rich regions were identified and used to design four species-specific primer pairs, each containing a diagnostic 3′-terminal nucleotide. These primers were combined with a PBS-based DNA extraction workflow optimized for single-insect samples that minimizes dependence on column-based purification. The assay achieved a practical detection limit of 1 ng per reaction, demonstrated species-specific amplification, and maintained reproducible amplification at DNA inputs of ≥1 ng per reaction. Notably, PCR inhibition caused by crude extracts was effectively alleviated by fivefold dilution. Although the chemical identities of the inhibitors remain unknown, interspecific variation in inhibition strength was observed, with T. hawaiiensis exhibiting the strongest suppression, possibly due to differences in lysate composition. This integrated framework balances target specificity, operational simplicity, and dilution-mitigated inhibition, providing a field-adaptable tool for thrips species identification and invasive species monitoring. Moreover, it provides a species-specific molecular foundation for downstream integration with visual nucleic acid detection platforms, such as the CRISPR/Cas12a system, thereby facilitating the future development of portable molecular identification workflows for small agricultural pests. Full article

Background: Sheep (Ovis aries) exhibit significant diversity in adipose tissue deposition, which influences meat quality, environmental adaptation, and economic value. Tail fat, in particular, varies widely among breeds, yet the transcriptomic basis of this variation remains incompletely understood. This study aims to systematically compare the transcriptional profiles of five adipose depots across five sheep breeds to identify molecular mechanisms underlying fat deposition and tail phenotype divergence. Methods: We analyzed 250 publicly available RNA-seq samples from five adipose tissues (caul, subcutaneous, perirenal, intermuscular, and tail fat) of five sheep breeds (Altay, Tibetan, Merino, Wadi, Small-tailed Han). Data were processed using FastQC, STAR, and featureCounts. Differential expression analysis was performed with DESeq2, followed by GO and KEGG enrichment analyses. Breeds were grouped into three tail phenotypes: fat-tailed, short fat-tailed, and thin-tailed. Cross-tissue and phenotype-specific pathway analyses were conducted to identify key regulatory genes. Results: Transcriptional divergence was most pronounced in subcutaneous and intermuscular fat, while tail fat exhibited both conserved and phenotype-specific pathways. Fat-tailed breeds showed enrichment in mitochondrial oxidative phosphorylation and lipid biosynthesis genes (TAFAZZIN, GPAM, COQ family). Short fat-tailed breeds were characterized by extracellular matrix remodeling genes (MMP9, MMP12, MMP19). Thin-tailed sheep lacked these pro-lipogenic and structural remodeling pathways. A dual-axis model of tail fat development is proposed to explain phenotypic diversity. Conclusions: This study reveals that distinct molecular mechanisms underpin tail fat phenotypes in sheep: fat-tailed breeds prioritize metabolic efficiency, short fat-tailed breeds rely on ECM remodeling, and thin-tailed breeds lack these enhancements. The identified candidate genes may serve as potential targets for molecular breeding strategies aimed at optimizing fat deposition and adaptive traits in sheep. Full article

Puerarin is a naturally occurring isoflavone with reported anticancer activity, yet its topical translation is constrained by limited stability and suboptimal dermal delivery. A Puerarin-loaded proniosomal gel was developed as a potential dermal delivery platform, and we performed an initial assessment of its antimelanoma activity and safety. The gel was produced by coacervation–phase separation using Span 60, Tween 80, phosphatidylcholine, and cholesterol. Physicochemical characterization included pH, entrapment efficiency, rheology, FTIR, DSC, and vesicle properties (DLS, PDI, ζ-potential). In silico geometry optimization and docking were carried out for melanoma-associated targets (MITF and DNMT3B). Biological effects were investigated in vitro on A375 melanoma cells using MTT, morphological analysis, and nuclear/mitochondrial staining, while irritation potential was evaluated in ovo by HET-CAM. The optimized formulation exhibited a skin-compatible pH and an entrapment efficiency of 62 ± 0.26%. DLS indicated a multimodal population, with a major number-weighted vesicle population in the 100–200 nm range, and a ζ-potential of −34.9 ± 0.14 mV. FTIR and DSC supported component incorporation without evidence of chemical incompatibility. The gel showed non-Newtonian, pseudoplastic, thixotropic flow, which is advantageous for topical use. Docking predicted meaningful affinities of Puerarin toward MITF and DNMT3B. The formulation reduced A375 viability in a dose-dependent manner (to 44.66% at 200 µg/mL) and, at higher concentrations, produced nuclear condensation and disruption of the mitochondrial network. HET-CAM classified the gel as non-irritant. The Puerarin-loaded proniosomal gel represents a promising topical platform with preliminary in vitro antimelanoma cytotoxic potential, warranting additional studies to validate skin delivery, efficacy, and safety. Full article

Background: Triple-negative breast cancer (TNBC) remains primarily treated with chemotherapy due to the lack of effective therapeutic targets, but this approach carries significant systemic toxicity and a high risk of drug resistance. Curcumin (Cur), despite its multifaceted antitumor activity, faces limitations in clinical application due to poor water solubility and weak targeting properties. This study aims to develop a folate/mitochondria dual-targeted curcumin–copper chelate liposome (Cu-Cur DTLPs) formulation that enables copper accumulation within tumor cells and induces copper-mediated cell death, thereby providing an effective and relatively low-toxicity therapeutic strategy for triple-negative breast cancer. Methods: Curcumin–copper chelates (Cu-Cur) were first synthesized and characterized using mass spectrometry, NMR, and infrared spectroscopy. Subsequently, dual-targeted liposomes (Cu-Cur DTLPs) were prepared via the thin-film dispersion method, with systematic evaluation of particle size, zeta potential, encapsulation efficiency, and in vitro release profiles. In vitro cytotoxicity was assessed against 4T-1 and MDA-MB-231 cells using the MTT assay. In a 4T-1 tumor-bearing BALB/c mouse model, comprehensive evaluation of targeting efficiency, antitumor efficacy, and mechanisms of action was conducted via in vivo imaging, tumor volume monitoring, immunohistochemistry (detecting FDX1 and DLAT proteins), and TUNEL staining. Results: Cu-Cur DTLPs with a uniform particle size of approximately 104.4 nm were successfully synthesized. In vitro and in vivo studies demonstrated that compared to free curcumin and conventional liposomes, Cu-Cur DTLPs significantly enhanced drug accumulation in tumor tissues and exhibited effective tumor growth inhibition. Mechanistic studies confirmed that this formulation specifically accumulates copper ions within tumor cells, upregulates FDX1, promotes DLAT oligomerization, and induces mitochondrial dysfunction, thereby driving copper death. TUNEL staining ruled out apoptosis as the primary mechanism. Safety evaluation revealed no significant toxicity in major organs. Conclusions: The Cu-Cur DTLPs developed in this study effectively induce copper-mediated death in TNBC through a dual-targeted delivery system, significantly enhancing antitumor activity with favorable safety profiles. This establishes a highly promising novel nanotherapeutic strategy for TNBC treatment. Full article

Nitrite pollution in aquatic environments, often driven by human activity, can disrupt fish physiology. Nitrite is absorbed by freshwater fish through their gills, leading to internal accumulation and interference with nitric oxide (NO) signaling, redox state, and the oxygen-carrying capacity of blood. The effects of nitrite are concentration-dependent. Although moderate environmental nitrite levels have little impact on oxygen transport, they may still interfere with NO homeostasis and cellular metabolism. We report the effects of 72 h of exposure to 10 μM nitrite on adult zebrafish blood’s O₂-carrying capacity and on muscle mitochondrial activity, metabolism, and redox state. The results show that this environmentally relevant but moderate concentration of nitrite leads to decreases in fish routine oxygen consumption (rMO₂) and spontaneous activity, an increase in blood nitrosyl hemoglobin (HbNO), indicating increased NO production in the blood, accumulation of nitrite in muscle tissue, oxidative stress, and changes in muscle aerobic capacity linked to a rise in mitochondrial efficiency. Parallel to these effects, increases in antioxidant capacity, arginase activity, and urea and lactate levels were observed. Globally, these results are consistent with altered NO homeostasis in the fish body induced by nitrite stress. Full article

The integration of omics technologies, including genomics, proteomics, metabolomics, and microbiomics, has transformed sports science, particularly soccer, by providing new opportunities to optimize player performance, reduce injury risk, and enhance recovery. This systematic literature review was conducted in accordance with PRISMA 2020 guidelines and structured using the PICOS/PECOS framework. Comprehensive searches were performed in PubMed, Scopus, and Web of Science up to August 2025. Eligible studies were peer-reviewed original research involving professional or elite soccer players that applied at least one omics approach to outcomes related to performance, health, recovery, or injury prevention. Reviews, conference abstracts, editorials, and studies not involving soccer or omics technologies were excluded. A total of 139 studies met the inclusion criteria. Across the included studies, a total of 19,449 participants were analyzed. Genomic investigations identified numerous single-nucleotide polymorphisms (SNPs) spanning key biological pathways. Cardiovascular and vascular genes (e.g., ACE, AGT, NOS3, VEGF, ADRA2A, ADRB1–3) were associated with endurance, cardiovascular regulation, and recovery. Genes related to muscle structure, metabolism, and hypertrophy (e.g., ACTN3, CKM, MLCK, TRIM63, TTN-AS1, HIF1A, MSTN, MCT1, AMPD1) were linked to sprint performance, metabolic efficiency, and muscle injury susceptibility. Neurotransmission-related genes (BDNF, COMT, DRD1–3, DBH, SLC6A4, HTR2A, APOE) influenced motivation, fatigue, cognitive performance, and brain injury recovery. Connective tissue and extracellular matrix genes (COL1A1, COL1A2, COL2A1, COL5A1, COL12A1, COL22A1, ELN, EMILIN1, TNC, MMP3, GEFT, LIF, HGF) were implicated in ligament, tendon, and muscle injury risk. Energy metabolism and mitochondrial function genes (PPARA, PPARG, PPARD, PPARGC1A, UCP1–3, FTO, TFAM) shaped endurance capacity, substrate utilization, and body composition. Oxidative stress and detoxification pathways (GSTM1, GSTP1, GSTT1, NRF2) influenced recovery and resilience, while bone-related variants (VDR, P2RX7, RANK/RANKL/OPG) were associated with bone density and remodeling. Beyond genomics, proteomics identified markers of muscle damage and repair, metabolomics characterized fatigue- and energy-related signatures, and microbiomics revealed links between gut microbial diversity, recovery, and physiological resilience. Evidence from omics research in soccer supports the potential for individualized approaches to training, nutrition, recovery, and injury prevention. By integrating genomics, proteomics, metabolomics, and microbiomics data, clubs and sports practitioners may design precision strategies tailored to each player’s biological profile. Future research should expand on multi-omics integration, explore gene–environment interactions, and improve representation across sexes, age groups, and competitive levels to advance precision sports medicine in soccer. Full article

Background: Aristolochia clematitis L. (AC), a plant with diverse traditional uses, has gained increasing scientific interest due to its rich content of bioactive compounds such as flavonoids and polyphenols. However, its systemic use is limited by the presence of aristolochic acids, which are known for their nephrotoxic and carcinogenic potential. Methods: In this context, the present study investigates the therapeutic potential of A. clematitis extract by encapsulating it in liposomes with the aim of enhancing its topical efficacy. Results: The extract was characterized in terms of its flavonoid content (67.23 ± 0.33 mg QE/g DW (quercetin/dry plant material)) and polyphenols expressed as gallic acid equivalents (64.38 ± 0.16 mg GAE/g DW), as well as its antioxidant capacity using the reagents 1,1-diphenyl-2-picrylhydrazyl (DPPH − IC₅₀ = 0.1619 mg/mL extract) and diammonium 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS − IC₅₀ = 205.57 μg/mL extract). Four types of liposomes were synthesized (two loaded with extract and two empty), and their characterization was performed using Atomic Force Microscopy (AFM), Dynamic Light Scattering (DLS), Zeta Potential, polydispersity index, and in vitro release studies. Conclusions: The results demonstrated a high entrapment efficiency (over 82%), good stability over 30 days, and controlled release of flavonoids. Microbiological studies revealed relevant antimicrobial activity against Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, and Pseudomonas aeruginosa strains. The evaluation on HaCaT skin-derived cells (at 10–100 µg/mL) proved that the samples displayed good overall tolerability, slightly decreasing cell viability (the most statistically significant being associated with AC treatment) and showing no structural, nuclear, or mitochondrial morphological changes. Full article

Background: Irisin, an exercise-induced myokine, has emerged as a potent neuroprotective factor, though a systematic synthesis of its role across neurological disorders is lacking. This review systematically evaluates clinical and preclinical evidence on irisin’s association with neurological diseases and its underlying mechanisms. Methods: Following PRISMA 2020 guidelines, a systematic search of PubMed/MEDLINE, Scopus, Web of Science, Embase, and Cochrane Library was conducted. The review protocol was prospectively registered in PROSPERO. Twenty-one studies were included, comprising predominantly preclinical evidence (n = 14), alongside clinical observational studies (n = 6), and a single randomized controlled trial (RCT) investigating irisin in cerebrovascular diseases, Parkinson’s disease (PD), Alzheimer’s disease (AD), and other neurological conditions. Eligible studies were original English-language research on irisin or FNDC5 and their neuroprotective effects, excluding reviews and studies without direct neuronal outcomes. Risk of bias was independently assessed using SYRCLE, the Newcastle–Ottawa Scale, and RoB 2, where disagreements between reviewers were resolved through discussion and consensus. Results were synthesized narratively, integrating mechanistic, pre-clinical, and clinical evidence to highlight consistent neuroprotective patterns of irisin across disease categories. Results: Clinical studies consistently demonstrated that reduced circulating irisin levels predict poorer outcomes. Lower serum irisin was associated with worse functional recovery and post-stroke depression after ischemic stroke, while decreased plasma irisin in PD correlated with greater motor severity, higher α-synuclein, and reduced dopamine uptake. In AD, cerebrospinal fluid irisin levels were significantly correlated with global cognitive efficiency and specific domain performance, and correlation analyses within studies suggested a closer association with amyloid-β pathology than with markers of general neurodegeneration. However, diagnostic accuracy metrics (e.g., AUC, sensitivity, specificity) for irisin as a standalone biomarker are not yet established. Preclinical findings revealed that irisin exerts neuroprotection through multiple mechanisms: modulating microglial polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype, suppressing NLRP3 inflammasome activation, enhancing autophagy, activating integrin αVβ5/AMPK/SIRT1 signaling, improving mitochondrial function, and reducing neuronal apoptosis. Irisin administration improved outcomes across models of stroke, PD, AD, postoperative cognitive dysfunction, and epilepsy. Conclusions: Irisin represents a critical mediator linking exercise to brain health, with consistent neuroprotective effects across diverse neurological conditions. Its dual ability to combat neuroinflammation and directly protect neurons, demonstrated in preclinical models, positions it as a promising therapeutic candidate for future investigation. Future research must prioritize the resolution of fundamental methodological challenges in irisin measurement, alongside investigating pharmacokinetics and sex-specific effects, to advance irisin toward rigorous clinical evaluation. Full article