Search Results (284)

Photobiomodulation (PBM) is a non-invasive therapeutic strategy that uses red and near-infrared (NIR) light in the 590–950 nm range to modulate the cellular and molecular pathways involved in retinal homeostasis. At the molecular level, PBM acts primarily through photon absorption by cytochrome c oxidase (CcO, complex IV of the mitochondrial electron transport chain), whose four metal centres—two copper (CuA and CuB) and two heme groups (heme a and heme a₃)—absorb light across approximately 600–1000 nm. Photon capture promotes photodissociation of inhibitory nitric oxide (NO) from the binuclear CuB–heme a₃ centre, accelerates electron transfer, restores the proton-motive force and increases ATP synthesis. These primary events trigger a coordinated molecular programme that includes (i) transient mitochondrial reactive oxygen species (ROS) bursts that activate the Nrf2/Keap1/ARE axis and upregulate phase II antioxidant enzymes (HO-1, NQO1, GCLC, SOD2, catalase, GPx); (ii) calcium- and cAMP-dependent secondary signalling that converges on PI3K/Akt, MAPK/ERK, AMPK and mTOR pathways; (iii) suppression of NF-κB-driven cytokine production (TNF-α, IL-1β, IL-6) and of NLRP3 inflammasome activation; (iv) downregulation of the HIF-1α/VEGF axis, particularly at 590 nm; (v) anti-apoptotic remodelling of the Bcl-2/Bax ratio with reduced cytochrome c release and caspase-3/9 activation; and (vi) PGC-1α/TFAM/NRF1-driven mitochondrial biogenesis, alongside restoration of fission/fusion homeostasis (Drp1, Mfn1/2, Opa1) and PINK1/Parkin-mediated mitophagy. Wavelength specificity has a defined molecular basis: 590 nm modulates VEGF signalling and RPE pump activity, 660 nm interacts with the CuB centre and enhances O₂ binding at CcO, and 850 nm is absorbed by CuA and supports electron entry into complex IV. A second molecular axis is the bidirectional crosstalk between PBM and the circadian system: mitochondrial respiration, ATP turnover and CcO activity oscillate over the 24 h cycle under the control of the BMAL1/CLOCK and PER/CRY core machinery, the NAD⁺/SIRT1–SIRT3 axis and REV-ERBα. Preliminary preclinical and human observations suggest that NIR-induced bioenergetic and functional gains may be coupled to this rhythm, with greater benefit reported when light is delivered in the morning window (≈08:00–11:00); this time dependence should be regarded as an emerging hypothesis rather than an established clinical principle. The clinical evidence is unevenly developed across indications. It is most robust for non-exudative age-related macular degeneration, where multiwavelength PBM (590/660/850 nm; Valeda Light Delivery System) has shown disease-modifying potential in randomized controlled trials (LIGHTSITE I–III and the LIGHTSITE IIIB extension), with sustained BCVA gains and reduced incidence of geographic atrophy over 24 months and beyond. Evidence for retinitis pigmentosa, central serous chorioretinopathy and, with red-light monotherapy, childhood myopia is at present limited to small or short-term studies and remains preliminary. This narrative review synthesizes the molecular machinery engaged by PBM, integrates clinical findings across retinal diseases and discusses how chronotherapeutic delivery of light, aligned with the molecular clock, may further optimize therapeutic efficacy. Full article

Mitochondria are central hubs of antiviral immunity and cellular metabolism, yet the links between SARS-CoV-2–induced mitochondrial remodeling, antiviral gene regulation, and post-translational control remain incompletely understood. Here, we investigated mitochondrial–immune remodeling in SARS-CoV-2–infected lung-derived LC-HK2 cells at 48 and 96 h post-infection using confocal and high-content imaging, colocalization analysis, CellProfiler quantification, RT-qPCR, proteomics, cytokine profiling, and conditioned-medium analysis. Infection induced a time-dependent mitochondrial phenotype. At 48 hpi, cells displayed early mitochondrial stress and fission-associated signatures, including increased DRP1, transient upregulation of mitochondrial respiratory genes, and reduced MFN1/2. At 96 hpi, mitochondria shifted toward elongated perinuclear networks, accompanied by increased fusion/biogenesis markers and partial ISG15–MFN2 colocalization, indicating a spatial association between ISG15-related antiviral/stress responses and mitochondrial remodeling. Antiviral and ISG-related transcripts were consistently upregulated, but IFN-α2 secretion remained limited, suggesting partial uncoupling between antiviral transcriptional activation and downstream interferon output. SUMO2/3 was dynamically modulated and showed time-dependent colocalization with mitochondrial dynamics proteins and MAVS. Together, these data support a coordinated mitochondrial–immune regulatory axis involving mitochondrial remodeling, ISG15-associated responses, and SUMO-dependent regulation during SARS-CoV-2 infection. Full article

Fatty liver disease represents a major metabolic disorder affecting domestic animals worldwide, with significant implications for animal health, welfare, and agricultural productivity. Disrupted communication between mitochondria and other organelles—particularly the endoplasmic reticulum, lipid droplets, and lysosomes—plays a critical role in disease pathogenesis. This review synthesizes knowledge on inter-organellar communication across domestic animals, with emphasis on species-specific adaptations. We address the “Dairy Cow Paradox”—periparturient dairy cows develop severe hepatic steatosis (>30% liver fat), yet under sterile conditions, they have a higher threshold for progressing to sterile steatohepatitis compared to rodents and humans. However, it is critical to note that severe fatty liver in dairy cows is indeed associated with impaired autophagy, inflammation, and liver damage, particularly when accompanied by ketosis or concurrent infections, and 39% of transition cows exhibit moderate to severe lymphocytic hepatitis. We propose that the tolerance to severe steatosis in dairy cows arises from three adaptations: (1) attenuated innate immune sensing via the cGAS-STING pathway; (2) enhanced lipid buffering from perilipin 5 (PLIN5) with a hypothesized ruminant-specific Val152 substitution that may stabilize lipid droplet–mitochondria contacts; and (3) dampened calcium signaling due to ER–mitochondria membrane lipid raft rigidity, elevated inositol 1,4,5-trisphosphate receptor 2 (IP₃R2) expression, and reduced mitochondrial calcium uniporter (MCU) conductance. We contrast this with the inflammatory steatohepatitis common in rodent models driven by calcium overload and mitochondrial DNA (mtDNA) release, and glucocorticoid-mediated mitofusin 1 (MFN1) suppression, causing mitochondrial fragmentation in poultry. We identify critical knowledge gaps, including the need to define bovine and avian mitochondria-associated endoplasmic reticulum membrane (MAM) proteomes and spatially resolve hepatic zonal communication patterns. Targeting organellar communication hubs with nutraceuticals or pharmacological agents offers promising therapeutic strategies. Full article

The kidney is a highly specialized organ that maintains systemic homeostasis through tightly coordinated cellular and molecular mechanisms. Renal parenchymal cells regulate metabolic waste excretion, electrolyte and acid–base balance, and blood pressure control—functions that rely on the dynamic integration of intracellular organelles. Recent advances in molecular and biochemical research have highlighted how inter-organelle communication is essential for preserving renal cell function and adaptive responses to stress. This review focuses on the molecular crosstalk among key organelles—including the nucleus, endoplasmic reticulum (ER), Golgi apparatus, mitochondria, lysosomes, and peroxisomes—primarily in tubular epithelial cells. We discuss how these interactions coordinate metabolic signaling, protein homeostasis, redox balance, and energy production and how their disruption contributes to maladaptive pathways during acute kidney injury (AKI), ultimately promoting chronic kidney disease (CKD) transition. Particular focus is placed on emerging pathways linking organelle dysfunction to inflammation, fibrosis, and metabolic reprogramming. Furthermore, we highlight recent advances in genetics and molecular therapeutics targeting organelle communication, including modulation of ER stress responses, mitochondrial biogenesis, and lysosomal function. Clinically approved agents, such as mTOR inhibitors, and experimental approaches—such as chemical chaperones and mitochondrial transplantation—demonstrate the potential to restore organelle homeostasis and mitigate renal injury. Overall, elucidating the molecular networks governing organelle crosstalk provides critical insights into kidney disease pathogenesis and identifies novel targets for therapeutic intervention in AKI-to-CKD transition. Full article

The use of substances that modulate mitochondrial dynamics in cells of nervous tissue represents a new direction in targeted therapy for neurodegeneration. The aim of this study was to evaluate the effect of mitochondrial division inhibitor-1 (Mdivi-1) on neurons and microgliocytes of the substantia nigra under conditions of partial damage to the dopaminergic system. This study was conducted using the 6-hydroxydopamine model of parkinsonism in rats; a separate experimental group of animals received Mdivi-1 intraperitoneally at a dose of 20 mg/kg for 5 days. The intensity of immunofluorescence staining for Tomm20, MTCO1, pDrp1, and Mfn2 was evaluated in neurons of the substantia nigra, and microglial activation was morphologically assessed. It was found that unilateral administration of 6-OHDA led to pro-inflammatory changes in microglia and changes in mitochondrial markers of neurons on the side of the substantia nigra contralateral to the toxin injection. Mdivi-1 did not affect the damage and mitochondrial proteins of neurons in pars compacta of the substantia nigra; however, it changed mitochondrial markers in nervous cells of the pars reticulata. The use of Mdivi-1 to address abnormal processes in neurodegeneration requires additional studies that include a differential assessment of its effects on various cell types. Full article

Background: Dystonia is a heterogeneous hyperkinetic movement disorder characterized by sustained or intermittent muscle contractions causing abnormal movements and postures. Although numerous genes associated with dystonia have been identified, the genetic background remains unknown in many patients. Data on genotype–phenotype correlations in Polish populations remain limited. Objective: To analyze the clinical characteristics of patients with generalized dystonia and compare clinical features between individuals with and without genetically confirmed dystonia-causative variants in a Polish cohort. Methods: A retrospective analysis of patients diagnosed with generalized dystonia at a single neurological center was performed. Diagnosis was established according to MDS criteria. Genetic analysis included whole-exome sequencing, targeted NGS genetic panel, MLPA, Sanger sequencing and PCR_RFLP analysis. Clinical and demographic data were extracted from medical records. Clinical characteristics of individuals with and without causative variants were compared. Results: A total of 113 patients with generalized dystonia were included. Genetic variants were identified in 13 patients (11.5%). These included variants within the TOR1A, THAP1, SGCE, GCH1, NKX2-1, SLC2A1, KMT2B, PDHA1, MFN2, and GNAL genes. We found detailed clinical data of 46 patients included in the study. Our comparative analysis of patients with causative (n = 7) and without causative variants (n = 39) revealed no statistically significant differences in age of onset, initial symptom localization, treatment response, family history, or associated neurological features. Conclusions: In this cohort of Polish patients with generalized dystonia, we identified pathogenic variants in approximately 11.5% of cases. No significant clinical differences were observed between patients with genetically confirmed dystonia and those without identified variants. In this study, we report the first two Polish cases with DYT-GNAL variants. Further studies are required to reveal the clinical heterogeneity of dystonia and characterize dystonia subtypes. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent global health concern. Although pharmacotherapies such as Resmetirom and semaglutide have recently gained approval by FDA/EMEA, therapeutic options remain limited, necessitating the exploration of novel natural compounds. Our previous research indicated that lycopene exerts protective effects against MASLD; however, its underlying molecular mechanisms remain incompletely understood. The present study aimed to investigate whether lycopene alleviates MASLD by modulating mitophagy, with a focus on the PINK1/Parkin pathway. C57BL/6J mice were fed with high-fat diet for 12 weeks to induce MASLD and daily gavage of lycopene (10/40 mg/kg). In vitro, AML12 cells were treated with lycopene and Mdivi-1 to assess the role of PINK1/Parkin-mediated mitophagy against lipid accumulation, oxidative stress, and apoptosis. The results found that lycopene supplementation significantly ameliorated HFD-induced weight gain, dyslipidemia, hepatic steatosis, pathological liver injury, and elevated serum liver enzymes. It reduced hepatic reactive oxygen species (ROS) overproduction and suppressed the mitochondrial apoptotic pathway, as evidenced by decreased cytochrome c release and caspase cascade activation. Concurrently, lycopene restored ATP levels and mitochondrial membrane potential, improved ultrastructural integrity, and balanced mitochondrial dynamics by downregulating DRP1 and upregulating MFN2 and OPA1. Crucially, lycopene activated PINK1/Parkin-mediated mitophagy, leading to an increased LC3-II/LC3-I ratio and Beclin1 expression, alongside decreased levels of mitochondrial proteins TOM20 and COX IV. In vitro, the lycopene partially reversed the exacerbating effects of Mdivi-1 on lipid accumulation, ROS generation, apoptosis, and the suppression of the PINK1/Parkin pathway. Collectively, lycopene ameliorates MASLD by activating PINK1/Parkin-mediated mitophagy and improving mitochondrial homeostasis, thereby reducing hepatic lipid accumulation and attenuating hepatocyte apoptosis. Full article

Ship classification in synthetic aperture radar (SAR) imagery is essential for maritime surveillance but remains challenging due to limited resolution, insufficient textural details, and difficulties in effectively fusing multimodal information. Existing methods either rely on handcrafted features with limited adaptability or employ simplistic fusion strategies that fail to fully exploit the complementary guidance across modalities. To address these issues, we propose a multimodal fusion network based on a learnable feature preprocessing front-end (LFPF-MFN), which integrates polarimetric, textural, and geometric information in an end-to-end learnable manner. Specifically, LFPF-MFN introduces a learnable preprocessing front-end to embed scattering and enhanced textural features. Meanwhile, geometric information from the Automatic Identification System (AIS) is incorporated through textual embedding, and effective multimodal fusion is achieved via a bidirectional cross-attention mechanism. Extensive experiments on the OpenSARShip 2.0 dataset demonstrate that the proposed method achieves state-of-the-art performance in both three-class and six-class classification tasks, validating the effectiveness of each designed module and the superiority of the multimodal fusion strategy. Full article

Chemotherapy-induced metabolic reprogramming of glioblastoma multiforme (GBM) cells increases intracellular levels of reductive and energetic carriers, thereby fueling drug-relocation and retention systems and enhancing GBM drug-resistance. We have previously shown the role of this process in the adaptation of poly(morpho)nuclear “giant” cells (PGCs) in T98G populations to doxorubicin (DOX)-induced stress. Here, we addressed the role of a “resistance triad”, which coordinates metabolic T98G reprogramming with the activation of the drug-relocation and drug-retention axis, in the recovery of GBM populations from chemotherapeutic stress. A combination of proteomic analyses with metabolic and phenotypic profiling of pulse DOX-treated T98G cells revealed the significance of mitochondrial dynamics for the efficiency of the T98G “resistance triad”. DOX-induced mobilization of ATP-generating systems and ATP-dependent anabolic pathways was accompanied by the formation of DOX-negative, “mosaic” mitochondrial networks and the upregulation of mitofusin-2 (MFN2) in T98G PGCs. Transient MFN2 down-regulation correlated with the respiratory capacity of T98G cells, while impairing cell welfare in the absence and presence of DOX. However, minute fractions of PGCs, which withstood combined MFN2 down-regulation and pulse DOX treatment, retained mitochondrial networks and displayed efficient ABC transporter-/V-type channel-dependent lysosomal DOX retention. Collectively, a “triad” of mitochondrial activation, ABC transporter-dependent perinuclear redistribution and V-type channel-mediated lysosomal DOX compartmentalization determines DOX resistance of T98G cells. Whereas MFN2-dependent mitochondrial rearrangements may contribute to these processes, complementary adaptative mechanisms can compensate MFN2 dysfunction, limiting its potential as a therapeutic target. Full article

Pneumoconiosis, characterized by progressive pulmonary fibrosis, remains a predominant occupational disease in China, with coal workers’ pneumoconiosis (CWP) and silicosis being the primary subtypes. Despite extensive research, its underlying pathogenic mechanisms are not yet fully understood. Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are crucial subcellular microdomains that govern Ca²⁺ transport, sustain cellular bioenergetics, and maintain systemic homeostasis. Emerging evidence has linked the structural and functional dysregulation of MAMs to the pathogenesis of various fibrotic disorders. Apoptosis, a highly regulated cell death process, is a key driver in pneumoconiosis progression, in which Ca²⁺ imbalance serves as a critical signaling cascade. Mitofusin 2 (MFN2), a core regulator of MAMs’ structural integrity, mediates mitochondrial fusion and directly bridges the ER with the outer mitochondrial membrane, thereby stabilizing ER–mitochondrial coupling. However, whether MFN2 mitigates fibrosis by preserving MAMs’ integrity and subsequently suppressing Ca²⁺-dependent apoptosis remains elusive. In this study, we established SD rat and A549 cell models of CWP. Our results demonstrated that MFN2 expression was downregulated after coal dust exposure, accompanied by MAMs impairment, Ca²⁺ imbalance, and increased apoptosis, which ultimately drove the pathological progression of pulmonary fibrosis. Notably, MFN2 overexpression restored MAMs’ structure and Ca²⁺ homeostasis, alleviated abnormal apoptosis, and subsequently inhibited fibrosis. This study highlights the importance of the MFN2–MAMs–Ca²⁺–apoptosis axis and identifies MFN2 as a potential therapeutic target for pneumoconiosis. Full article

Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease affecting the axial skeleton, characterized by progressive structural damage and functional impairment. Although biologic therapies targeting tumor necrosis factor and interleukin-17 have improved clinical outcomes, a substantial proportion of patients fail to achieve sustained disease control. Emerging evidence suggests that metabolic alterations may contribute to AS pathogenesis; however, systematic characterization of metabolism-related biomarkers and their regulatory networks remains limited, and the interplay between metabolic dysfunction and immune dysregulation in AS is poorly understood. Two whole-blood GEO datasets (GSE25101, GSE73754; n = 104) were integrated as the primary analytical cohort. A third dataset (GSE11886, n = 18; monocyte-derived macrophages) was included for exploratory cross-tissue analysis. Differential expression analysis identified 847 DEGs, which were refined to 16 metabolism-related genes through weighted gene co-expression network analysis (WGCNA) and GeneCards database filtering. Eleven machine learning algorithms with 5-fold cross-validation were applied to construct diagnostic models and identify hub genes. Validation analyses included immune cell infiltration estimation using CIBERSORT, metabolic pathway activity assessment via ssGSEA, single-cell transcriptomics from GSE268839, functional enrichment through GSEA/GSVA, and chromosomal localization analysis. A competing endogenous RNA (ceRNA) regulatory network was constructed to map post-transcriptional regulation. Natural compounds from 66 AS-treating traditional Chinese medicines were screened against hub genes using deep learning-based binding prediction. Multiple machine learning algorithms achieved comparable cross-validated performance (CV AUC range 0.741–0.836; top five models: 0.805–0.836) using the six hub genes (MFN2, SLC27A3, RHOB, SMG7, AKR1B1, LCOR) identified through SHAP-based feature importance analysis of the PLS model. Leave-one-dataset-out validation between the two whole-blood cohorts showed that all algorithms exceeded an AUC of 0.77 in Round 1 (validate: GSE73754, n = 72; best AUC 0.861), while Round 2 (validate: GSE25101, n = 32) yielded more modest performance (best AUC, 0.715) reflecting the smaller validation sample. Exploratory application to GSE11886 (macrophage-derived samples) showed near-chance performance, consistent with the tissue-source discrepancy. AS patients exhibited significant downregulation of oxidative phosphorylation, TCA cycle, and glycolysis pathways (p < 0.01), accompanied by elevated glutathione metabolism (p < 0.001). Immune cell deconvolution revealed reduced CD8+ T cell proportions correlating with MFN2 downregulation, and increased neutrophil frequencies correlating with SLC27A3 upregulation. Exploratory single-cell analysis indicated that RHOB expression was relatively enriched in border-associated macrophages and fibroblasts, while AKR1B1 was more prominently expressed in vascular endothelial cells and plasmacytoid dendritic cells. The ceRNA network identified 21 miRNAs and 65 lncRNAs forming 86 regulatory interactions, with four key regulatory axes (SATB1-AS1/miR-539-5p/LCOR, FAM95B1/miR-223-3p/RHOB, LINC01106/miR-106a-5p/MFN2, AATBC/miR-185-5p/SMG7) predicted to regulate hub gene expression. Compound screening identified betaine, pyruvic acid, citric acid, etc., as top-ranking candidates, with MFN2 showing the highest binding capacity among hub genes. This study provides an integrative framework linking metabolic reprogramming with immune dysfunction in AS. The six-gene diagnostic signature showed preliminary discriminatory ability in the available datasets, while the ceRNA regulatory network and natural compound screening results prioritize candidate regulatory pathways and compounds for future validation. These findings advance our understanding of AS pathogenesis and may guide future biomarker development and targeted intervention strategies. Full article

Onion peel represents a valuable food by-product rich in bioactive phenolic compounds. Building on previous phytochemical investigations, an onion peel extract from the Rossadi Tropea variety was developed as a standardized bioactive ingredient (OPI-T), defined by flavonol (quercetin and its glycosylated and oxidized derivatives) and anthocyanin (cyanidin derivatives) markers, ensuring batch-to-batch consistency, and evaluated for its potential against hepatic steatosis. The present study aimed to assess the protective effects of OPI-T against palmitate-induced steatosis and oxidative stress in HepG2 cells, a widely used in vitro model of hepatic lipid accumulation. An onion peel extract derived from the Ramata di Montoro variety was included as a natural negative reference to account for varietal variability. HepG2 cells were co-treated with palmitate (500 µM) and OPI-T (25 or 50 µg/mL). Lipid accumulation was evaluated by Oil Red O and BODIPY staining, while oxidative stress was assessed by the DCF assay. Mitochondrial dynamics and autophagy were investigated through the analysis of key protein markers, including MFN2, DRP1, SQSTM1/p62 and LC3 II/I. OPI-T significantly attenuated palmitate-induced lipid accumulation (−18%) and reduced intracellular ROS production (−75%), while modulating mitochondrial dynamics toward a reduced fission phenotype with a marked increase in the MFN2/DRP1 ratio (1.66) and improving autophagy flux. In contrast, the Ramata di Montoro variety showed weaker or inconsistent effects under the same experimental conditions. Overall, these findings support the functional validation of a standardized onion peel-derived ingredient, highlighting its potential application as a bioactive component for functional food or nutraceutical development targeting hepatic steatosis and oxidative stress. Full article

(1) Background: Mild traumatic brain injury (mTBI), the most prevalent form of traumatic brain injury, often results from repetitive impacts to the head and is associated with long-term neurological impairment. The pathophysiology of mTBI is multifactorial and involves alterations in mitochondrial bioenergetics, a key determinant of neuronal function and survival. Although mitochondrial dysfunction is recognized as a hallmark of mTBI, its long-term effects on bioenergetics and the roles of regulatory cytosolic and mitochondrial proteins remain poorly understood. We hypothesized that repeated mTBI (rmTBI) induces sustained deficits in mitochondrial bioenergetics that are associated with long-term changes in key bioenergetic and other regulatory proteins. (2) Methods: Using the repeated CHIMERA injury model in adult male rats, randomly assigned to sham or rmTBI groups, we assessed mitochondrial respiration in isolated mitochondria and whole cerebral cortex homogenates using a Clark O₂ electrode and an Oroboros O₂k respirometer at time points ranging from 1 day to 2 months post-injury. Western blotting was performed for expression of regulatory proteins HKI, DRP1, MFN2, VDAC1, and ANT2. (3) Results: At 2 months post-rmTBI, respiration was faster and uncoupled, while ATP synthesis was significantly slowed compared with sham rats. This was accompanied by decreased expression of mitochondrial MFN2 and ANT2, by increased mitochondrial expression of DRP1, and by decreased translocation of HKI to mitochondria. There was no significant difference in VDAC1 expression. Earlier time points showed no significant differences in bioenergetics or protein expression, but neuro-inflammatory markers (GFAP and Iba1) were significantly elevated at these earlier time points of post-injury. (4) Conclusions: These findings indicate that rmTBI leads to a delayed long-term impairment of mitochondrial bioenergetics associated with alterations in proteins critical for bioenergetic regulation and mitochondrial control. This suggests a pathophysiologic mechanism for the persistent cognitive and behavioral deficits observed following rmTBI. Full article

The etiology of autism spectrum disorder (ASD) implicates genetic predispositions and environmental chemicals, such as polybrominated diphenyl ethers (PBDEs). We aimed to identify whether mitochondrial quality control (MQC) was involved in ASD-relevant behavioral changes induced by decabromodiphenyl ether (deca-BDE, BDE-209) and the alleviation by melatonin. Pregnant rats exposed to BDE-209 (50 mg/kg i.g.) were administrated melatonin through drinking water (0.2 mg/mL) during gestation and lactation. Behavioral assessments integrated open-field test, three-chamber social test, and Morris water maze; mitochondrial detections took transmission electron microscopy, immunofluorescence, and homeostasis together; hippocampal molecular network was identified through transcriptomics profiles, combining dendritic morphology analysis after Golgi-Cox staining. Melatonin supplementation attenuated BDE-209-reduced social and cognitive ability, accompanied by improvements in hippocampal synaptic plasticity (dendritic spines, PSD95, SNAP25). Mitochondrial dysfunctions, shown as decreases in complex IV activity, ATP content, and mtDNA copies, plus redox imbalance (ROS/SOD2) and resultant mitochondrial membrane potential disruption and apoptosis, together with fusion/fission dynamic (MFN2/DRP1), biogenesis (SIRT1-PGC1α-TFAM), and mitophagy (SIRT3-FOXO3-PINK1) suppression, were reversed by melatonin partially through SIRT1 (Sirtuin-1)-dependent pathways, as these protections were abolished by inhibitor EX527. This study highlighted the SIRT1–SIRT3 axis in MQC and behavioral effects, providing novel intervention for PBDEs’ neurodevelopmental impairment. Full article

Background: Main risk factors associated with the development of sarcopenia (coexistence of muscle mass loss and dysfunction) are a sedentary lifestyle coupled with obesity. Associated mitochondrial dysfunction leads to energy deficits and perturbations in the balance between protein synthesis and degradation, thereby triggering muscle dysfunction or atrophy. Aside from exercise, which is challenging to implement and maintain, particularly in women, treatments for diminishing sarcopenia are scarce. The objective of the present study was to evaluate the effect of the flavanol (−)-epicatechin (EC) in a hypercaloric diet-induced obese female rat model. Muscle strength and endurance, as well as relative mitochondrial DNA content in skeletal muscle, were assessed. Methods: Female rats were fed a hypercaloric diet to induce obesity, as evidenced by increases in body weight, Lee index, and lipid profile alterations, and by abdominal fat accumulation, and to promote a sarcopenic phenotype. Functional tests of grip strength and mobility (treadmill) were performed. Mitochondrial relative content was evaluated by measuring the ratio of mtDNA/nuclear DNA, and the expression of genes related to mitochondrial biogenesis (Pgc1-α, Tfam), fusion (Mfn1 and Opa1), fission (Drp1 and Fis1), and mitophagy (Pink1 and Pkn), and function; citrate synthase and Ucp3 were also evaluated. Results: A significant decrease in mobility and strength was observed in obese female rats, accompanied by reduced mitochondrial numbers, activity, and dynamics, but not by changes in muscle size or weight. Treatment with EC induced mitochondrial biogenesis and positive changes in mitochondrial dynamics (fission and fusion) and activity, as measured indirectly by changes in citrate synthase and Ucp3 expression. Discussion: Results reinforce the potential of EC as a modulator of mitochondrial function in dysfunctional conditions associated with obesity, thereby attenuating the mechanisms underlying sarcopenia. Full article