Search Results (410)

Background: Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder characterized by motor and non-motor symptoms. As conventional diagnostic methods are limited in their ability to detect early-stage PD or monitor its progression, there is growing interest in identifying molecular biomarkers with clinical utility. This systematic review synthesizes recent advancements in the application of metabolomics to PD, with a specific focus on human studies published between 2019 and 2024, a period of notable growth in the research area. Methods: Following PRISMA 2020 guidelines, a comprehensive literature search was conducted across major scientific databases. After screening, 16 eligible original studies were selected based on predefined criteria. Key features extracted included study design, biofluid type, analytical platform, statistical approach, and main findings. Results: Consistent metabolic alterations were observed across several biological pathways, including amino acid metabolism, lipid regulation, mitochondrial energy production, oxidative stress, polyamine metabolism, as well as in gut microbiota-derived metabolites. Biofluids analyzed included plasma, serum, cerebrospinal fluid, saliva, urine, and sebum. While plasma and serum remained the most studied matrices, emerging interest in non-invasive fluids such as saliva and sebum reflects their potential in clinical settings. Methodological heterogeneity was noted across studies, particularly in confounder adjustment and study design. Conclusions: Despite certain limitations, the included studies collectively point to the potential of metabolomics in identifying robust diagnostic and prognostic signatures for PD. This review emphasizes the need for longitudinal studies, methodological standardization, and integration with other omics approaches to advance biomarker discovery and support the development of precision medicine strategies for PD. Full article

The Strait of Sicily represents a biogeographically rich and complex region. The diverse geological origin and past continental connection of its islands have shaped a highly heterogeneous fauna, mainly composed of both African and European taxa. The Italian sea-slater, Ligia italica (Fabricius, 1798), is a small isopod inhabiting rocky shores of the Mediterranean Sea, Black Sea, and Atlantic Ocean. Despite its wide distribution, the phylogeography of this species is poorly understood, with limited available data suggesting a remarkable level of cryptic diversity. In this study, we investigated the mitochondrial genetic diversity (COX1) of L. italica across nine Italian and Maltese islands across the Strait of Sicily, aiming to clarify the biogeographic patterns underlying the distribution of these insular populations. Our results reveal an unexpectedly high genetic diversity within our study area, with eight different haplogroups, each characterized by low internal genetic variation and mutual distances ranging from 5.5% to 17.9%. These values are comparable to those associated with species-level rank within the genus Ligia. Overall, the phylogenetic relationships between the lineages appear well supported; however, the same relationships are not clearly correlated with geographic proximity or connectivity among the sampled localities. The distribution patterns of some of the detected haplogroups suggest possible passive dispersal mechanisms (e.g., rafting), while others indicate more intricate biogeographic scenarios. The overall diversity of L. italica within the Strait of Sicily, as well as the unclear origin of some insular populations, cannot be fully explained with the current data. In particular, the high genetic structure observed within the Maltese Archipelago, may partially reflect human-mediated dispersal (e.g., maritime transport), possibly involving source populations that remain unsampled or genetically uncharacterized. Our results highlight that the Strait of Sicily can be considered a diversity hot spot for L. italica and support the designation of this taxon as a putative species complex, with a cryptic diversity worthy of an exhaustive taxonomic revision. Full article

Post-stroke rehabilitation has evolved to encompass advanced approaches that aim to optimize recovery for ischemic stroke survivors. Despite this progress, recovery remains limited, partly due to persistent oxidative stress and mitochondrial dysfunction that contribute to neuronal and muscular impairment. One such promising avenue is the stimulation of antioxidant capacity and the enhancement of mitochondrial function. Mitochondria are crucial for energy production and neuroprotection, which are essential for neurorecovery. This review explores the mechanisms involved in the role of mitochondrial function and antioxidant therapies, focusing on motor recovery after ischemic stroke and “brain-muscle axis” interplay in post-stroke rehabilitation. A comprehensive synthesis of clinical trial data is provided, highlighting interventions targeting mitochondrial bioenergetics, redox regulation, and mitochondrial dynamics. Furthermore, the review delves into the potential of recent mitochondrial-targeted therapies as adjuncts to traditional rehabilitation techniques, providing a more holistic approach to recovery. Emerging evidence suggests these therapies can reduce oxidative injury and support neuroplasticity; however, translation into consistent clinical benefit remains uncertain due to heterogeneity in study designs, endpoints, and patient populations. By understanding and leveraging the dynamics of mitochondrial function, healthcare providers can significantly enhance the rehabilitation outcomes for people with a range of conditions, from musculoskeletal disorders to neurological impairments. Full article

Mitochondrial genomes are powerful tools for taxonomic delimitation and species identification, yet they remain scarce for Chironomidae (Diptera). In this study, we assembled and annotated 63 new mitochondrial genomes, encompassing 63 species within 39 genera in Orthocladiinae sensu lato (including Prodiamesinae and Orthocladiinae) and Chironominae by whole-genome sequencing, marking the first report of mitochondrial genome data for the Xiaomyini. Comparative analyses revealed structural variation, including transfer RNA gene rearrangements, along with strong nucleotide composition bias, codon usage patterns, and gene-specific selection pressure differences. Distinct evolutionary dynamics were detected among protein-coding genes, ribosomal RNAs, transfer RNAs, and the control region. Heterogeneity analyses and phylogenetic analyses showed that amino acid datasets perform better for basal branch of Orthocladiinae relationships, although the resolution within non-basal branches of Orthocladiinae remains limited. By substantially increasing both the number and taxonomic breadth of mitochondrial genomes in Chironomidae, this study delivers a vital foundation for future multi-marker phylogenetic reconstruction, taxonomic revision, and rapid species identification, with direct applications to biodiversity conservation and freshwater ecosystem monitoring. Full article

Background: Glaucoma is a progressive optic neuropathy marked by retinal ganglion cells (RGCs), apoptosis, vascular insufficiency, oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. While intraocular pressure (IOP) reduction remains the primary intervention, many patients continue to lose vision despite adequate pressure control. Emerging neuroprotective agents—citicoline, coenzyme Q10 (CoQ10), pyruvate, nicotinamide, pyrroloquinoline quinone (PQQ), homotaurine, berberine, and gamma-aminobutyric acid (GABA)—target complementary pathogenic pathways in experimental and clinical settings. Methods: This literature review synthesizes current evidence on glaucoma neuroprotection, specifically drawing on the most relevant and recent studies identified via PubMed. Results: Citicoline enhances phospholipid synthesis, stabilizes mitochondrial membranes, modulates neurotransmitters, and improves electrophysiological and visual field outcomes. CoQ10 preserves mitochondrial bioenergetics, scavenges reactive oxygen species, and mitigates glutamate-induced excitotoxicity. Pyruvate supports energy metabolism, scavenges reactive oxygen species, and restores metabolic transporter expression. Nicotinamide and its precursor nicotinamide riboside boost NAD⁺ levels, protect against early mitochondrial dysfunction, and enhance photopic negative response amplitudes. PQQ reduces systemic inflammation and enhances mitochondrial metabolites, while homotaurine modulates GABAergic signaling and inhibits β-amyloid aggregation. Berberine attenuates excitotoxicity, inflammation, and apoptosis via the P2X7 and GABA-PKC-α pathways. Preclinical models demonstrate synergy when agents are combined to address multiple targets. Clinical trials of fixed-dose combinations—such as citicoline + CoQ10 ± vitamin B3, citicoline + homotaurine ± vitamin E or PQQ, and nicotinamide + pyruvate—show additive improvements in RGCs’ electrophysiology, visual function, contrast sensitivity, and quality of life without altering IOP. Conclusions: A multi-targeted approach is suitable for glaucoma’s complex neurobiology and may slow progression more effectively than monotherapies. Ongoing randomized controlled trials are essential to establish optimal compound ratios, dosages, long-term safety, and structural outcomes. However, current evidence remains limited by small sample sizes, heterogeneous study designs, and a lack of long-term real-world data. Integrating combination neuroprotection into standard care holds promise for preserving vision and reducing the global burden of irreversible glaucoma-related blindness. Full article

Background: Traditional morphology-based classification of the Oriental Plover (Anarhynchus veredus) is inconsistent with molecular evidence, underscoring the necessity of incorporating molecular data to elucidate its evolutionary relationships within Charadriidae. Methods: Here, we present the first complete mitochondrial genome of A. veredus by Illumina NovaSeq Sequencing and explore its evolutionary implications within Charadriidae. Results: The mitogenome spans 16,886 bp and exhibits conserved structural features typical of Charadriidae, including gene order, overlapping coding regions, and intergenic spacers. Nucleotide composition analysis revealed a GC content of 44.3%, aligning with other Charadriidae species (44.5–45.8%), and hierarchical GC distribution across rRNA, tRNA, and protein-coding genes (PCGs) reflects structural and functional optimization. Evolutionary rate heterogeneity was observed among PCGs, with ATP8 and ND6 showing accelerated substitution rates (Ka/Ks = 0.1748 and 0.1352) and COX2 under strong purifying selection (Ka/Ks = 0.0678). Notably, a conserved translational frameshift in ND3 (position 174) was identified. Phylogenetic analyses (ML/NJ) of 88 Charadriiformes species recovered robust topologies, confirming that the division of Charadriidae into four monophyletic clades (Pluvialis, Vanellus, Charadrius, and Anarhynchus) and supporting the reclassification of A. veredus under Anarhynchus. Conclusions: This study resolves the systematic position of A. veredus and highlights the interplay between conserved mitochondrial architecture and lineage-specific adaptations in shaping shorebird evolution. Full article

Background: Patients with ulcerative colitis (UC) suffer from a chronic relapsing-remitting inflammatory bowel disease and show heterogeneous disease severity and therapy response. It was recently reported that rectal biopsies from patients with UC show a downregulation of various mitochondrial genes during active UC. Methods: We used dextran sulfate sodium (DSS)-induced colitis as a preclinical mouse model for UC to study metabolic characteristics of ex vivo colonic lamina propria CD4+ and CD8+ T cells, B cells, eosinophils, neutrophils and intestinal epithelial cells during experimental acute and chronic inflammatory bowel disease and remission state. Results: Our results indicate that CD4+ and CD8+ T cells in the colon produce significantly less mitochondrial reactive oxygen species and possess smaller mitochondria during chronic DSS-induced colitis, which is resolved during remission state. In addition, CD4+ and CD8+ T cells exhibit increased glucose uptake during acute but defective glucose consumption during chronic DSS colitis. Conclusions: Together, our data provide evidence for an atypical mitochondrial phenotype of colonic CD4+ and CD8+ T cells during chronic colitis that is resolved during the remission phase of the disease. Full article

Suruga fundicola, one of the few known deep-dwelling gobies, is found in Japan, South Korea, and China. Owing to the limited availability of specimens, little is known about its mitogenome characterization, phylogenetic relationship, and adaptive evolution. In this study, we sequenced four complete mitogenomes using the DNBSEQ platform and Sanger sequencing. The mitogenomes in length ranged from 17,138 to 17,352 bp, primarily due to the variation in the number of long tandem repeat (LTR) sequences within variable region 3 (VR3). Although the gene composition and arrangement of the S. fundicola mitogenome are largely consistent with those of other gobies, we identified an expansion of the ND2 gene (78 bp), and an unexpected noncoding region (NC, 35 bp) located between the ND2 and tRNA^trp genes. To further investigate the variation in VR3, we sequenced this region in all nineteen individuals with the Sanger sequencing method. We detected eight distinct LTR types, containing one–three mutation sites, which formed ten different VR3 patterns. Most VR3 patterns (14/19) consisted of a single type of pure LTR, while the remaining five exhibited heterogeneous patterns composed of two different LTRs. Notably, in LTR types T1 and T3, which co-occur in heterogeneous patterns P1 and P9, we found their respective pure patterns (P2–3 and P7). Recombination provides a better, more plausible mechanism for generating the heterogeneity patterns than slipped-strand mispairing, which better explains the homogeneous LTR expansions. These findings provide evidence of recombination in the control region of a vertebrate mitogenome. A phylogenetic analysis confirmed that S. fundicola has a close relationship with Am. hexanema and C. stigmatias. Compared to five shallow-water species of the AcanthogobiusGroup, the deep-dwelling goby S. fundicola was found to be under stronger purifying selection. Within its mitochondrial protein-coding genes (PCGs), ND2 and ND6 genes were subject to stronger purifying selection than the others. Additionally, four genes showed signs of selection sites with high credibility (one in ATP6, ND3, and ND4; eight in ND2). This study provides valuable genomic resources for S. fundicola and enhances our understanding of the phylogenetic relationship, mitogenome recombination, and adaptive evolution of the goby. Full article

Background: Pediatric mitochondrial cytopathies (MCs) are rare, multisystemic, and heterogeneous disorders that require harmonized collection of clinical, biochemical, and genetic data to better understand their natural history, optimize patient care, and support translational research. In this context, developing a regionally adapted Minimum Data Set (MDS) is a critical step toward establishing a structured registry. Methods: A two-round Delphi study was conducted involving 16 Moroccan–Tunisian experts from diverse specialties to assess the relevance of 382 initially proposed variables. Robust statistical analyses were applied to all composite questions using Content Validity Index (CVI), Kappa coefficient, and Content Validity Ratio (CVR), alongside retention rate assessments. Results: The overall relevance score assigned by the experts was high (4.5 ± 0.41), with a final retention rate of 90.1% (347 variables retained out of 382). Section-wise S-CVI/Ave scores ranged from 0.91 to 0.99, with the paraclinical section achieving the highest value (0.99) and the evolutive section the lowest (0.91). The more stringent S-CVI/UA revealed greater variability (from 0.36 in clinical data to 0.83 in paraclinical data). Kappa index calculations led to the exclusion of a subclass of five therapeutic variables due to insufficient inter-rater agreement. The CVR further supported the content validity of the 46 retained subclasses. The results demonstrated strong consensus, particularly across the neurological, biochemical, molecular, and medical follow-up domains. Additionally, the registry design survey revealed strong expert support for a secure and interoperable digital platform incorporating longitudinal follow-up and advanced search and reporting functionalities. Conclusions: This validated Moroccan–Tunisian pediatric MDS offers a solid foundation for a regional mitochondrial cytopathy registry. It standardizes data collection, strengthens clinical research, and improves diagnosis and care for affected children in the Maghreb. Moreover, it lays the groundwork for future interoperability with international registries, contributing to a more inclusive and collaborative precision medicine landscape. Full article

Sepsis is a complex condition characterized by an uncontrolled inflammatory response to infection, which can trigger multi-organ dysfunction and is associated with high mortality rates. In this context, oxidative stress plays a key role in the progression of tissue damage. Reduced glutathione (GSH), the primary non-enzymatic intracellular antioxidant, serves as a fundamental pillar in redox defense, acting as a key modulator of immune response, endothelial barrier integrity, and mitochondrial metabolism. This review explores the multifaceted role of GSH in the pathophysiology of sepsis, with emphasis on its biphasic effect on both innate and adaptive immunity, as well as its involvement in vascular alterations and mitochondrial dysfunction. The molecular mechanisms of GSH depletion during sepsis are analyzed, including excessive consumption by reactive species, disruption of its synthesis, and its intracellular compartmentalization. Additionally, the available clinical evidence in humans regarding the functional consequences of GSH loss is reviewed, particularly concerning organ failure—understood more as a bioenergetic and functional disruption than a structural one—and mortality, highlighting the methodological limitations and heterogeneity of the reported findings. Altogether, this analysis intends to provide a comprehensive view of the role of glutathione in redox dysregulation and the pathophysiological mechanisms underlying sepsis. Furthermore, it seeks to consolidate current pathophysiological and clinical knowledge to emphasize the potential role of glutathione as a prognostic marker and possible target for future therapeutic strategies in addressing this complex condition. Full article

Amyotrophic lateral sclerosis (ALS) is still a heterogeneous neurodegenerative disorder that can be identified clinically and biologically, without a strong set of biomarkers that can adequately measure its fast rate of progression and molecular heterogeneity. In this review, we intend to consolidate the most relevant and timely advances in ALS biomarker discovery, in order to begin to bring molecular, imaging, genetic, and digital areas together for potential integration into a precision medicine approach to ALS. Our goal is to begin to display how several biomarkers in development (e.g., neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), TDP-43 aggregates, mitochondrial stress markers, inflammatory markers, etc.) are changing our understanding of ALS and ALS dynamics. We will attempt to provide a framework for thinking about biomarkers in a systematic way where our candidates are not signals alone but part of a tethered pathophysiological cascade. We are particularly interested in the fast progressor phenotype, a devastating and under-characterized subset of ALS due to a rapid axonal degeneration, early respiratory failure, and very short life span. We will try to highlight the salient molecular features of this ALS subtype, including SOD1 A5V toxicity, C9orf72 repeats, FUS variants, mitochondrial collapse, and impaired autophagy mechanisms, and relate these features to measurable blood and CSF (biomarkers) and imaging platforms. We will elaborate on several interesting tools, for example, single-cell transcriptomics, CSF exosomal cargo analysis, MRI techniques, and wearable sensor outputs that are developing into high-resolution windows of disease progression and onset. Instead of providing a static catalog, we plan on providing a conceptual roadmap to integrate biomarker panels that will allow for earlier diagnosis, real-time disease monitoring, and adaptive therapeutic trial design. We hope this synthesis will make a meaningful contribution to the shift from observational neurology to proactive biologically informed clinical care in ALS. Although there are still considerable obstacles to overcome, the intersection of a precise molecular or genetic association approach, digital phenotyping, and systems-level understandings may ultimately redefine how we monitor, care for, and treat this challenging neurodegenerative disease. Full article

Fertility potential ever more diminishes due to the complex, multifactorial, and still not entirely clarified process of reproductive aging in women and men. Gamete quality and reproductive lifespan are compromised by biologic factors like mitochondrial dysfunction, increased oxidative stress (OS), and incremental telomere shortening. Clinically confirmed biomarkers, including follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH), are used to estimate ovarian reserve and reproductive status, but these markers have limited predictive validity and an incomplete representation of the complexity of reproductive age. Recent advances in artificial intelligence (AI) have the capacity to address the integration and interpretation of disparate and complex sets of data, like imaging, molecular, and clinical, for consideration. AI methodologies that improve the accuracy of reproductive outcome predictions and permit the construction of personalized treatment programs are machine learning (ML) and deep learning. To promote fertility evaluations, here, as part of its critical discussion, the roles of mitochondria, OS, and telomere biology as latter-day biomarkers of reproductive aging are presented. We also address the current status of AI applications in reproductive medicine, promises for the future, and applications involving embryo selection, multi-omics set integration, and estimation of reproductive age. Finally, to ensure that AI technology is used ethically and responsibly for reproductive care, model explainability, heterogeneity of data, and other ethical issues remain as residual concerns. Full article

Myopathies and muscular dystrophies are a diverse group of rare or ultra-rare diseases that significantly impact patients’ quality of life and pose major challenges for diagnosis and treatment. Despite their heterogeneity, many share common molecular mechanisms, particularly involving sarcomeric dysfunction, impaired autophagy, and disrupted gene expression. This review explores the genetic and pathophysiological foundations of major myopathy subtypes, including cardiomyopathies, metabolic and mitochondrial myopathies, congenital and distal myopathies, myofibrillar myopathies, inflammatory myopathies, and muscular dystrophies. Special emphasis is placed on the role of autophagy dysregulation in disease progression, as well as its therapeutic potential. We discuss emerging diagnostic approaches, such as whole-exome sequencing, advanced imaging, and muscle biopsy, alongside therapeutic strategies, including physiotherapy, supplementation, autophagy modulators, and gene therapies. Gene therapy methods, such as adeno-associated virus (AAV) vectors, CRISPR-Cas9, and antisense oligonucleotide, are evaluated for their promise and limitations. The review also highlights the potential of drug repurposing and artificial intelligence tools in advancing diagnostics and personalized treatment. By identifying shared molecular targets, particularly in autophagy and proteostasis networks, we propose unified therapeutic strategies across multiple myopathy subtypes. Finally, we discuss international research collaborations and rare disease programs that are driving innovation in this evolving field. Full article

Cellular senescence can occur with similar phenotypes in normal cells, during aging, and in tumor cells, spontaneously or after cytostasis. The fall or increase in proliferative activity are key aspects of the respective conditions, in which the levels of reactive oxygen species can vary, affecting the cellular redox homeostasis. This work aimed to study the relationships between senescence and transformation by comparing cells with different proliferative activities and phenotypes attributable to transformation (NIHs cultures) or senescence (NIHv cultures), before and after incubation with hydrogen peroxide. Both cultures were derived from the NIH/3T3 cell line, which was used here as a reference (NIHb), after the serum starvation. Our experimental model can be representative of the heterogeneity of cell subpopulations, with different degrees of transformation and senescence, found in some tumors. The characterization of the functional properties of NIHb, NIHs, and NIHv cells was performed by a morphocytometric analysis of the cell cycle progression, mitochondrial and lysosomal content/activity, and superoxide anion production. The efficiency of the lysosomal compartment was also assessed by estimating the autophagic activity and measuring lipofuscin autofluorescence. Comparisons of nuclear and cytoplasmic parameters before and after the incubation with hydrogen peroxide revealed differences in the expression and modulation of cellular senescence patterns. The treatment effects were very limited in the NIHb culture; the senescence condition was essentially maintained in the NIHv cells, while the most relevant changes were found in the NIHs cells. In the latter, the acquisition of the senescent phenotype, also demonstrated by the positivity of SA-β-galactosidase, was correlated with a decrease in proliferative activity and a change in the content/activity of the mitochondria and lysosomes, which showed similarities with the basal senescence conditions of NIHv cells. In NIHs cells, increased autophagy events and lipofuscin accumulation also indicate the establishment of cytoplasmic dynamics typical of senescence. The variable responses to hydrogen peroxide, besides depending on the different basal cytokinetic activity of the cultures examined, appeared to be related to the specific cell redox state resulting from the balance between endogenous ROS and those produced after treatment. Especially in NIHs cells, the slowing down of the cell cycle was linked to dynamic interconnections between the mitochondrial and lysosomal compartments. This would indicate that transformed cells, such as NIHs, may express morpho-functional aspects and markers typical of cellular senescence, as a consequence of the modulation of their redox state. Full article

Pancreatic neuroendocrine tumors (pNETs) are rare malignancies, accounting for 1–2% of pancreatic cancers, with an incidence of ≤1 case per 100,000 individuals annually. Originating from pancreatic endocrine cells, pNETs display significant clinical and biological heterogeneity. Traditional classification based on proliferative grading does not fully capture the complex mechanisms involved, such as oxidative stress, mitochondrial dysfunction, and tumor-associated macrophage infiltration. Recent advances in molecular profiling have revealed key oncogenic drivers, including MEN1 (menin 1), DAXX (death domain–associated protein), ATRX (alpha thalassemia/mental retardation syndrome X-linked), CDKN1B (cyclin-dependent kinase inhibitor 1B) mutations, chromatin remodeling defects, and dysregulation of the mTOR pathway. Somatostatin receptors, particularly SSTR2, play a central role in tumor biology and serve as important prognostic markers, enabling the use of advanced diagnostic imaging (e.g., Gallium-68 DOTATATE PET/CT) and targeted therapies like somatostatin analogs and peptide receptor radionuclide therapy (PRRT). Established biomarkers such as Chromogranin A and the Ki-67 proliferation index remain vital for diagnosis and prognosis, while emerging markers, like circulating tumor DNA and microRNAs, show promise for enhancing disease monitoring and diagnostic accuracy. This review summarizes the molecular landscape of pNETs and highlights genomic, transcriptomic, proteomic, and epigenomic factors that support the identification of novel diagnostic, prognostic, and therapeutic biomarkers, ultimately advancing personalized treatment strategies. Full article