Search Results (104)

Mixed dementia (MD), characterized by overlapping features of Alzheimer’s disease (AD) and vascular dementia (VaD), represents the most prevalent form of late-life cognitive decline. Increasing evidence identifies oxidative stress as a unifying molecular mechanism driving both neurodegenerative and vascular pathologies in MD. Reactive oxygen species (ROS) contribute to amyloid-β aggregation, tau hyperphosphorylation, endothelial dysfunction, and blood–brain barrier disruption, creating a self-perpetuating cycle of neuronal and vascular injury. Mechanistic models demonstrate how chronic hypoperfusion and mitochondrial dysfunction exacerbate ROS generation and neuroinflammation, while impaired Nrf2-mediated antioxidant defense further amplifies damage. Therapeutically, classical antioxidants show inconsistent efficacy, shifting focus toward mitochondrial protection, Nrf2 activation, and lifestyle-based oxidative load reduction. Therefore, we sought to outline therapeutic approaches capable of broadly targeting these mechanisms, through focused narrative analysis of recent studies employing delivery systems for antioxidant proteins and/or redox-regulating miRNAs. In particular, experimental interventions using mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) demonstrate neuroprotective and anti-inflammatory effects via the Nrf2 pathway, suggesting promising avenues for multimodal treatment. Integrating oxidative, vascular, and neurodegenerative paradigms is essential for advancing diagnostic precision and developing targeted interventions capable of addressing the complex pathophysiology of mixed dementia. Full article

Ovarian aging (OA) results from the senescence of different cell types present in the ovary, decreasing female fertility and quality of life and augmenting the risk of a variety of fertility-unrelated pathological conditions. The changes observed in the ovarian cells are accompanied by changes occurring in various elements of the hypothalamic–pituitary–ovarian (HPO) axis, the complex endocrine system that regulates the female reproductive cycle. Issues pertaining to the HPO axis have been addressed in animal models via hormonal treatments with preparations inhibiting ovarian follicular recruitment at the level of the receptors of gonadotropin-releasing hormone (GnRH)-secreting neurons, mainly acting on glutamate- and gamma-aminobutyric acid (GABA)-driven signaling. GnRH agonists and antagonists have also been used in women exposed to chemotherapeutics. HPO-independent OA can be delayed through the administration of different antioxidants and mitochondria-protecting agents, among which melatonin has been shown to be particularly useful. Other therapeutic approaches used with success in women include hormonal and growth factor (GF) modulators, such as growth hormone (GH), insulin-like growth factor 1 (IGF-1), vascular endothelial growth factors (VEGF), and dehydroepiandrosterone (DHEA), and the development of patient-tailored combination-based therapies (IGF-1 + VEGF + DHEA) has also been suggested. Intraovarian injection of autologous platelet-rich plasma (PRP), mitochondrial donation through pronuclear transfer, and ovarian tissue cryopreservation and autotransplantation have also yielded promising results in women, and their use can preserve not only fertility but also the ovarian endocrine function. Personalized mixtures of specific agents (desatinib, quercetin, rapamycin, metformin, resveratrol, melatonin, and coenzyme Q10) targeting different cell types in the ovary are currently under investigation. Overall, this review aims to present a global view of the subject, uniting the physiological and molecular background of this pathology with the history and development of potential treatment strategies and new perspectives in this domain. As such, this study may be helpful both to clinicians facing problems resulting from OA and to researchers pursuing further developments in this field. Full article

Thraustochytrium aureum ssp. strugatskii, a marine protist belonging to the class Labyrinthulea, exhibits a complex life cycle characterized by alternating motile and vegetative phases. Using an integrative multimodal microscopy approach, we reconstructed its full developmental cycle and analyzed the coordination between cellular morphology, subcellular architecture, and population-level behavior. Transmission and scanning electron microscopy, combined with fluorescence and time-lapse imaging, revealed the dynamics of nuclear division, organelle rearrangement, and zoospore formation. Morphometric analysis of serial ultrathin sections demonstrated distinct changes in mitochondrial distribution, Golgi apparatus, and lipid droplet abundance during transitions between stages. We have shown that vegetative cells undergo synchronized karyokinesis coupled with stable nuclear-to-cytoplasmic ratios, leading to the emergence of multinucleate stages prior to zoospore formation. The integration of ultrastructural and dynamic data enabled us to propose a systems-level model linking metabolic state, morphogenesis, and population structure. This model highlights feedback regulation between nutrient availability, biomass accumulation, and developmental synchronization. Our results establish that T. aureum ssp. strugatskii has good potential to serve as a tractable model organism for systems-level studies of protists and provide an initial framework for predictive modeling of its life cycle under controlled conditions. Full article

MicroRNAs (miRNAs) are small non-coding RNAs that play pivotal roles in post-transcriptional gene regulation, influencing development, differentiation, and disease pathogenesis. Since their discovery in 1993, miRNAs have been recognized for their evolutionary conservation and pleiotropic effects, with the 2024 Nobel Prize underscoring their significance in post-transcriptional regulation via the RNA interference (RNAi) pathway. This review synthesizes the complete life cycle of miRNAs—from transcription and processing to function and decay—emphasizing regulatory mechanisms and their implications in human diseases, particularly cancer. We discuss how epitranscriptomic modifications influence miRNA biogenesis and activity, explore their nuclear and mitochondrial functions, and address emerging challenges in miRNA-based therapeutics, including the expanding small RNA landscape such as tRNA-derived small RNAs (tsRNAs), and Argonaute (AGO)-independent activities. Despite hurdles such as modest multi-target effects, off-target interactions, and delivery challenges, miRNAs remain promising as both biomarkers and therapeutic agents, underscoring the need for sustained research to bridge preclinical insights with clinical applications. Full article

Malaria remains a major global health threat, particularly in low- and middle-income countries, where children under five and pregnant women are most vulnerable. Despite notable progress in reducing malaria-related morbidity and mortality, the rise of drug-resistant Plasmodium falciparum strains continues to undermine eradication efforts. In this context, the parasite’s mitochondrion has emerged as a promising target for novel antimalarial therapies due to its essential role in parasite viability throughout all life cycle stages and its marked structural and biochemical differences from the human counterpart. This review highlights recent advances in the development of compounds targeting mitochondrial function in P. falciparum and discusses the utility of Saccharomyces cerevisiae as a powerful model organism for antimalarial drug discovery. Owing to its shared eukaryotic features, genetic tractability, and capacity for heterologous expression of parasite mitochondrial proteins, S. cerevisiae offers a cost-effective and experimentally accessible platform for elucidating drug mechanisms and accelerating therapeutic development. Full article

Feline cytauxzoonosis is an emerging tick-borne disease in Europe. While infections have been reported in different European countries, the tick vector remains unknown. This study investigated 665 ticks collected in 2019 (n = 160), 2022 (n = 7), and 2024 (n = 498) in a Cytauxzoon spp. hotspot region in central Switzerland (62 ticks from cats; 603 ticks from vegetation). Ticks were morphologically characterized, pooled by origin and life-stage, and screened for Cytauxzoon spp. 18S rRNA by qPCR and conventional PCR, and positive samples confirmed by sequencing. All ticks belonged to Ixodes ricinus (50 males, 83 females, 532 nymphs). Four tick pools from 2019 tested Cytauxzoon spp. positive: one pool of 3 non-engorged male ticks from two cats and three pools of 5–6 nymphs each from vegetation. All ticks collected in 2022 and 2024 tested negative. Amplification of the almost full-length (1535 bp, one pool) or partial (140–219 bp, three pools) 18S rRNA gene revealed a sequence identity of 98.6–100% with Cytauxzoon spp. previously detected in cats from this area. The detection of Cytauxzoon spp. in questing I. ricinus nymphs suggests a potential role of this tick species in the parasites’ transmission cycle in Central Europe and raises the possibility of transstadial or potentially transovarial transmission. Mitochondrial gene sequencing was unsuccessful, but the detected Cytauxzoon spp. likely represent Cytauxzoon europaeus. Discrepancies between qPCR and conventional PCR results point to possible amplification of tick endosymbionts, highlighting the importance of confirmatory sequencing, particularly when testing tick-derived DNA. Thus, the 18S rRNA qPCR assay used appears suboptimal for screening tick samples, as its specificity in this matrix was limited. In conclusion, this is the first report of Cytauxzoon spp. in questing I. ricinus ticks in Europe. Our findings underscore the need for further research to confirm vector competence and clarify transmission dynamics. Full article

Vanadium is a transition metal whose environmental presence has increased due to human activities such as fossil fuel combustion and industrial processes. A central mechanism of its toxicity involves mitochondrial dysfunction, as vanadium exposure disrupts energy metabolism, enhances reactive oxygen species (ROS) generation, and triggers oxidative stress, ultimately leading to genetic damage and alterations in cellular signaling. These mitochondrial alterations contribute to its potential carcinogenic, immunotoxic, and neurotoxic properties, affecting multiple systems, including the neurological, renal, immune, and reproductive systems. Since there are no specific treatments for vanadium intoxication, natural compounds—particularly plant-derived metabolites with antioxidant, mitochondrial-targeted, and chelating properties—have been investigated as potential therapeutic agents to counteract its toxicity. In this context, simple models such as the nematode Caenorhabditis elegans (C. elegans), the fruit fly (Drosophila melanogaster), and the zebrafish (Danio rerio) have emerged as valuable experimental systems for studying vanadium-induced mitochondrial dysfunction and evaluating protective strategies. These organisms offer key advantages, including a short life cycle, ease of handling, and conservation of essential biological pathways with mammals, making them effective tools in environmental toxicology. The aim of this review is to outline the mitochondrial-related toxic effects of vanadium across different biological models and to explore plant-based therapeutic approaches capable of mitigating its harmful health impacts. We also propose the use of simple models, such as D. melanogaster, D. rerio, and, most notably, C. elegans, as versatile and complementary experimental platforms to advance research in this field. Full article

Brown adipose tissue (BAT) has shifted from being considered a transient thermogenic organ of infancy to a metabolically dynamic and multifunctional tissue throughout life. Histologically and developmentally distinct from white and beige adipocytes, BAT originates from a myogenic lineage and is characterised by a high mitochondrial density, multilocular lipid droplets, and abundant sympathetic innervation. Its defining function, non-shivering thermogenesis, is mediated by uncoupling protein 1 (UCP1) and complemented by alternative mechanisms such as futile creatine and calcium cycling. Beyond heat production, thermogenic fat is crucial in regulating whole-body metabolism. It contributes to glucose, lipid, and branched-chain amino acid homeostasis, and engages in endocrine and paracrine signalling through a rich secretome of batokines, lipid mediators, and extracellular vesicle-bound microRNAs. These signals orchestrate crosstalk with the liver, skeletal muscle, pancreas, and immune system, enhancing insulin sensitivity, vascularisation, and anti-inflammatory responses. Brown/Beige fat also exhibits notable anti-fibrotic properties and supports adipose tissue remodelling, maintaining structural and functional plasticity under metabolic stress. This review offers a comprehensive synthesis of thermogenic adipose tissue biology, integrating its structural, developmental, and molecular features with its expanding physiological functions, highlighting its pivotal role in energy balance as well as its emerging therapeutic potential in obesity, type 2 diabetes, and related metabolic disorders. Full article

Mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD), are among the leading causes of disability worldwide and are frequently associated with treatment resistance, functional impairment, and high comorbidity with metabolic dysfunction. Increasing evidence implicates insulin resistance (IR) as a key pathophysiological factor linking metabolic and psychiatric illness. IR is associated with chronic low-grade inflammation, hypothalamic–pituitary–adrenal (HPA) axis dysregulation, impaired neuroplasticity, mitochondrial dysfunction, and altered reward processing mechanisms that may contribute to core depressive features such as anhedonia, cognitive slowing, and emotional dysregulation. These processes are further exacerbated by the metabolic side effects of many psychotropic medications, creating a self-perpetuating cycle that worsens both psychiatric and physical health outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially developed for type 2 diabetes and obesity, have emerged as promising candidates to address this metabolic–psychiatric interface. Beyond improving glycemic control and promoting weight loss, GLP-1 RAs exert central actions relevant to mood disorders, including modulation of dopaminergic reward pathways, enhancement of hippocampal neurogenesis, attenuation of neuroinflammation, and regulation of appetite and energy balance. Preclinical studies demonstrate that GLP-1 RAs reduce microglial activation, promote hippocampal neurogenesis, and normalize stress-induced behavioral changes. Early clinical trials in patients with metabolic disorders suggest improvements in depressive symptoms, quality of life, and cognitive function, with some effects independent of weight loss or glycemic outcomes. Observational evidence also indicates reduced antidepressant use and psychological distress in diabetic and obese populations receiving GLP-1 RAs. While these findings are promising, large randomized controlled trials in primary psychiatric populations are lacking. Key challenges include clarifying dose–response relationships, disentangling central from peripheral effects, and addressing safety and adherence concerns in individuals with comorbid psychiatric conditions. Future research should focus on biomarker-informed stratification, comparative trials with standard treatments, and integration of GLP-1 RAs into multimodal care frameworks. Overall, GLP-1 RAs represent a biologically plausible and clinically relevant approach to bridging metabolic and psychiatric care, with the potential to improve outcomes in patients with mood disorders who carry a high metabolic burden. Full article

To identify the root-knot nematodes (RKNs) infecting onions in Yuanmou County, Yunnan Province, morphological and molecular biological techniques were used. Observation of their life cycle and pathogenicity was conducted through artificial inoculation experiments in a greenhouse. The results show that the morphological characteristics and measurement data of the second-stage juveniles (J2s) and females of RKNs infecting onion roots are highly consistent with those of Meloidogyne graminicola (M. graminicola). Sequence alignment of the mitochondrial DNA (mtDNA) COXI region and 28S rDNA D2-D3 region revealed sequence similarities of 99.51–100.00% and 99.48–99.61%, respectively, compared with M. graminicola sequences from GenBank. The specific primers Mg-F3/Mg-R2 reliably amplified a characteristic 369 bp band. Inoculation experiments confirmed that the pathogen can complete its entire life cycle (approximately 26 days (ds)) on the roots of healthy onion seedlings, inducing typical root-knot symptoms and females. In conclusion, the pathogen was identified as M. graminicola, which is the first report of M. graminicola infecting onions in China. This study provides important theoretical support for the molecular diagnosis of onion root-knot nematode disease and the green control of Allium L. vegetables in China. Full article

Ovarian aging is characterized by a gradual decline in both reproductive and endocrine functions, ultimately culminating in the cessation of ovarian activity around the age of 50, when most women experience natural menopause. The decline begins early, as follicular attrition is initiated in utero and continues throughout childhood and reproductive life. Most follicles undergo atresia without progressing through substantial stages of growth. With increasing age, a pronounced reduction occurs in the population of resting follicles within the ovarian reserve, accompanied by a decline in the size of growing follicular cohorts. Around the age of 38, the rate of follicular depletion accelerates, sometimes resulting in diminished ovarian reserve (DOR). The subsequent menopausal transition involves complex, irregular hormonal dynamics, manifesting as increasingly erratic menstrual patterns, primarily driven by fluctuations in circulating estrogens and a rising incidence of anovulatory cycles. In parallel with the progressive depletion of the follicular pool, the serum concentrations of anti-Müllerian hormone (AMH) decline gradually, while reductions in inhibin B levels become more apparent during the late reproductive years. The concomitant decline in both inhibin B and estrogen levels leads to a compensatory rise in circulating follicle-stimulating hormone (FSH) concentrations. Together, these endocrine changes, alongside the eventual exhaustion of the follicular reserve, converge in the onset of menopause, which is defined by the absence of menstruation for twelve consecutive months. The mechanisms contributing to ovarian aging are complex and multifactorial, involving both the oocyte and the somatic cells within the follicular microenvironment. Oxidative stress is thought to play a central role in the age-related decline in oocyte quality, primarily through its harmful effects on mitochondrial DNA integrity and broader aspects of cellular function. Although granulosa cells appear to be relatively more resilient, they are not exempt from age-associated damage, which may impair their hormonal activity and, given their close functional relationship with the oocyte, negatively influence oocyte competence. In addition, histological changes in the ovarian stroma, such as fibrosis and heightened inflammatory responses, are believed to further contribute to the progressive deterioration of ovarian function. A deeper understanding of the biological processes driving ovarian aging has facilitated the development of experimental interventions aimed at extending ovarian functionality. Among these are the autologous transfer of mitochondria and stem cell-based therapies, including the use of exosome-producing cells. Additional approaches involve targeting longevity pathways, such as those modulated by caloric restriction, or employing pharmacological agents with geroprotective properties. While these strategies are supported by compelling experimental data, robust clinical evidence in humans remains limited. Full article

Respiration rates in insects are critical for survival and environmental adaptation, being influenced by developmental stages, environmental conditions, and the regulation of mitochondrial protein-coding genes. However, methods for field-based measurements in small-sized insects remain limited. In this study, we established a portable photosynthesis system to quantify respiration rates in five small-sized insects (body length < 8 mm): Acyrthosiphon pisum, Aphis citricidus, Tuta absoluta, Tribolium castaneum, and Bactrocera dorsalis. We tested its effectiveness across life stages and under diverse treatments, including light/dark cycles, insecticides, temperature shifts, starvation, mitochondrial inhibitors, and RNA interference. The system exhibited high sensitivity and reproducibility rates, revealing stage-specific respiration patterns. Various treatments, as well as expression changes in mitochondrial protein-coding genes, significantly affected respiration rates. This study validates the portable system as a reliable tool for insect respiration studies and highlights regulatory networks associated with respiratory plasticity. These findings enhance experimental methodologies and advance our understanding of insect adaptation to environmental stressors and pest control strategies. Full article

Background: The limited regenerative capacity of adult mammalian cardiomyocytes (CMs) poses a significant challenge for cardiac repair following myocardial infarction. In contrast to adult mammals, CMs in zebrafish and newt hearts retain a lifelong capacity for proliferation and cardiac regeneration. Likewise, neonatal mice exhibit a brief postnatal period, during which CMs retain the ability to proliferate and contribute to myocardial repair, which markedly diminishes within the first week of life. Emerging evidence indicates that adult CM cell cycle progression is critically influenced by oxidative stress. Adult mammalian CMs possess a high mitochondrial content to meet their substantial energy demands. However, this also leads to elevated reactive oxygen species (ROS) production, resulting in DNA damage and subsequent cell cycle arrest. We hypothesize that reducing the mitochondrial content in adult CMs will mitigate ROS production, thereby facilitating cell cycle progression. Methods: Adult CMs were isolated from adult rats (≥12 weeks old). To induce mitophagy, adult CMs were transfected with parkin-expressing plasmid and then treated with carbonyl cyanide 3-chlorophenylhydrazone (CCCP), a mitochondrial protonophore, for 7 days. Post-treatment assessments included the quantification of adult CM proliferation, mitochondrial content, and ROS levels. Results: CCCP-treated adult CMs exhibited a significant increase in proliferation markers, including EdU incorporation, KI67, phospho-histone H3, and Aurora B. Furthermore, CCCP treatment significantly reduced the mitochondrial content, as evidenced by decreased MitoTracker, TMRM, and Tom20 staining compared to controls. This was accompanied by electron microscopy analysis, which showed a significant reduction in the mitochondrial number in the adult CM after CCCP treatment. Moreover, our results also demonstrate a marked reduction in oxidative stress, demonstrated by lower 123-dihydro-rhodamine (123-DHR), CellROX signals, and VDAC. Conclusions: Our findings demonstrate that CCCP-mediated mitochondrial depletion reduces oxidative stress and promotes cell cycle re-entry in adult CM. This study provides direct experimental evidence and substantiates the role of elevated mitochondria and ROS levels in adult CM cell cycle exit. Full article

A new species of jellyfish, Phyllorhiza yurena Chen, Hu & Xing sp. nov., is described from the East China Sea based on an integrative approach combining morphological and molecular data. Specimens were collected from coastal waters and cultured in the laboratory to observe their complete life cycle, including polyps, ephyrae, and medusae. Distinct morphological features such as the blue lappet stems in ephyrae, white warts on the exumbrella, and multiple short club-shaped appendages on the mouth arms distinguish the new species from its congeners. Phylogenetic analyses based on mitochondrial (COI, 16S) and nuclear (18S, 28S) gene markers confirmed its taxonomic distinctiveness, with COI and 16S markers providing the most resolution. The study highlights the importance of combining life history observations with molecular tools for accurate jellyfish taxonomy and provides a revised identification key for the genus Phyllorhiza. This discovery contributes to the understanding of jellyfish biodiversity in the East China Sea and offers a baseline for future ecological and biogeographic studies. Full article

Over the years, caloric intake has remained a subject of profound scrutiny. Within the scientific community, there has been rigorous debate to ascertain which path is most ideal for enhancing quality of life and extending the human lifespan. Caloric restriction has been shown to be a promising contributor towards longevity and delaying the onset of age-related diseases. This diet consists of a reduction in caloric intake while maintaining essential energy and nutritional requirements to achieve optimal health while avoiding malnutrition. However, the effects of this nutritional regimen on male reproductive health have not yet been comprehensively studied. Nevertheless, such a complex process will certainly be regulated by a variety of metabolic sensors, likely sirtuins. Evidence has been gathered regarding this group of enzymes, and their ability to regulate processes such as chromatin condensation, the cell cycle, insulin signaling, and glucose and lipid metabolism, among many others. Concerning testicular function and male fertility, sirtuins can modulate certain metabolic processes through their interaction with the hypothalamic–pituitary–gonadal axis and mitochondrial dynamics, among many others, which remain largely unexplored. This review explores the impact of caloric restriction on male fertility, highlighting the emerging role of sirtuins as key regulators of male reproductive health through their influence on cellular metabolism. Full article