Search Results (248)

Lead (Pb) exposure poses a significant public health concern due to its neurotoxic effects. While mitochondrial dysfunction is implicated in lead neurotoxicity, the precise molecular mechanisms, particularly the role of non-coding RNA-mediated competing endogenous RNA networks, remain underexplored. SH-SY5Y neuroblastoma cells were treated with 10 μM lead acetate. Cell viability was assessed by Cell Counting Kit-8 (CCK-8). Mitochondrial ultrastructure and quantity were analyzed via transmission electron microscopy (TEM). Key mitochondrial dynamics proteins were examined by Western blot. Comprehensive transcriptome sequencing, including long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs) and mRNAs, was performed followed by functional enrichment and ceRNA network construction. Selected RNAs and hub genes were validated using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Lead exposure significantly reduced SH-SY5Y cell viability and induced mitochondrial damage (decreased quantity, swelling, fragmentation). Western blot confirmed an imbalance in mitochondrial dynamics, as indicated by decreased mitofusin 2 (MFN2), increased total and phosphorylated dynamin-related protein 1 (DRP1). Transcriptomic analysis revealed widespread differential expression of lncRNAs, circRNAs, miRNAs, and mRNAs. Enrichment analysis highlighted mitochondrial function and oxidative stress pathways. A ceRNA network identified five key hub genes: SLC7A11, FOS, HMOX1, HGF, and NR4A1. All validated RNA and hub gene expression patterns were consistent with sequencing results. Our study demonstrates that lead exposure significantly impairs mitochondrial quantity and morphology in SH-SY5Y cells, likely via disrupted mitochondrial dynamics. We reveal the potential regulatory mechanisms of lead-induced neurotoxicity involving ceRNA networks, identifying hub genes crucial for cellular stress response. This research provides a foundational framework for developing therapeutic strategies against lead-induced neurotoxicity. Full article

Long-chain fatty acids (LCFAs) have emerged as important regulators of cancer metabolism, but their impact on hormone receptor expression in breast cancer (BCA) remains poorly understood. In this study, we investigated the effects of five LCFAs—linoleic acid (LA), oleic acid (OA), elaidic acid (EA), palmitic acid (PA), and α-linolenic acid (LNA)—on two BCA cell lines: luminal-type MCF7 and triple-negative MDA-MB-231 (MB231). All LCFAs suppressed cell viability and mitochondrial function in a dose-dependent manner, accompanied by decreased membrane potential, increased reactive oxygen species production, and a metabolic shift. Notably, OA reduced both mRNA and nuclear protein levels of estrogen receptor alpha (ERα) in MCF7 cells, leading to impaired responses to estradiol and tamoxifen. In contrast, PA induced nuclear ERα expression in MB231 cells, although ER signaling remained inactive. MicroRNA profiling revealed that OA upregulated ER-suppressive miR-22 and miR-221 in MCF7, while PA increased miR-34a in MB231, contributing to ERα induction. These findings suggest that specific LCFAs modulate ER expression through epigenetic and post-transcriptional mechanisms, altering hormonal responsiveness in BCA. Our results offer new insights into how dietary lipids may influence therapeutic efficacy and tumor behavior by regulating nuclear receptor signaling. Full article

Noise-induced hearing loss (NIHL) is a significant occupational health issue, characterized by permanent damage to the cochlea due to prolonged exposure to high-intensity noise. Circulating microRNAs (c-miRNAs) have emerged as promising non-invasive indicators of inner ear pathology and potential modulators of cellular stress responses. Nevertheless, their specific roles in NIHL remain inadequately characterized. This study evaluated miRNA expression in the peripheral blood of individuals with bilateral NIHL (n = 12) and matched healthy controls (n = 6) using GeneChip^® miRNA 4.0 arrays. The Transcriptome Analysis Console software was used for differential expression analysis, and bioinformatic predictions of gene targets and pathway enrichment were performed using TargetScan (version 8.0) and the Enrichr tool. Among the 72 differentially expressed miRNAs (FDR < 0.05), hsa-miR-486-2, hsa-miR-664b-3p, hsa-miR-4485, hsa-miR-501, and hsa-miR-663b were notably upregulated, while hsa-miR-6723, hsa-miR-194-2, hsa-miR-668-5p, hsa-miR-4722-3p, and hsa-miR-4716 showed significant downregulation. Enrichment analyses indicated involvement in apoptosis regulation, mitochondrial stability, and cell cycle control. Principal component analysis (PCA) and clustering methods revealed clear molecular distinctions between the patient and control groups. The observed alterations in c-miRNA profiles highlight their relevance to NIHL-related cellular stress and degeneration. These findings support their utility as candidate biomarkers for diagnosis and prognosis, warranting further validation in functional and longitudinal studies. Full article

Soybean (Glycine max L.) is grown worldwide to obtain edible oil, livestock feed, and biodiesel. However, drought and salt stress are becoming serious challenges to global soybean cultivation as they retard the growth of soybean plants and cause significant yield losses. Voltage-dependent anion-selective channel (VDAC) proteins are well-known for their role in drought and salt tolerance in crop plants. In this study, we identified 111 putative VDAC genes randomly distributed in genomes of 14 plant species, including cultivated soybean (Glycine max) and wild soybean (Glycine soja). The comparative phylogenetic studies classified these genes into six different clades and found the highest structural similarities among VDAC genes of G. max and G. soja. From the conserved domain database, porin-3 (PF01459) was found to be the conserved domain in all VDAC proteins. Furthermore, gene annotation studies revealed the role of GmaVDAC proteins in voltage-gated anion channel activity. These proteins were also found to interact with other proteins, especially mitochondrial receptors. A total of 103 miRNAs were predicted to target fifteen GmaVDAC genes. In G. max, these genes were found to be segmentally duplicated and randomly distributed on twelve chromosomes. Transcriptomic analysis revealed that the GmaVDAC18.2 gene showed overexpression in root nodules, whereas the GmaVDAC9.1, GmaVDAC18.1, and GmaVDAC18.2 genes showed overexpression under drought and salt stress conditions. Full article

The global obese population accounts for approximately 30% of the total population and continues to increase. White adipocytes, which accumulate in the body for energy storage, are associated with obesity. Mechanisms that activate browning of white adipocytes are an attractive therapeutic target for obesity and metabolic disorders. Exosomes are nano-sized biovesicles that play a role in cell-to-cell communication though the transfer of cargos such as microRNAs. Although milk exosomes contain many endogenous microRNA molecules, the role of microRNAs in milk exosomes is limited. Therefore, the aim of this study was to investigate the effects of milk exosomes on the browning of white adipocyte. Mouse pre-adipocytes (3T3-L1) and human adipose-derived stem cells (hADSCs) were differentiated and exposed to milk exosomes. Compared to control, milk exosomes promoted the expression of thermogenic genes and cellular mitochondrial energy metabolism in both 3T3-L1 cells and hADSCs. Additionally, milk exosomes were orally administered to mice fed a high-fat diet. As the intake of milk exosomes increased, the mice’s body weight decreased. Milk exosomes also increased the protein levels of thermogenic genes and mitochondrial-related genes in mouse adipose tissue. The overexpression of miR-11987, which is abundant in milk exosomes, in both 3T3-L1 cells and hADSCs led to the increased expression of thermogenic genes and mitochondrial activity. Our results support that bovine-specific miR-11987 in milk exosomes promotes the browning of white adipocytes. Therefore, milk exosome and milk exosomal miR-11987 could have significant clinical implications for obesity and metabolic syndrome. Full article

Exosomal microRNAs (ex-miRs), encapsulated in extracellular vesicles (EVs), play a vital role in facilitating paracrine communication among granulosa cells (GCs), cumulus cells (CCs), and the oocyte inside follicular fluid (FF). These small non-coding RNAs are crucial for regulating folliculogenesis, oocyte maturation, and early embryonic development via modulating intracellular signaling networks. Dysregulation o has been associated with reproductive disorders such as polycystic ovarian syndrome (PCOS), diminished ovarian reserve (DOR), and inadequate ovarian response (POR), impacting oocyte quality and fertility outcomes. This narrative review consolidates molecular data from current human and animal studies regarding ex-miR expression patterns, functional targets, and pathway involvement within the context of assisted reproductive technologies (ARTs). A literature-based analysis was undertaken, focusing on signaling pathways, pathogenic processes, and clinical implications. Specifically, ex-miRs—such as miR-21, miR-34c, miR-143-3p, miR-155-5p, miR-339-5p, and miR-424-5p—were identified as regulators of critical pathways including phosphoinositide 3-kinase (PI3K)–AKT, ERK1/2, TGF-β/SMAD, and Rb–E2F1. These ex-miRs regulate apoptosis, glycolysis, mitochondrial function, and cell cycle expansion to influence oocyte competence. Pathological patterns in PCOS and POR are associated with altered ex-miR expression that disrupts metabolic and developmental signaling. Research utilizing animal models confirmed that modifications in EV-associated miRNA influence in vitro maturation (IVM) efficiency and blastocyst quality. Ex-miRs serve as intriguing non-invasive biomarkers and potential therapeutic targets for ARTs. Their mechanical involvement in oocyte and follicular physiology positions them for integration into forthcoming precision-based infertility therapies. For its implementation in reproductive medicine, EV profiling requires standardization and further functional validation in clinical environments. Full article

Background/Objectives: The rising global prevalence of metabolic diseases (e.g., obesity, type 2 diabetes mellitus) underscores the need for effective interventions. Omega-3 polyunsaturated fatty acids (PUFAs) exhibit therapeutic potential, yet their molecular mechanisms remain unclear. This systematic review synthesizes a decade (2014–2024) of omics research to elucidate Omega-3 PUFA mechanisms in metabolic diseases and identify future directions. Methods: A PRISMA-guided search of the Web of Science identified studies on Omega-3 PUFAs, metabolic diseases, and omics. After excluding reviews, non-English articles, and irrelevant studies, 72 articles were analyzed (16 multi-omics, 17 lipidomics, 10 transcriptomics/metabolomics/microbiomics each, and 6 proteomics). Results: Omics studies demonstrated that Omega-3 PUFAs, particularly EPA and DHA, improve metabolic health through interconnected mechanisms. They regulate epigenetic processes, including DNA methylation and miRNA expression, influencing genes linked to inflammation and insulin sensitivity. Omega-3 PUFAs reduce oxidative stress by mitigating protein carbonylation and enhancing antioxidant defenses. Gut microbiota modulation is evident through increased beneficial taxa (e.g., Bacteroidetes, Akkermansia) and reduced pro-inflammatory species, correlating with improved metabolic parameters. Mitochondrial function is enhanced via upregulated fatty acid oxidation and TCA cycle activity, while anti-inflammatory effects arise from NF-κB pathway suppression and macrophage polarization toward an M2 phenotype. Challenges include interindividual variability in responses and a limited understanding of dynamic metabolic interactions. Conclusions: Omega-3 PUFAs target multiple pathways to improve metabolic health. Future research should prioritize chemoproteomics for direct target identification, multi-omics integration, and personalized strategies combining Omega-3 with therapies like calorie restriction. Full article

Heart failure (HF) remains a leading cause of morbidity and mortality worldwide, driven by diverse pathophysiological mechanisms. Among its major risk factors, obesity has emerged as a lobal public health concern affecting individuals across all age groups. The rising prevalence of obesity significantly increases the risk of cardiovascular complications, including the development and progression of HF. MicroRNAs (miRNAs), small non-coding RNA molecules, have garnered attention for their regulatory roles in cardiovascular disease, particularly through post-transcriptional modulation of gene expression. This review highlights the involvement of miRNAs in key pathological processes observed in the obese heart, including cardiac remodeling, apoptosis, angiogenesis, inflammation, mitochondrial dysfunction, and myocardial lipotoxicity. Understanding how specific miRNAs and their targets contribute to HF in the context of obesity may inform the development of novel RNA-based therapeutic strategies for cardiometabolic disease. Full article

Cystic fibrosis (CF), a severe genetic disorder stemming from mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, is characterized by a complex interplay of chronic inflammation and heightened oxidative stress, resulting in substantial patient morbidity. The diverse array of CFTR mutations, categorized into seven distinct classes based on their functional impact on the CFTR protein, presents a significant obstacle to effective therapeutic intervention. While CFTR modulator therapies offer clinical benefits, their applicability is restricted to specific mutation classes, leaving a considerable portion of the CF patient population with unmet therapeutic needs. This review provides a critical analysis of the intricate role of oxidative stress in CF, meticulously examining its origins, mechanistic pathways and downstream pathological consequences, with particular emphasis on lipid peroxidation (LPO). It elucidates the nuanced connection between LPO and inflammatory processes driven by cellular stressors such as endoplasmic reticulum dysfunction, mitochondrial impairment and persistent bacterial infections. Furthermore, it evaluates the current landscape of therapeutic proposals targeting oxidative stress, including antioxidant interventions, and explores the potential of microRNAs (miRNAs) as novel targets. This review aims to synthesize existing research to provide a comprehensive understanding of oxidative stress involvement in CF pathogenesis while critically appraising the advantages and limitations of current antioxidant therapeutic strategies. Full article

Background: Whether intestinal epithelial cells can regulate distant adipose tissue remains a mystery. Methods: Cold-stimulated intestinal epithelial cell-derived exosomes (Cold IEC-Exo) play a pivotal role in enhancing adipose thermogenesis and metabolic homeostasis, as demonstrated in this study. Results: IEC-Exo can accumulate in adipose tissue. Compared with IEC-Exo derived from room temperature mice (RT IEC-Exo), Cold IEC-Exo significantly enhanced the thermogenesis of adipose. In vitro, Cold IEC-Exo directly stimulated thermogenesis in primary adipocytes by elevating oxygen consumption rate, proton leak, and fatty acid uptake, with no effect on glucose uptake. Small RNA sequencing identified miR-674-3p as a key mediator enriched in Cold IEC-Exo. miR-674-3p mimicry replicated Cold IEC-Exo effects, augmenting Ucp1 expression, mitochondrial uncoupling, and fatty acid utilization in adipocytes. Local overexpression of miR-674-3p in BAT and sWAT via AAV in vivo enhanced thermogenesis and attenuated diet-induced glucose intolerance. Conclusions: These findings establish that Cold IEC-Exo, via miR-674-3p transfer, drive adipose thermogenic activation and mitigate metabolic dysfunction, highlighting their therapeutic potential in obesity-related disorders. Full article

This study aimed to elucidate the mitochondrial genome organization of Chlorogomphus papilio and the phylogenetic relationships of Chlorogomphidae. We used the Illumina MiSeq sequencing platform to sequence the mitochondrial genome of C. papilio, which was subsequently assembled, annotated, and analyzed. Bayesian inference, maximum likelihood, and maximum parsimony methods were employed to construct the mitochondrial phylogenetic tree of 25 species of Chlorogomphidae based on 16S rRNA and cox1 genes. We observed that the mitochondrial genome of C. papilio is 15,251 bp in length and includes 13 protein-coding genes (PCGs), 22 tRNA genes, 2 rRNA genes, and a non-coding control region. All PCGs start with a typical ATN codon. While cox1, cox2, cox3, and nad5 end with an incomplete termination codon (T), the remaining PCGs terminate with TAG. The secondary structure of the 22 tRNAs showed that only the trnS1 gene lacked the dihydrouracil arm (DHU arm), whereas the rest formed a typical cloverleaf structure. Additionally, 32 G-U mismatches were observed in the secondary structure. Phylogenetic analyses indicated that C. papilio and C. magnificus are sister species. Divergence time analyses indicated that Chlorogomphidae originated around 111.04 Ma, with C. papilio diverging from the common ancestor shared with C. magnificus approximately 58.51 Ma. This divergence is likely linked to the Paleocene–Eocene Thermal Maximum (PETM) and the tectonic uplift of the Himalayas, which created warm, humid habitats and contributed to geographic isolation. This study contributes to a better understanding of the mitochondrial genome and phylogeny of C. papilio, providing valuable molecular markers for further genetic studies. Full article

Background: Colubridae, known to be one of the most species-rich snake families, remains relatively understudied in termshe context of complete mitochondrial genome research. This study provide the first systematic characterization of the mitochondrial genomes of six colubrid species: Lycodon subcinctus, Lycodon rosozonatus, Lycodon fasciatus, Lycodon gongshan, Lycodon futsingensis, and Lycodon aulicus. Method: In this study, mitochondrial genomes were sequenced using Sanger sequencing. The raw data were subjected to quality- filtered withing using Fastp and subsequently assembled into complete mitochondrial genomes via SPAdes. Gene annotation was performed by Tblastn, Genewise (for CDS coding sequences), MiTFi (for transfer RNAs), and Rfam (for ribosomal RNAs). Sequence analyses were conducted with various tools, including MEGA, tRNAscan-SE, DnaSP, MISA, and REPuter. Finally, phylogenetic trees were reconstructed based on 13 protein-coding genes from 14 species. Results:The mitogenomes of these six species ranged from 17,143 to 17,298 bp in length and con-sisted of 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs), and 2 control regions. The nucleotide composition of the Colu-bridae mitogenomes was comparable with an A + T composition ranging from 52.1% to 58.8% except for the trnS1 and trnC. All the tRNAs could fold into a stable secondary structure. The Pi and Ka/Ks values suggested that atp8 was the fastest-evolving gene, while cox1 was the most conserved gene. Bayesian inference and maximum likelihood phylogenetic analyses yielded consistent results, with the six sequenced species clus-tering together with their congeneric species. These findings will provide valuable references for further research on the phylogeny of Colubridae. Full article

The therapeutic potential of presumed cardiac progenitor cells (CPCs) in heart regeneration has garnered significant interest, yet clinical trials have revealed limited efficacy due to challenges in cell survival, retention, and expansion. Priming CPCs to survive the hostile hypoxic environment may be key to enhancing their regenerative capacity. We demonstrate that microRNA-210 (miR-210), known for its role in hypoxic adaptation, significantly improves CPC survival by inhibiting apoptosis through the downregulation of Casp8ap2, a ~40% reduction in caspase activity, and a ~90% decrease in DNA fragmentation. Contrary to the expected induction of Bnip3-dependent mitophagy by hypoxia, miR-210 did not upregulate Bnip3, indicating a distinct anti-apoptotic mechanism. Instead, miR-210 reduced markers of mitophagy and increased mitochondrial biogenesis and oxidative metabolism, suggesting a role in metabolic reprogramming. Furthermore, miR-210 enhanced the secretion of paracrine growth factors from CPCs, with a ~1.6-fold increase in the release of stem cell factor and of insulin growth factor 1, which promoted in vitro endothelial cell proliferation and cardiomyocyte survival. These findings elucidate the multifaceted role of miR-210 in CPC biology and its potential to enhance cell-based therapies for myocardial repair by promoting cell survival, metabolic adaptation, and paracrine signalling. Full article

Background/Objectives: TDP-43 mutation-driven Amyotrophic Lateral Sclerosis (ALS) motor neuron disease is one of the most prominent forms (approximately 97%) in cases of sporadic ALS. Dysfunctional autophagy and lysosomal function are the prime mechanisms behind ALS. Mitoxantrone (Mito), a synthetic doxorubicin analog, is an inhibitor of DNA and RNA synthesis/repair via intercalating with nitrogenous bases and inhibiting topoisomerase II. The therapeutic potential of miRNAs associated with disease conditions has also been reported. This study explores the therapeutic potential of Mito along with miRNAs against mutated TDP-43 protein-induced proteinopathy in human-induced pluripotent stem cell (hiPSC)-derived human neural progenitor cells (hNPCs). Methods: HiPSCs mutated for TDP-43 were differentiated into hNPCs and used to explore the therapeutic potential of Mito at a concentration of 1 μM for 24 h (the identified non-cytotoxic dose). The therapeutic effects of Mito on miRNA expression and various cellular parameters such as mitochondrial dynamics, autophagy, and stress granules were assessed using the high-throughput Open Array technique, immunocytochemistry, flow cytometry, immunoblotting, and mitochondrial bioenergetic assay. Results: Mutated TDP-43 protein accumulation causes stress granule formation (G3BP1), mitochondrial bioenergetic dysfunction, SOD1 accumulation, hyperactivated autophagy, and ER stress in hNPCs. The mutated hNPCs also show dysregulation in six miRNAs (miR-543, miR-34a, miR-200c, miR-22, miR-29b, and miR-29c) in mutated hNPCs. A significant restoration of TDP-43 mutation-induced alterations could be witnessed upon the exposure of mutated hNPCs to Mito. Conclusions: Our study indicates that miR-543, miR-29b, miR-22, miR-200c, and miR-34a have antisense therapeutic potential alone and in combination with Mitoxantrone. Full article

Mitochondrial miRNAs (mitomiRs), which are miRNAs that located within mitochondria, have emerged as crucial regulators in a variety of human diseases, including multiple types of cancers. However, the specific role of mitomiRs in clear cell renal cell carcinoma (ccRCC) remains elusive. In this study, we employed a combination of experimental and bioinformatic approaches to uncover the diverse and abundant subcellular distribution of miRNAs within mitochondria in ccRCC. Notably, RNA sequencing after mitochondrial fractionation identified miR-134-5p as a miRNA predominantly detected in the mitochondria of 786O cells, and its expression is significantly upregulated compared to that in 293T cells. Differential expression and survival analyses from TCGA reveal that the upregulation of miR-134-5p is prevalent and closely associated with poor survival outcomes in ccRCC patients. Functionally, exogenous overexpression of miR-134-5p mimics promotes migration in both 786O and Caki-1 cells. Mechanistically, overexpressing the miR-134-5p mimic dramatically downregulates the mRNA levels of CHST6, SFXN2, and GRIK3, whereas the miR-134-5p inhibitor markedly upregulates their expression. Notably, these target mRNAs also predominantly detected in the mitochondria of 786O cells. The downregulated expression signatures of CHST6, SFXN2, and GRIK3 are also closely correlated with poor survival outcomes in ccRCC patients. Taken together, our work identifies a novel mitomiR, miR-134-5p, in ccRCC, provides potential targets that could serve as effective biomarkers for ccRCC diagnosis and prognosis, and opens new avenues for understanding the mitomiR-directed regulatory network in ccRCC progression. Full article