Biological Research最新文献

{"title":"Subthreshold Kir and I_h currents modulate excitability of layer 1 VIP interneurons in the medial prefrontal cortex.","authors":"Claudio Moreno, Denise Riquelme, Camila Cornejo, Paula Leyton, Elias Leiva-Salcedo","doi":"10.1186/s40659-026-00673-2","DOIUrl":"10.1186/s40659-026-00673-2","url":null,"abstract":"<p><p>Cortical layer 1 (L1) is a key site for integrating top-down and bottom-up information and is populated by inhibitory interneurons, including vasoactive intestinal peptide (VIP)-expressing cells. These interneurons regulate information flow across the cortical column by disinhibiting pyramidal neurons, yet the subthreshold ionic mechanisms that shape their excitability in the medial prefrontal cortex (mPFC) remain poorly understood. Here, we characterize the electrophysiological properties of L1b VIP interneurons in mouse mPFC, focusing on the role of the hyperpolarization-activated cation current (I_h) and inward-rectifying potassium current (Kir). Using whole-cell recordings in acute slices, we find that L1b VIP interneurons exhibit constitutively active I_h and Kir conductances. Inhibition of I_h with ZD-7288 hyperpolarized the resting membrane potential (RMP), increased input resistance (R_in), and prolonged action potential (AP) duration without altering rheobase or firing frequency, while increasing EPSP-spike coupling probability. Blocking Kir with BaCl₂ depolarized the RMP, increased R_in and membrane time constant, reduced rheobase, increased firing frequency, and similarly enhanced EPSP-spike probability and AP duration. Voltage-clamp experiments confirmed the presence of ZD-7288-sensitive I_h and BaCl₂-sensitive Kir currents of small amplitude but operating on a high-resistance membrane, consistent with a strong impact on excitability. In contrast, neither I_h nor Kir inhibition affected the amplitude or frequency of spontaneous or miniature EPSCs, indicating that these currents do not measurably alter basal excitatory synaptic transmission. Immunofluorescence revealed weak somatic HCN1 and no detectable HCN2 expression in L1b VIP interneurons. Notably, Kir inhibition unmasked an I_h-dependent voltage sag during hyperpolarizing steps, suggesting that constitutive Kir activity normally masks I_h recruitment at subthreshold potentials. Together, these results indicate that I_h and Kir are active near RMP in L1b VIP interneurons and jointly regulate their passive properties, intrinsic excitability, and EPSP-spike coupling, therefore shaping how L1 VIP cells filter incoming signals and influence information flow within the prefrontal cortical column.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12988632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146193781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shear stress-induced Ca²⁺ influx triggers endoplasmic reticulum stress and cardiomyocyte apoptosis: implications for mitral regulation.","authors":"Wei-Ting Chang, Jun-Ming Su, Fan-E Mo, Jhih-Yuan Shih, Wen-Tai Chiu","doi":"10.1186/s40659-026-00671-4","DOIUrl":"10.1186/s40659-026-00671-4","url":null,"abstract":"<p><p>BACKGROUND: Mitral regurgitation is highly prevalent and elevates the risk of heart failure. Regurgitant flow induced shear stress disrupts Ca2+ homeostasis in atrial cardiomyocytes. Overloaded Ca2+ is a crucial regulator of endoplasmic reticulum stress-mediated apoptosis, although the regulatory mechanisms remain unclear. We aimed to explore the relationship between shear stress and Ca2+ homeostasis. METHODS AND RESULTS: Through employing an in vitro model replicating atrial cardiomyocytes during mitral regurgitation, we observed that shear stress increased Ca2+ oscillation and the amplitude of Ca2+ waves through extracellular Ca2+ influx. Suppression of mechanosensitive Ca2+ channels or store-operated calcium entry resulted in decreased intracellular Ca2+ concentration and oscillation. Conversely, the inhibition of voltage-gated Ca2+ channels did not significantly impact the Ca2+ concentration. Remarkably, shear stress elevated the expression of endoplasmic reticulum stress and apoptosis-related proteins in HL-1 cells in a time-dependent manner. Also, in a novel rodent mitral regurgitation model, shear stress increased apoptosis and endoplasmic reticulum stress expression compared to sham rats. CONCLUSIONS: Our findings underscore that shear stress induces apoptosis through mechanosensitive and store-operated Ca2+ channels, leading to Ca2+ overload and endoplasmic reticulum stress. Understanding the mechanisms behind shear stress-disturbed Ca2+ homeostasis may enhance the treatment of mitral regurgitation-induced heart failure. </p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12983577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue-specific role of dTrmO in threonine decoding during Drosophila melanogaster development.","authors":"Deborah Cuper, Valentina Muñoz-Madrid, Rodolfo Moreno, Francisca Brown, Yueh-Lin Tsai, Álvaro Glavic","doi":"10.1186/s40659-026-00667-0","DOIUrl":"10.1186/s40659-026-00667-0","url":null,"abstract":"<p><p>BACKGROUND: Translation is an extremely fine-tuned process. Both speed and fidelity are required to sustain translational demand and protein homeostasis in cells, traits that depend on several elements, including transfer RNA (tRNA) modifications. Additionally, it has been demonstrated that proliferative and differentiated tissues display differential susceptibilities to deficiencies in certain tRNA modifications. METHODS: By using the Gal4/UAS system we manipulated the expression levels of the Drosophila melanogaster orthologue of TrmO (dTrmO), a tRNA-methyltransferase that methylates t6A in position 37 of tRNAs decoding ACY codons, during development. RESULTS: Our results show that this protein is necessary for proper translation of ACT codons, and its function is differentially required in proliferative and non-proliferative tissues. Furthermore, we observed that reductions of dTrmO are detrimental for cell growth and proliferation, and muscle function due to impaired translation of Msp300, a nuclear membrane protein specific of muscle fibres. Strikingly, the translation-related phenotypes produced caused by decreased levels of dTrmO in the wing and eye-antenna imaginal disc, fat body, striated muscles, as well as overall organismal growth defects, can be rescued by overexpression of tRNA-Thr-AGT. CONCLUSIONS: Results point to the importance of dTrmO in translation of ACT codons and consequently in cell proliferation and growth of tissues, thus providing further insight about the active role of tRNA modifications in the context of eumetazoan development. </p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12977680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UBA5 deficiency disrupts mitochondrial autophagy via the PINK1-parkin pathway and impairs myoblast proliferation.","authors":"Haoran Shi, YaFei Cai, Yang Liu","doi":"10.1186/s40659-026-00676-z","DOIUrl":"10.1186/s40659-026-00676-z","url":null,"abstract":"<p><p>Maintaining a healthy and dynamic mitochondrial network is essential for development and for cellular adaptation to physiological and stress conditions. UFMylation is an emerging post-translational modification, yet its involvement in mitochondrial quality control has remained largely unexplored. Here, we establish a previously unrecognized functional link between the UFMylation machinery and mitochondrial homeostasis by identifying the E1-like activating enzyme UBA5 as a key regulator of mitochondrial quality control. We show that UBA5 loss disrupts mitochondrial homeostasis, leading to persistent accumulation of damaged mitochondria and increased ROS accumulation, which in turn triggers p53 activation and DNA damage responses, enforces p21-associated G2/M arrest, and promotes early apoptosis. Mechanistically, although the PINK1–Parkin damage response is engaged, mitophagy execution is inefficient in UBA5-deficient cells, resulting in impaired clearance of dysfunctional mitochondria and exacerbated oxidative stress. Collectively, our findings uncover a previously unreported UFMylation–mitophagy axis and expand current understanding of how UBA5 governs mitochondrial homeostasis and cell fate decisions.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12973624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting endoplasmic reticulum stress in diabetic retinopathy: mechanistic insights and emerging therapies.","authors":"Junting Weng, Rongjie Guo, Danjuan Liu, Shanjiao Huang, Shuoyun Weng","doi":"10.1186/s40659-026-00675-0","DOIUrl":"10.1186/s40659-026-00675-0","url":null,"abstract":"<p><strong>Purpose: </strong>To summarize the role of endoplasmic reticulum stress (ERS) in the pathogenesis of diabetic retinopathy (DR) and evaluate potential ERS-targeted interventions.</p><p><strong>Methods: </strong>This review analyzes recent preclinical and clinical studies focusing on the molecular mechanisms of ERS and its impact on retinal inflammation, oxidative stress, and angiogenesis in DR.</p><p><strong>Results: </strong>ERS, triggered by hyperglycemia-induced oxidative stress and glucotoxicity, activates the unfolded protein response (UPR) via inositol-requiring enzyme 1 (IRE1), PKR-like endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6) pathways. While initially protective, prolonged ERS leads to apoptosis, chronic inflammation, and neovascularization. Key downstream mediators include C/EBP homologous protein (CHOP), X-box binding protein 1 (XBP1), and activating transcription factor 4 (ATF4). ERS inhibitors such as 4-phenylbutyric acid and tauroursodeoxycholic acid, along with selective modulators of UPR signaling, have shown neuroprotective and anti-inflammatory effects in DR models. Combination therapies integrating antioxidants and anti-inflammatory agents demonstrate synergistic efficacy. However, clinical translation remains limited by delivery barriers and incomplete understanding of UPR-specific actions in the human retina.</p><p><strong>Conclusion: </strong>Targeting ERS presents a promising therapeutic strategy for DR, with the potential to preserve vision and improve outcomes for diabetic patients. Future research should focus on elucidating the precise molecular pathways and developing targeted, personalized ERS-modulating therapies.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"59 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12924270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146257301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vascular smooth muscle cell RNA-binding protein U2AF2 induces copper death by regulating C1qbp expression, delaying development of atherosclerosise.","authors":"Yang Yang, Hongxu Chen, Qijun Yu, Qihui Chen, Xinyue Zhou, Shanshan Zhou, Tingjiao Liu, Jinghan Lin","doi":"10.1186/s40659-026-00672-3","DOIUrl":"10.1186/s40659-026-00672-3","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis (AS) is the main pathological basis of atherosclerosis-related cardiovascular and cerebrovascular diseases. The phenotypic conversion and death mechanisms of vascular smooth muscle cells (VSMCs) are crucial during its development. This study reveals the molecular mechanisms of the C1qbp-DLAT axis and the U2AF2 (U2 Small Nuclear RNA Auxiliary Factor 2)-NEAT1 network in regulating cuproptosis in AS.</p><p><strong>Methods: </strong>In this study, an ApoE^-/- mouse model was constructed by high-fat diet (HFD) induction. Cell culture, molecular biology, immunology and histology methods were employed to explore the role of the U2AF2-C1qbp-copper death regulatory axis in the development of AS. Techniques such as qRT-PCR, Western blot, immunoprecipitation, RNA pull-down and RIP were used to detect the expression of related genes and proteins and analyze their functions.</p><p><strong>Results: </strong>The study revealed elevated copper ion levels and dysregulated cuproptosis-related genes in an AS model. U2AF2 stabilized C1qbp mRNA, enhancing C1qbp protein expression, which promoted DLAT oligomerization to regulate cuproptosis. LncRNA NEAT1 facilitated this process by scaffolding U2AF2-C1qbp mRNA interaction. Targeted inhibition of U2AF2 significantly improved AS pathological characteristics, reduced lipid deposition, collagen deposition and macrophage infiltration within the plaque, increased smooth muscle cell content and lowered serum levels of total cholesterol (TC), total triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C).</p><p><strong>Conclusion: </strong>This study revealed the role of the U2AF2-C1qbp-copper death regulatory axis in the development of AS, providing new targets and a theoretical basis for the treatment of AS. Targeted inhibition of U2AF2 may become an effective strategy to delay progression of AS.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"59 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12924209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146257296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lifelong cGAS deficiency leads to altered lipid storage and cholesterol homeostasis.","authors":"Daniela Carrillanca, Ian Riquelme, Matías Mansilla-Jaramillo, Camila Sánchez-Pérez, Andrea Monterroza, Natalia Lepio, Fabián Rojas, Gonzalo I Cancino, Paola Murgas","doi":"10.1186/s40659-026-00669-y","DOIUrl":"10.1186/s40659-026-00669-y","url":null,"abstract":"<p><strong>Background: </strong>The complex interaction between the immune system and metabolic homeostasis is becoming recognized, as immune sensors affect key metabolic tissues, including the liver and adipose tissue. The cGAS-cGAMP-STING pathway, previously recognized as a cytosolic DNA-sensing pathway, is currently associated with lipid metabolism in addition to its inflammatory function. Although STING is acknowledged for its connection to cholesterol, the metabolic functions of its upstream component molecules-the DNA sensor cGAS and the resulting product cGAMP-are largely unexplored. We propose that cGAS and cGAMP serve as crucial, previously unidentified regulators of systemic lipid homeostasis throughout the lifetime.</p><p><strong>Results: </strong>We investigated the long-term metabolic consequences of intrinsic cGAS deficiency, leading to the absence of cGAMP, in male mice fed on a standard chow diet. cGAS knockout (cGASKO) mice demonstrated a consistent increase in body weight across their lifespan, primarily attributed to adipocyte hypertrophy and increased adipose tissue mass. Increased weight correlated with elevated adiposity. This condition was associated with reduced weight-bearing strength, despite unchanged general locomotor activity and food intake during young age. Liver histology revealed modest cellular infiltration and absent steatosis, suggesting potential low-grade inflammation. Circulating triglyceride and glucose levels exhibited transient, age-dependent variations-decreased glucose and increased triglycerides in young age, which stabilized in adult and old ages, reflecting a possible compensatory metabolic adaptation with time. Conversely, total cholesterol levels were consistently and significantly elevated across all age groups, underscoring the importance of the cGAS-cGAMP axis in cholesterol homeostasis throughout life.</p><p><strong>Conclusions: </strong>Our study identified the cGAS-cGAMP axis as an interesting regulator of cholesterol homeostasis and fat accumulation in aging, independent of STING activation. The persistent deficiency of cGAS and cGAMP leads to lifelong hypercholesterolemia and adipose hypertrophy. This research highlights an unexpected metabolic function of the cGAS-cGAMP pathway and indicates the necessity of evaluating this axis in relation to physiological aging and metabolic disorders.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":"12"},"PeriodicalIF":5.4,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12918002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146059880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ameliorative effect of pomegranate peel extract nanoparticles and ovarian stem cells-derived exosomes on cyclophosphamide-induced premature ovarian insufficiency.","authors":"Hamdy Y Ismail, Mariam F Farid, Nora A Shaker, Tahsin Shoala, Adel F Tohamy, Marwa A Ibrahim, Hamdy Rizk, Y R Wally","doi":"10.1186/s40659-025-00664-9","DOIUrl":"10.1186/s40659-025-00664-9","url":null,"abstract":"<p><strong>Background: </strong>Premature ovarian insufficiency (POI) is a fertility disorder impacting women under 40, characterized by an early deterioration of ovarian function, and is one of the major side effects caused by chemotherapy. Cyclophosphamide is a powerful chemotherapeutic agent used in various cancers; however, it inflicts substantial harm on other tissues, particularly the gonads, leading to temporary or permanent infertility.</p><p><strong>Materials and methods: </strong>Forty female albino rats (Rattus norvegicus) were divided into four groups. Group I (control group) received normal saline, then premature ovarian insufficiency was induced in the remaining groups by intraperitoneal injections of cyclophosphamide (CLP). After that, Group II received no treatment. Group III was administered a daily oral dose of pomegranate (Punica granatum) nanoparticles for one month. Group IV received a daily oral dose of pomegranates, as did group III, plus ovarian stem cell-derived exosomes via intraperitoneal injection twice weekly for one month. Rats were euthanized 30 days post-POI induction; blood was then collected to evaluate hormone levels, and sections of the ovaries were collected for histopathological analysis. Frozen sections were procured for gene expression and oxidative stress studies.</p><p><strong>Results: </strong>The hormonal assessment of groups indicated a notable reduction in estrogen (E2) level and an elevation of follicle-stimulating hormone (FSH) in group II compared to the control and treated groups. Additionally, the ovaries of group II exhibited pronounced degeneration of ovarian follicles, accompanied by the desquamation of granulosa cells. Gene expression study indicated a downregulation of FSHR, CYP19A1, and AMH in the same group. Rats in both groups III and IV exhibited an increased number of follicles, improved ovarian shape, a considerable elevation in blood E2, a marked decrease in serum FSH levels, and an up-regulation of the three examined genes.</p><p><strong>Aim of work: </strong>The study aimed to assess the therapeutic efficacy of pomegranate (Punica granatum) peel extract nanoparticles alone and their synergistic effect with ovarian stem cell exosomes in reversing premature ovarian insufficiency (POI) caused by cyclophosphamide.</p><p><strong>Conclusion: </strong>Treatment with (Punica granatum) nanoparticles and exosomes partially enhanced the structure and function of the ovaries, thereby alleviating the adverse effects of Cyclophosphamide.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":"11"},"PeriodicalIF":5.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12903222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146009000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rewiring brain structural and functional disconnection with acupuncture in rat model of vascular cognitive impairment and dementia.","authors":"Lu Wang, Ji-Ping Zhao, Yan Cao, Si-Ming Ma, Jing-Wen Yang, Xin-Tong Su, Jin Huang, Qing-Yong Wang, Cun-Zhi Liu","doi":"10.1186/s40659-026-00670-5","DOIUrl":"10.1186/s40659-026-00670-5","url":null,"abstract":"<p><p>BACKGROUND: Connectional “diaschisis” theory indicates that the remote functional network disconnection resulting from focal white matter damage contributes to the cognitive dysfunction in vascular cognitive impairment and dementia (VCID). Acupuncture has been reported to attenuate white matter lesions and improve cognitive dysfunction of VCID individuals. However, whether these benefits are associated with the connectional diaschisis remains unclear. METHODS: Here, 12-time acupuncture treatment was administered to the rat model of VCID. After behavioral tests, functional and diffusion magnetic resonance imaging were performed to analyze the connectivity of brain networks and white matter integrity. Pathological changes in myelin loss, axon injury, and glial activation were also observed. To clarify the interrelation of function and structure, correlation and mediation analyses were conducted. RESULTS: Acupuncture ameliorated spatial working memory loss, reconnected the disruption of the default mode network, and prevented myelin and axon in the corpus callosum from the inflammatory attack. The association between restored corpus callosum integrity and spatial working memory was partially mediated by the increased functional connectivity of the anterior cingulate cortex. CONCLUSIONS: These evidence suggest that rewiring the corpus callosum-anterior cingulate cortex axis may be an integrated mechanism for the acupuncture effects on brain structure and function in VCID. </p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":"10"},"PeriodicalIF":5.4,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12903555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of sheep follicular fluid-derived exosomes and miR-148a on theca cell function in vitro.","authors":"Kai Liu, Runqing Chi, Runan Zhang, Qing Liu, Feng Xing, Yufang Liu, Mingxing Chu","doi":"10.1186/s40659-026-00668-z","DOIUrl":"10.1186/s40659-026-00668-z","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Exosomes facilitate intercellular communication by transporting proteins, nucleic acids, and other biomolecules, impacting recipient cell functions. In follicular development, exosomes from follicular fluid, secreted by granulosa cells, oocytes, and theca cells (TCs), are essential for follicle health. TCs are key in this process, influencing both development and hormonal output. However, the impact of sheep follicular fluid exosomes on TCs proliferation and the roles of the miRNAs they carry remain unclear. This study aims to investigate these effects, examining how exosomes and their miRNAs influence TCs development and hormone secretion through high-throughput sequencing.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this study, exosomes were isolated from sheep follicular fluid by ultracentrifugation, and their integrity was confirmed by determining the particle size distribution by nanoparticle tracking analysis (NTA) and detecting marker proteins such as CD63 and TSG101 by Western blot. Subsequently, an in vitro isolation and culture system for sheep theca cells (TCs) was established, and the cells were treated with 200 µg/mL of exosomes. The functional effects of exosomes were assessed by EdU proliferation assay and ELISA for steroid hormone secretion. The exosome small RNAs were extracted and sequenced, and the 20 miRNAs with the highest expression abundance were screened, and the target genes were predicted using TargetScan8.0 and miRDB, and the predicted genes were analysed by GO and KEGG enrichment. For miR-148a, its mimic and inhibitor were synthesised and transfected into TCs to verify its effects on cell proliferation and hormone secretion; the targeting relationship between miR-148a and transforming growth factor β2 (TGFβ2) was verified by combining with a dual luciferase reporter system, and TGFβ2 was further knocked down by siRNA to evaluate its role in the proliferation of TCs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The results showed that exosomes with a particle size distribution of 30-150 nm were successfully obtained by ultracentrifugation, which expressed CD63 and TSG101 with good integrity. Screening of exosome concentration showed that 200 µg/mL of exosomes significantly increased the proliferation rate and the secretion level of steroid hormones in TCs. Small RNA sequencing results showed that 130 miRNAs were identified, and the top 20 high-abundance miRNAs predicted 37,343 target genes. GO and KEGG analyses showed that these target genes were significantly enriched in follicle development-related signalling pathways, such as PI3K-AKT, MAPK, Rap1 and Ras. Functional experiments demonstrated that miR-148a mimics could significantly promote TCs proliferation, but had no significant effect on steroid hormone secretion. Dual luciferase and siRNA experiments showed that miR-148a directly targeted the 3'UTR of TGFβ2. Knock-down of TGFβ2 by transfecting its siRNA significantly enhances the proliferation rate of TC","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":"9"},"PeriodicalIF":5.4,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12888617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}