Journal of Molecular Histology最新文献

{"title":"17β-estradiol facilitates the proliferation, migration, and collagen production in uterosacral ligament fibroblasts from patients with pelvic organ prolapse by activating HOXA13/TIMP1 axis","authors":"Ying Xiong,&nbsp;Yan Li,&nbsp;Chongdong Liu","doi":"10.1007/s10735-025-10558-5","DOIUrl":"10.1007/s10735-025-10558-5","url":null,"abstract":"<div>\u0000 \u0000 <p>Local estrogen therapy is clinically employed for pelvic organ prolapse (POP) management, demonstrating efficacy in promoting collagen synthesis and maintaining pelvic connective tissue integrity. This study aimed to investigate the roles and mechanisms of estrogen 17β-estradiol (E2) in regulating proliferation, migration, and collagen production of human uterosacral ligament fibroblasts (hUSLFs) from POP patients. Primary hUSLFs from POP patients and controls were isolated and treated with 10^− 7, 10^− 8, 10^− 9 M E2, respectively. Cell proliferation, migration, apoptosis, collagen I/III levels, and matrix metalloproteinase 2 (MMP2)/MMP9 expression were examined. Homeobox A13 (HOXA13) levels were measured in clinical uterosacral ligament (USL) tissues and E2-treated hUSLFs. Gain- and loss-of-function experiments were conducted to investigate the role of HOXA13 in hUSLFs. Chromatin immunoprecipitation (ChIP) and luciferase assays verified HOXA13-mediated transcription regulation of tissue inhibitor of metalloproteinase 1 (TIMP1) in hUSLFs. Rescue experiments was conducted to investigate the roles of E2/HOXA13/TIMP1 axis in hUSLF functions. E2 remarkably promoted proliferation, migration, and collagen production while inhibiting apoptosis and MMP2/MMP9 expression in hUSLFs. The concentration at 10^− 8 M showed the optimal efficacy. HOXA13 was downregulated in USL tissues of POP patients compared with controls. HOXA13 overexpression promoted proliferation, migration, and collagen production while reducing apoptosis in hUSLFs. Whereas HOXA13 knockdown showed the opposite results. E2 treatment upregulated HOXA13 expression in hUSLFs. HOXA13 knockdown abrogated E2-mediated functional enhancement of hUSLFs. Moreover, HOXA13 transcriptionally activated TIMP1 expression. TIMP1 knockdown reversed the positive effects of HOXA13 on the proliferation, migration, and collagen production of hUSLFs. E2 facilitates proliferation, migration, and collagen production of hUSLFs from POP patients through upregulating the HOXA13/TIMP1 axis. Our findings provide important mechanistic insights into the protective effects of estrogen on POP fibroblasts and identify HOXA13 as a potential therapeutic target worthy of further investigation.</p>\u0000 </div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Daidzein alleviates renal damage in streptozotocin induced diabetes in Sprague Dawley rats by targeting NOX-4 and RAC-1","authors":"Ankit P. Laddha,&nbsp;Yogesh A. Kulkarni","doi":"10.1007/s10735-025-10430-6","DOIUrl":"10.1007/s10735-025-10430-6","url":null,"abstract":"<div>\u0000 \u0000 <p>Diabetic nephropathy is a prevalent and serious complication in patients with diabetes, resulting from long-term elevated blood sugar levels, which cause significant kidney damage. The underlying mechanisms of oxidative stress and inflammation are crucial in both the onset and progression of this condition. Daidzein, a naturally occurring isoflavone found in soybeans, has gained attention due to its antioxidant and anti-inflammatory effects. Nevertheless, its role in diabetic nephropathy remains to be fully understood. This research was conducted to explore the renoprotective potential of daidzein in an experimental diabetic nephropathy model. Diabetes was induced in male Sprague Dawley rats using Streptozotocin (STZ)., Daidzein was administred to the diabetic rats at doses of 25, 50, and 100 mg/kg, alongside lisinopril at 10 mg/kg, orally for four weeks after four weeks of STZ injection. The 100 mg/kg dose of daidzein notably improved biochemical markers, enhanced urine creatinine and urea levels, and promoted better kidney function. Additionally, daidzein helped preserve antioxidant enzymes in the kidney tissue and reduced the expression of NOX-4 and RAC-1, as demonstrated by Western blot analysis. Histopathological studies further indicated that daidzein treatment alleviated kidney tissue damage. Overall, these findings suggest that daidzein may slow the progression of diabetic nephropathy, potentially by inhibiting NOX-4 and RAC-1, highlighting its promise as a therapeutic agent in this condition.</p>\u0000 </div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144814434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asprosin protects against ischemia/reperfusion-induced kidney injury in mice","authors":"Tuba Keskin,&nbsp;Engin Korkmaz,&nbsp;Azibe Yıldız,&nbsp;Çiğdem Tekin,&nbsp;Ali Beytur,&nbsp;Suat Tekin","doi":"10.1007/s10735-025-10555-8","DOIUrl":"10.1007/s10735-025-10555-8","url":null,"abstract":"<div><p>Ischemia–reperfusion (IR)-induced acute kidney injury (AKI) is a complex pathophysiological process involving inflammation, oxidative stress, and apoptosis. Asprosin (ASP), a fasting-induced glucogenic hormone, has been shown to influence oxidative and apoptotic pathways in various tissues. This study investigated the potential renoprotective effects of ASP in a murine model of IR-induced AKI. Thirty-two male <i>Balb/c</i> mice were randomly assigned to four groups (n = 8): Control, IR, ASP1 (1 µg/kg ASP), and ASP10 (10 µg/kg ASP). While the control group received no treatment. Vehicle and ASP (1 or 10 µg/kg) were administered intravenously five minutes before ischemia to the IR and ASP-treated groups, respectively. Renal ischemia was induced for 22 min, followed by a 24-h reperfusion period. Renal function markers, inflammatory cytokines, oxidative stress parameters, and caspase-3 expression were evaluated. Histopathological alterations were assessed using hematoxylin–eosin staining. IR significantly increased BUN, creatinine, IL-1β, TNF-α, MDA levels, and caspase-3 expression, while reducing antioxidant enzymes (SOD, CAT). ASP pretreatment effectively reversed these changes (<i>p</i> &lt; 0.05), as reflected by improved renal function, reduced inflammation and oxidative stress, and decreased apoptotic activity. These functional and molecular improvements were also supported by histological evidence showing reduced kidney damage following ASP treatment. Collectively, the findings suggest that ASP protects against IR-induced AKI by alleviating inflammation, oxidative stress, and apoptosis.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144814433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coptisine alleviates high glucose-induced HUVEC dysfunction in vitro and inhibits gestational diabetes mellitus in vivo","authors":"Lan Wang,&nbsp;Wei Xiong,&nbsp;Yunyun Jiang","doi":"10.1007/s10735-025-10542-z","DOIUrl":"10.1007/s10735-025-10542-z","url":null,"abstract":"<div><p>The dysfunction of vascular endothelial cells (VECs) is an important cause of diabetes-related cardiovascular diseases. Coptisine is a bioactive component of <i>Rhizoma coptidis</i> with anti-diabetes property. The aim of this present study was to clarify the role and possible mechanism of coptisine underlying VEC dysfunction during gestational diabetes mellitus (GDM). Human umbilical vein endothelial cells (HUVECs) were treated with coptisine and/or high glucose (HG) medium. A GDM rat model was established by high-fat diet feeding and streptozotocin injection. Cell viability, migration, and angiogenesis were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, wound healing assay, Transwell assay, and tube formation assay. The levels of angiogenesis-related proteins and the key markers in the Adenosine monophosphateactivated protein kinase (AMPK)/nuclear factor-erythroid 2-related factor 2 (NRF2) signaling pathway were tested by western blot analysis. The pathological changes of placental tissues were observed by HE staining. We found that the cell viability of HUVECs was repressed in HG conditions in a dose-dependent manner, and 25 mM HG reduced the HUVEC viability in a time-dependent manner. Coptisine (5 to 5o μM) did not cause cytotoxicity to HUVECs. In addition, HG-induced the decrease in cell viability and migration of HUVECs were rescued by coptisine in a dose-dependent manner. Coptisine restored the angiogenetic ability of HG-induced HUVECs by upregulating the protein expression of fibroblast growth factor 2, vascular endothelial-derived growth factor, and Angiotensin 1. Moreover, coptisine treatment re-activated the AMPK/NRF2 pathway in HG-stimulated HUVECs. Importantly, inhibition of AMPK/NRF2 signaling reverses the effect of coptisine on cell viability, migration, and angiogenesis of HUVECs. The in vivo study demonstrated that coptisine suppresses hyperglycemia and placenta injury in GDM rats. Coptisine protected HUVECs from hyperglycemic insult, suggesting the potential of coptisine which might be used as a therapeutic agent for VEC dysfunction in GDM.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"hsa_circ_0099682 exacerbates the development of diabetic retinopathy by promoting pathological neoangiogenesis via the miR-125b-5p/HNRNPU axis","authors":"Ge Yang,&nbsp;Mei Xu,&nbsp;HongWei Zhang,&nbsp;Bo Zhang,&nbsp;YuLian Xie,&nbsp;YueHua Chen,&nbsp;Qin Hu,&nbsp;ZiYu Luo,&nbsp;Jie Lin,&nbsp;ZhengWen Qin","doi":"10.1007/s10735-025-10535-y","DOIUrl":"10.1007/s10735-025-10535-y","url":null,"abstract":"<div><h3>Objective</h3><p>Diabetic retinopathy (DR) is a leading cause of vision loss, driven by hyperglycemia-induced human retinal microvascular endothelial cell (HRMEC) dysfunction, mitochondrial impairment, oxidative stress, inflammation, and aberrant angiogenesis. Circular RNAs (circRNAs) have emerged as critical regulators in various ocular pathologies, yet their contributions to DR remain unclear. This study identified and characterized hsa_circ_0099682, derived from the alpha motif domain-containing protein 1B (ANKS1B) gene, and investigated its role and molecular mechanism in high glucose (HG)-induced HRMEC injury.</p><h3>Methods</h3><p>Hsa_circ_0099682 was validated as a genuine circRNA through bioinformatic analyses (circPrism, circBank), RNase R digestion, actinomycin D treatment, and PCR with divergent/convergent primers. HG-exposed HRMECs were transfected with siRNAs targeting hsa_circ_0099682, miR-125b-5p inhibitors, or heterogeneous nuclear ribonucleoprotein U (HNRNPU) overexpression constructs. Mitochondrial function was assessed by reactive oxygen species (ROS) measurement and JC-1 staining for mitochondrial membrane potential. Inflammatory and oxidative stress markers (interleukin [IL]-6, IL-1β, superoxide dismutase [SOD], and malondialdehyde [MDA]) were quantified by enzyme-linked immunosorbent assay (ELISA) and commercial kits. Apoptosis and tube formation assays evaluated cell survival and angiogenic potential. Luciferase reporter and RNA immunoprecipitation assays confirmed ceRNA interactions. streptozotocin-induced DR rats were treated with AAV-shRNA to silence hsa_circ_0099682. Hematoxylin and eosin staining, immunofluorescence, ELISA, and Western blot analyses were performed to assess retinal structure, inflammation, oxidative stress, and angiogenic markers.</p><h3>Results</h3><p>Hsa_circ_0099682 showed stable circular configuration and abundant cytoplasmic localization. In HG-stressed HRMECs, hsa_circ_0099682 knockdown reduced ROS accumulation, preserved mitochondrial membrane potential, diminished IL-6 and IL-1β secretion, enhanced antioxidant capacity, lowered apoptosis, and suppressed tube-forming ability. Mechanistically, hsa_circ_0099682 functioned as a sponge for miR-125b-5p, thereby relieving miR-125b-5p-mediated repression of HNRNPU. Inhibiting miR-125b-5p or overexpressing HNRNPU reversed the protective effects of hsa_circ_0099682 knockdown. In DR rats, silencing hsa_circ_0099682 improved retinal structural integrity, mitigated inflammation and oxidative stress, and restored balance in angiogenesis-related protein expression.</p><h3>Conclusion</h3><p>Hsa_circ_0099682 accelerates DR progression by suppressing miR-125b-5p, enhancing HNRNPU expression, and inducing mitochondrial dysfunction, inflammation, and irregular neoangiogenesis.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effect of cartilage oligomeric matrix protein (COMP) on osteoarthritis-like chondrocytes based on the nuclear factor kappa B (NF-κB) pathway","authors":"Wei Weng,&nbsp;Rong Wu,&nbsp;Zhenguo Sun,&nbsp;Haidong Li,&nbsp;Yuxin Shen,&nbsp;Heng Li,&nbsp;Jikang Min","doi":"10.1007/s10735-025-10538-9","DOIUrl":"10.1007/s10735-025-10538-9","url":null,"abstract":"<div>\u0000 \u0000 <p>To explore the potential regulatory mechanism of the nuclear factor kappa B (NF-κB) pathway and cartilage oligomeric matrix protein (COMP) in the pathogenesis of osteoarthritis (OA), and to provide possible targets for the treatment and prevention of OA. Mouse bone marrow mesenchymal stem cells (BMSCs) were isolated and cultured in vitro. The third-generation cells were taken to identify the expression of surface markers CD90, CD29, CD34, and CD11b by flow cytometry. The BMSCs with higher purity were selected. Dexamethasone was used to induce cartilage differentiation, and the surface characteristics of osteoblasts were detected by alkaline phosphatase staining and alizarin red staining. Interleukin-1β (IL-1β) was used to induce chondrocytes to establish an in vitro OA-like cell model. The activation of the NF-κB pathway was detected by enzyme-linked immunosorbent assay (ELISA). The NF-κB pathway was activated by RNAi interference, and mRNA levels of inflammatory factors interleukin-6 (IL-6),cyclooxygenase 2 (COX-2), matrix metalloproteinases-3(MMP-3) and MMP-9 regulated by NF-κB pathway were detected by real-timepolymerase chain reaction (RT-PCR).The effect of activation of the NF-κB pathway on the expression of the <i>COMP</i> gene was detected by RT-PCR and chromatin immunoprecipitation (ChIP) analysis. RT-PCR and ELISA were used to detect the effect of exogenously added COMP on the apoptosis pathway mediated by the NF-κB pathway and the expression of inflammatory factors. Isolated and purified mouse BMSCs can undergo chondrogenic differentiation. During the induction of IL-1β, the contents of IL-6 and COX-2 in chondrocytes were significantly increased, and the activity of chondrocytes was significantly decreased. The mRNA levels of IL-6 and COX-2 and MMP-3 and MMP-9 in OA-like chondrocytes were significantly increased, and this effect was partially suppressed following NF-κB pathway inhibition. Transient activation of the NF-κB pathway down-regulates the expression of the <i>COMP</i> gene mRNA levels. Exogenous COMP has a protective effect on OA-like chondrocytes, and its mechanism may be to reduce inflammation and apoptosis by regulating downstream signaling events of NF-κB activation. These findings extend our current understanding of the pathological mechanism of OA and provide an important target for its treatment and prevention.</p>\u0000 </div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of METTL14 regulates HBV-HCC malignant progression by mediating m6A modification of FOXP3 and thus transcriptional activation of ALDOB","authors":"Yu Fang,&nbsp;Xiaobin Shi,&nbsp;Jian Ge","doi":"10.1007/s10735-025-10551-y","DOIUrl":"10.1007/s10735-025-10551-y","url":null,"abstract":"&lt;div&gt;&lt;p&gt;Hepatocellular carcinoma (HCC) is a severe form of liver malignancy characterized by high incidence and mortality rates, complex etiology, and significant variability in prognosis. Forkhead box P3 (FOXP3), an essential transcription factor, plays a pivotal role in tumorigenesis, progression, and prognosis. This study aims to explore the function and underlying mechanism of FOXP3 in the malignant progression of HCC. The expression level of FOXP3 was predicted using the TNMplot database. The Kaplan–Meier Plotter for Survival Analysis (Kaplan–Meier Plotter) website was utilized to analyze the correlation between gene expression and prognosis. Gene expression levels were determined by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. The viability, proliferation, apoptosis, and invasion capacities of the cells were detected by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 5-ethynyl-2’-deoxyuridine (EdU) staining, flow cytometry, and transwell assay, respectively. The qPCR assay was used to detect the replication of hepatitis B virus (HBV). The enzyme-linked immunosorbent assay (ELISA) was utilized to detect hepatitis B surface antigen (HBsAg). The glucose consumption and lactate production of the cells were measured by special kits. The presence of m6A modification on FOXP3 was jointly predicted using the RNA Modification Base (RMbase) and the sequence-based RNA adenosine methylation site predictor (SRAMP) databases. Relevant predictions were conducted using the Gene Expression Profiling Interactive Analysis (GEPIA) database, the Encyclopedia of RNA Interactomes (ENCORI) database, and The Cancer Genome Atlas (TCGA) database to explore the expression correlation between genes. The N6-methyladenosine (m6A) methylation modification level of the FOXP3 was determined using the methylated RNA immunoprecipitation (MeRIP) assay. RNA immunoprecipitation (RIP) was used to detect the interaction of methyltransferase-like 14 (METTL14) or insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) with FOXP3. After cells were treated with actinomycin D (Act D), mRNA stability was measured by RT-qPCR. The dual luciferase reporter assay and chromatin immunoprecipitation (ChIP) were used to detect the interaction between FOXP3 and aldolase B (ALDOB). Mouse xenograft assays were used for in vivo validation. Gene expression in HCC tumor tissue was measured by immunohistochemistry (IHC) assay. FOXP3 was lowly expressed in HBV-related HCC and was associated with the poor prognosis of patients. Overexpression of FOXP3 inhibited the proliferation, metastasis, and glycolysis of HBV-related HCC cells. METTL14 stabilized FOXP3 mRNA through the m6A-IGF2BP1-dependent manner, and METTL14 inhibited the malignant behaviors of HBV-related HCC cells by targeting FOXP3. As a transcription factor, FOXP3 triggered the activation of transcription of ALDOB, thereby inhibiting the malignant behavio","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histological investigation of pseudobranch during reproductive migration of Van Fish (Alburnus tarichi, Güldenstädt, 1814)","authors":"Zehra Alkan Çekiç","doi":"10.1007/s10735-025-10552-x","DOIUrl":"10.1007/s10735-025-10552-x","url":null,"abstract":"<div><p>Lake Van is the largest lake in Turkey and one of the few soda lakes in the world. The Lake Van fish (<i>Alburnus tarichi</i>), an endemic carp species, has fully adapted to the soda water in this lake. As an anadromous fish, it migrates from the lake to Freshwater (FW) every year between April-July. During migration, the fish activate osmoregulatory mechanisms to maintain water and salt balance. This study examined the pseudobranch tissues of Lake Van fish from both Lake Van and Karasu Stream. Morphological analysis showed that the pseudobranch, located on both opercular valves, was covered with transparent connective tissue. Histologically, the tissue contained different cell types, including pavement, pillar cells, and erythrocytes. Higher mucous cell density were found in the stream environment, while immunohistochemical (IHC) analysis showed more Na+/K+-ATPase-positive cells in the stream fish. These results suggest that the pseudobranch plays a key role in osmoregulation, helping the fish adapt during migration.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin A supplementation restores neuroanatomical integrity and behavior in a valproic acid-induced autism model","authors":"Fatima Ezzahra Kacimi,&nbsp;Hicham Esselmani,&nbsp;Soumia Ed-day,&nbsp;Habiba Nechchadi,&nbsp;Mohamed Merzouki,&nbsp;Mhamed Ramchoun,&nbsp;Fatima-Zahra Azzaoui,&nbsp;Samira Boulbaroud","doi":"10.1007/s10735-025-10553-w","DOIUrl":"10.1007/s10735-025-10553-w","url":null,"abstract":"<div><p>Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by social deficits, repetitive behaviors, and cognitive impairments. Evidence suggests that Vitamin A deficiency (VAD) may exacerbate ASD-related abnormalities, while Vitamin A supplementation (VAS) may offer neuroprotection. This study investigates the effects of Vitamin A modulation on neuronal integrity, cognitive function, and social behavior in a valproic acid (VPA)-induced ASD rat model, focusing on histological changes, behavioral outcomes, and serum Vitamin A levels. Pregnant Wistar rats received VPA (500 mg/kg) on gestational day 12.5. Offspring were divided into Control, VPA, VAD, VPA + VAD, and VPA + VAS (2000 IU/kg diet) groups. Serum Vitamin A levels were quantified using spectrophotometry. Histopathological analysis of the hippocampus, cerebellum, and prefrontal cortex (PFC) assessed neuronal and glial cell densities. Behavioral tests included the Three-Chamber Social Interaction Test for sociability and the Novel Object Recognition Test for memory function. Serum analysis showed significantly lower Vitamin A levels in VAD and VPA + VAD groups, while VAS restored levels. Histological analysis revealed reduced neuronal density and increased glial activation in VPA, VAD, and VPA + VAD groups. The VPA + VAS group exhibited partial neuronal recovery. Behaviorally, VAS improved sociability and memory performance, correlating with neuronal preservation. These findings suggest that Vitamin A deficiency worsens ASD-related impairments, while supplementation restores neuronal integrity and cognitive function, highlighting its potential therapeutic role in ASD.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protocol for the purification and culture of primary retinal ganglion cells and development of common pathological models","authors":"Xiaoding Shui,&nbsp;Yan Wang,&nbsp;Yu Luo,&nbsp;Xiaoyu Liang,&nbsp;Tao Chen,&nbsp;Yanting Xia,&nbsp;Qiping Wei,&nbsp;Liang Liao","doi":"10.1007/s10735-025-10536-x","DOIUrl":"10.1007/s10735-025-10536-x","url":null,"abstract":"<div><p>To establish a standardized protocol for purifying and culturing primary RGC from postnatal KM mice and to optimize the establishment of three in vitro injury models that mimic hyperglycemia, oxidative stress, and H/R. Retinas from 15 postnatal KM mice (≤ 24 h old) were dissociated and purified via Thy1.2 monoclonal antibody-based immunopanning. RGC identity was confirmed by Brn3a (an RGC-specific marker) immunofluorescence, Tuj1 (a neuronal marker) immunostaining, flow cytometry, and trypan blue exclusion. Pathological models were constructed as follows: ①. Hyperglycemia: RGC were treated with 40–80 mM glucose for 24/48 h. ②. Oxidative stress: RGC were exposed to 80–320 μM H₂O₂ for 24 h. ③. H/R injury: Hypoxia (1% O₂, 4 h) followed by reoxygenation (21% O₂, 12 h), with/without AS-IV (50–200 μM) pretreatment. Purified RGC exhibited characteristic morphology and robust viability (93.33% ± 2.1%). Brn3a immunostaining confirmed the identity of the RGC (95.07% purity via flow cytometry). ① Hyperglycemia model: IC₅₀ values were 67.143 mM (24 h) and 58.406 mM (48 h) (<i>P</i> &lt; 0.05 vs. control).② In the oxidative stress model, the IC₅₀ H₂O₂ concentration was 255.262 μM (24 h, <i>P</i> &lt; 0.05), accompanied by dose-dependent increases in ROS levels and HO-1 mRNA upregulation (<i>P</i> &lt; 0.05). ③. H/R model: AS-IV (100 μM) maximally preserved RGC viability (80% survival, <i>P</i> &lt; 0.05 vs. the injury group), downregulating HIF-1α expression postreoxygenation. This study provides a reproducible protocol for high-purity RGC isolation and validates three pathophysiological models that recapitulate key drivers of optic neuropathies. These models offer a robust platform for mechanistic studies and neuroprotective drug screening.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}