Journal of Molecular Histology最新文献

{"title":"Therapeutic potential of Angelica sinensis derivatized carbon dots in ameliorating chemotherapy-induced anemia","authors":"Ruolan Kong,&nbsp;Yujiao Yuan,&nbsp;Jiaxing Liu,&nbsp;Kai Cheng,&nbsp;Yifan Zhang,&nbsp;Xiwen Zhang,&nbsp;Peng Zou,&nbsp;Yan Huang,&nbsp;Jinyu Ma,&nbsp;Chenxin He,&nbsp;Hui Kong,&nbsp;Yan Zhao,&nbsp;Huihua Qu","doi":"10.1007/s10735-025-10518-z","DOIUrl":"10.1007/s10735-025-10518-z","url":null,"abstract":"<div>\u0000 \u0000 <p>Aplastic anemia, a prevalent disorder of the hematopoietic system, may develop as a result of bone marrow suppression induced by chemotherapeutic agents. Given its iatrogenic nature, the identification of affordable and effective therapeutic interventions remains a clinical priority. <i>Angelica sinensis</i> Radix (ASR) has been widely utilized in traditional Chinese medicine for anemia management and is supported by extensive clinical application. The aim of the present study is to examine the physicochemical characteristics of <i>A. sinensis</i> Radix-derived carbon dots (ASR-CDs) and to evaluate their therapeutic effects on hematopoietic injury in murine models exposed to chemotherapeutic agents. ASR-CDs were synthesized via calcination of ASR. The resulting nanomaterials were characterized in terms of particle morphology and surface functional groups. A Cell Counting Kit-8 (CCK-8) assay was used to assess biocompatibility. A zebrafish anemia model was employed to compare the anti-anemic efficacy of ASR-CDs with that of other therapeutic agents. A murine model of hematopoietic injury was established using cyclophosphamide and busulfan to investigate the effects of ASR-CDs on hematopoietic function. ASR-CDs displayed a nanoscale particle size range (1.444–4.006 nm) and surface groups including amino, carboxyl, and hydroxyl functionalities. Cellular assays involving RAW264.7 cells indicated no cytotoxicity, indicating favorable biosafety. In the zebrafish anemia model, ASR-CDs demonstrated superior efficacy in alleviating anemia compared to other tested agents. In mice, ASR-CDs significantly diminished chemotherapy-induced reduction in body weight, immune organ indices (liver, spleen, thymus), and peripheral blood cell counts (white blood cells, red blood cells, and platelets). Furthermore, ASR-CDs modulated hematopoiesis-related serum factors, with higher dosages producing more pronounced regulatory effects. ASR-CDs exerted a beneficial effect on chemotherapy-induced anemia. These results support the therapeutic potential of herbal-derived carbon dots and highlight the applicability of nanomaterials in pharmaceutical development.</p>\u0000 </div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144914744","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":"LncRNA HOTAIR promotes cell proliferation and migration in papillary thyroid carcinoma cells by sponging miR-206/c-Met axis","authors":"Xifeng Du,&nbsp;Yufei Hao,&nbsp;Min Liu,&nbsp;Zhihui Hu,&nbsp;Tao Yang,&nbsp;Lizhen Lan","doi":"10.1007/s10735-025-10574-5","DOIUrl":"10.1007/s10735-025-10574-5","url":null,"abstract":"<div>\u0000 \u0000 <p>The long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR), a tumor suppressor associated with various human cancers, regulates multiple cellular processes. However, the role of HOTAIR in papillary thyroid carcinoma remains unclear. Therefore, the purpose of the present study was to investigate the effect of HOTAIR on the proliferation and migration of PTC cells, and to explore its possible mechanism. The initial step involves conducting an analysis in The Cancer Genome Atlas database of the HOTAIR expression level between PTC and normal tissue samples. Reverse transcription-quantitative PCR was conducted to detect HOTAIR and microRNA (miRNA, miR)-206 expression in each cell line. We assessed cell proliferation using the CCK-8 and MTT assays. We employed the wound-healing and transwell assays to evaluate cell migration. The HOTAIR/miR-206/c-Met targeting relations were verified through dual-luciferase reporter assay. We analyzed changes in protein expression downstream of the c-Met/AKT/mTOR pathway by Western blotting. Our results showed that HOTAIR was highly expressed in PTC cells. Silencing HOTAIR significantly inhibited the proliferation and migration of PTC cells. Conversely, miR-206 expression was downregulated in PTC cells. Importantly, overexpressing miR-206 significantly inhibited PTC cell proliferation and migration. In conclusion, HOTAIR acts as a sponge for miR-206, thereby alleviating its repression of c-Met and activating the AKT/mTOR signaling pathway in PTC cells.</p>\u0000 </div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144914641","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":"Cardioprotective effects of ghrelin and Wharton’s jelly-derived mesenchymal stem cells, alone and in combination, in doxorubicin-induced myocardial injury in rats","authors":"Amy F. Boushra,&nbsp;Christina Sabry Yacoub,&nbsp;Hamed Mohamed Osman,&nbsp;Amani M. El Amin Ali,&nbsp;Azza Mohamed Elamir,&nbsp;Asmaa Mohamed Elsayed,&nbsp;Sarah Mahmoud Gamal","doi":"10.1007/s10735-025-10567-4","DOIUrl":"10.1007/s10735-025-10567-4","url":null,"abstract":"<div>\u0000 \u0000 <p>Cardiovascular diseases represent one of the most serious health issues, accounting for worldwide morbidity and mortality. Doxorubicin (DOX) induces cardiotoxicity through the formation of free radicals. Stem cell therapy appears to be a promising alternative to existing treatments for myocardial injury, as it can produce growth factors and cytokines that are involved in wound healing. Besides its orexigenic properties, ghrelin was proven to have a cardiovascular protective effect. The present study was designed to compare the possible protective role of ghrelin to Wharton jelly-derived mesenchymal stem cells (WJ-MSCs) as well as their combined effect in doxorubicin-induced cardiotoxicity in rats. Forty adult male albino rats were divided into five groups: Group (I): normal control group, Group (II): DOX induced cardiotoxicity group, Group (III): ghrelin treated group, Group (IV): MSCs treated group and Group (V): ghrelin and MSCs (combined) treated group. Cardiac enzymes, oxidative stress markers, apoptotic markers in cardiac tissue and cardiac performance parameters using Langendorff apparatus and echocardiography, were assessed. At the end of the experiment, histopathological evaluation of the injured myocardium was conducted using hematoxylin and eosin (H&amp;E), Masson’s trichrome staining, and immunohistochemical analysis for nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Our results revealed a significant amelioration of the aforementioned parameters almost towards normal values in the three treatment groups. Histopathological examination and immunohistochemical assessment of Nrf2 &amp; HO-1 revealed improvement in the three treated groups, particularly those receiving stem cell therapy.</p>\u0000 </div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144914743","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":"Coenzyme Q10 may protect ovarian tissue against by the nearly century-old drug methotrexate caused gonadotoxicity: a biochemical, flow cytometric, and histopathological study","authors":"Zuleyha Erisgin,&nbsp;Hasan Serdar Mutlu,&nbsp;İsmail Turkoglu,&nbsp;Esma Cinar,&nbsp;M. Zuhal Barak,&nbsp;Ismail Aydin,&nbsp;Murat Usta,&nbsp;Yavuz Tekelioglu","doi":"10.1007/s10735-025-10566-5","DOIUrl":"10.1007/s10735-025-10566-5","url":null,"abstract":"<div><p>Methotrexate (MTX) is still a broad-spectrum drug that has been used for almost a century for leukemia, rheumatoid arthritis, ectopic pregnancy. This study investigates the protective effects of coenzyme Q10 (CoQ10) on MTX induced gonadotoxicity. Twenty-four female wistar albino rats were divided into four groups. Control group; 1 ml corn oil was applied by oral gavage (p.o.). CoQ10 group; 100 mg/kg CoQ10 (in 1 ml corn oil) was applied by p.o. for seven days. MTX group; 20 mg/kg MTX intraperitoneal (i.p.) was used one time on the first day of the experiment. MTX + CoQ10 group; 20 mg/kg MTX i.p. one time and 100 mg/kg CoQ10 (in 1 ml corn oil) was applied p.o. for seven days. At the end of the experiment, all animals were euthanized under anesthesia, and blood samples were taken from intracardiac. The both sides ovaries were taken out and were put in to neutral formalin. Biochemical analysis for serum anti-mullerian hormone (AMH), flow cytometry for apoptosis (Annexin V), and histopathologic analysis with follicle counting were performed in ovarian tissues. According to results of follicle counting, apoptosis, morphometric and AMH analysis; there was no statistically significant difference in terms of follicle numbers and ovarium diameter between all groups. However, apoptosis significantly increased in the MTX group and decreased in the MTX + CoQ10 group. AMH level was decreased in the MTX group and interestingly significantly increased in the only CoQ10 treatment group and. As a result, CoQ10 has protective effects in terms of apoptosis and AMH against MTX induced gonadotoxicity.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144914742","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":"Voacangine targeting of PI3K/Akt/ERK via the knockdown of inflammation in DEN-induced liver cancer: in vivo and in silico approach","authors":"Xi Chen,&nbsp;Periyannan Velu,&nbsp;Annamalai Vijayalakshmi,&nbsp;Haoyu Zhang","doi":"10.1007/s10735-025-10577-2","DOIUrl":"10.1007/s10735-025-10577-2","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) is a type of primary liver cancer characterized by inflammation and liver damage. It is a serious disease that progresses rapidly and is often diagnosed at an advanced stage. Voacangine (VCG), a well-known alkaloid, has been shown to possess anti-inflammatory and antitumor properties. This study investigated the effectiveness of VCG in counteracting diethylnitrosamine (DEN)-induced HCC by targeting the ERK/PI3K/Akt signaling pathways. Male Wistar albino rats were divided into four groups: a normal control group (NC) receiving PBS, a VCG-alone group (5 mg/kg body weight), a DEN-induced HCC model group (100 mg/kg in drinking water), and a DEN + VCG group (5 mg/kg body weight) for 22 weeks. Molecular docking studies, specifically XP and IFD using Schrodinger’s Glide Module, were performed and validated via in vivo and in silico experiments. The results revealed that VCG significantly reduced several indicators of HCC progression in DEN-treated rats, including body weight loss, increased liver weight, elevated hepatic marker enzymes, oxidative stress, inflammation, and architectural damage to hepatocytes. Furthermore, VCG increased the mRNA expression of proapoptotic genes such as Bcl-2-associated protein x (Bax), the tumor protein p53 (p53), caspase-9, and caspase-3 while decreasing antiapoptotic B-cell lymphoma 2 (Bcl-2) levels. Oral administration of VCG to rats intoxicated with DEN resulted in marked down-regulation of the hepatic PI3K, AKT, and ERK gene expressions. These findings suggest that VCG has the potential to prevent liver cancer. Its multitarget efficacy, particularly its ability to inhibit the PI3K/Akt/ERK signaling pathway, was demonstrated through both in vivo and in silico studies, supporting its use as a potential therapeutic agent for hepatic cancer.</p>\u0000 </div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144914639","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":"Gallic acid enhanced reproductive function by modulating oxidative stress mediators in gentamicin-treated rats","authors":"Reza Norouzirad,&nbsp;Nadia Shahinzadeh,&nbsp;Leila Jafaripour,&nbsp;Mohammad Mehdi Behvandi,&nbsp;Mahsa Tadayon Nejad,&nbsp;Susan Sabbagh","doi":"10.1007/s10735-025-10539-8","DOIUrl":"10.1007/s10735-025-10539-8","url":null,"abstract":"<div>\u0000 \u0000 <p>Gentamicin (GEN), commonly used to treat gram-negative bacterial infections, can cause testicular damage, maybe by increasing oxidative stress. Gallic acid (GA) a polyphenolic acid, has antioxidant, anti-bacterial, anti-viral, and anti-allergic activities. The study aimed to investigate the effects of GA on GEN-induced testicular toxicity. Thirty Wistar rats were randomly divided into five groups: Control, which received only normal saline, and GEN, which received 100 mg/kg/day of GEN intra-peritoneally for six days. The rats in groups 3, 4, and 5 received GA by gavage at 60, 90, and 120 mg/kg for 14 consecutive days and six intraperitoneal injections of 100 mg/kg/day of GEN from nine to fourteen days, respectively. After the last treatment, rats were sacrificed, and testicular weights, sperm parameters (viability, number, and motility of sperm), serum testosterone and gonadotropin hormones, tissue superoxide dismutase and malondialdehyde, and testicular histology were evaluated. Gentamicin reduced sperm count, viability, motility, and testicular-weight, as well as serum levels of testosterone, FSH, LH, and SOD. Testicular-weight in GEN + 60, 90, and 120 mg/kg GA groups had significantly increased compared to GEN group. All GA doses in the GEN + GA groups, increased FSH (except dose of 60), LH and testosterone (<i>p</i> &lt; 0.05). In the rats received 120 mg/kg GA, MDA decreased and SOD increased significantly (<i>p</i> &lt; 0.05). Histopathological findings showed that the administration of GA could significantly reduce the adverse effects of GEN on the structure of seminiferous tubules and the number of germ cells (<i>p</i> &lt; 0.05). Administration of GA adjunct with GEN might be beneficial in men who were under GEN therapy.</p>\u0000 </div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144914745","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":"YTHDF3-associated m6A regulation and cuproptosis-related gene expression in steroid-induced osteonecrosis of the femoral head","authors":"Yong Cui,&nbsp;Aikeremujiang Alken,&nbsp;Wu Wang,&nbsp;Tao Huang,&nbsp;Zhongwei Li","doi":"10.1007/s10735-025-10544-x","DOIUrl":"10.1007/s10735-025-10544-x","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aims to explore the role of N6-methyladenosine (m6A) RNA modification in regulating Cuproptosis in steroid-induced osteonecrosis of the femoral head (SONFH), providing insights into its underlying mechanisms and therapeutic targets. Gene expression profiles from both human (GSE123568; 30 SONFH patients and 10 controls) and rat femoral head samples (GSE26316; 3 SONFH and 3 controls) were analyzed to identify differentially expressed genes (DEGs) and enriched pathways. In a matched case-control study, femoral head tissues from SONFH patients and non-SONFH controls were collected. The expression of YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) and dihydrolipoamide dehydrogenase (DLD) was measured using qRT-PCR and Western blotting. Functional validation was performed in human bone marrow mesenchymal stem cells (BMSCs) via siRNA-mediated knockdown of YTHDF3 and treatment with elesclomol, a cuproptosis inducer. In the GSE26316 and GSE123568 datasets, we identified 708 common DEGs. Cuproptosis were activated in SONFH. The expression levels of YTHDF3 and DLD were elevated in SONFH tissues. Knockdown of YTHDF3 reduced the DLD expression and mitigated the inhibitory effects of elesclomol on BMSC proliferation and osteogenesis. YTHDF3 may contribute to SONFH progression by regulating DLD expression and cuproptosis, offering a potential important molecular target for novel therapeutic strategies.</p>\u0000 </div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10735-025-10544-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144914692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ephrin-B1 and EphB4 expression and localization in steroidogenic cells of mouse adrenal gland","authors":"Jahagir Alam,&nbsp;Kazushige Ogawa","doi":"10.1007/s10735-025-10572-7","DOIUrl":"10.1007/s10735-025-10572-7","url":null,"abstract":"<div>\u0000 \u0000 <p>Erythropoietin-producing hepatocellular (Eph) receptors and their ligands ephrin are membrane-bound molecules that modulate diverse cellular functions in various tissues. We recently reported the co-expression of <i>Efnb1</i> (ephrin-B1) and <i>Ephb4</i> (EphB4) in steroidogenic cells of the ovary. Based on these previous findings, we examined the expression and localization of ephrin-B1 and EphB4 in steroidogenic cells of the mouse adrenal gland using RT-PCR and immunofluorescence techniques. To the best of my knowledge, ephrin-B1 and EphB4 expression patterns in the adrenal gland are virtually unknown. We found that ephrin-B1 and EphB4 were co-expressed in steroidogenic cells of zona glomerulosa (zG) and zona fasciculata (zF) in the adrenal cortex of mice. Ephrin-B1 and EphB4 were also co-expressed in cells of x-zone (xZ) in female mice. We also found that ephrin-B1 and EphB4 expression in zG was strong and weak respectively. Ephrin-B1 and EphB4 expression in cells of zF were faint in cells of both mice while strong in juxtamedullary cells of zF in male mice. Ephrin-B1 and EphB4 expression were faint and weak in xZ in female mice respectively. The study represents the first expression analysis of ephrin-B1 and EphB4 in steroidogenic cells in the adrenal glands of the male and female mice.</p>\u0000 </div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144914759","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":"Kurarinone protects against renal injury and fibrosis after unilateral ureteral obstruction through enhancement of the Nrf-2 signaling pathway","authors":"Tiancao Dong,&nbsp;Dongyang Zhao,&nbsp;Sen Jiang,&nbsp;Yi Gu,&nbsp;Chunxue Wang,&nbsp;Qian Yang,&nbsp;Tong Liu,&nbsp;Xiandong Liu","doi":"10.1007/s10735-025-10578-1","DOIUrl":"10.1007/s10735-025-10578-1","url":null,"abstract":"<div><h3>Background</h3><p>Chronic kidney disease (CKD) is an epidemic with higher cardiovascular risk, and this pathology involves renal injury and fibrosis. Kurarinone (KAR) has anti-inflammatory and anticancer effects, which can regulate immune responses and macrophage polarization. This study aimed to investigate the effect of KAR on model-induced unilateral ureteral obstruction (UUO) renal injury and fibrosis.</p><h3>Methods</h3><p>We constructed the rat model of sham, UUO, UUO + low (10 IU/kg), medium (20 IU/kg) and high (40 IU/kg) doses of KAR groups in vivo, and we analyzed pathologic changes and expression of vimentin and α-smooth muscle actin (α-SMA), cluster of differentiation group 206, F4/80, FN, Snail1, Kim1, small mother against decapentaplegic (Smad) 3 and transforming growth factor-beta [TGF-β1]. Furthermore, we developed the HK-2 cell fibrosis model using TGF-β1 (5 ng/ml) for 24 h in vitro. We used real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemistry to detect α-SMA protein, TGF-β1, Smad3, and p-Smad3 levels in renal tissues. We examine protein levels of the Keap1/Nrf2 pathway using the Nrf-2 inhibitor, ML385, and downregulation of Nrf-2 expression using Western blotting.</p><h3>Results</h3><p>Our results revealed that KAR improved renal function and downregulated α-SMA protein. Furthermore, KAR induced the polarization of M2 macrophages. KAR improved fibrosis by inhibiting the TGF-β1/Smad3 pathway. KAR inhibited renal fibrosis and inflammation by activating the Keap1/Nrf2 pathway in vivo and in vitro.</p><h3>Conclusions</h3><p>KAR inhibited renal fibrosis and inflammation through the Keap1/Nrf-2 pathway, indicating that it may become a small molecular drug for chronic kidney disease.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10735-025-10578-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144914758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kaempferol alleviates cypermethrin induced reproductive toxicity in rats via Nrf2-mediated antioxidant and apoptotic regulation with histopathological evidence: in vivo and in silico study","authors":"Fahad Kabeer,&nbsp;Shaista Anjum,&nbsp;Atique Ahmed Behan,&nbsp;Muhammad Usman,&nbsp;Nazima Yousaf khan,&nbsp;Muhammad Azeem,&nbsp;Hafiz Misbah Ud Din,&nbsp;Muhammad Adeel Arshad,&nbsp;Sadaf Nazir,&nbsp;Shiping Cheng,&nbsp;Jameel Ahmed Buzdar","doi":"10.1007/s10735-025-10554-9","DOIUrl":"10.1007/s10735-025-10554-9","url":null,"abstract":"<div><p>Cypermethrin (CYP), a common synthetic pyrethroid pesticide, is associated with oxidative stress-mediated female reproductive toxicity. With increasing concern over reproductive failures, exploring natural alternatives to mitigate this problem is crucial. For this purpose, thirty–six female SD rats were divided into six different (<i>n</i> = 6) groups such as negative control (group I), while disease control (group II) was treated to CYP-induced toxicity. Group III received 5 mg/kg Clomiphene Citrate, a standard drug, and groups IV, V, and VI were subjected with Kaempferol (KAE) dosage of 25, 50 and 100 mg/kg, respectively, for 14 days after induction of toxicity. CYP exposure significantly impaired the fertility status of female rats, disrupted the estrous cycle, altered ovarian and uterine coefficients. It also reduced antioxidant enzyme activity while elevating malondialdehyde levels. KAE supplementation effectively reversed these changes by restoring fertility status, normalizing antioxidant enzyme activity and reducing MDA levels, and improving ovarian and uterine coefficients. Histopathological analysis revealed preserved uterine and ovarian integrity in KAE-treated groups. Furthermore, KAE regulated the mRNA expression of key apoptotic and oxidative stress markers including Bcl2, Bax, caspase-3, caspase-9, and Nrf2. Further, gene ontological study revealed that these genes are involved in apoptotic signaling, immune homeostasis and neuronal regulation due to strong enrichment in mitochondrial and protease related function. Molecular docking analysis demonstrated that KAE exhibited significantly, inhibit Nrf2-KEAP1 bonding compared to Clomiphene citrate, indicated by well docking score. It is concluded that KAE holds therapeutic potential as a safe, natural alternative to combat CYP induced oxidative stress, apoptosis, and reproductive toxicity.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144891434","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}