Journal of Molecular Histology最新文献

{"title":"Wenyang Yishen Tongluo prescription synergizes with bone marrow mesenchymal stem cells to alleviate rheumatoid arthritis via inhibiting IL-6","authors":"Rong Su,&nbsp;Shiyun Yin,&nbsp;Lingli Gu,&nbsp;Weichao Liu,&nbsp;Weitian Yan,&nbsp;Weijian Zhou,&nbsp;Jiangyun Peng","doi":"10.1007/s10735-026-10875-3","DOIUrl":"10.1007/s10735-026-10875-3","url":null,"abstract":"<div><p>This study investigated the synergistic anti-arthritic effects of Wenyang Yishen Tongluo Prescription (TLP) combined with bone marrow mesenchymal stem cells (BMSCs) in rheumatoid arthritis (RA). A collagen-induced arthritis (CIA) rat model was established, and animals were divided into groups receiving TLP, BMSCs, or combination therapy. Network pharmacology identified IL-6 as a core target of TLP, which was further validated by molecular docking and cellular thermal shift assay (CETSA). The combination therapy reduced arthritis index score by 34.41% compared with the model group, alleviated synovial hyperplasia and fibrosis, synergistically downregulated autoantibody rheumatoid factor (RF), pro-inflammatory factors (TNF-α, MMP-9, VEGFA), and bone-resorptive factor RANKL, while upregulating bone-protective factors (BMP-7, OPG) and immunosuppressive molecules (TGF-β1, PD-1, FOXP3). Mechanistically, TLP restored BMSC function by inhibiting IL-6 and its downstream phosphorylation of NF-κB, STAT3, and Akt pathways, as demonstrated by IL-6 overexpression experiments. These findings demonstrate that TLP combined with BMSCs synergistically ameliorates the inflammatory microenvironment, restores immune balance, and reduces bone damage in RA by targeting IL-6 and its downstream signaling, offering a safe and effective integrative treatment strategy.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148323966","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":"Green fabrication of silver nanoparticles using Corallocarpus epigaeus (Hook.f.) Cogn. rhizome extract: phytochemical characterization and evaluation of antioxidant, antimicrobial, and anticancer activity against HT-29 cells","authors":"Nagarajan Kalimuthu","doi":"10.1007/s10735-026-10852-w","DOIUrl":"10.1007/s10735-026-10852-w","url":null,"abstract":"<div><p><i>Corallocarpus epigaeus</i> is an ethnomedical plant with numerous bioactive phytochemicals but the potential of the plant in green nanotechnology and anticancer studies is underexplored<b>.</b> Phytochemical screening was conducted and AgNPs biosynthesis was done using rhizome extract as a reducing and capping agent. The nanoparticles were characterized using UV–Vis spectroscopy, GC–MS, FTIR, Raman spectroscopy, AFM, and SEM, DLS and Zeta potential analyser. Antioxidant activity was measured using Phosphomolybdenum assay, antibacterial using agar well diffusion with <i>Escherichia coli</i> (MTCC 40), (MTCC 121) and cytotoxicity of HT-29 colon cancer cells using MTT assay. Alkaloids were in large quantity, flavonoids, phenolics, saponins and phytosteroids were in moderate amounts and trace amounts of tannins and quinones. UV–Visible spectroscopy confirmed nanoparticle formation with a stable surface plasmon resonance peak at 430 nm. XRD analysis revealed a highly crystalline nanostructure with well-defined diffraction peaks, confirming the formation of nanocrystalline silver. DLS analysis indicated a predominant nanoscale population with an average hydrodynamic size of 55–86 nm, although some aggregation was observed. Zeta potential measurement (− 21.0 mV) suggested moderate colloidal stability due to phytochemical capping. SEM and AFM analyses confirmed predominantly spherical, moderately dispersed nanoparticles with nanoscale morphology with a 55 nm diameter. The AgNPs had a higher antioxidant capacity (0.0251 absorbance units) compared to crude extract (0.0078). It showed a strong antibacterial activity with the inhibition zones of 25 mm (<i>B. subtilis</i>) and 24 mm (<i>E. coli</i>) achievable at 150 µL. The AgNPs demonstrated a high level of cytotoxicity towards HT-29 cells with an IC50 of 31.2 ug/ml and-apoptotic morphology. AgNPs (55 nm) mediated by <i>C. epigaeus</i> rhizome exhibits good antioxidant, antibacterial and anticancer effects that can be used to justify the possibility of using <i>C. epigaeus</i> rhizome as plant-based nanotherapeutics. Moreover, the eco-friendly approach contributes to the global objectives of United Nations Sustainable Development Goal 3: Good Health and Well-Being, United Nations Sustainable Development Goal 9: Industry, Innovation and Infrastructure, and United Nations Sustainable Development Goal 12: Responsible Consumption and Production, by promoting sustainable nanotechnology, innovative biomedical research, and environmentally responsible production methods.</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":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148323384","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":"Hippocampal modifications partially mediates the boosted effects of seizure induction on ASD-related behaviors in maternally separated mice, while HMGB1 and MeCP2 mRNA levels remained unchanged","authors":"Amir Hossein Mousavi,&nbsp;Shima Balali-Dehkordi,&nbsp;Mohammad Rahimi-Madiseh,&nbsp;Elham Zarean,&nbsp;Hossein Amini-Khoei","doi":"10.1007/s10735-026-10876-2","DOIUrl":"10.1007/s10735-026-10876-2","url":null,"abstract":"<div><p>Autism spectrum disorder (ASD) has some comorbidities like seizure. Maternal separation (MS) provoke ASD-related behaviors. There are discrepancies regarding effect of MS on seizure susceptibility. Structural alterations in the pyramidal layer of the hippocampus as well as MeCP2 and HMGB1 are implicated in the physiopathology of ASD and seizure. This study aimed to determine the possible alterations in the expression of MeCP2 and HMGB1 mRNA in the hippocampus and PFC as well as histopathological amendments in the hippocampus in seizures susceptibility subsequent of MS-induced ASD-related phenotype in male mice. 32 male mice divided in to 4 groups including control, pentylenetetrazol (PTZ)—induced seizure, MS and MS + PTZ. Seizure threshold and behaviors related to ASD were performed. Diameter, neuronal density, and percent of dark neurons in the CA1 and CA3 areas of the hippocampus in addition to expression of MeCP2 and HMGB1 mRNA in the hippocampus and prefrontal cortex (PFC) were assessed. Finding: MS decreased seizure threshold. MS associated with ASD- like behaviors. MS and seizure potentiated negative effects of each other on the structural amendments in the CA1 and CA3 areas. The expression of MeCP2 mRNA decreased in the PFC and hippocampus of MS mice, while any difference did observe in the PTZ and MS + PTZ groups. HMGB1 mRNA expression showed any difference among groups. We conclude that, partially, structural changes in the hippocampus may has role in the bilateral effect of MS and PTZ on comorbid autistic-like behaviors and susceptibility to seizure in mice.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148323531","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":"HIPK2 mediated regulation of ferroptosis and inflammatory signaling in sepsis-induced myocardial injury","authors":"Changyan Hu,&nbsp;Ying Zhang,&nbsp;Juanjuan Miao,&nbsp;Qihong Zhao","doi":"10.1007/s10735-026-10873-5","DOIUrl":"10.1007/s10735-026-10873-5","url":null,"abstract":"<div><p>Sepsis-induced myocardial injury (SIMI) is a major contributor to the high mortality of septic shock, yet its underlying mechanisms remain incompletely understood. This study investigated the role of ferroptosis in myocardial damage and inflammatory responses during sepsis, focusing on its regulation by HIPK2 and the NF-κB/STAT3 signaling pathways. Using a cecal ligation and puncture (CLP)-induced sepsis mouse model and lipopolysaccharide (LPS)-treated H9c2 cardiomyocytes, we demonstrated that ferroptosis is a central driver of myocardial injury, evidenced by mitochondrial structural abnormalities, elevated lipid peroxidation, and impaired cardiac function. Ferroptosis inhibition with ferrostatin-1 (Fer-1) significantly improved survival, preserved myocardial ultrastructure, reduced inflammatory cytokine levels, and alleviated oxidative stress. HIPK2 expression was markedly suppressed during sepsis, correlating with enhanced ferroptosis and activation of NF-κB/STAT3 signaling pathway. Overexpression of HIPK2 <i>in</i> <i>vitro</i> mitigated ferroptosis and downregulated NF-κB-p65 and STAT3 phosphorylation, suggesting a dual regulatory role in ferroptosis and inflammation. Furthermore, Fer-1 treatment not only inhibited ferroptosis but also reduced systemic inflammation, highlighting its therapeutic potential in sepsis. These findings establish ferroptosis as a critical mechanism in septic myocardial injury and identify HIPK2 as one of the key regulators, offering new insights into the interplay between ferroptosis and inflammatory signaling. Targeting ferroptosis may represent a promising dual therapeutic strategy to protect cardiac function and modulate systemic inflammation in sepsis.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148323532","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":"Prophylactic potential of Astragalus membranaceus extract in experimental pulmonary Candidiasis in Albino rats","authors":"Mariham George Loqa,&nbsp;Ahmed A. Morsi,&nbsp;Sylvana Nady Gaber,&nbsp;Enas Gomaa Ibrahim Ali,&nbsp;Amany Nasr Ahmed,&nbsp;Rehab Ahmed Mohammed,&nbsp;Azza Mohamed Zaki,&nbsp;Alshaymaa M. Abdelmenem","doi":"10.1007/s10735-026-10860-w","DOIUrl":"10.1007/s10735-026-10860-w","url":null,"abstract":"<div><p>Invasive candidiasis is a fungal infection with potentially serious outcomes, requiring novel therapies to overcome drug resistance. <i>Astragalus membranaceus</i> (AM) dried root extract has been shown to have anti-inflammatory and immunomodulatory properties. This study aimed to examine the anticandidal potential of AM versus fluconazole and explore the mechanisms underlying the antifungal effect in a model of lung candidiasis. Four groups (<i>n</i> = 6, in each) of twenty-four mature male Wistar albino rats were created: non-infected control, <i>Candida</i>-infected, AM-treated, and fluconazole-treated groups. Lung candidiasis was induced by a single intravenous inoculation of <i>Candida albicans</i> on the 10th day. In AM- and fluconazole-treated groups, the infected rats received AM extract (1000 mg/kg/day) and fluconazole (10 mg/kg/day) orally for 11 days. On day 12, the animals were sacrificed, and the lung tissues were harvested for microbiological, biochemical, and histological analyses. Lung tissue homogenates were subjected to ELISA and polymerase chain reaction (PCR)-based measurement of <i>IL-1β, IL-4, IL-6, IL-10, IL-12</i>, and <i>TNF-α.</i> Also, immunohistochemistry of NF-κB and i-NOS was conducted. In vitro evaluation using disc diffusion and minimum inhibitory concentration assays were used to evaluate AM's antifungal efficacy. AM improved lung histology, reduced the pulmonary fungal load, decreased lung cytokine levels, and increased the lung tissue levels of IL-12, compared to the infected group. Also, AM increased the iNOS expression at gene and protein levels, meanwhile downregulated NF-κB, in comparison with the infected group. In summary, AM protected against the lung damage caused by <i>Candida,</i> possibly by modulating the inflammatory response and NF-κB/IL-12/iNOS signaling pathway.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148323345","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":"Alveolar socket preservation with human umbilical cord mesenchymal stem cell-seeded hydroxyapatite–chitosan scaffolds: An in vivo assessment of osteoprotegerin and receptor activator of nuclear factor-κB expression","authors":"Dhafer Abdulwasea Alshaibani,&nbsp;Michael Josef Kamadjaja,&nbsp;Ratri Maya Sitalaksmi,&nbsp;Dwi Wahyu Indrawati,&nbsp;Darmawan Setijanto,&nbsp;Sultan Ainoosah,&nbsp;Ahmed Yaseen Alqutaibi,&nbsp;Redhwan Saleh Al-Gabri","doi":"10.1007/s10735-026-10874-4","DOIUrl":"10.1007/s10735-026-10874-4","url":null,"abstract":"<div><p>Tooth extraction is a common procedure often followed by alveolar bone resorption, which may compromise future implant placement, prosthetic rehabilitation, esthetics, and periodontal support. Hydroxyapatite–chitosan (HA–Chi) scaffolds combined with human umbilical cord mesenchymal stem cells (hUCMSCs) may enhance bone healing by modulating bone remodeling pathways. This study evaluated the effects of hUCMSC-seeded HA–Chi scaffolds on osteoprotegerin (OPG) and receptor activator of nuclear factor-κB (RANK) expression during alveolar socket healing. In this randomized controlled in vivo experiment, 45 male Wistar rats underwent mandibular incisor extraction and were allocated to three groups: untreated control (C), HA–Chi scaffold only (T1), and hUCMSC-seeded HA–Chi scaffold (T2). Each group included 15 animals, with five evaluated at 7, 14, and 28 days. OPG and RANK expression were assessed immunohistochemically and data were analyzed using one-way ANOVA followed by Tukey’s post hoc test. OPG expression increased progressively over time in all groups, whereas RANK expression decreased. The hUCMSC-seeded HA–Chi scaffold group consistently showed the highest OPG and lowest RANK expression at all observation periods. Overall intergroup differences were significant for both markers (<i>p</i> &lt; 0.001). For OPG, no significant difference was observed between T1 and T2 at day 7, whereas significant differences emerged at days 14 and 28. For RANK, the hUCMSC-seeded group showed significantly lower expression than the control group at all-time points and than the scaffold-only group at day 28. hUCMSC-seeded HA–Chi scaffolds promoted a favorable bone remodeling profile by upregulated OPG and downregulated RANK, indicating strong potential for alveolar socket preservation after tooth extraction.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148323346","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":"Correction: Anti-Inflammatory and bone-protective effects of Pimpinella brachycarpa extract in a rat periodontitis model","authors":"Su-Bin Park,&nbsp;Yun Mi Lee,&nbsp;Hwa Young Yu,&nbsp;Jae-Eun Jung,&nbsp;Eunjung Son,&nbsp;Junghyun Kim","doi":"10.1007/s10735-026-10858-4","DOIUrl":"10.1007/s10735-026-10858-4","url":null,"abstract":"","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10735-026-10858-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148323430","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":"Leukemia inhibitory factor drives malignant progression in lung squamous cell carcinoma via the PI3K/AKT/GSK-3β/β-catenin axis","authors":"Sainv Si,&nbsp;Mengxue Zhou,&nbsp;Liping Chen,&nbsp;Jianjun Ge,&nbsp;Shan Wei,&nbsp;Wanjun Yu,&nbsp;Huaying Wang","doi":"10.1007/s10735-026-10870-8","DOIUrl":"10.1007/s10735-026-10870-8","url":null,"abstract":"<div><p>Leukemia inhibitory factor (LIF) is an established oncogenic driver in multiple cancers. However, its functional contribution and mechanistic underpinnings in lung squamous cell carcinoma (LSCC) remain incompletely defined. To delineate the role of LIF in LSCC progression, and elucidate the underlying molecular mechanisms. LIF protein expression in clinical LSCC tissues was assessed by immunohistochemistry (IHC) and Western blotting. LIF gain-of-function (using recombinant LIF protein) and loss-of-function (via LIF knockdown) assays were performed in vitro to assess its impact on the malignant phenotypes of LSCC cells. The changes in signaling pathways were analyzed by Western blotting and immunofluorescence. The functional role of LIF was further validated in patient-derived organoid models and a nude mouse xenograft model. LIF protein was significantly upregulated in LSCC tissues, and its high expression was correlated with unfavorable clinical outcomes. Recombinant LIF (rLIF) significantly enhanced the proliferation, migration, and invasion of LSCC cells in vitro in a dose-dependent manner, and the dosage of 200 ng/mL exerted the most pronounced effects. Conversely, LIF knockdown suppressed these malignant phenotypes. LIF activated the PI3K/AKT pathway, leading to inhibitory phosphorylation of GSK-3β at Ser 9, which consequently stabilized β-catenin and facilitated its nuclear accumulation. Furthermore, rLIF also promoted the growth of patient-derived organoids, and upregulated the expression of Ki-67 and α-SMA. In contrast, LIF knockdown significantly attenuated the growth of LSCC xenografts in vivo, and this effect was partially reversed by exogeneous rLIF. The oncogenic effects of LIF were associated with increased expression levels of p-AKT, p-GSK-3β, and β-catenin. LIF mediates LSCC progression by activating the PI3K/AKT/GSK-3β/β-catenin pathway. Therefore, LIF and its effectors warrant further study as potential diagnostic biomarkers and therapeutic targets in LSCC.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148323957","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":"Jaboticaba peel extract limits castration-resistant prostate cancer aggressiveness by counteracting EMT through steroid hormone and TGF-β signaling modulation","authors":"Fabiana Regina Schievano,&nbsp;Jaqueline de Souza Gianchetto,&nbsp;Felipe Rabelo Santos,&nbsp;Mário Roberto Maróstica Júnior,&nbsp;Valéria Helena Alves Cagnon,&nbsp;Fabio Montico","doi":"10.1007/s10735-026-10851-x","DOIUrl":"10.1007/s10735-026-10851-x","url":null,"abstract":"<div><p>Androgen deprivation therapy (ADT) is recommended for treating prostate cancer (PCa) that relapses after first-line approaches. However, tumors often evolve to a highly aggressive and metastatic castration-resistant phenotype (CRPC). Epithelial-to-mesenchymal transition (EMT) stands out due to its contribution to hormone resistance and metastatic spread. We investigated the potential of a jaboticaba peel extract (JPE) as an adjuvant agent in CRPC tumors from the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model, focusing on EMT regulation. Sixteen-week-old mice underwent surgical and chemical castration (10 mg/Kg enzalutamide), alone or in combination with JPE (5.8 g/Kg). Control animals were sham-castrated and received either placebo or the plant extract. JPE reduced the ratio of widespread prostatic tumors in mice undergoing ADT, despite not affecting metastases. It also reduced the protein levels of the EMT drivers ZEB1 and N-Cadherin, apart from contributing to the maintenance of a periacinar layer primarily composed of smooth muscle cells. Mechanistically, JPE-induced effects in castrated mice involved decrease of AR protein expression as well as ERβ beneficial actions, which included a putative stimulation of TGF-β tumor-suppressive actions. In conclusion, JPE prevented the progression of poorly differentiated tumors with CRPC traits in the TRAMP model by hampering EMT and modulating steroid hormone and TGF-β signaling.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10735-026-10851-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148292925","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":"Protective effects of Withania somnifera (Ashwagandha) against chronic unpredictable mild stress-induced testicular damage in adolescent rats","authors":"Selim Demirtaş,&nbsp;Gul Sahika Gokdemir,&nbsp;Mehmet Tahir Gokdemir,&nbsp;Nazan Baksi","doi":"10.1007/s10735-026-10865-5","DOIUrl":"10.1007/s10735-026-10865-5","url":null,"abstract":"<div><p>This study aimed to comparatively investigate the protective effects of Ashwagandha and Sertraline treatments on chronic stress-induced testicular damage and reproductive dysfunction in adolescent rats, through hormonal, biochemical, and apoptotic pathways. Twenty-eight adolescent male Wistar albino rats were divided into four groups: Control, Chronic Unpredictable Mild Stress (CUMS)-induced Depression, Depression+Sertraline, and Depression+Ashwagandha. Testicular testosterone and cyclic guanosine monophosphate (cGMP) levels, as well as oxidative stress markers and inflammatory cytokines in the testicular tissue, were measured. Johnsen scoring and H&amp;E staining were performed to evaluate histopathological changes. Immunohistochemically, Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), marker of proliferation Ki-67 (Ki67), and Sirtuin 6 (SIRT6) antibodies were evaluated. Chronic stress exposure led to a significant decrease in testicular testosterone and cGMP levels, while causing an increase in oxidative stress and inflammation markers. Histopathological examinations revealed desquamation of the seminiferous tubule epithelium, tubular degeneration, and a severe reduction in the Johnsen score in the depression group. At the molecular level, it was observed that stress increased Bax expression and suppressed Bcl-2 expression. Ki67 and SIRT6 levels were decreased in the Depression group. Both treatment modalities increased Bcl-2, Ki67, and SIRT6 immunoreactivities. It was observed that the Bax/Bcl-2 ratio in the Ashwagandha group approached the levels of the control group. Both treatment methods alleviated oxidative, inflammatory, and apoptotic changes triggered by chronic stress in the testes of adolescent rats. Mitigating testosterone depletion and strengthening anti-apoptotic defense mechanisms, Ashwagandha provides more comprehensive protection compared to Sertraline. These findings suggest that Ashwagandha may serve as a potential phytotherapeutic supportive agent in mitigating stress-induced damage within the testicular tissue.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 4","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275207","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}