Journal of Molecular Histology最新文献

{"title":"TGF-β signaling regulates gene expression, phagocytosis, and cell proliferation and supports glial cell survival in primary rat mixed glial cell cultures","authors":"Takayuki Nakajima,&nbsp;Yusei Wada,&nbsp;Ryunosuke Yamada,&nbsp;Tomohiro Kondo,&nbsp;Takashi Tanida","doi":"10.1007/s10735-025-10633-x","DOIUrl":"10.1007/s10735-025-10633-x","url":null,"abstract":"<div><p>Glial cells, including astrocytes, microglia, and oligodendrocytes, play an important role in the repair of damaged central nervous system tissue. In our previous study, we showed that transforming growth factor-beta (TGF-β) signaling occurs in glial cells in the hippocampus after ischemia. However, the functional significance of TGF-β signaling in the hippocampus after ischemia remains unclear. In the present study, transcriptome analysis was performed to comprehensively examine the TGF-β signaling-induced gene expression changes in primary cultured rat mixed glial cells. TGF-β1 upregulated 287 genes and downregulated 272 genes. Representative genes upregulated by TGF-β1 included genes encoding extracellular matrix-related proteins. Conversely, representative genes downregulated by TGF-β1 included genes encoding proteins related to immune response. These results suggest the diverse effects of TGF-β1 on gene expression. Since genes downregulated by TGF-β1 included genes involved in cell phagocytosis, proliferation, and survival, the effects of TGF-β1 and -β2 on cell phagocytosis, proliferation, and survival were investigated in mixed glial cells. TGF-β1 and -β2 suppressed astrocyte and microglial proliferation, and promoted and suppressed astrocyte and microglial phagocytosis, respectively. Additionally, TGF-β1 or -β2 canceled the serum-free culture−induced increase in the ratio of TUNEL-labeled microglia and oligodendrocytes. Furthermore, the culture in a medium containing the TGF-β signaling inhibitor SB525334 reduced glial cell survival and increased the expressions of genes encoding cell death-related molecules. Our study results suggest that TGF-β contributes to postischemic brain tissue repair by regulating glial cell gene expression, phagocytosis, and proliferation, and supporting glial cell survival.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342705","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":"3-TYP protects against heart failure with preserved ejection fraction by inhibiting Sirtuin 3","authors":"Ziwei Zhu,&nbsp;Yuqin Wang,&nbsp;Jianshu Chen,&nbsp;Yongnan Li,&nbsp;Hong Ding,&nbsp;Wenbin Wu,&nbsp;Xiaowei Zhang","doi":"10.1007/s10735-025-10614-0","DOIUrl":"10.1007/s10735-025-10614-0","url":null,"abstract":"<div><p>Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction and is commonly observed in elderly, diabetic, hypertensive, and obese patients. Accumulating evidence suggests a close relationship between sirtuins and myocardial damage in HFpEF. This study aimed to explore whether sirtuin 3 (Sirt3) is involved in HFpEF. Wistar-Kyoto (WKY) rats served as the controls, while spontaneously hypertensive rats (SHRs) were randomly divided into three groups: the SHR group, HFpEF group, and HFpEF + 3-TYP group. Except for rats in the WKY and SHR groups, rats in the other groups were subjected to a high-fat diet (45%) and an intraperitoneal (i.p.) injection of streptozotocin (35 mg/kg) to establish the HFpEF model. Moreover, Sirt3 was inhibited using 3-TYP to further explore the regulatory mechanism of key molecules in this process. Cardiac function was evaluated by echocardiography, histological changes were examined by microscopy, and the morphology of the ER and mitochondria was observed through transmission electron microscopy. Western blotting was used to measure the levels of endoplasmic reticulum stress (ERS) and mitophagy-related proteins. Following high-fat feeding and i.p. injection of streptozotocin, SHRs presented markedly impaired diastolic function, decreased exercise tolerance, increased cardiac hypertrophy and fibrosis, and increased Sirt3 protein expression. Treatment with 3-TYP led to a significant reversal of these changes. When Sirt3 expression increased, endoplasmic reticulum stress and mitochondrial autophagy increased. Sirt3 silencing markedly reduced the excessive ERS and mitophagy levels induced by metabolic stress. 3-TYP can mitigate cardiac hypertrophy and improve function in HFpEF patients by inhibiting Sirt3, thereby protecting against metabolic disorders and excessive endoplasmic reticulum stress. These findings suggest that 3-TYP may be a promising therapeutic candidate for patients with metabolic syndrome-related HFpEF.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342586","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":"EDIL3 induced by GLIS2 suppresses the anti-tumor activity of CD8+ T cells and expedites epithelial-mesenchymal transition in thyroid cancer","authors":"Xu Qian,&nbsp;Bo Fu,&nbsp;Shuangfu Peng,&nbsp;Meiling Xue,&nbsp;Zhaohui Zhu,&nbsp;Dan Yao","doi":"10.1007/s10735-025-10643-9","DOIUrl":"10.1007/s10735-025-10643-9","url":null,"abstract":"<div><p>Despite the discoveries of new and promising therapeutics, effective treatments for advanced and metastatic thyroid cancer (THCA) are still lacking. Epithelial-to-mesenchymal transition (EMT) is crucial for developing an invasive phenotype in tumor cells and, therefore, a hallmark of metastatic disease. We here investigate the effect of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3) on EMT in THCA and the mechanism involved. THCA cells with EDIL3 knockdown were generated to analyze the effect on EMT, proliferation, migration, invasion, and angiogenesis. THCA cells with knockdown of EDIL3 had increased expression of E-cadherin and decreased expression of Vimentin and Slug, proliferation, migration, invasion, and angiogenesis. GLI-similar 2 (GLIS2) bound to the EDIL3 promoter to activate its expression. Knockdown of GLIS2 promoted the killing activity of CD8⁺ T cells, while overexpression of EDIL3 reversed phenotypic changes and suppressed the anti-tumor responses of T cells. Overexpression of EDIL3 also reversed the inhibitory effects of knocking down GLIS2 alone on tumor metastasis in BALB/c nude mice. Together, our results demonstrate that EDIL3 induced by GLIS2 inhibits the anti-tumor activity of CD8⁺ T cells and promotes EMT in THCA.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342730","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":"Vortioxetine protects against methotrexate-induced ovarian toxicity through anti-inflammatory, antioxidant and antiapoptotic pathways: a multi-marker immunohistochemical study","authors":"Emine Sarman,&nbsp;Halil Asci,&nbsp;Kadriye Nilay Ozcan,&nbsp;Oznur Kolay,&nbsp;Irem Nazıroglu","doi":"10.1007/s10735-025-10642-w","DOIUrl":"10.1007/s10735-025-10642-w","url":null,"abstract":"<div><h3>Aims</h3><p>Methotrexate (MTX), a commonly used chemotherapeutic and immunosuppressive agent, is known to induce significant ovarian toxicity through mechanisms involving oxidative stress, inflammation, and apoptosis. Vortioxetine (VTX), a novel antidepressant with proven neuroprotective and anti-inflammatory properties, has not yet been evaluated in the context of chemotherapy-induced gonadotoxicity. This study aimed to investigate the protective effects of VTX against MTX-induced ovarian injury in a rat model by employing comprehensive histopathological and immunohistochemical evaluations.</p><h3>Methods and Results</h3><p>Thirty-two adult female Wistar Albino rats (300–350 g) were randomly divided into four equal groups (n = 8): Control, MTX, MTX + VTX, and VTX. Ovarian damage was induced with a single intraperitoneal injection of MTX (20 mg/kg), while VTX was administered daily (10 mg/kg) by oral gavage for five days. Rats were sacrificed on day 5, and bilateral ovaries were collected. Histopathological evaluation included follicular degeneration, vascular congestion, hemorrhage, and inflammatory cell infiltration. Immunohistochemical analyses were performed for 8-Hydroxy-2'-deoxyguanosine (8-OHdG), nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), caspase 3 (Cas-3), and Anti-Müllerian hormone (AMH) to assess oxidative stress, inflammation, apoptosis, and ovarian reserve. MTX administration caused severe follicular atresia, hemorrhage, and dense neutrophil infiltration. Immunohistochemically, 8-OHdG, NF-κB, TNF-α, and Cas-3 expressions were significantly elevated, while AMH was markedly reduced. VTX co-treatment significantly attenuated histological damage and modulated the expression of all biomarkers, indicating potent protective effects. VTX alone did not induce deleterious changes.</p><h3>Conclusion</h3><p>VTX exhibits a robust protective effect against MTX-induced ovarian injury via suppression of oxidative stress, inflammatory response and apoptotic pathways, while simultaneously preserving ovarian reserve. These findings highlight a novel application for VTX in fertility preservation strategies during chemotherapeutic interventions.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342708","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":"Hyperin attenuates cerulein-induced acute pancreatitis by regulating inflammation and oxidative stress","authors":"İhsan Karaboğa,&nbsp;Hamza Malik Okuyan,&nbsp;Fatin Rüştü Polat,&nbsp;Nurcan Bıçakçı,&nbsp;Yasin Duran,&nbsp;İhsan Gündüz,&nbsp;Yüksel Beyaz","doi":"10.1007/s10735-025-10645-7","DOIUrl":"10.1007/s10735-025-10645-7","url":null,"abstract":"<div><p>Acute pancreatitis (AP) is a serious inflammatory condition of the pancreas often requiring hospitalisation and characterised by abdominal pain, nausea, and vomiting. Hyperin (HP), a natural flavonoid, possesses antioxidant and anti-inflammatory characteristics. However, the effect of HP on AP remains unclear. This study aimed to evaluate the protective effects of HP in a cerulein-induced AP model in rats, focusing on histopathological damage, inflammatory cytokines, and oxidative stress markers. All rats were randomly assigned into control (n = 8), AP (n = 8), and AP + HP (50 mg/kg) groups (n = 8). We created an AP rat model by intraperitoneal cerulein injections. We evaluated histopathologically pancreatic tissues using hematoxylin–eosin staining. NF-κB and TNF-α expressions were analysed using immunohistochemical method. Oxidative stress markers such as MDA, SOD, CAT, GPx as well as serum amylase and lipase levels were assessed using biochemical methods. IL-6 and IL-10 levels were measured using ELISA. HP treatment significantly reduced histological damage scores, including oedema, necrosis, and vacuolisation. Moreover, expression levels of NF-κB and TNF-α were markedly decreased in the AP + HP group. HP restored SOD activity and reduced MDA levels, indicating attenuated oxidative stress. HP decreased serum IL-6 and increased IL-10 levels, along with significant reductions in amylase and lipase. HP exerts both anti-inflammatory and antioxidant effects in cerulein-induced AP, primarily through NF-κB and TNF-α inhibition and SOD activation. These findings suggest that HP may be a promising natural compound for the adjunctive treatment of AP.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342743","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":"TAK-242 inhibits toll-like receptor-4 signaling and attenuates cancer-associated muscle atrophy via the p38-C/EBPβ pathway","authors":"Yongfei You,&nbsp;Zhouzhou Su,&nbsp;Haozheng Wang,&nbsp;Shanshan Liu,&nbsp;Jiayi Wang,&nbsp;Feng Qiu,&nbsp;Zhiqun Jiang,&nbsp;Jianxin Wang,&nbsp;Yong Li,&nbsp;Guohua Zhang","doi":"10.1007/s10735-025-10587-0","DOIUrl":"10.1007/s10735-025-10587-0","url":null,"abstract":"<div><h3>Background and Aims</h3><p>Cancer cachexia is a paraneoplastic syndrome characterized by progressive muscle atrophy, which negatively impacts treatment efficacy, quality of life, and survival in individuals with cancer. Despite extensive research, no effective medical intervention has completely reversed cachexia, primarily due to an incomplete understanding of its pathogenesis. Toll-like receptor 4 (TLR4) plays an important role in inflammation and metabolic regulation. In this study, the role of TLR4 in muscle catabolism was investigated, with a focus on its regulation of the p38 mitogen-activated protein kinase (MAPK)-mediated activation of C/enhancer-binding protein beta (C/EBPβ) pathway.</p><h3>Methods</h3><p>TLR4 expression was silenced in C2C12 myotubes using specific small interfering RNAs (siRNAs). Conditioned medium derived from various cancer cell types was applied to C2C12 myotubes to simulate the tumor microenvironment. The pharmacological TLR4 inhibitor TAK-242 was administrated to C2C12 myotubes and C26 tumor-bearing mice to evaluate its effects on muscle atrophy. Western blot analysis and immunofluorescence microscopy were performed on C2C12 myotubes, while muscle tissues from C26 tumor-bearing mice, a model of cancer cachexia, were analyzed using western blot and histological examination.</p><h3>Results</h3><p>Exposure to conditioned medium from cachexia-associated cancer cell lines induced p38 MAPK–C/EBPβ in C2C12 myotubes, leading to upregulation of Ubr2 and Atrogin-1, myosin heavy chain degradation, and myotube atrophy. Silencing or inhibition of TLR4 using siRNA or TAK-242 prevented these catabolic effects in vitro. In C26 tumor-bearing mice, TAK-242 administration significantly attenuated cancer-associated muscle atrophy.</p><h3>Conclusions</h3><p>TLR4 plays a critical role in cancer-associated muscle atrophy through the p38β MAPK–C/EBPβ signaling pathway in both in vitro and in vivo models. Pharmacological inhibition of TLR4 with TAK-242 effectively attenuated muscle atrophy, highlighting its potential therapeutic value.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342675","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":"Investigation of the protective effects of ethanolic extract of ferula orientalis on lung tissue in sepsis model rat","authors":"Serdar Yigit,&nbsp;Fatma Necmiye Kaci,&nbsp;Arzu Gezer,&nbsp;Muhammed Yayla,&nbsp;Lale Duysak,&nbsp;Erdem Toktay,&nbsp;Pınar Aksu Kilicle,&nbsp;Nilnur Eyerci,&nbsp;Gül Esma Akdogan Karadag,&nbsp;Seyit Ali Bingol","doi":"10.1007/s10735-025-10639-5","DOIUrl":"10.1007/s10735-025-10639-5","url":null,"abstract":"<div><p>The study aimed to investigate the histological, biochemical, and molecular effects of ethanol extract of <i>Ferula orientalis</i> in rats that had undergone cecal ligation and puncture (CLP). We chose Ferula orientalis because of its antioxidant and antibacterial properties. We divided 30 female rats into five equal groups. Group 1: Sepsis group, Group 2: Sepsis + <i>Ferula</i> LD, Group 3: Sepsis + <i>Ferula</i> HD, Group 4: Sham group, Group 5: Control. The cecum was removed from the abdomen and ligated with 4/0 sutures. After that two holes were created in the distal cecum by using 16-gauge needle to the CLP model. Histopathological (H&amp;E, TUNEL, PERIODIC ACID-SCHIFF), Biochemical (SOD,CAT,GSH,MDA), and molecular (TNF–α, p53) analyses were performed. According to H&amp;E findings, neutrophil infiltration, thickening of the alveolar walls, and areas of inflammation were quite remarkable in the sepsis group. In the TUNEL staining, a high density of apoptotic cells was noted in the sepsis group, while a dose dependent decrease in a density apoptotic cells was observed depending on the dose increase when the <i>Ferula</i> ethanol extract was applied. Antioxidant enzyme (SOD, CAT, and GSH) activity increased in the <i>Ferula orientalis</i> sepsis groups compared to the sepsis group (<i>p &lt; 0.05</i>). The high-dose Ferula group showed the highest enzyme activity but had the highest level of <i>TNF–α</i> gene expression (<i>p &lt; 0.05</i>). This suggests that Ferula may trigger different immune responses depending on the dose. The ethanol extract of <i>Ferula orientalis</i> improved the CLP sepsis model in rats by decreasing oxidative stress, inflammation and cell apoptosis.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342662","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":"Butein attenuates cardiac fibrosis by mediating TGF-β1/Smad signaling pathway after myocardial infarction","authors":"Mengmeng Deng,&nbsp;Rui Ma,&nbsp;Jinlei Li,&nbsp;Pan Lu,&nbsp;Rong Tan,&nbsp;Zhen Chen,&nbsp;Xin Guo","doi":"10.1007/s10735-025-10641-x","DOIUrl":"10.1007/s10735-025-10641-x","url":null,"abstract":"<div><h3>Background</h3><p>Myocardial fibrosis has been found to accelerate heart dysfunction after myocardial infarction (MI). Butein is a chalcone compound possessing multiple biological properties. However, its effect on MI-induced myocardial fibrosis remains unclear.</p><h3>Methods</h3><p>A mouse MI model was established by left anterior descending ligation. Human cardiac fibroblasts (HCFs) were stimulated with TGF-β1 in vitro. Mouse cardiac function was evaluated by assessing EF and FS. Masson’s trichrome staining showed the fibrosis area in murine hearts. Western blotting evaluated protein levels of fibrosis markers and signaling-related markers. CCK-8, EdU, and Transwell assays were used to evaluate HCF proliferation and migration.</p><h3>Results</h3><p>Butein improved MI-induced cardiac dysfunction and reduced the fibrosis area in mice. Butein inactivated TGF-β1/Smad signaling in MI mice and TGF-β1-stimulated HCFs. Butein inhibited TGF-β1-induced proliferation, migration, and collagen synthesis in HCFs, which were similar to the effects of LY2109761, a pharmacological inhibitor of TGF-β signaling.</p><h3>Conclusion</h3><p>Butein mitigated MI development by inhibiting cardiac fibrosis and ECM deposition by inactivating the TGF-β1/Smad signaling pathway.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342677","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":"Salvigenin: a natural ally against nasopharyngeal carcinoma's malignant phenotypes and immune evasion","authors":"Di Jiang,&nbsp;Zhengquan Lin,&nbsp;Zhiqiang Mao,&nbsp;Ming Fu","doi":"10.1007/s10735-025-10630-0","DOIUrl":"10.1007/s10735-025-10630-0","url":null,"abstract":"<div><p>Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in Southeast Asia, particularly in southern China. Salvigenin is a natural compound with anti-inflammatory, antioxidant, and anti-tumor properties. The purpose of this research is to explore how Salvigenin impacts the malignant characteristics and immune evasion of NPC cells, as well as to clarify the molecular mechanisms involved. The viability and invasion of NPC cells (HK-1 and C666-1) were assessed using CCK-8 assays and Transwell assays, respectively. The expressions of epithelial-mesenchymal transition (EMT) markers and proteins in AKT/NF-κB pathway were analyzed by Western blot. Additionally, the impact of Salvigenin on tumor growth and immune evasion was examined in a xenograft mouse model. Salvigenin significantly inhibited proliferation and invasion of NPC cells in a dose-dependent manner. Besides, Salvigenin reduced the expression of PD-L1, inhibited CD8 + T cell apoptosis, and increased IFN-γ secretion, indicating attenuation of immune escape. After administration of Salvianin, the IFN-γ⁺ subpopulation was increased, but the TIM-3⁺ subpopulation was significantly reduced, indicating that Salvianin can inhibit T cell depletion. Mechanistically, Salvigenin inhibited the activity of AKT/NF-κB pathway, as evidenced by decreased levels of p-AKT and p-NF-κB. In addition, Salvigenin reduced tumor growth and immune evasion in vivo. Salvigenin exerts anti-tumor effects in NPC by inhibiting proliferation, invasion, EMT, and immune evasion via inactivation of the AKT/NF-κB pathway. Our findings illustrate that Salvigenin has potential as a new treatment option for NPC.</p><h3>Graphical abstract</h3><p>Salvigenin inhibits NPC cell proliferation, invasion and immune evasionthrough AKT/ NF-κB signaling pathway.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342681","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":"Bevacizumab alleviates kidney damage by modulating inflammation, necroptosis and apoptosis: a preclinical study of renal ischaemia/reperfusion injury in rats","authors":"Ali M. Janabi,&nbsp;Heider Qassam,&nbsp;Nadhim K. Hante","doi":"10.1007/s10735-025-10635-9","DOIUrl":"10.1007/s10735-025-10635-9","url":null,"abstract":"<div><p>Renal ischemia/reperfusion injury is a critical clinical problem caused by kidney and heart surgery and can lead to acute kidney injury (AKI). Bevacizumab is a humanized monoclonal antibody that binds to circulating soluble isoforms of VEGF-A, thereby inhibiting the activation of VEGF molecular pathways and eliciting antiangiogenic effects. This study assessed the nephroprotective potential of bevacizumab in a rat model of renal ischemia/reperfusion injury (I/R). Twenty-four Sprague–Dawley rats were allocated into four groups: Sham, I/R, I/R + normal saline, and I/R + bevacizumab. The sham group was subjected to laparotomy without I/R induction. The I/R, I/R + normal saline, and I/R + bevacizumab groups were subjected to 30 min of bilateral renal ischemia, followed by 24 h of reperfusion. The rats in the I/R + normal saline and I/R + bevacizumab groups were administered normal saline (vehicle for bevacizumab) and 0.1 mg/kg bevacizumab via intraperitoneal injection 60 min before ischemia, respectively. Renal damage markers (creatinine and KIM-1), inflammatory and oxidative markers (TNF-α, IL-1β, NF-κB, F8-isoprostane and SOD), and an apoptotic marker (caspase-3) were measured via ELISA. Nrf2 and MLKL were assessed by IHC, and RIPK1 and HO-1 were assessed by RT‒qPCR, in addition to histological examination and molecular docking. Compared with the sham group, the I/R and I/R + normal saline groups presented significant increases in creatinine, KIM-1, NF-κB, TNF-α, IL-1β, F8-isoprostane, caspase-3, RIPK1, and MLKL and a reduction in SOD. Compared with those in the sham group, the histological findings in the I/R and I/R + normal saline groups revealed notable structural damage. Conversely, bevacizumab significantly reduced renal damage, inflammatory marker levels, cellular death, and histopathological findings. In bevacizumab-treated rats, the nuclear translocation of Nrf2 and HO-1 increased. Moreover, molecular docking analysis revealed that bevacizumab interacted with Keap1. Bevacizumab has nephroprotective effects against renal IRI by diminishing inflammation, necroptosis, apoptosis, and necrosis through the activation of the Nrf2/HO-1 pathway and the inhibition of the RIPK1/MLKL pathway.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342594","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}