Cytotechnology最新文献

{"title":"Differential effects of thymoquinone under low-glucose stress in LKB1-null A549 and LKB1-wild-type H1299 lung cancer cells.","authors":"Betül Yılmaz Öztürk, Bükay Yenice Gürsu, İlknur Dağ, Onur Koyuncu","doi":"10.1007/s10616-026-01009-4","DOIUrl":"https://doi.org/10.1007/s10616-026-01009-4","url":null,"abstract":"<p><p>Lung cancer remains one of the leading causes of cancer-related deaths worldwide, and the effects of thymoquinone on lung cancer cells have been increasingly investigated in recent years. Rapidly proliferating cancer cells exhibit increased metabolic activity and energy requirements, and the Liver Kinase B1 (LKB1) plays a crucial role in metabolic adaptation. In this study, the effects of thymoquinone on LKB1-null (A549) and LKB1-wild-type (H1299) lung cancer cell lines were investigated under high and low glucose stress conditions. Under high glucose conditions, thymoquinone showed a dose- and time-dependent cytotoxic effect in H1299 cells, with a 24-hour IC₅₀ value of 23.4 µM. In A549 cells, a hormetic response was observed at low and moderate doses, cytotoxicity occurred only at high doses, and the 24-hour IC₅₀ value was determined as 69.45 µM. Under low glucose conditions, the cytotoxic effect of thymoquinone was increased in both cell lines; 24-hour IC₅₀ values were determined as 15 µM for H1299 and 16 µM for A549 cells. Overall, H1299 cells were found to be more sensitive to thymoquinone, especially at lower doses and earlier time points. Thymoquinone and glucose levels affected autophagy differently depending on the cell line. In H1299 cells, low glucose and thymoquinone administration significantly increased autophagy, while in A549 cells, both low glocose stress and thymoquinone suppressed autophagy. In contrast, thymoquinone increased apoptosis in both cell lines; this increase was particularly pronounced in late-stage apoptosis and was observed at much higher rates in A549 cells. However, LKB1 status alone may not be sufficient to determine the metabolic stress response, and additional molecular factors such as p53 protein may play a role in this process. A possible mechanistic explanation for this observed difference could be that H1299 cells are <i>TP53</i>-null, whereas A549 cells are harbor wild-type <i>TP53</i>. Our findings suggest that the effects of thymoquinone may vary depending on the cellular genetic background and are shaped by multidimensional mechanisms under conditions of metabolic stress, and detailed studies on this subject are needed.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s10616-026-01009-4.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"78 4","pages":"138"},"PeriodicalIF":2.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13275984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148293805","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":"Extracellular reticulocalbin-2 exacerbates cartilage endplate degeneration by promoting calcification via the cAMP/PKA signaling pathway.","authors":"Kuijing Han, Han Gao, Wendong Zhang, Wenzhong Zhang, Jijun Huang, Yongxiang Wang","doi":"10.1007/s10616-026-00997-7","DOIUrl":"https://doi.org/10.1007/s10616-026-00997-7","url":null,"abstract":"<p><p>Cartilaginous endplate (CEP) degeneration is a hallmark feature of intervertebral disc degeneration (IDD) and has been closely linked to the development of low back pain and progressive loss of disc height. Despite its clinical significance, the molecular mechanisms underlying CEP degeneration remain inadequately elucidated. Our study investigated the role of reticulocalbin-2 (RCN2) in CEP cell calcification and inflammation using an in vitro inflammatory model. Gene interference and overexpression experiments demonstrated that RCN2 plays a pivotal role in promoting CEP cell calcification and inflammatory responses by activating the intracellular cAMP/PKA signaling pathway, leading to upregulated expression of calcification-related genes. Further analysis revealed that exosomes secreted by CEP cells contain increased levels of RCN2, which in turn activates the cAMP/PKA signaling pathway and induces calcification in recipient cells. Knockdown of exosomal RCN2 significantly diminished its pro-calcifying effects, thereby establishing RCN2 as a critical mediator. Collectively, these findings elucidate a previously unrecognized molecular mechanism underlying CEP calcification and support RCN2 as a potential therapeutic target for IDD.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"78 4","pages":"126"},"PeriodicalIF":1.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148053211","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":"Association of gingival crevicular fluid chemerin and Th1/Th2 imbalance with early response to root surface debridement in periodontitis.","authors":"Feng Wei, Dan Wang, XiMeng Zhang, YuKun Lv","doi":"10.1007/s10616-026-01021-8","DOIUrl":"10.1007/s10616-026-01021-8","url":null,"abstract":"<p><p>Chemerin is a chemokine-like protein closely related to inflammation and immune regulation. Studies have indicated that it may be involved in the immune inflammatory process of periodontitis. Th1/Th2 cell imbalance is also important for the occurrence and development of periodontitis, but the relationship between Chemerin and Th1/Th2 cell imbalance and its effect on the early response to root surface debridement (RSD) remains unclear. This single-center, prospective observational study included 82 healthy controls and 129 periodontitis patients (Stage II-IV). Gingival crevicular fluid (GCF) samples were collected to measure Chemerin, interferon-gamma (IFN-γ), and interleukin-4 (IL-4) levels, with Th1/Th2 balance assessed by the IFN-γ/IL-4 ratio. C-reactive protein (CRP) and periodontal parameters were recorded. All periodontitis patients underwent RSD and were classified into good (<i>n</i> = 88) or poor (<i>n</i> = 41) early response groups after 6 weeks. Statistical analyses included correlation analysis, multivariate logistic regression, ROC curve analysis with bootstrap internal validation, model calibration, and decision curve analysis. Compared to controls, periodontitis patients showed significantly elevated GCF-Chemerin (4.82 ± 1.01 vs. 2.21 ± 0.38 ng/mL, <i>p</i> < 0.001) and IFN-γ/IL-4 ratio (2.34 ± 0.71 vs. 1.26 ± 0.29, <i>p</i> < 0.001), with increased IFN-γ and decreased IL-4 (both <i>p</i> < 0.001). GCF-Chemerin correlated positively with IFN-γ/IL-4 ratio (<i>r</i> = 0.40, <i>p</i> < 0.001). The poor early response group exhibited higher baseline levels of both biomarkers, which remained elevated post-treatment. Multivariate analysis identified Chemerin (OR = 9.00, <i>p</i> < 0.001), IFN-γ/IL-4 ratio (OR = 8.31, <i>p</i> < 0.001), clinical attachment level (CAL), and probing pocket depth (PPD) as independent factors associated with early response. The combined model (AUC = 0.886, bootstrap-corrected = 0.884) significantly outperformed individual biomarkers (<i>p</i> < 0.05), achieving 87.8% sensitivity and 75.0% specificity. Sensitivity analyses confirmed stable internal performance, and calibration and decision curve analyses demonstrated good internal predictive accuracy and clinical utility. GCF Chemerin and IFN-γ/IL-4 ratio are elevated in periodontitis and associated with immune imbalance. Their combined assessment provides good internal predictive performance for early response after RSD, with potential value as adjunctive biomarkers for personalized risk stratification in periodontitis management pending external validation.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"78 4","pages":"157"},"PeriodicalIF":2.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13369073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454727","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":"Bavachinin induces oxidative stress-associated apoptosis and modulates NF-κB-associated inflammatory gene expression in cervical cancer cells.","authors":"Yu Wang, Xiaofeng Gui","doi":"10.1007/s10616-026-01008-5","DOIUrl":"10.1007/s10616-026-01008-5","url":null,"abstract":"<p><p>Cervical cancer remains a major cause of mortality among women worldwide. Natural products provide anticancer leads with comparatively low toxicity. Bavachinin, a flavanone from <i>Psoralea corylifolia</i>, has documented bioactivities, yet its mechanisms in cervical cancer remain unclear. To determine whether bavachinin suppresses HeLa cell survival by inducing oxidative-stress-driven mitochondrial apoptosis and by downregulating NF-κB-regulated inflammatory signaling. Cytotoxicity across 5-40 µM was quantified by MTT. Oxidative stress and antioxidant status were assessed by TBARS and reduced glutathione (GSH). Apoptotic indices were evaluated by intracellular ROS generation, loss of mitochondrial membrane potential (ΔΨm), lactate dehydrogenase (LDH) release, AO/PI staining, Annexin V/PI flow cytometry, and DNA damage analyses. mRNA levels of NF-κB p65, TNF-α, IL-6, Bcl-2, and Bax <b>were</b> measured by quantitative RT-PCR. One-way ANOVA analyzed data with appropriate post hoc testing. Bavachinin decreased cervical cancer cell viability and induced apoptosis in a dose-dependent manner. Treatment increased ROS and TBARS, depleted GSH, disrupted mitochondrial membrane potential (ΔΨm), and elevated LDH release, accompanied by AO/PI-defined apoptotic morphology and DNA fragmentation. Annexin V/PI flow cytometry analysis in SiHa cervical cancer cells confirmed a dose-dependent increase in apoptotic cell populations following bavachinin treatment. Transcriptionally, NF-κB p65, TNF-α, IL-6, and Bcl-2 were downregulated, whereas Bax expression was increased, indicating modulation of apoptosis-associated and inflammatory signaling pathways. Bavachinin exhibited anti-inflammatory and pro-apoptotic activities against HeLa cells, likely through oxidative stress-associated apoptosis and modulation of NF-κB-associated inflammatory gene expression. These findings support further mechanistic validation and in vivo evaluation of bavachinin as a potential therapeutic candidate for cervical cancer.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"78 4","pages":"159"},"PeriodicalIF":2.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13369106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454824","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":"Transcriptomics identifies mild hyperthermia-conditioned tumor supernatant as an inducer of HepG2 transition.","authors":"Li Zheng, Yiheng Ding, Yuting Ma, Xinhao Li, Jinsheng Qi, Jianmin Liu, Yanning Li","doi":"10.1007/s10616-026-01011-w","DOIUrl":"10.1007/s10616-026-01011-w","url":null,"abstract":"<p><p>Inducing the transition of tumor cells into normal hepatocyte-like cells represents a promising therapeutic strategy for hepatocellular carcinoma (HCC). However, safe and effective inducers are currently lacking, and the underlying mechanisms remain poorly understood. This study aimed to investigate whether tumor supernatant (Tsn) under mild hyperthermia conditions could induce the transition of HepG2 cells into normal hepatocyte-like cells and to elucidate the potential mechanisms involved. HepG2 cells were treated at 42.5 °C for 60 min, and the post-treatment tumor supernatant (42.5Tsn) was collected. Transcriptome sequencing was performed to identify differentially expressed genes (DEGs) between the 42.5Tsn and 37Tsn treatment groups. Compared with the 37Tsn group, 446 DEGs were identified in the 42.5Tsn group. These DEGs were enriched in pathways related to DNA damage repair, cell cycle arrest, and nuclear receptor signaling. Among the 33 core genes, tumor suppressor genes (BRCA1, PALB2, SLX4) were significantly upregulated, while nuclear transcription factors that maintain stemness, such as HEY1, were significantly downregulated. Tsn induced by mild hyperthermia demonstrates the potential to promote the transition of HepG2 cells toward normal hepatocyte-like cells while suppressing their metastatic potential. However, due to the complex composition of Tsn and the transcriptome-only level of this analysis, the specific active factors, causal regulatory mechanisms, and in vivo efficacy require further validation through component analysis, functional assays, and animal models.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s10616-026-01011-w.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"78 4","pages":"141"},"PeriodicalIF":2.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13291309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148327550","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":"Homoharringtonine in combination with Tanshinone IIA suppresses the progression of lymphoma cells by downregulating the Akt/MMP signaling pathway.","authors":"Yanping Zhang, Jian Yin, Rui Liu, Jiyu Miu, Zeshi Liu, Jianhong Zhu, Aili He","doi":"10.1007/s10616-026-01031-6","DOIUrl":"10.1007/s10616-026-01031-6","url":null,"abstract":"<p><p>Lymphoma can seriously affect the quality of life of patients. Both homoharringtonine (HHT) and tanshinone IIA (Tan IIA) have shown robust anti-proliferation and apoptosis-inducing effects in lymphoma cells. However, it is unclear whether they can be used in combination to treat acute myeloid leukemia and lymphoma. Cell Counting Kit-8 (CCK-8) was employed to measure cell viability, the 5-Ethynyl-20-deoxyuridine assay (EdU) was used to quantify cell proliferation, and the transwell migration assay was used to assess cell migration in U937 and Raji cells. Additionally, transmission electron microscopy and nanoparticle tracking analysis assays were used to observe and identify exosomal structure, respectively. Combined HHT and Tan IIA treatment synergistically inhibited the viability and proliferation of U937 and Raji cells, induced apoptosis, and reduced vascular endothelial growth factor (VEGF) levels in these cells. Additionally, VEGFA and VEGFC levels were significantly reduced in exosomes derived from Raji cells that had been treated with HHT and Tan IIA (Exo^{HHT + Tan IIA}). Moreover, absorption of Exo^{HHT + Tan IIA} significantly inhibited the viability, proliferation, and migration of human umbilical vein endothelial cells by downregulating the expression of serine/threonine kinase 1 (Akt), matrix metalloproteinase-2 (MMP2) and MMP9. Exo^{HHT + Tan IIA} suppressed the tumor microenvironment. HHT and Tan IIA combined therapy synergistically suppressed lymphoma progression by downregulating the Akt/MMP signaling pathway, suggesting their use in treating lymphomas. Clinical trial number: Not applicable.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"78 4","pages":"155"},"PeriodicalIF":2.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13354732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419501","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":"Sanyang Xuedai enhances radiosensitivity in human non-small cell lung cancer cells through the activation of TLR2 to increase iNOS/NO production-mediated autophagy.","authors":"Li Wang, Jingyan Gao, Fei Lu, Yanli Li, Songqin Li, Man Li, Renyi Dong","doi":"10.1007/s10616-026-01027-2","DOIUrl":"10.1007/s10616-026-01027-2","url":null,"abstract":"<p><p>Radiotherapy (RT) is a key treatment for non-small cell lung cancer (NSCLC) patients who are ineligible for surgery. Sanyang Xuedai (SYKT), a traditional Chinese herbal formula, has previously been shown to enhance the effectiveness of RT in advanced NSCLC tumors. This study aimed to investigate the effects of SYKT combined with RT on RT-resistant NSCLC and to elucidate the underlying mechanisms involved. RT-resistant NCI-H460R cells were established by continuous exposure to ionizing radiation (IR). A xenograft model was generated by injecting NCI-H460R cells into the left back of nude mice. Gene and protein expression levels of key factors were assessed using RT‒qPCR, western blotting, immunofluorescence, and immunohistochemistry. Cell proliferation and apoptosis were evaluated through a CCK-8 assay, EdU staining, and flow cytometry. The results show that the combined intervention of SYKT and IR inhibited the proliferation of NCI-H460R cells and suppressed tumor growth in nude mice (one-way ANOVA with Tukey's post-hoc test, <i>P</i> < 0.05). Moreover, SYKT combined with IR increased the proportion of cells in the G2/M phase, reduced the proportion of cells in the G0/G1 phase, and promoted apoptosis (one-way ANOVA with Tukey's post-hoc test, <i>P</i> < 0.05). In addition, the combination therapy also upregulated the expression of the autophagy-related proteins LC3 II/I and Beclin 1 and the cell cycle proteins Cyclin B1 and CDC2, as well as iNOS, while inhibiting p62 expression and promoting NO production (one-way ANOVA with Tukey's post-hoc test, <i>P</i> < 0.05). Mechanistically, SYKT enhances NO synthesis by activating the TLR2/iNOS signaling axis, which in turn induces autophagy and increases the sensitivity of NSCLC to radiotherapy. This study demonstrated that SYKT can increase the radiosensitivity of NSCLC by activating TLR2 to increase iNOS/NO production, thereby mediating autophagy. Clinically, combining SYKT with radiotherapy may provide a promising and well-tolerated strategy to overcome acquired radioresistance and improve the efficacy of radiotherapy in patients with inoperable or radioresistant NSCLC.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s10616-026-01027-2.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"78 4","pages":"163"},"PeriodicalIF":2.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148583572","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":"Iodine-125 seed induces ferroptosis through inhibiting RNF216-mediated ubiquitination of p53 in cholangiocarcinoma cells.","authors":"Jing Wu, Xiaoning Chang, Jianjun Song, Fuping Kang","doi":"10.1007/s10616-026-01018-3","DOIUrl":"10.1007/s10616-026-01018-3","url":null,"abstract":"<p><p>Iodine-125 (¹²⁵I) seed has effectively treated cholangiocarcinoma (CCA) in previous research. Ferroptosis, a new form of programmed cell death, is linked to cancers including CCA. However, the relationship between ¹²⁵I seed and ferroptosis in CCA requires further investigation. Five pairs of CCA and adjacent normal tissue were collected, CCA tissues then were subjected to ¹²⁵I seed brachytherapy. The optimal ¹²⁵I seed dose for irradiating RBE cells was determined using the CCK-8 assay, and the cells were treated with ferroptosis inhibitors or MG132. RNF216 expression was modulated by short interfering RNA (siRNA) or overexpression plasmid. Cell viability, proliferation, and apoptosis were evaluated by CCK-8, EdU assays, TUNEL staining, and flow cytometric analysis. Intracellular Fe²⁺ levels, Lipid reactive oxygen species (ROS) and the GSH/GSSG ratio were detected by an iron assay kit, C11-BODIPY 581/591 and the EZ-Glutathione Assay Kit, respectively. The expression of RNF216, p53, SLC7A11 and GPX4 were analyzed by RT-qPCR and Western Blot. Ubiquitination of p53 by RNF216 was verified through ubiquitination immunoprecipitation. In CCA cell and tissues, ¹²⁵I seed induced ferroptosis and reduced RNF216 expression. Additionally, ¹²⁵I seed inhibited cell viability and proliferation but promoted apoptosis, and these trends were reversed by RNF216 overexpression or ferroptosis inhibitors. RNF216 was a key regulator of ¹²⁵I seed-induced ferroptosis. Mechanistically, RNF216 promoted p53 degradation through ubiquitination, leading to upregulated SLC7A11 expression and ultimately inhibiting ferroptosis.¹²⁵I seed inhibited SLC7A11 expression by preventing RNF216-mediated ubiquitination of p53, ultimately inducing ferroptosis in CCA. This provides crucial molecular evidence for the anticancer effects of ¹²⁵I seed.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"78 4","pages":"147"},"PeriodicalIF":2.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13310862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350983","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":"Effect of quercetin on osteoblast dysfunction in osteoporotic rats by regulating Nrf2/SLC7A11/GPX4 pathway-mediated ferroptosis.","authors":"Lijin He, Yangli Zheng, Zhiwei Zeng, Chenlan Lin","doi":"10.1007/s10616-026-00998-6","DOIUrl":"https://doi.org/10.1007/s10616-026-00998-6","url":null,"abstract":"<p><p>This study aims to explore the effect of quercetin on osteoblast dysfunction in osteoporotic rats and to clarify its role in regulating ferroptosis mediated by the Nrf2/SLC7A11/GPX4 signaling pathway, in order to provide new experimental evidence and potential therapeutic targets for the prevention and treatment of osteoporosis. Female SD rats were randomly divided into a control group, model group, and quercetin low-, medium- and high-dose groups. The osteoporosis model was established by bilateral ovariectomy. Micro-CT was used to detect femoral microstructural parameters (BV/TV, Tb.Th, Tb.N, and Tb.Sp), and RT-qPCR was used to detect the mRNA expression levels of osteogenic-related genes ALP, BMP2, OPN, RUNX2, FN, TNMD, COL-I, and COL-III in femoral tissue. ELISA and kits were used to detect oxidative stress indicators SOD, GSH, CAT, and MDA, and iron ion content in femoral tissue homogenate. Western blot was used to detect the expression levels of Nrf2, SLC7A11, and GPX4 proteins in femoral tissue. In vitro experiments were conducted using MC3T3-E1 cells, with third-passage cells specifically utilized to induce osteogenic mineralization. Cell viability was assessed using the CCK-8 assay, while cell death rates were determined via Annexin V-FITC/PI double-staining flow cytometry. Intracellular iron ion content was evaluated through biochemical assays, and the mRNA expression levels of ALP and RUNX2 were detected using RT-qPCR. Quercetin alleviated osteoporosis symptoms in rats by enhancing bone microstructure and stimulating osteogenic differentiation. These improvements were characterized by significant increases in BV/TV, Tb.Th, and BMD alongside a reduction in Tb.Sp. Furthermore, Quercetin promoted bone formation by upregulating the expression of key osteogenic markers, including ALP, BMP2, OPN, RUNX2, FN, TNMD, COL-I, and COL-III. Quercetin could suppress inflammation. In addition, quercetin also inhibited ferroptosis by reducing oxidative stress (increasing SOD and CAT activities and reducing MDA content) and iron overload (reducing iron ion content) and activating the Nrf2/SLC7A11/GPX4 signaling pathway, thereby further protecting bone tissue from damage. In vitro experiments demonstrate that quercetin effectively inhibits Erastin-induced ferroptosis in MC3T3-E1 cells, attenuates cellular damage, and restores their impaired osteogenic differentiation capacity. Quercetin can improve bone microarchitecture and osteoblast dysfunction in osteoporotic rats, which involves reducing oxidative stress and iron overload in bone tissue and activating the Nrf2/SLC7A11/GPX4 signaling pathway, thereby inhibiting the occurrence of ferroptosis.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"78 4","pages":"131"},"PeriodicalIF":1.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13226736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155584","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":"Apigenin attenuates hepatocyte senescence in metabolic dysfunction-associated steatotic liver disease by targeting the TGF-β signaling pathway.","authors":"Lijun Cao, Yongna Zhao","doi":"10.1007/s10616-026-01020-9","DOIUrl":"10.1007/s10616-026-01020-9","url":null,"abstract":"<p><p>This study aimed to investigate whether the natural flavonoid apigenin attenuates hepatocyte senescence and ameliorates high-fat diet (HFD)-induced metabolic dysfunction-associated steatotic liver disease (MASLD) by inhibiting the transforming growth factor-β (TGF-β)/Smad signaling pathway. Both <i>in vivo</i> and <i>in vitro</i> experiments were conducted. <i>In vivo</i>, an HFD-induced MASLD model was established in C57BL/6J mice, which were then treated with apigenin. Hepatic steatosis, inflammation, and fibrosis were assessed by histopathological staining, and the expression of hepatocyte senescence markers (p16, p21, and γH2AX) and key proteins of the TGF-β/Smad pathway were detected by western blotting, immunohistochemistry, and immunofluorescence. Serum lipid metabolism and indicators of liver injury were evaluated using biochemical methods. <i>In vitro</i>, senescence was induced in AML12 mouse hepatocytes with palmitic acid (PA), and the cells were treated with apigenin; anti-senescence effects and TGF-β pathway inhibition were confirmed by senescence-associated β-galactosidase (SA-β-gal) staining and western blotting. In the HFD-induced mouse model, apigenin alleviated hepatic steatosis, inflammation, and fibrosis, and reduced serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). It also decreased senescence markers (p16, p21, and γH2AX) in liver tissues and inhibited TGF-β expression and Smad2/3 phosphorylation. In the PA-treated AML12 cells, apigenin lowered senescence-associated proteins and SA-β-gal-positive cells while suppressing TGF-β/Smad pathway activation. Overexpression of TGF-β partially reversed the anti-senescence effect of apigenin, whereas pharmacological inhibition of TGF-β receptor I with SB431542 further reduced senescence markers and lipid accumulation. These findings indicate that apigenin may mitigate HFD/PA-induced hepatocyte senescence and MASLD-related pathological changes by inhibiting the TGF-β/Smad signaling pathway, offering new insights into its hepatoprotective effects.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"78 4","pages":"149"},"PeriodicalIF":2.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13328522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148390202","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}