Apoptosis最新文献

{"title":"Targeting cell signaling pathway ALKBH5/Beclin1/ULK1 in lung cancer by 5-flurouracil- loaded P (AAm/SA) nanogel in rats.","authors":"Ahmad S Kodous, Eman S Eldin, Hebatallah E Mohamed, Mohamed Mohamady Ghobashy, Dina F El-Maghraby","doi":"10.1007/s10495-025-02102-3","DOIUrl":"https://doi.org/10.1007/s10495-025-02102-3","url":null,"abstract":"<p><strong>Purpose: </strong>Lung cancer is the second most common Cancer in the United States; however, it remains the leading cause of cancer-related death in the United States and worldwide. 5-fluorouracil (5-FU) is among the most administrated chemotherapeutic agents for various neoplasms. This study focused on synthesizing and characterizing P(AAm/SA)/5-Fu nanogels as a potential drug delivery system.</p><p><strong>Methods: </strong>The nanogels were prepared by combining sodium alginate (SA) and acrylamide (AAm) monomers, followed by gamma irradiation-induced polymerization at a dose of 5 kGy. Then, the obtained nanogel was loaded with 500 ppm of 5-Fu. Transmission electron microscopy (TEM) imaging was utilized to characterize the nanogels' morphology and monodispersity with a particle size of (50 nm). Rats were randomly assigned to four groups (six animals per group): Group 1: (Control): normal healthy. Group 2: Cancer-bearing animals (animals injected with diethylnitrosamine (DEN) 20 mg/kg body weight for 3 months. Group 3: Cancer+ 5-fluorouracil (12 mg/kg body weight). Group4: Cancer+ 5-Flurouracil- Loaded P (AAm/SA) Nanogel.</p><p><strong>Results: </strong>DEN markedly increased PTGS2, Cox2, PKB, PFKm, and ERK1 levels. Also, observed up-regulation in ALKBH5, Beclin1, ULK1, and P53 gene expressions in the cancer-bearing animal group compared with the control group. 5-fluorouracil nano gel significantly ameliorated the above-mentioned parameters and immunohistochemistry study. 5-fluorouracil nanogel significantly ameliorated the parameters mentioned above, as well as the immunohistochemistry study.</p><p><strong>Conclusion: </strong>The 5-FU-loaded P(AAm/SA) nanogel could serve as a promising approach for targeting tumor cell proliferation, speeding up autophagic processes, and overcoming chemotherapy resistance in lung carcinoma.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PANoptosis: a potential target of atherosclerotic cardiovascular disease.","authors":"Xiao Jin, Yanan Zhu, Lina Xing, Xinyue Ding, Zongjun Liu","doi":"10.1007/s10495-025-02089-x","DOIUrl":"https://doi.org/10.1007/s10495-025-02089-x","url":null,"abstract":"<p><p>PANoptosis is a newly discovered cell death pathway triggered by the innate immunizer, which in turn promotes the assembly of the PANoptosome and activates downstream effectors. As a special cell death mode, it is characterized by apoptosis, pyroptosis, and necroptosis at the same time; therefore, it is not feasible to inhibit PANoptosis by suppressing a single cell death pathway. However, active ingredients targeting the PANoptosome can effectively inhibit PANoptosis.Given the importance of cell death in disease, targeting PANoptosis would be an important therapeutic tool. Previous studies have focused more on infectious diseases and cancer, and the role of PANoptosis in the cardiovascular field has not been comprehensively addressed. While ASCVD is the number one killer of cardiovascular diseases, it is important to explore new targets to determine future research directions. Therefore, this review focuses on the assembly of PANoptosome, the molecular mechanism of PANoptosis, and the related mechanisms of PANoptosis leading to ASCVD such as myocardial infarction, ischemic cardiomyopathy and ischemic stroke, in order to provide a new perspective for the prevention and treatment of ASCVD.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YTHDF1-mediated m6A modification promotes cisplatin resistance in ovarian cancer via the FZD7/Wnt/β-catenin pathway.","authors":"Jintian Miao, Xinyan Jiang, Siyun Wang","doi":"10.1007/s10495-025-02094-0","DOIUrl":"https://doi.org/10.1007/s10495-025-02094-0","url":null,"abstract":"<p><p>Cisplatin resistance significantly hinders the efficacy of ovarian cancer treatment, presenting a major challenge in improving patient outcomes. This study identifies the m6A reader protein YTHDF1 as a key regulator of cisplatin resistance in ovarian cancer through its modulation of the FZD7/Wnt/β-catenin signaling pathway. Using cisplatin-resistant ovarian cancer cell lines (A2780/DDP and SKOV3/DDP), we observed elevated YTHDF1 expression, which positively correlated with tumor cell proliferation and migration. Silencing YTHDF1 reduced FZD7 expression, inhibited Wnt/β-catenin signaling, and restored cisplatin sensitivity both in vitro and in vivo. Mechanistic investigations revealed that YTHDF1 binds to m6A-modified FZD7 mRNA, enhancing its stability and translation. Functional studies in xenograft mouse models demonstrated that targeting YTHDF1 suppressed tumor growth and enhanced apoptosis in cisplatin-resistant ovarian cancer cells. These findings highlight the YTHDF1-FZD7 axis as a novel therapeutic target for overcoming cisplatin resistance, paving the way for improved treatment strategies in ovarian cancer.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted intervention in obesity-associated atrial fibrosis using nanoparticle-loaded fusion protein.","authors":"Changying Wang, Xiaodong Zhang, Guangwei Zeng","doi":"10.1007/s10495-025-02104-1","DOIUrl":"https://doi.org/10.1007/s10495-025-02104-1","url":null,"abstract":"<p><p>The association between obesity and atrial fibrillation (AF) has garnered increasing attention. Obesity is a significant risk factor for cardiovascular diseases and promotes the occurrence of AF through multiple mechanisms. This study aims to explore the molecular mechanisms of obesity-induced AF using GLP-1R/GIPR dual-target agonist fusion protein (Fc) loaded into adipose-derived mesenchymal stem cell (ADSC) exosome-liposome hybrid nanoparticles (LE@Fc NPs). We successfully constructed and purified the Fc, verifying its purity and functional activity through SDS-PAGE and UV absorption spectroscopy. The fusion protein was then loaded into nanovesicles, and their morphology, size, and stability were assessed using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and dynamic light scattering (DLS). In vitro experiments demonstrated that LE@Fc NPs exhibit high fusion efficiency and targeted delivery capability. In vivo experimental results show that LE@Fc NPs significantly inhibit ferroptosis in the epicardial adipose tissue (EAT) of obese mice (iron content: 3.69 ± 0.36 vs. 0.88 ± 0.09), by restoring GSH levels (0.45 ± 0.08 vs. 0.87 ± 0.08) and Gpx4 expression (0.32 ± 0.06 vs. 1.01 ± 0.16), and reducing ROS (12.01 ± 0.95 vs. 2.68 ± 0.17), MDA (3.17 ± 0.29 vs. 0.95 ± 0.09), and 4-HNE (3.74 ± 0.51 vs. 0.91 ± 0.09) levels. Furthermore, LE@Fc NPs treatment significantly improved the inflammatory response (IL-1β: 44.08 ± 3.74 vs. 12.07 ± 0.65, IL-6: 515.59 ± 47.70 vs. 288.43 ± 16.81, MCP-1: 1401.04 ± 194.88 vs. 600.28 ± 45.54, TNF-α: 39.96 ± 2.48 vs. 18.01 ± 0.85). LE@Fc NPs also reduced atrial fibrosis, thereby effectively lowering the incidence of AF. Echocardiography and electrocardiogram monitoring revealed that LE@Fc NPs treatment significantly improved atrial remodeling and reduced the occurrence of AF in obese mice. In addition, LE@Fc NPs significantly improved obesity-induced systemic inflammation and metabolic disorders. In conclusion, LE@Fc NPs show great potential for the treatment of obesity-related AF.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An in vivo imaging approach for simultaneously assessing tumor response and cytotoxicity-induced tissue response in chemotherapy.","authors":"Steven E Johnson, Chad R Haney, Alisha N Spann, Nigar Khurram, Farres Obeidin, Jungwha Lee, Ming Zhao","doi":"10.1007/s10495-025-02118-9","DOIUrl":"https://doi.org/10.1007/s10495-025-02118-9","url":null,"abstract":"<p><p>In chemotherapeutic treatments, while cancer cells are the primary target, cytotoxic side effects are an important consideration. In the current study, we applied an in vivo imaging tool for characterizing chemotherapeutic response in a preclinical setting. The study focused on simultaneously examining the tumor and tissue response as a result of treatment with bortezomib, a mainstay proteasome inhibitor for treating multiple myeloma, in a preclinical model. OPM-2 tumor-bearing SCID-beige mice were designated as control or treated with bortezomib (1 mg/kg, i.v., every 4 days) (n = 8 per group). ^99mTc-duramycin SPECT/CT whole-body scans were acquired 2 days before treatment as baseline and at days 1, 3 and 5 after treatment. Radioactivity uptake in tissues and organs was determined and quantitatively compared between control and bortezomib-treated group at each of the time points. Based on the imaging data, separate groups of tumor-bearing mice (n = 3 each) were included as control and bortezomib treated and the tissues were collected on day 5 for histopathology. In vivo imaging data identified significantly elevated ^99mTc-duramycin uptake in the tumor, particularly in tumoral periphery. This was accompanied with signal changes in multiple organs and tissues including the adipose tissue, major bones, abdominal regions, spleen and testes. The imaging findings were consistent with known cytotoxic side effects of bortezomib and were supported by histopathology. The outcome of the study demonstrated potential utilities of the technology by enabling timely determination of the efficacy of anticancer treatments and the effect on collateral tissues as a result of systemic cytotoxic treatment.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory effect of Wnt signaling on mitochondria in cancer: from mechanism to therapy.","authors":"Jinping Han, Yimeng Yuan, Jianhua Zhang, Yifan Hou, Hongtao Xu, Xiaobo Nie, Zhenhua Zhao, Junqing Hou","doi":"10.1007/s10495-025-02114-z","DOIUrl":"https://doi.org/10.1007/s10495-025-02114-z","url":null,"abstract":"<p><p>Cancer is one of the most significant public health challenges in the new millennium, and complex mechanisms are at work to contribute to its pathogenesis and progression. The Wnt signaling pathways, which are crucial conserved cascades involved in embryological development and tissue homeostasis, and mitochondria, the intracellular powerhouses responsible for energy production, calcium and iron homeostasis, as well as mitochondrial apoptosis in eukaryotic cells, have their own mechanisms regulating these pathological processes. In the past decade, accumulating evidence has indicated that Wnt signaling pathways directly regulate mitochondrial biogenesis and function under physiological and pathological conditions. In this review, we systemically summarize the current understanding of how Wnt signaling pathways, particularly the canonical Wnt cascade, regulate mitochondrial fission, respiration, metabolism, and mitochondrial-dependent apoptosis in cancer. In addition, we discuss recent advancements in the research of anticancer agents and related pharmacological mechanisms targeting the signaling transduction of canonical Wnt pathway and/or mitochondrial function. We believe that the combined use of pharmaceuticals targeting Wnt signaling and/or mitochondria with conventional therapies, immunotherapy and targeted therapy based on accurate molecular pathological diagnosis will undoubtedly be the future mainstream direction of personalized cancer treatment, which could benefit more cancer patients.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolism-related ALDH1B1 acts as potential predictor and therapeutic target for primary gastrointestinal diffuse large B-cell lymphoma.","authors":"Qiqi Qiao, Bingyu Liu, Juanjuan Shang, Wenyue Sun, Xiaoli Zhou, Xiaosheng Fang, Shunfeng Hu, Xin Wang","doi":"10.1007/s10495-025-02112-1","DOIUrl":"https://doi.org/10.1007/s10495-025-02112-1","url":null,"abstract":"<p><p>Primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) is the most common extra-nodal DLBCL. Metabolism-related factors have been associated with tumor progression, but the relationship between abnormal metabolism and prognosis of PGI-DLBCL remains unelucidated. In our study, consensus clustering based on metabolism-related genes classified PGI-DLBCL patients into two metabolic subtypes, and poor prognosis was associated with immunosuppressive microenvironment. A prognostic signature based on five metabolism-related genes (APOE, ALDH6 A1, PLOD2, IKBKB and ALDH1B1) was developed. Patients in high-risk group had a worse prognosis, with an immunosuppressive microenvironment. Moreover, 159 PGI-DLBCL patients were enrolled and divided into training cohort (n = 87) and validation cohort (n = 72). Univariate and multivariate Cox regression analysis showed metabolism-related factors were independent prognostic factors in PGI-DLBCL. A novel model (A-IPI score) combining APOA and NCCN-IPI was developed, and A-IPI score was better than NCCN-IPI score in predicting the prognosis of PGI-DLBCL patients. Furthermore, immunohistochemistry showed that ALDH1B1 was highly expressed in PGI-DLBCL and patients with high ALDH1B1 expression displayed worse prognosis. Moreover, cell proliferation assay revealed that the treatment with IGUANA-1, ALDH1B1 inhibitor, suppressed cell proliferation in DLBCL and IGUANA-1 exerted synergistic anti-tumor effects with PI3K inhibitor duvelisib. Additionally, we found that immune scores, ESTIMATE scores, and stromal scores were higher and the immune checkpoints (CTLA-4, PD-1, PD-L1) were down-regulated in patients with high ALDH1B1 expression. Collectively, our study constructed a novel metabolism-related prognostic model and highlighted the potential of metabolism-related gene ALDH1B1 as prognostic biomarker and drug target in PGI-DLBCL, providing new insights for the development of precision therapies in PGI-DLBCL patients.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal melatonin reprograms liver injury in male pups caused by maternal exposure to a high-fat diet and microplastics.","authors":"Yu-Jen Chen, Hong-Ren Yu, Ching-Chou Tsai, Mao-Meng Tiao","doi":"10.1007/s10495-025-02111-2","DOIUrl":"https://doi.org/10.1007/s10495-025-02111-2","url":null,"abstract":"<p><p>Prenatal exposure to a high-fat diet (HFD) or microplastics can impact liver fat accumulation in offspring. This study investigates the protective effects of prenatal melatonin on liver injury in male pups resulting from maternal exposure to a HFD and microplastics. Pregnant Sprague-Dawley rats were fed either an HFD or a normal chow diet, with some groups exposed to microplastics alone or in combination with melatonin. Male pups were evaluated on postnatal day 7. Results indicated that pups in the HFD-microplastics group (HFD-Mi) exhibited increased liver lipid accumulation (observed in histological staining), apoptosis (elevated cleaved caspase 3, phospho-AKT, and TUNEL staining), inflammation (higher IL- 6 and TNF-α), and oxidative stress (elevated malondialdehyde). Conversely, melatonin treatment (HFD-Mi + M) significantly reduced these effects, including lipid accumulation, apoptosis, and inflammation, while enhancing antioxidant enzyme glutathione peroxidase activity and improving lipid metabolism (reduced SREBP- 1 expression). These findings suggest that prenatal melatonin mitigates liver injury caused by maternal HFD and microplastics through its anti-inflammatory, antioxidative, and lipid-regulating properties, underscoring its potential hepatoprotective role.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: The analog of cGAMP, c-di-AMP, activates STING mediated cell death pathway in estrogen-receptor negative breast cancer cells.","authors":"Hitesh Vasiyani, Anjali Shinde, Milton Roy, Minal Mane, Kritarth Singh, Jyoti Singh, Dhruv Gohel, Fatema Currim, Khushali Vaidya, Mahesh Chhabria, Rajesh Singh","doi":"10.1007/s10495-025-02110-3","DOIUrl":"https://doi.org/10.1007/s10495-025-02110-3","url":null,"abstract":"","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Atorvastatin inhibits the apoptosis of human umbilical vein endothelial cells induced by angiotensin II via the lysosomalmitochondrial axis.","authors":"Ye Chang, Yuan Li, Ning Ye, Xiaofan Guo, Zhao Li, Guozhe Sun, Yingxian Sun","doi":"10.1007/s10495-025-02100-5","DOIUrl":"https://doi.org/10.1007/s10495-025-02100-5","url":null,"abstract":"","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}