International Journal of Biochemistry & Cell Biology最新文献

{"title":"Fungal-mediated synthesis of silver nanoparticles using Porostereum spadiceum and their antioxidant, anti-inflammatory, and antidiabetic activities.","authors":"Adil Sher, Shan Zaib, Ahmad Sohail, Abbas Ahmad, Ali Shan, Abid Ali, Gauhar Rehman","doi":"10.1016/j.biocel.2026.106967","DOIUrl":"https://doi.org/10.1016/j.biocel.2026.106967","url":null,"abstract":"<p><strong>Background: </strong>Nano-biotechnology offers promising strategies to improve human health. This study explores the biosynthesis of silver nanoparticles using Porostereum spadiceum extract (PS-AgNPs) and evaluates their antidiabetic, antioxidant, and anti-inflammatory potential.</p><p><strong>Methods: </strong>PS-Ag-NPs were characterized using UV-Vis spectroscopy, FTIR, XRD, EDX, and SEM. In vitro antidiabetic activity was assessed via α-amylase and α-glucosidase inhibition, glucose adsorption, and yeast glucose uptake assays. Antioxidant activity was evaluated by DPPH radical scavenging, while anti-inflammatory effects were measured through protein denaturation, HRBC membrane stabilization, and heat-induced hemolysis assays. In vivo studies involved alloxan-induced diabetic mice and xylene-induced ear edema models to assess anti-diabetic and anti-inflammatory activities, respectively.</p><p><strong>Results: </strong>Characterization confirmed smooth, spherical, crystalline nanoparticles with functional groups stabilizing bioactive compounds. P. spadiceum extract and PS-Ag-NPs consistently demonstrated enhanced in vitro antidiabetic, antioxidant, and anti-inflammatory activities compared to the extract alone. PS-Ag-NPs exhibited stronger α-amylase (21.4-70.50%; IC₅₀ = 33.12µg/mL) and α-glucosidase inhibition (up to 77.73%; IC₅₀ = 37.76µg/mL) than the extract (12.84-67.69%; IC₅₀ = 42.93µg/mL and 69.55%; IC₅₀ = 51.63µg/mL), while standards showed the highest inhibition (81-84% at 100µg/mL). Similarly, PS-Ag-NPs showed improved yeast glucose uptake (8.83-61.73%; IC₅₀ = 55.47µg/mL) and glucose adsorption (2.10-9.10%; IC₅₀ = 49.24µg/mL) compared to the extract (3.47-57.64%; IC₅₀ = 62.07µg/mL and 1.37-8.33%; IC₅₀ = 50.05µg/mL). In antioxidant analysis, PS-Ag-NPs showed strong DPPH radical scavenging activity (84.76 ± 1.95%; IC₅₀ = 39.90µg/mL), followed by the extract (72.76 ± 1.28%; IC₅₀ = 52.53µg/mL), while the standard exhibited the highest activity (93.73 ± 1.84%; IC₅₀ = 36.49µg/mL). Anti-inflammatory assays showed dose-dependent inhibition, where PS-Ag-NPs exhibited higher protein denaturation inhibition (79.84 ± 1.37%; IC₅₀ = 58.05µg/mL), HRBC membrane stabilization (74.86%; IC₅₀ = 56.25µg/mL), and heat-induced hemolysis inhibition (72.95%; IC₅₀ = 62.76µg/mL) than the extract, while standard drugs showed superior effects. In vivo studies confirmed that PS-Ag-NPs significantly reduced blood glucose levels in diabetic mice and exhibited dose-dependent anti-inflammatory activity comparable to standard drugs.</p><p><strong>Conclusion: </strong>Porostereum spadiceum extract and PS-Ag-NPs demonstrated potent multifunctional bioactivities, indicating their potential as promising nanomedicine candidates for managing oxidative stress, inflammation, and hyperglycemia.</p>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":" ","pages":"106967"},"PeriodicalIF":2.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elaiophylin Exerts Antitumor Effects in Human Breast Cancer Cells by Inducing Apoptosis and Modulating MAPK Signaling: Therapeutic Implications.","authors":"Di Zhang, Shu Li, Jinfeng Zhang, Hongrui Xia, Hui Gao, Xiumin Liang, Weihuan Li","doi":"10.1016/j.biocel.2026.106968","DOIUrl":"https://doi.org/10.1016/j.biocel.2026.106968","url":null,"abstract":"<p><p>Breast cancer (BC) is a leading contributor to cancer-associated deaths among women, underscoring the urgent need for novel therapeutic options. Elaiophylin, a macrocyclic lactone antibiotic, has attracted increasing interest because of its potential antitumor activity. We evaluated the effects of Elaiophylin in human BC cell lines (MCF-7 and MDA-MB-231) and in the non-tumorigenic mammary epithelial cell line MCF-10A. Elaiophylin inhibited breast cancer cell growth and induced G2/M-phase arrest. It also promoted apoptosis, accompanied by increased Bax expression and reduced Bcl-2 levels. Mechanistically, Elaiophylin decreased ERK phosphorylation while increasing p38 MAPK phosphorylation, consistent with modulation of MAPK signaling. Elaiophylin showed comparatively limited cytotoxicity in MCF-10A cells, suggesting preferential activity toward malignant cells. These findings provide mechanistic insight into the antitumor activity of Elaiophylin and support its further preclinical evaluation in breast cancer.</p>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":" ","pages":"106968"},"PeriodicalIF":2.8,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Luteolin prevents hyperoxaluria-induced renal injury by inhibiting crystal deposition and renal inflammation","authors":"Zhenghui Jin ,&nbsp;Shiqing Zhu ,&nbsp;Chengwei Wang ,&nbsp;Tao Wang ,&nbsp;Jihong Liu ,&nbsp;Yue Wu","doi":"10.1016/j.biocel.2026.106909","DOIUrl":"10.1016/j.biocel.2026.106909","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the protective effects of Luteolin (LUT) against hyperoxaluria-induced renal injury and calcium oxalate (CaOx) crystal deposition, and to explore the underlying molecular mechanisms.</div></div><div><h3>Method</h3><div>The targets related to LUT and kidney stones were screened in a variety of databases, and the potential targets and pathways were identified by network pharmacology. Subsequently, the interaction between LUT and the core targets was verified by molecular docking and molecular dynamics simulation. Finally, a glyoxylate-induced kidney stone mouse model and high oxalate-induced HK2 cells were used to verify the effect and potential mechanism of LUT on kidney stone formation.</div></div><div><h3>Results</h3><div>Network pharmacology identified 223 intersecting targets between kidney stones and LUT, with KEGG enrichment highlighting the PI3K/Akt signaling pathway. Molecular docking revealed a strong binding affinity between LUT and p85α (-6.947 kcal/mol), and molecular dynamics simulations confirmed complex stability after 25 ns. In vivo, LUT significantly reduced renal calcium oxalate (CaOx) crystal deposition and alleviated tissue injury in the mouse model. In vitro, LUT effectively inhibited oxalate-induced PI3K/Akt activation and inflammatory cytokine production in HK-2 cells. Furthermore, CETSA analysis suggested a potential target engagement between LUT and p85α.</div></div><div><h3>Conclusion</h3><div>This study suggests a protective effect of LUT against kidney stone formation at multiple levels. Our results indicate that LUT attenuates renal calcium crystal deposition, potentially through the inhibition of the PI3K/Akt signaling pathway. These findings provide new insights into the use of natural products for the prevention of nephrolithiasis.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"194 ","pages":"Article 106909"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146161875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EFNA3-mediated autophagy suppression drives breast cancer proliferation, EMT and metastasis via PI3K/AKT/mTOR axis","authors":"Luoqiang Lin,&nbsp;Yupeng Yang,&nbsp;Zhenlong Zhang,&nbsp;Xihai Chen","doi":"10.1016/j.biocel.2026.106928","DOIUrl":"10.1016/j.biocel.2026.106928","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer is a major contributor to cancer mortality in women, and progression, metastasis, and therapy resistance remain key clinical challenges. Ephrin-A3 (EFNA3) has been implicated in various cancers, but its role in breast cancer and underlying mechanisms remain unclear.</div></div><div><h3>Objective</h3><div>To investigate the clinical significance, functional role, and underlying mechanisms of EFNA3 in breast cancer progression.</div></div><div><h3>Methods</h3><div>EFNA3 expression was assessed in breast cancer tissues and cell lines using sequencing, GEPIA, immunohistochemistry, and western blot. Cell proliferation, apoptosis, migration, invasion, and autophagy were evaluated using standard functional assays, LC3 staining, TEM, and western blot. The xenograft model was established using BALB/c nude mice. The effect of EFNA3 knockdown was evaluated by measuring tumor volume, weight, and relevant biomarkers.</div></div><div><h3>Results</h3><div>EFNA3 was upregulated in breast cancer tissues and was associated with poor prognosis. Silencing EFNA3 inhibited cell proliferation and metastasis, and induced apoptosis and autophagy. Mechanistically, our data suggest that EFNA3 activates the PI3K/AKT/mTOR pathway, which is accompanied by reduced autophagy and enhanced tumor progression. Moreover, in a xenograft model, EFNA3 knockdown reduced tumor growth, enhanced autophagy, and inhibited the PI3K/AKT/mTOR pathway.</div></div><div><h3>Conclusions</h3><div>Collectively, our findings suggest that EFNA3 may promote breast cancer progression, at least in part, by activating PI3K/AKT/mTOR signaling and suppressing autophagy. EFNA3 may represent a potential prognostic biomarker and therapeutic target, pending further clinical validation.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"194 ","pages":"Article 106928"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147322515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ipragliflozin Exerts Anti-Fibrotic Effects via a Novel Multi-Pathway Mechanism: Targeting TLR4/NF-κB /TGF-β1 Cascade.","authors":"Mahdi H Alsugoor, Naif ALSuhaymi, Passant E Moustafa, Mevidette Elmadani, Nehal A Afifi, Ahmed Derzawy, Noha E Ibrahim, Hany M Fayed, Sally A El Awdan","doi":"10.1016/j.biocel.2026.106964","DOIUrl":"https://doi.org/10.1016/j.biocel.2026.106964","url":null,"abstract":"<p><p>Hepatic fibrogenesis represents a significant and escalating global health challenge with few effective treatments. This research explored the anti-fibrotic potential of the sodium-glucose cotransporter 2 (SGLT2) inhibitor Ipragliflozin (IPRA) in a rat model of hepatic fibrogenesis caused by thioacetamide (TAA), with a specific focus on critical pathways of inflammation, fibrosis, and oxidative stress. Groups were designated as follows: a control; a model group receiving TAA (100mg/kg, twice weekly for 6 weeks); and two therapeutic groups receiving TAA plus either a low (3mg/kg/day) or high (6mg/kg/day) oral dose of Ipragliflozin during the final 4 weeks. TAA administration induced severe liver fibrosis, characterized by significant increases in serum ALT, AST, triglycerides, cholesterol, oxidative stress (↓GSH, ↓CAT, ↑MDA), and pro-inflammatory/pro-fibrotic signaling (↑TLR4, ↑IL-1β, ↑NF-κB, ↑TGF-β1). Ipragliflozin treatment, particularly at the 6mg/kg dose, dose-dependently and significantly attenuated these changes. It restored liver function, normalized the lipid profile, reversed oxidative stress by boosting antioxidant defenses, and suppressed the core inflammatory and profibrotic TLR4/IL-1β/TGF-β1/NF-κB axis. Histopathological and immunohistochemical findings confirmed a reduction in fibrosis and inflammation. These findings highlight Ipragliflozin's promise as a multi-faceted therapeutic agent for liver fibrosis.</p>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":" ","pages":"106964"},"PeriodicalIF":2.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147822768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulated epoxy fatty acid metabolism as a driver of pathophysiology: Biosynthesis, metabolism, and therapeutic implications.","authors":"G Akash, Vignesh Sakthivel, M Chandhru, Muhammad Obaid M Alotaibi, Yahya Madkhali, Manikandan Palanisamy, Ajay Guru, Jesu Arockiaraj, S Vijaya Bharathi","doi":"10.1016/j.biocel.2026.106966","DOIUrl":"10.1016/j.biocel.2026.106966","url":null,"abstract":"<p><p>Epoxy fatty acids (EpFAs) are lipid mediators with dual physiological roles. They promote protective vascular and inflammatory responses when enzymatically balanced yet may drive pathological dysfunction when metabolic regulation is disrupted. Recent evidence indicates that, their effects are altered under conditions of metabolic stress, oxidative imbalance or prolonged dietary overexposure. Dysregulated cytochrome P450 (CYP) activity or elevated soluble epoxide hydrolase (sEH) expression disrupts the natural epoxide-to-diol balance, enhancing the formation of diol metabolites increasingly linked to cytotoxicity, mitochondrial dysfunction, and tissue injury. Exogenous EpFAs generated during repeated high-temperature frying accumulate in the diet at levels capable of promoting toxic diol formation, particularly from linoleic acid (LA) derived epoxy hydroxy octadecenoic acids (EpHOMEs). These metabolites have been associated with pulmonary injury and immune dysfunction in critical illness. In contrast, omega-3-derived epoxy metabolites demonstrate opposing actions, limiting angiogenesis and tumour dissemination. Together, the contrasting actions of EpFAs reflect a delicately balanced metabolic system in which enzymatic equilibrium determines whether these lipid mediators act as cytoprotective signals or drivers of pathology. Understanding EpFAs biosynthesis, dietary sources, and sEH - dependent bioactivation is important for developing targeted therapeutic strategies and establishing a clear regulatory framework for edible oil safety.</p>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":" ","pages":"106966"},"PeriodicalIF":2.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147822790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircTHBS1 aggravates peritoneal fibrosis by sponging miR-18a-5p and interacting with CTGF","authors":"Yanhong Guo ,&nbsp;Silu Zhao ,&nbsp;Xuewen Zhang,&nbsp;Liuwei Wang,&nbsp;Yulin Wang,&nbsp;Qiuhong Li,&nbsp;Zihan Zhai,&nbsp;Lu Yu,&nbsp;Lin Tang","doi":"10.1016/j.biocel.2026.106907","DOIUrl":"10.1016/j.biocel.2026.106907","url":null,"abstract":"<div><h3>Background</h3><div>Peritoneal fibrosis is a serious complication of long-term peritoneal dialysis (PD). Previous studies have demonstrated that circular RNAs (circRNAs) play an important role in organ fibrosis. However, whether circRNAs are involved in the progression of peritoneal fibrosis remains largely elusive. This study aimed to investigate the role of circRNAs in peritoneal fibrosis and clarify the underlying mechanisms.</div></div><div><h3>Methods</h3><div>CircRNA expression in peritoneal mesothelial cells derived from peritoneal dialysis effluent was profiled using a human circRNA microarray. The function of circTHBS1 was studied through gene silencing and overexpression. qRT-PCR and western blotting were used to detect the expression of relevant molecules. PD mouse models with adeno-associated virus (AAV)-mediated circTHBS1 knockdown were established to investigate the role of circTHBS1 in peritoneal fibrosis using histological staining and peritoneal function analyses.</div></div><div><h3>Results</h3><div>CircTHBS1 was significantly upregulated in peritoneal mesothelial cells from long-term PD patients and was positively correlated with the expression of fibronectin, alpha-smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF). Silencing circTHBS1 suppressed epithelial-mesenchymal transition (EMT) in HMrSV5 cells. In vivo, circTHBS1 knockdown significantly alleviated peritoneal thickening and fibrosis, lowered α-SMA expression, and improved peritoneal function in PD mice. Mechanistically, circTHBS1 acted as a sponge for miR-18a-5p, relieving its repression of CTGF, and directly interacted with CTGF, thereby enhancing its stability. CTGF silencing partially attenuated EMT induced by circTHBS1 overexpression and miR-18a-5p inhibition.</div></div><div><h3>Conclusion</h3><div>This study suggests that circTHBS1 could be a candidate target for the treatment of peritoneal fibrosis.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"193 ","pages":"Article 106907"},"PeriodicalIF":2.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MFN2 interacts with phosphorylated AMPK to mediate mitophagy in MCF-7 cells","authors":"Shixian Zhai ,&nbsp;Zihong Huang ,&nbsp;Chunchun An,&nbsp;Lu Gao,&nbsp;Tongsheng Chen","doi":"10.1016/j.biocel.2026.106906","DOIUrl":"10.1016/j.biocel.2026.106906","url":null,"abstract":"<div><div>Mitofusin 2 (MFN2) has been reported to play an important role in mitophagy, but how MFN2 mediates mitophagy remains incompletely understood. Here, we establish that MFN2 upregulation is a key driver of mitophagy in MCF-7 cells. MFN2 overexpression triggers mitochondrial degradation, as verified by multiple mitophagy markers, whereas MFN2 knockdown abolishes the mitophagic response induced by Leflunomide (Lef), a compound that promotes mitophagy by upregulating MFN2. To elucidate the underlying mechanism, fluorescence imaging and subcellular fractionation reveal that MFN2 promotes AMP-activated protein kinase (AMPK) phosphorylation at Thr172 and facilitates translocation of AMPK from the cytoplasm to mitochondria. Quantitative Förster resonance energy transfer (FRET) analysis supports phosphorylation-dependent formation of an MFN2–AMPK complex in cells, and site-directed mutagenesis supports Thr172 phosphorylation dependence, as the phosphomimetic AMPK (T172D) mutant exhibits enhanced complex formation with MFN2, while the phosphodeficient AMPK (T172A) mutant shows little or no complex formation with MFN2. Co-immunoprecipitation further supports an MFN2–AMPK complex in cells. The MFN2-AMPK complex is essential for mitophagy: Compound C, a pharmacological inhibitor of AMPK, prevents both MFN2-AMPK complex formation and mitophagy, even in cells overexpressing MFN2. Notably, AMPK activation through Acadesine (AICAR) treatment is insufficient to induce mitophagy, but it markedly enhances mitophagy markers when combined with MFN2 overexpression. In conclusion, MFN2 mediates efficient mitophagy by recruiting Thr172-phosphorylated AMPK to mitochondria through a phosphorylation-dependent MFN2–AMPK complex.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"193 ","pages":"Article 106906"},"PeriodicalIF":2.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research and application of direct current in medicine: From cellular and molecular mechanisms to clinical application in ophthalmology","authors":"Chunyang Cai ,&nbsp;Yuntian Wan ,&nbsp;Qingquan Wei ,&nbsp;Xinyi Lai ,&nbsp;Qinghua Qiu","doi":"10.1016/j.biocel.2026.106908","DOIUrl":"10.1016/j.biocel.2026.106908","url":null,"abstract":"<div><div>Direct current (DC) is a direction-constant current, and the research on its biological mechanism is expanding from traditional physical therapy to the field of precision medicine. This comprehensive review systematically summarizes the physical properties of DC and its core biological effects (ion migration, electroosmosis, and electrophoresis) and focuses on the cellular mechanisms and clinical applications in tissue repair and regeneration (e.g., wound healing and angiogenesis) and neurological disease treatment (e.g., modulation of neuroplasticity by transcranial DC stimulation). This review focuses on the field of ophthalmology, where DC stimulation has been shown to promote orderly corneal repair, modulate aqueous humor dynamics to reduce intraocular pressure in patients with glaucoma, and ameliorate retinal degenerative diseases and central visual dysfunction. Although DC therapy in ophthalmology has shown unique advantages, including precise targeting, minimal invasiveness, synergistic drug enhancement, and regenerative potential, its clinical translation still faces challenges in safety control, precise targeted delivery, and individualized treatment. In the future, it is necessary to promote the integration of medical and engineering fields, explore electro-drug synergistic strategies, develop intelligent closed-loop systems, and standardize clinical protocols, so as to provide new solutions to break through the bottleneck of the treatment of refractory ocular disease.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"193 ","pages":"Article 106908"},"PeriodicalIF":2.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PROTAC-mediated degradation of Class I HDACs by JPS016 alleviates septic cardiomyopathy via mitophagy-driven exopher formation and mitochondrial quality control","authors":"Zhaokai Li,&nbsp;Weijian Zhang,&nbsp;Guoqiang Zhang","doi":"10.1016/j.biocel.2026.106910","DOIUrl":"10.1016/j.biocel.2026.106910","url":null,"abstract":"<div><div>Septic cardiomyopathy (SCM) is a severe complication of sepsis with limited targeted treatment options, largely due to mitochondrial dysfunction in cardiomyocytes. Exophers, extracellular vesicles responsible for removing damaged mitochondria, represent a newly recognized mechanism of mitochondrial quality control, yet their upstream regulation remains unclear. This study tested the hypothesis that targeted degradation of Class I histone deacetylases (HDACs) using a PROTAC compound, JPS016, could alleviate SCM by promoting mitophagy-dependent exopher formation. An <em>in vitro</em> SCM model was established in HL-1 cardiomyocytes treated with lipopolysaccharide (LPS), and the effects of JPS016 on mitochondrial homeostasis, HDAC degradation, histone modifications, mitophagy, and exopher production were assessed using molecular and imaging techniques. JPS016 treatment significantly enhanced cell viability, reduced mitochondrial damage, and increased both histone acetylation and lactylation. Mechanistically, JPS016 activated the PINK1/Parkin mitophagy pathway and markedly increased the formation of exophers. Pharmacological inhibition experiments demonstrated that mitophagy, rather than general autophagy, was essential for exopher biogenesis and the protective effect of JPS016. These findings identify HDAC degradation as a novel upstream regulator of exopher-mediated mitochondrial clearance and support the therapeutic potential of PROTAC-based interventions in SCM.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"192 ","pages":"Article 106910"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146195934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}