Acquired cisplatin resistance poses a major challenge in ovarian cancer management. This study investigated the role of protein arginine methyltransferase 5 (PRMT5) in this context. Using cisplatin-resistant ovarian cancer cell lines (A2780/DDP and SKOV3/DDP), we found that PRMT5 knockdown significantly inhibited cell proliferation, colony formation, migration, and invasion, while promoting apoptosis. Mechanistically, co-immunoprecipitation assays revealed that PRMT5, in complex with MEP50, interacts with and specifically methylates Smad7 at the R57 site in vitro. This methylation event was essential for activating the STAT3 signaling pathway and driving the observed malignant phenotypes. Consistent with a key oncogenic role for Smad7, in vivo knockdown of Smad7 in a xenograft mouse model markedly suppressed tumor growth and downregulated markers of proliferation (Ki67), invasion (MMP9, N-cadherin), while upregulating the tumor suppressor E-cadherin. In conclusion, our work identifies Smad7 as a critical driver of cisplatin resistance in vivo and delineates a novel in vitro mechanism whereby PRMT5 promotes oncogenic signaling through R57 methylation of Smad7. This PRMT5-Smad7 axis presents a promising therapeutic target for overcoming cisplatin resistance in ovarian cancer.
{"title":"Smad7 drives cisplatin resistance in ovarian cancer via a PRMT5-dependent mechanism","authors":"Jinlong Ji, Kexin Wang, Geshuyi Chen, Manman Zhao, Cong Wan, Yun Han, Yanli Zheng","doi":"10.1016/j.tice.2025.103304","DOIUrl":"10.1016/j.tice.2025.103304","url":null,"abstract":"<div><div>Acquired cisplatin resistance poses a major challenge in ovarian cancer management. This study investigated the role of protein arginine methyltransferase 5 (PRMT5) in this context. Using cisplatin-resistant ovarian cancer cell lines (A2780/DDP and SKOV3/DDP), we found that PRMT5 knockdown significantly inhibited cell proliferation, colony formation, migration, and invasion, while promoting apoptosis. Mechanistically, co-immunoprecipitation assays revealed that PRMT5, in complex with MEP50, interacts with and specifically methylates Smad7 at the R57 site in vitro. This methylation event was essential for activating the STAT3 signaling pathway and driving the observed malignant phenotypes. Consistent with a key oncogenic role for Smad7, in vivo knockdown of Smad7 in a xenograft mouse model markedly suppressed tumor growth and downregulated markers of proliferation (Ki67), invasion (MMP9, N-cadherin), while upregulating the tumor suppressor E-cadherin. In conclusion, our work identifies Smad7 as a critical driver of cisplatin resistance in vivo and delineates a novel in vitro mechanism whereby PRMT5 promotes oncogenic signaling through R57 methylation of Smad7. This PRMT5-Smad7 axis presents a promising therapeutic target for overcoming cisplatin resistance in ovarian cancer.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103304"},"PeriodicalIF":2.5,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145967288","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}
Pub Date : 2025-12-30DOI: 10.1016/j.tice.2025.103299
Jing Yan , Yifeng Pan , Zhu Liu , Yulin Chen , Kai Hu , Yuanyuan Liu , Guangyao Wang , Liqun Li , Sheng Xie
Background
Xuan-Bi-Qing-Ying Decoction (XBQYD), a Traditional Chinese Medicine (TCM) formula modified based on clinical experience, has demonstrated efficacy and safety in the treatment of septic liver injury (SLI).
Methods
The absorbed components of XBQYD were characterized in vivo using LC-MS/MS. A rat model of septic liver injury (SLI) was then established by cecal ligation and puncture. To evaluate the preventive efficacy of XBQYD, rats were pretreated with the formula for seven days prior to injury induction. Subsequently, we evaluated liver histopathology (HE staining), measured serum inflammatory cytokines (IL-1β, IL-6, TNF-α), oxidative stress markers (MDA, SOD) with commercial kits, and assessed liver function via biochemical analysis. To investigate the mechanism, network pharmacology was combined with Mendelian randomization (MR) analysis, which identified HIF1A as a core predicted target. Based on this prediction, the influence of XBQYD pretreatment on the HIF‑1α pathway was measured in liver tissue at both mRNA and protein levels, along with its downstream effects on autophagy and apoptosis. Finally, molecular docking and dynamics simulations were used to investigate potential direct interactions between key XBQYD constituents and HIF-1α.
Results
A total of 22 bioactive components derived from XBQYD were identified in vivo. In SLI rats, pretreatment with XBQYD significantly mitigated liver histological damage, decreased pro-inflammatory cytokine levels and oxidative stress, and restored liver function. Network pharmacology revealed 233 intersecting targets of XBQYD and SLI. KEGG and PPI analyses highlighted the HIF-1 signaling pathway and 50 core targets, including HIF1A. MR analysis confirmed that HIF1A may increase the risk of sepsis and sepsis-related 28-day mortality. This preventive effect was associated with the inhibition of the HIF-1α pathway activation by XBQYD pretreatment, which correlated with enhanced autophagy and suppressed apoptosis. Molecular docking and dynamics simulations demonstrated stable interactions between key XBQYD constituents (Quercetin, Delphinidin, and Azaleatin) and HIF-1α.
Conclusion
Our study demonstrates that pretreatment with XBQYD exerts a preventive effect against SLI in rats by inhibiting the HIF-1α signaling pathway. These findings provide a mechanistic basis for considering XBQYD as a potential preventive strategy for SLI.
{"title":"Modified Xuan-Bi-Qing-Ying decoction alleviates septic liver injury by regulating autophagy and apoptosis via HIF-1α signaling pathway","authors":"Jing Yan , Yifeng Pan , Zhu Liu , Yulin Chen , Kai Hu , Yuanyuan Liu , Guangyao Wang , Liqun Li , Sheng Xie","doi":"10.1016/j.tice.2025.103299","DOIUrl":"10.1016/j.tice.2025.103299","url":null,"abstract":"<div><h3>Background</h3><div>Xuan-Bi-Qing-Ying Decoction (XBQYD), a Traditional Chinese Medicine (TCM) formula modified based on clinical experience, has demonstrated efficacy and safety in the treatment of septic liver injury (SLI).</div></div><div><h3>Methods</h3><div>The absorbed components of XBQYD were characterized in vivo using LC-MS/MS. A rat model of septic liver injury (SLI) was then established by cecal ligation and puncture. To evaluate the preventive efficacy of XBQYD, rats were pretreated with the formula for seven days prior to injury induction. Subsequently, we evaluated liver histopathology (HE staining), measured serum inflammatory cytokines (IL-1β, IL-6, TNF-α), oxidative stress markers (MDA, SOD) with commercial kits, and assessed liver function via biochemical analysis. To investigate the mechanism, network pharmacology was combined with Mendelian randomization (MR) analysis, which identified HIF1A as a core predicted target. Based on this prediction, the influence of XBQYD pretreatment on the HIF‑1α pathway was measured in liver tissue at both mRNA and protein levels, along with its downstream effects on autophagy and apoptosis. Finally, molecular docking and dynamics simulations were used to investigate potential direct interactions between key XBQYD constituents and HIF-1α.</div></div><div><h3>Results</h3><div>A total of 22 bioactive components derived from XBQYD were identified in vivo. In SLI rats, pretreatment with XBQYD significantly mitigated liver histological damage, decreased pro-inflammatory cytokine levels and oxidative stress, and restored liver function. Network pharmacology revealed 233 intersecting targets of XBQYD and SLI. KEGG and PPI analyses highlighted the HIF-1 signaling pathway and 50 core targets, including HIF1A. MR analysis confirmed that HIF1A may increase the risk of sepsis and sepsis-related 28-day mortality. This preventive effect was associated with the inhibition of the HIF-1α pathway activation by XBQYD pretreatment, which correlated with enhanced autophagy and suppressed apoptosis. Molecular docking and dynamics simulations demonstrated stable interactions between key XBQYD constituents (Quercetin, Delphinidin, and Azaleatin) and HIF-1α.</div></div><div><h3>Conclusion</h3><div>Our study demonstrates that pretreatment with XBQYD exerts a preventive effect against SLI in rats by inhibiting the HIF-1α signaling pathway. These findings provide a mechanistic basis for considering XBQYD as a potential preventive strategy for SLI.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103299"},"PeriodicalIF":2.5,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883415","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}
Pub Date : 2025-12-29DOI: 10.1016/j.tice.2025.103301
Abdullah Albelasi , Suad A. Alghamdi , Mohammed Alissa
Diabetic wounds are characterized by delayed healing due to impaired angiogenesis, chronic inflammation, and defective extracellular matrix formation. This study evaluated the therapeutic potential of a fibrin hydrogel incorporating microspheres loaded with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) (FHM) in promoting wound repair in a streptozotocin-induced diabetic rat model. Rats were randomly assigned to control, fibrin hydrogel alone (FH), or FHM groups, and wounds were assessed on days 7 and 14. Mechanical properties, stereological parameters, collagen deposition, and cytokine expression were analyzed. FHM treatment significantly improved tensile strength and stress-bearing capacity of the wound tissue compared to FH and control groups (P < 0.05). Stereological analysis revealed increased fibroblast proliferation and neovascularization, with a concomitant reduction in inflammatory cell infiltration in FHM-treated wounds at both time points (P < 0.05). Masson's trichrome staining demonstrated enhanced collagen deposition and maturation in the FHM group, indicating improved extracellular matrix remodeling. Molecular analysis showed elevated transforming growth factor beta (TGF-β) and VEGF expression, alongside decreased pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β), suggesting a dual effect of promoting regeneration while attenuating inflammation. This multimodal approach holds promise as a potential therapeutic strategy for chronic diabetic wounds, offering both functional and structural benefits. Further long-term studies and clinical translation are warranted to evaluate safety and efficacy in human patients.
{"title":"Fibrin hydrogel incorporated with microspheres containing vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) accelerated the healing of diabetic wounds in rats","authors":"Abdullah Albelasi , Suad A. Alghamdi , Mohammed Alissa","doi":"10.1016/j.tice.2025.103301","DOIUrl":"10.1016/j.tice.2025.103301","url":null,"abstract":"<div><div>Diabetic wounds are characterized by delayed healing due to impaired angiogenesis, chronic inflammation, and defective extracellular matrix formation. This study evaluated the therapeutic potential of a fibrin hydrogel incorporating microspheres loaded with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) (FHM) in promoting wound repair in a streptozotocin-induced diabetic rat model. Rats were randomly assigned to control, fibrin hydrogel alone (FH), or FHM groups, and wounds were assessed on days 7 and 14. Mechanical properties, stereological parameters, collagen deposition, and cytokine expression were analyzed. FHM treatment significantly improved tensile strength and stress-bearing capacity of the wound tissue compared to FH and control groups (P < 0.05). Stereological analysis revealed increased fibroblast proliferation and neovascularization, with a concomitant reduction in inflammatory cell infiltration in FHM-treated wounds at both time points (P < 0.05). Masson's trichrome staining demonstrated enhanced collagen deposition and maturation in the FHM group, indicating improved extracellular matrix remodeling. Molecular analysis showed elevated transforming growth factor beta (TGF-β) and VEGF expression, alongside decreased pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β), suggesting a dual effect of promoting regeneration while attenuating inflammation. This multimodal approach holds promise as a potential therapeutic strategy for chronic diabetic wounds, offering both functional and structural benefits. Further long-term studies and clinical translation are warranted to evaluate safety and efficacy in human patients.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103301"},"PeriodicalIF":2.5,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883479","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}
Pub Date : 2025-12-29DOI: 10.1016/j.tice.2025.103303
Ruiting Qin , Zhijuan Liu , Ran Li , Yongxia Li , Yuan Yang , Li Ai
Background
Chronic intermittent hypoxia (CIH) is a typical pathological feature of obstructive sleep apnea (OSA), and CIH can induce lung injury and aggravate the existing lung injury. The inflammatory response, oxidative stress and apoptosis are the key events of CIH-induced lung injury, while Sirtuin 6 (SIRT6) plays a key role in the regulation of biological processes such as inflammation, cell proliferation and oxidative stress. Therefore, this study aimed to further investigate the function of SIRT6 in CIH-induced lung injury.
Methods
We established CIH-induced rat lung (O2, 5–20.9 %; cycle frequency, 90 s; duration of exposure, 8 h/day for 4weeks) and human bronchial epithelial cells (BEAS-2B) (1 % O2 for 60 min; 21 % O2 for 30 min; 24 h exposure) injury models. The expression of related proteins was detected by ELISA, western blotting, and immunohistochemistry. The damage of lung tissues was detected via Masson staining and HE staining.
Results
This study revealed that the expression of SIRT6 decreased, while inflammatory cytokines IL-6, TNF-α, and IL-1β and cell apoptosis increased, and the level of oxidative stress rose in CIH-induced rat lung tissue and BEAS-2B cells. The overexpression of SIRT6 inhibited the levels of inflammatory cytokines, oxidative stress and apoptosis in CIH-induced rat lung tissue and BEAS-2B cells and relieved the lung injury. Mechanistically, SIRT6 stabilized NRF2 expression via deacetylation to promote NRF2 nuclear translocation and activate HO-1 expression, thereby inhibiting CIH-induced inflammation, oxidative stress and apoptosis and thus alleviating CIH-induced lung injury.
Conclusion
Our study revealed that SIRT6 inhibited CIH-induced lung injury through the NRF2/HO-1 signaling axis and that SIRT6 may be a new target for the treatment of CIH-induced lung injury.
{"title":"SIRT6 inhibits intermittent hypoxia-induced lung injury by stabilizing NRF2","authors":"Ruiting Qin , Zhijuan Liu , Ran Li , Yongxia Li , Yuan Yang , Li Ai","doi":"10.1016/j.tice.2025.103303","DOIUrl":"10.1016/j.tice.2025.103303","url":null,"abstract":"<div><h3>Background</h3><div>Chronic intermittent hypoxia (CIH) is a typical pathological feature of obstructive sleep apnea (OSA), and CIH can induce lung injury and aggravate the existing lung injury. The inflammatory response, oxidative stress and apoptosis are the key events of CIH-induced lung injury, while Sirtuin 6 (SIRT6) plays a key role in the regulation of biological processes such as inflammation, cell proliferation and oxidative stress. Therefore, this study aimed to further investigate the function of SIRT6 in CIH-induced lung injury.</div></div><div><h3>Methods</h3><div>We established CIH-induced rat lung (O<sub>2</sub>, 5–20.9 %; cycle frequency, 90 s; duration of exposure, 8 h/day for 4weeks) and human bronchial epithelial cells (BEAS-2B) (1 % O<sub>2</sub> for 60 min; 21 % O<sub>2</sub> for 30 min; 24 h exposure) injury models. The expression of related proteins was detected by ELISA, western blotting, and immunohistochemistry. The damage of lung tissues was detected via Masson staining and HE staining.</div></div><div><h3>Results</h3><div>This study revealed that the expression of SIRT6 decreased, while inflammatory cytokines IL-6, TNF-α, and IL-1β and cell apoptosis increased, and the level of oxidative stress rose in CIH-induced rat lung tissue and BEAS-2B cells. The overexpression of SIRT6 inhibited the levels of inflammatory cytokines, oxidative stress and apoptosis in CIH-induced rat lung tissue and BEAS-2B cells and relieved the lung injury. Mechanistically, SIRT6 stabilized NRF2 expression via deacetylation to promote NRF2 nuclear translocation and activate HO-1 expression, thereby inhibiting CIH-induced inflammation, oxidative stress and apoptosis and thus alleviating CIH-induced lung injury.</div></div><div><h3>Conclusion</h3><div>Our study revealed that SIRT6 inhibited CIH-induced lung injury through the NRF2/HO-1 signaling axis and that SIRT6 may be a new target for the treatment of CIH-induced lung injury.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103303"},"PeriodicalIF":2.5,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883478","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}
Pub Date : 2025-12-29DOI: 10.1016/j.tice.2025.103302
Jingwen Chen , Feilong Li , Zhengwen Su , Yuheng He , Tao Liu , Yingjin Luo , Xianghan Hou , Chao Song , Zongchao Liu , Pandeng Hao
The pathological mechanism of osteoarthritis (OA) has evolved from being viewed as "simple mechanical wear" to being recognized as a chronic inflammatory disease driven by immune responses, metabolic imbalance, and mechanical stress. Synovial macrophages play a central role in the remodeling of the immune microenvironment, and their heterogeneity along with the imbalance between M1/M2 polarization can synergistically enhance joint inflammation, reprogram cartilage metabolism, and exacerbate tissue damage. Signaling networks such as NF-κB/MAPK, JAK/STAT, PI3K/Akt/mTOR–AMPK, Nrf2, Notch, and Wnt/β-catenin collectively regulate their polarization spectrum and functional states. The NLRP3 inflammasome–caspase-1–GSDMD axis-mediated pyroptosis serves as a key driver of disease initiation and progression, establishing a "polarization–metabolism–pyroptosis" tripartite pathological framework. The tripartite interaction among chondrocytes, fibroblast-like synoviocytes, and macrophages (CC–FLS–MC) further forms a cross-cellular inflammatory amplification network.Targeting these mechanisms, intervention strategies focus on multi-level immune modulation, including blocking the NLRP3–caspase-1–GSDMD pyroptosis axis, regulating macrophage polarization and metabolic reprogramming, and developing cell/nanocarrier-based drug delivery systems. Specific approaches encompass small-molecule inhibitors (e.g., NLRP3 and pyroptosis inhibitors), Nrf2/PPARγ agonists, MSC- or M2 macrophage-derived exosomes, and biomimetic nanoplatforms. These strategies aim to achieve "inhibition of the M1–pyroptosis–inflammatory cascade and promotion of M2–repair–metabolic reprogramming." In summary, comprehensive immune regulation targeting the coupling of macrophage polarization and pyroptosis, along with its metabolic basis, holds promise for providing new theoretical foundations and translational pathways for disease-modifying therapies and precision management of OA.
{"title":"Coupling regulation the pyroptosis and polarization of macrophage: Novel insights into the pathogenesis and immunotherapy of osteoarthritis","authors":"Jingwen Chen , Feilong Li , Zhengwen Su , Yuheng He , Tao Liu , Yingjin Luo , Xianghan Hou , Chao Song , Zongchao Liu , Pandeng Hao","doi":"10.1016/j.tice.2025.103302","DOIUrl":"10.1016/j.tice.2025.103302","url":null,"abstract":"<div><div>The pathological mechanism of osteoarthritis (OA) has evolved from being viewed as \"simple mechanical wear\" to being recognized as a chronic inflammatory disease driven by immune responses, metabolic imbalance, and mechanical stress. Synovial macrophages play a central role in the remodeling of the immune microenvironment, and their heterogeneity along with the imbalance between M1/M2 polarization can synergistically enhance joint inflammation, reprogram cartilage metabolism, and exacerbate tissue damage. Signaling networks such as NF-κB/MAPK, JAK/STAT, PI3K/Akt/mTOR–AMPK, Nrf2, Notch, and Wnt/β-catenin collectively regulate their polarization spectrum and functional states. The NLRP3 inflammasome–caspase-1–GSDMD axis-mediated pyroptosis serves as a key driver of disease initiation and progression, establishing a \"polarization–metabolism–pyroptosis\" tripartite pathological framework. The tripartite interaction among chondrocytes, fibroblast-like synoviocytes, and macrophages (CC–FLS–MC) further forms a cross-cellular inflammatory amplification network.Targeting these mechanisms, intervention strategies focus on multi-level immune modulation, including blocking the NLRP3–caspase-1–GSDMD pyroptosis axis, regulating macrophage polarization and metabolic reprogramming, and developing cell/nanocarrier-based drug delivery systems. Specific approaches encompass small-molecule inhibitors (e.g., NLRP3 and pyroptosis inhibitors), Nrf2/PPARγ agonists, MSC- or M2 macrophage-derived exosomes, and biomimetic nanoplatforms. These strategies aim to achieve \"inhibition of the M1–pyroptosis–inflammatory cascade and promotion of M2–repair–metabolic reprogramming.\" In summary, comprehensive immune regulation targeting the coupling of macrophage polarization and pyroptosis, along with its metabolic basis, holds promise for providing new theoretical foundations and translational pathways for disease-modifying therapies and precision management of OA.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103302"},"PeriodicalIF":2.5,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878953","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}
The vitreous humor is a gel-like substance that fills the vitreous cavity. Its function is to transmit light to the retina and to provide structural support. With aging or diabetic vitreopathy, vitreous detachment can lead to visual impairment, highlighting an urgent need for innovative diagnostics and therapies. Exosomes are nanovesicles of the intercellular space, composed of biomolecules such as RNA, lipids, and proteins. Exosomes play critical roles in both ocular physiology and pathology, including within the vitreous. Essentially, the vitreous fluid is an intermediary for the exchange of these vesicles. Exosomes through facilitating communication between retinal cells, influence cellular functions, and promote regeneration modulation of inflammatory responses, and ultimately play a key role in maintaining ocular health. This review synthesizes current evidence on vitreous exosomes as mediators of ocular homeostasis, disease biomarkers, and novel therapeutic vehicles.
{"title":"Vitreous exosomes and ocular regeneration: Emerging roles in intercellular communication, biomarkers, and therapeutic delivery","authors":"Gelavizh Rostaminasab , Farbod Ghobadinezhad , Parnian Yavari , Fatemeh Zoghi , Armin Mansourisarabbadieh , Masood Bagheri , Amirhossein Haghbar , Leila Rezakhani","doi":"10.1016/j.tice.2025.103300","DOIUrl":"10.1016/j.tice.2025.103300","url":null,"abstract":"<div><div>The vitreous humor is a gel-like substance that fills the vitreous cavity. Its function is to transmit light to the retina and to provide structural support. With aging or diabetic vitreopathy, vitreous detachment can lead to visual impairment, highlighting an urgent need for innovative diagnostics and therapies. Exosomes are nanovesicles of the intercellular space, composed of biomolecules such as RNA, lipids, and proteins. Exosomes play critical roles in both ocular physiology and pathology, including within the vitreous. Essentially, the vitreous fluid is an intermediary for the exchange of these vesicles. Exosomes through facilitating communication between retinal cells, influence cellular functions, and promote regeneration modulation of inflammatory responses, and ultimately play a key role in maintaining ocular health. This review synthesizes current evidence on vitreous exosomes as mediators of ocular homeostasis, disease biomarkers, and novel therapeutic vehicles.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103300"},"PeriodicalIF":2.5,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878954","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}
Pub Date : 2025-12-26DOI: 10.1016/j.tice.2025.103295
Heba F. Ibrahim , Eman H. Thabet , Sara Assem , Basma Mady , Soha Elatrebi , Manal Ahmed Ali , Eiman I. Zaki
Chronic pancreatitis is a critical health problem that is usually complicated by pancreatic fibrosis and diabetes mellitus. Nicotine is a considerable etiological risk factor for this condition. Our research was constructed to explore and compare between the possible therapeutic roles of adipose tissue- derived mesenchymal stem cells (AT- MSCs) and puerarin (Pue) in improving nicotine-induced pancreatic fibrosis. Rats were randomly distributed into: group I; control rats and group II; nicotine- treated rats. Group II was further divided into; model, AT-MSCs- treated, Pue-treated and withdrawal groups. Weight gain study and intraperitoneal glucose tolerance tests were assessed. Pancreatic tissue was processed for measurement of amylase, lipase, interleukin- 6, malondialdehyde and superoxide dismutase. Furthermore, quantitative RT-PCR of caspase-3, transforming growth factor-beta1 (TGF- β1), alpha-smooth muscle actin (α-SMA) and collagen I, was performed. Histopathological, immunohistochemical and ultra-structural examinations were conducted as well. We found that administration of AT- MSCs and Pue helped to increase insulin secretion and suppress inflammatory oxidative stress parameters. In addition, apoptosis and fibrosis were receded through declining of caspase-3 and elements of TGF-β1/α-SMA/collagen I fibrotic pathway. The pancreatic architecture was restored to a great extent. However, AT-MSCs caused a marked pancreatic improvement and regeneration when compared to Pue which resulted in only a moderate amelioration. Insignificant and difficultly detectable spontaneous recovery was noticed in the withdrawal group. Both AT-MSCs and Pue have a promising effectiveness as targeted therapeutic agents against nicotine- induced pancreatic fibrosis, with a higher efficiency of AT- MSCs.
{"title":"Adipose tissue- derived mesenchymal stem cells versus puerarin for ameliorating nicotine- induced pancreatic fibrosis in rats","authors":"Heba F. Ibrahim , Eman H. Thabet , Sara Assem , Basma Mady , Soha Elatrebi , Manal Ahmed Ali , Eiman I. Zaki","doi":"10.1016/j.tice.2025.103295","DOIUrl":"10.1016/j.tice.2025.103295","url":null,"abstract":"<div><div>Chronic pancreatitis is a critical health problem that is usually complicated by pancreatic fibrosis and diabetes mellitus. Nicotine is a considerable etiological risk factor for this condition. Our research was constructed to explore and compare between the possible therapeutic roles of adipose tissue- derived mesenchymal stem cells (AT- MSCs) and puerarin (Pue) in improving nicotine-induced pancreatic fibrosis. Rats were randomly distributed into: group I; control rats and group II; nicotine- treated rats. Group II was further divided into; model, AT-MSCs- treated, Pue-treated and withdrawal groups. Weight gain study and intraperitoneal glucose tolerance tests were assessed. Pancreatic tissue was processed for measurement of amylase, lipase, interleukin- 6, malondialdehyde and superoxide dismutase. Furthermore, quantitative RT-PCR of caspase-3, transforming growth factor-beta1 (TGF- β1), alpha-smooth muscle actin (α-SMA) and collagen I, was performed. Histopathological, immunohistochemical and ultra-structural examinations were conducted as well. We found that administration of AT- MSCs and Pue helped to increase insulin secretion and suppress inflammatory oxidative stress parameters. In addition, apoptosis and fibrosis were receded through declining of caspase-3 and elements of TGF-β1/α-SMA/collagen I fibrotic pathway. The pancreatic architecture was restored to a great extent. However, AT-MSCs caused a marked pancreatic improvement and regeneration when compared to Pue which resulted in only a moderate amelioration. Insignificant and difficultly detectable spontaneous recovery was noticed in the withdrawal group. Both AT-MSCs and Pue have a promising effectiveness as targeted therapeutic agents against nicotine- induced pancreatic fibrosis, with a higher efficiency of AT- MSCs.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103295"},"PeriodicalIF":2.5,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145865682","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}
Extracellular vesicles (EVs) serve as crucial vehicles for the intercellular transfer of bioactive molecules. While the mechanisms of EV biogenesis are well characterized in mammals, they remain comparatively understudied in invertebrates. This knowledge gap is particularly notable for the medicinal leech, Hirudo nipponia. In this study, the ultrastructural features of Hirudo nipponia salivary glands in resting and secretory states were analyzed using scanning and transmission electron microscopy to investigate the biogenesis and release of EVs. For the first time, it is demonstrated that salivary gland cells possess dual pathways for EV biogenesis: a classical pathway and a unique pathway derived from secretory granules. These findings provide critical morphological evidence for the conservation of EV biogenesis in invertebrates and highlight a key secretory adaptation for specialized physiological functions.
{"title":"The unique biogenesis pathway of extracellular vesicles in Hirudo nipponia salivary gland cells","authors":"Ya-Li Zhu, Meng-Xiang Jia, Ru-Yu Qu, Qian Li, Xia Qiu, Wen-Chen Zhao, Yuan-Yuan Luo","doi":"10.1016/j.tice.2025.103296","DOIUrl":"10.1016/j.tice.2025.103296","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) serve as crucial vehicles for the intercellular transfer of bioactive molecules. While the mechanisms of EV biogenesis are well characterized in mammals, they remain comparatively understudied in invertebrates. This knowledge gap is particularly notable for the medicinal leech, <em>Hirudo nipponia</em>. In this study, the ultrastructural features of <em>Hirudo nipponia</em> salivary glands in resting and secretory states were analyzed using scanning and transmission electron microscopy to investigate the biogenesis and release of EVs. For the first time, it is demonstrated that salivary gland cells possess dual pathways for EV biogenesis: a classical pathway and a unique pathway derived from secretory granules. These findings provide critical morphological evidence for the conservation of EV biogenesis in invertebrates and highlight a key secretory adaptation for specialized physiological functions.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103296"},"PeriodicalIF":2.5,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145850549","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}
Substrate type play a pivotal role in regulating the morphology, mechanical properties, and cytoskeletal organization of cancer cells. In this study, we examined the response of U2OS osteosarcoma cells to substrate stiffness, with a particular focus on cytoskeletal remodeling, cell elasticity, and microparticle internalization. To simulate environments of moderate and high stiffness, cells were cultured on polyacrylamide (PA) hydrogels with a stiffness of 40 kPa and on rigid glass substrates, respectively. Changes in cell morphology and cytoskeletal organization were assessed using fluorescence microscopy, while cell mechanical properties were measured using AFM. To investigate the relationship between substrate mechanics and endocytic activity, carboxylated fluorescent 2 µm latex microspheres were introduced to the cell culture system.
U2OS cells cultured on glass exhibited a significantly larger surface area, more actin stress fibers, and a more organized, stretched cytoskeletal architecture compared to cells grown on 40 kPa PA gels. AFM measurements further demonstrated that cells on glass were mechanically stiffer than those on PA substrates. Microparticle uptake was also strongly influenced by substrate stiffness. Cells cultured on 40 kPa PA gels internalized a significantly greater number of fluorescent microspheres and notably, on 40 kPa PA gel formed “cup-like” structures around the beads, composed of microtubules. Three-dimensional image reconstructions revealed that these structures frequently encapsulate the particles in an asymmetrical manner, indicative of an active cytoskeletal remodeling. To better understand the molecular composition of microtubule-based structures, we analyzed the localization of selected microtubule-associated proteins (MAPs), including IQGAP1, CLIP1, and MARK2. Interestingly, only IQGAP1 was localized prominently to the microtubule cups on 40 kPa gels, often forming ring-like structures surrounding the beads. In some cases, these rings were observed independently of microtubules, suggesting the involvement of IQGAP1 in an active, possibly microtubule-initiated, endocytic process.
In conclusion, our findings demonstrate that substrate type modulates multiple aspects of U2OS cell behavior, including morphology, cytoskeletal arrangement, mechanical properties, and microparticle uptake. These results underscore the mechanosensitive nature of osteosarcoma cells and highlight novel roles for microtubule cup-like structures and MAPs, particularly IQGAP1 in cellular uptake mechanisms.
{"title":"Microtubule-based cup-like structures appear during microparticle uptake in U2OS cells cultured on different substrate types","authors":"Carina Rząca , Agata Kubisiak , Dominik Panek , Marta Targosz-Korecka , Zenon Rajfur","doi":"10.1016/j.tice.2025.103297","DOIUrl":"10.1016/j.tice.2025.103297","url":null,"abstract":"<div><div>Substrate type play a pivotal role in regulating the morphology, mechanical properties, and cytoskeletal organization of cancer cells. In this study, we examined the response of U2OS osteosarcoma cells to substrate stiffness, with a particular focus on cytoskeletal remodeling, cell elasticity, and microparticle internalization. To simulate environments of moderate and high stiffness, cells were cultured on polyacrylamide (PA) hydrogels with a stiffness of 40 kPa and on rigid glass substrates, respectively. Changes in cell morphology and cytoskeletal organization were assessed using fluorescence microscopy, while cell mechanical properties were measured using AFM. To investigate the relationship between substrate mechanics and endocytic activity, carboxylated fluorescent 2 µm latex microspheres were introduced to the cell culture system.</div><div>U2OS cells cultured on glass exhibited a significantly larger surface area, more actin stress fibers, and a more organized, stretched cytoskeletal architecture compared to cells grown on 40 kPa PA gels. AFM measurements further demonstrated that cells on glass were mechanically stiffer than those on PA substrates. Microparticle uptake was also strongly influenced by substrate stiffness. Cells cultured on 40 kPa PA gels internalized a significantly greater number of fluorescent microspheres and notably, on 40 kPa PA gel formed “cup-like” structures around the beads, composed of microtubules. Three-dimensional image reconstructions revealed that these structures frequently encapsulate the particles in an asymmetrical manner, indicative of an active cytoskeletal remodeling. To better understand the molecular composition of microtubule-based structures, we analyzed the localization of selected microtubule-associated proteins (MAPs), including IQGAP1, CLIP1, and MARK2. Interestingly, only IQGAP1 was localized prominently to the microtubule cups on 40 kPa gels, often forming ring-like structures surrounding the beads. In some cases, these rings were observed independently of microtubules, suggesting the involvement of IQGAP1 in an active, possibly microtubule-initiated, endocytic process.</div><div>In conclusion, our findings demonstrate that substrate type modulates multiple aspects of U2OS cell behavior, including morphology, cytoskeletal arrangement, mechanical properties, and microparticle uptake. These results underscore the mechanosensitive nature of osteosarcoma cells and highlight novel roles for microtubule cup-like structures and MAPs, particularly IQGAP1 in cellular uptake mechanisms.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103297"},"PeriodicalIF":2.5,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913085","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}
Pub Date : 2025-12-23DOI: 10.1016/j.tice.2025.103294
Mian Xie , Jiajia Hao , Chen Chao , Xi Chen , Qiuling Chen , Yao-wang Lin , Jiang-hua Li , Qi-yun Liu , Cheng Liu
Objective
Myocardial ischemia-reperfusion injury (MIRI) is a secondary condition following the reestablishment of blood flow to the heart, resulting in myocardial damage such as cardiomyocyte death, ferroptosis, fibrosis, and hypertrophy. However, there is still a lack of targeted therapeutic drugs to date.Aldometanib is a newly developed activator of AMP-activated protein kinase (AMPK) located on the lysosomal membrane, which exhibits significant pharmacological potential. Nevertheless, its role in MIRI remains incompletely understood.
Methods
This study assessed aldometanib's impact on myocardial ischemia-reperfusion injury using H9c2 and AC16 cardiomyocyte lines as in vitro models.
Results
Experimental data demonstrated that aldometanib promoted cardiomyocyte proliferation, reduced oxidative stress, and alleviated inflammatory responses. Furthermore, we identified that aldometanib could inhibit ferroptosis in cardiomyocytes. Mechanistically, our investigations revealed that aldometanib exerted a cardioprotective effect by alleviating cardiomyocyte damage through the regulation of mitochondrial function. Specifically, aldometanib enhanced mitophagy by activating lysosomal AMPK. Additionally, we found that aldometanib exerted an antioxidant effect via Nrf2, thereby mitigating ferroptosis. In animal models, we preliminarily confirmed that aldometanib treatment attenuated tissue damage and functional impairment following myocardial ischemia-reperfusion, further supporting its therapeutic potential.
Conclusions
This study uncovers the protective effect of aldometanib against MIRI and its underlying mechanism, providing experimental evidence and a potential candidate drug for targeting MIRI.
{"title":"Aldometanib attenuates OGD/R-induced cardiomyocyte injury via mitigation of mitochondrial dysfunction","authors":"Mian Xie , Jiajia Hao , Chen Chao , Xi Chen , Qiuling Chen , Yao-wang Lin , Jiang-hua Li , Qi-yun Liu , Cheng Liu","doi":"10.1016/j.tice.2025.103294","DOIUrl":"10.1016/j.tice.2025.103294","url":null,"abstract":"<div><h3>Objective</h3><div>Myocardial ischemia-reperfusion injury (MIRI) is a secondary condition following the reestablishment of blood flow to the heart, resulting in myocardial damage such as cardiomyocyte death, ferroptosis, fibrosis, and hypertrophy. However, there is still a lack of targeted therapeutic drugs to date.Aldometanib is a newly developed activator of AMP-activated protein kinase (AMPK) located on the lysosomal membrane, which exhibits significant pharmacological potential. Nevertheless, its role in MIRI remains incompletely understood.</div></div><div><h3>Methods</h3><div>This study assessed aldometanib's impact on myocardial ischemia-reperfusion injury using H9c2 and AC16 cardiomyocyte lines as <em>in vitro</em> models.</div></div><div><h3>Results</h3><div>Experimental data demonstrated that aldometanib promoted cardiomyocyte proliferation, reduced oxidative stress, and alleviated inflammatory responses. Furthermore, we identified that aldometanib could inhibit ferroptosis in cardiomyocytes. Mechanistically, our investigations revealed that aldometanib exerted a cardioprotective effect by alleviating cardiomyocyte damage through the regulation of mitochondrial function. Specifically, aldometanib enhanced mitophagy by activating lysosomal AMPK. Additionally, we found that aldometanib exerted an antioxidant effect via Nrf2, thereby mitigating ferroptosis. In animal models, we preliminarily confirmed that aldometanib treatment attenuated tissue damage and functional impairment following myocardial ischemia-reperfusion, further supporting its therapeutic potential.</div></div><div><h3>Conclusions</h3><div>This study uncovers the protective effect of aldometanib against MIRI and its underlying mechanism, providing experimental evidence and a potential candidate drug for targeting MIRI.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103294"},"PeriodicalIF":2.5,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913129","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号