Pub Date : 2026-05-01Epub Date: 2026-02-12DOI: 10.1016/j.prp.2026.156405
Juan Liu , Chinenye Jane Ugwah-Oguejiofor , Ling Zhu
Colitis is closely associated with immune system dysregulation in the gastrointestinal tract. The present study aimed to evaluate the impact of Granulocytic Myeloid-Derived Suppressor Cells (G-MDSCs)-derived extracellular vesicles (EVs) on disease activity and the immunologic profile in a murine model of colitis. G-MDSCs-EVs were administered to colitis-bearing mice and were evaluated for changes in body weight, disease activity index, colon histopathology, frequencies of Th17 and Tregs, and cytokine release from lymphocytes. The impact of G-MDSCs-EVs was also evaluated on the expression of immune-response-related genes and the intestinal microbiome. G-MDSCs-EVs prevented body weight loss and controlled the disease activity index on day 10. This treatment improved the Treg population along with a decrease in the release of IL-6, IL-17A, and IFN-γ from lymphocytes. Treatment with G-MDSCs-EVs modulated immune-response-related gene expression and influenced the gut microbiota and colon histopathology. G-MDSCs-EVs demonstrated a preliminary potential in expanding the Treg population and upregulating immunoregulatory cytokines, which contributed to improvements in disease activity index and histopathology of the affected tissue.
{"title":"Granulocytic myeloid derived suppressor cells derived extracellular vesicles ameliorate DSS-induced colitis via modulation of Th17/Treg balance","authors":"Juan Liu , Chinenye Jane Ugwah-Oguejiofor , Ling Zhu","doi":"10.1016/j.prp.2026.156405","DOIUrl":"10.1016/j.prp.2026.156405","url":null,"abstract":"<div><div>Colitis is closely associated with immune system dysregulation in the gastrointestinal tract. The present study aimed to evaluate the impact of Granulocytic Myeloid-Derived Suppressor Cells (G-MDSCs)-derived extracellular vesicles (EVs) on disease activity and the immunologic profile in a murine model of colitis. G-MDSCs-EVs were administered to colitis-bearing mice and were evaluated for changes in body weight, disease activity index, colon histopathology, frequencies of Th17 and Tregs, and cytokine release from lymphocytes. The impact of G-MDSCs-EVs was also evaluated on the expression of immune-response-related genes and the intestinal microbiome. G-MDSCs-EVs prevented body weight loss and controlled the disease activity index on day 10. This treatment improved the Treg population along with a decrease in the release of IL-6, IL-17A, and IFN-γ from lymphocytes. Treatment with G-MDSCs-EVs modulated immune-response-related gene expression and influenced the gut microbiota and colon histopathology. G-MDSCs-EVs demonstrated a preliminary potential in expanding the Treg population and upregulating immunoregulatory cytokines, which contributed to improvements in disease activity index and histopathology of the affected tissue.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"281 ","pages":"Article 156405"},"PeriodicalIF":3.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146196842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-05-01Epub Date: 2026-02-12DOI: 10.1016/j.prp.2026.156402
Rohan Bhadange, Anil Bhanudas Gaikwad
Chronic kidney disease (CKD) is a progressive disease leading to severe health complications. Repurposing of existing drugs offers an attractive avenue for advancing drug development in CKD. Ambrisentan (AMB), a selective ET-1A receptor antagonist used in pulmonary arterial hypertension, holds promise in CKD management. Hence, we aimed to investigate the potential of AMB in unilateral ureteral obstruction (UUO)-induced kidney fibrosis in Sprague-Dawley rats and in recombinant human-transforming growth factor-β1 (rh-TGF-β1)-induced fibrosis in NRK-52E cells. Animals were randomly assigned to the sham, UUO, and UUO + AMB (0.5 mg/kg, p.o., o.d.) groups for 21 days. Animals were sacrificed post-treatment, and plasma, urine, and kidney specimens were collected for biochemistry, histology, immunohistochemistry and qRT-PCR. Moreover, NRK-52E cells were exposed to AMB (100 µM) for 48 h and cell samples were collected for cell viability, morphology, immunocytochemistry, immunoblotting, and flow cytometry assays. AMB treatment significantly improves the left kidney weight, kidney mass ratio, kidney function parameters, and plasma protein levels of TGF-β1 and collagen I. Histopathology revealed that AMB treatment significantly preserved kidney histoarchitecture and interstitial fibrosis in UUO kidneys. Mechanistically, AMB suppressed phosphorylation of AKT and GSK-3β, downregulated α-SMA, vimentin and restored E-cadherin expression as shown by immunocytochemistry, immunohistochemistry and immunoblotting assay. Furthermore, AMB mitigated rh-TGF-β1-induced apoptosis, as assessed by flow cytometry, and modulated Bax, Bcl-2, and cleaved caspase-3 expression, as revealed by qRT-PCR and immunohistochemistry. Collectively, the findings indicate that the AMB modulates the AKT/GSK-3β axis, halting fibrotic progression in CKD, suggesting its clinical potential.
{"title":"Modulation of AKT/GSK-3β signaling by ambrisentan alleviates chronic kidney disease","authors":"Rohan Bhadange, Anil Bhanudas Gaikwad","doi":"10.1016/j.prp.2026.156402","DOIUrl":"10.1016/j.prp.2026.156402","url":null,"abstract":"<div><div>Chronic kidney disease (CKD) is a progressive disease leading to severe health complications. Repurposing of existing drugs offers an attractive avenue for advancing drug development in CKD. Ambrisentan (AMB), a selective ET-1<sub>A</sub> receptor antagonist used in pulmonary arterial hypertension, holds promise in CKD management. Hence, we aimed to investigate the potential of AMB in unilateral ureteral obstruction (UUO)-induced kidney fibrosis in Sprague-Dawley rats and in recombinant human-transforming growth factor-β1 (rh-TGF-β1)-induced fibrosis in NRK-52E cells. Animals were randomly assigned to the sham, UUO, and UUO + AMB (0.5 mg/kg, <em>p.o., o.d.</em>) groups for 21 days. Animals were sacrificed post-treatment, and plasma, urine, and kidney specimens were collected for biochemistry, histology, immunohistochemistry and qRT-PCR. Moreover, NRK-52E cells were exposed to AMB (100 µM) for 48 h and cell samples were collected for cell viability, morphology, immunocytochemistry, immunoblotting, and flow cytometry assays. AMB treatment significantly improves the left kidney weight, kidney mass ratio, kidney function parameters, and plasma protein levels of TGF-β1 and collagen I. Histopathology revealed that AMB treatment significantly preserved kidney histoarchitecture and interstitial fibrosis in UUO kidneys. Mechanistically, AMB suppressed phosphorylation of AKT and GSK-3β, downregulated α-SMA, vimentin and restored E-cadherin expression as shown by immunocytochemistry, immunohistochemistry and immunoblotting assay. Furthermore, AMB mitigated rh-TGF-β1-induced apoptosis, as assessed by flow cytometry, and modulated Bax, Bcl-2, and cleaved caspase-3 expression, as revealed by qRT-PCR and immunohistochemistry. Collectively, the findings indicate that the AMB modulates the AKT/GSK-3β axis, halting fibrotic progression in CKD, suggesting its clinical potential.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"281 ","pages":"Article 156402"},"PeriodicalIF":3.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146196841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-02-05DOI: 10.1016/j.prp.2026.156397
Ruhi Arisha , Shivam Sengupta , Hitesh Kumar Dewangan , Abdulaziz S. Saeedan , Mohd Nazam Ansari , Summya Rashid
Polycystic ovary syndrome (PCOS) represents the leading endocrine problem affecting women of reproductive age, leading to serious complications related to reproduction, metabolism, and psychosocial aspects. Nonetheless, due to the heterogeneous nature and complex pathophysiology associated with PCOS, this condition remains uncaptured or undertreated as it often gets diagnosed at an advanced age due to its prevalence. The pathophysiology associated with PCOS involves the combination of genetic factors, resistance, neuroendocrine imbalance, as well as environmental factors that contribute towards hyperandrogenism, ovulation defects, and metabolic disorders as well. Hence, a comprehensive literature survey was conducted using PubMed, Scopus, Web of Science, and Google Scholar, prioritizing international clinical guidelines, meta-analyses, randomized controlled trials, systematic reviews, and high-quality preclinical studies that covered publications from 2015 to 2025, with the search terms being keywords specific to the disease. At present, the treatments such as lifestyle correction, combined oral pills, and anti-insulin therapies along with anti-androgen drugs only have symptomatic roles with no impact on the underlying mechanism associated with PCOS. However, new therapeutic modalities have been proposed from the past few years that is addressed by this narrative review, including mesenchymal stem cell-based therapies, microbiome therapies, as well as second-generation pharmacotherapies such as GLP-1 agonists and SGLT2 inhibitors. This is being complemented by equal developments in artificial intelligence and the learning process. However, there is work that needs to be done in relation to harmonizing the criteria for diagnosis and the long-term safety and accessibility of effective treatments. Moving forward, the focus should be placed on phenotype-based, precision, and multidisciplinary treatments of PCOS, along with emphasizing the necessity of sturdy clinical validation before worldwide adoption.
多囊卵巢综合征（PCOS）是影响育龄妇女的主要内分泌问题，导致与生殖、代谢和心理社会方面相关的严重并发症。尽管如此，由于多囊卵巢综合征的异质性和复杂的病理生理，这种疾病仍然未被发现或治疗不足，因为它经常在高龄时被诊断出来。多囊卵巢综合征的病理生理涉及遗传因素、抵抗、神经内分泌失衡以及环境因素的综合，这些因素会导致高雄激素症、排卵缺陷和代谢紊乱。因此，我们使用PubMed、Scopus、Web of Science和谷歌Scholar进行了全面的文献调查，优先考虑国际临床指南、荟萃分析、随机对照试验、系统评价和高质量的临床前研究，涵盖2015年至2025年的出版物，搜索词为疾病特定的关键字。目前，生活方式矫正、口服药物联合治疗、抗胰岛素治疗及抗雄激素药物等治疗仅具有症状作用，对多囊卵巢综合征相关的潜在机制没有影响。然而，在过去的几年里，新的治疗方式被提出，包括基于间充质干细胞的治疗，微生物组治疗，以及第二代药物治疗，如GLP-1激动剂和SGLT2抑制剂。这与人工智能和学习过程的同等发展相辅相成。然而，在协调诊断标准以及有效治疗的长期安全性和可及性方面，还需要做一些工作。展望未来，重点应放在以表型为基础的、精确的、多学科的多囊卵巢综合征治疗上，同时强调在世界范围内采用前进行可靠的临床验证的必要性。
{"title":"The future of PCOS management: Disease modification through regenerative, metabolic, and digital therapeutics","authors":"Ruhi Arisha , Shivam Sengupta , Hitesh Kumar Dewangan , Abdulaziz S. Saeedan , Mohd Nazam Ansari , Summya Rashid","doi":"10.1016/j.prp.2026.156397","DOIUrl":"10.1016/j.prp.2026.156397","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS) represents the leading endocrine problem affecting women of reproductive age, leading to serious complications related to reproduction, metabolism, and psychosocial aspects. Nonetheless, due to the heterogeneous nature and complex pathophysiology associated with PCOS, this condition remains uncaptured or undertreated as it often gets diagnosed at an advanced age due to its prevalence. The pathophysiology associated with PCOS involves the combination of genetic factors, resistance, neuroendocrine imbalance, as well as environmental factors that contribute towards hyperandrogenism, ovulation defects, and metabolic disorders as well. Hence, a comprehensive literature survey was conducted using PubMed, Scopus, Web of Science, and Google Scholar, prioritizing international clinical guidelines, meta-analyses, randomized controlled trials, systematic reviews, and high-quality preclinical studies that covered publications from 2015 to 2025, with the search terms being keywords specific to the disease. At present, the treatments such as lifestyle correction, combined oral pills, and anti-insulin therapies along with anti-androgen drugs only have symptomatic roles with no impact on the underlying mechanism associated with PCOS. However, new therapeutic modalities have been proposed from the past few years that is addressed by this narrative review, including mesenchymal stem cell-based therapies, microbiome therapies, as well as second-generation pharmacotherapies such as GLP-1 agonists and SGLT2 inhibitors. This is being complemented by equal developments in artificial intelligence and the learning process. However, there is work that needs to be done in relation to harmonizing the criteria for diagnosis and the long-term safety and accessibility of effective treatments. Moving forward, the focus should be placed on phenotype-based, precision, and multidisciplinary treatments of PCOS, along with emphasizing the necessity of sturdy clinical validation before worldwide adoption.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"280 ","pages":"Article 156397"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The hallmark of aerobic glycolysis in cancer progression is well-established, yet its specific role in pancreatic cancer (PC) remains elusive. Here, we reported that TFAP2A is upregulated in PC tissues, and elevated TFAP2A expression correlates with poor prognosis in patients. Functionally, we found that TFAP2A boosted the viability, invasion, and migration of PC cells in vitro, whereas TFAP2A depletion restrained tumor growth in vivo. Moreover, TFAP2A knockdown hindered aerobic glycolysis of PC cells. Further investigation revealed that TFAP2A deletion decreased LDHA expression in PC cells. LDHA overexpression counteracted the impacts of TFAP2A deletion on cell viability, migration, invasion, and aerobic glycolysis. Mechanistically, TFAP2A was directly bound to the promoter of IGF2BP2, upregulating its expression. Additionally, IGF2BP2 was found to bind to the m6A site in LDHA mRNA, thereby enhancing its stability. Overall, TFAP2A facilitated aerobic glycolysis and PC progression via IGF2BP2-mediated stabilization of LDHA mRNA, providing novel insights for PC therapy.
{"title":"TFAP2A facilitates aerobic glycolysis and metastasis of pancreatic cancer via IGF2BP2-mediated LDHA m6A modification","authors":"Zhiying Xu, Xingyang Zhong, Zhishi Yang, Zhuangzhi Cong, Lianwei Peng, Qifei Zou","doi":"10.1016/j.prp.2026.156387","DOIUrl":"10.1016/j.prp.2026.156387","url":null,"abstract":"<div><div>The hallmark of aerobic glycolysis in cancer progression is well-established, yet its specific role in pancreatic cancer (PC) remains elusive. Here, we reported that TFAP2A is upregulated in PC tissues, and elevated TFAP2A expression correlates with poor prognosis in patients. Functionally, we found that TFAP2A boosted the viability, invasion, and migration of PC cells <em>in vitro</em>, whereas TFAP2A depletion restrained tumor growth <em>in vivo</em>. Moreover, TFAP2A knockdown hindered aerobic glycolysis of PC cells. Further investigation revealed that TFAP2A deletion decreased LDHA expression in PC cells. LDHA overexpression counteracted the impacts of TFAP2A deletion on cell viability, migration, invasion, and aerobic glycolysis. Mechanistically, TFAP2A was directly bound to the promoter of IGF2BP2, upregulating its expression. Additionally, IGF2BP2 was found to bind to the m<sup>6</sup>A site in LDHA mRNA, thereby enhancing its stability. Overall, TFAP2A facilitated aerobic glycolysis and PC progression via IGF2BP2-mediated stabilization of LDHA mRNA, providing novel insights for PC therapy.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"280 ","pages":"Article 156387"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-27DOI: 10.1016/j.prp.2026.156379
Jialong Zhang , Lexing Yang , Jun He , Weiyi Li, Hongzhi Wang, Chaozhao Liang
Previous studies suggested the link between sleep deprivation and prostate cancer, but its impact on disease progression is unclear. Moreover, clarifying this relationship could offer insights into prostate cancer mechanisms and potential treatments. In the present study, questionnaire and sleep monitoring of prostate cancer patients indicate that worse sleep quality correlates with higher Gleason scores. Subsequently, to study the effects of sleep deprivation in vivo, a sleep deprivation mouse model was established. Our findings show that sleep deprivation could accelerate tumor growth. Then, we performed transcriptome sequencing to infer the underlying mechanism. RNA sequencing found inflammation related pathways were activated in the sleep deprivation model. Moreover, we identified CXCL13 as a key mediator of sleep deprivation induced prostate progression. And inhibition of CXCR5, the receptor of CXCL13, reduced its tumor promoting effects. Molecular mechanism studies showed that CXCL13 enhanced cancer cell proliferation via activating JNK signaling pathway. In summary, our findings suggest that sleep deprivation may accelerate prostate cancer progression by activating the CXCL13/CXCR5/JNK signaling axis. These results provide preliminary insights into a potential therapeutic direction.
{"title":"The role of sleep deprivation in prostate cancer and a preliminary exploration of its mechanisms","authors":"Jialong Zhang , Lexing Yang , Jun He , Weiyi Li, Hongzhi Wang, Chaozhao Liang","doi":"10.1016/j.prp.2026.156379","DOIUrl":"10.1016/j.prp.2026.156379","url":null,"abstract":"<div><div>Previous studies suggested the link between sleep deprivation and prostate cancer, but its impact on disease progression is unclear. Moreover, clarifying this relationship could offer insights into prostate cancer mechanisms and potential treatments. In the present study, questionnaire and sleep monitoring of prostate cancer patients indicate that worse sleep quality correlates with higher Gleason scores. Subsequently, to study the effects of sleep deprivation in vivo, a sleep deprivation mouse model was established. Our findings show that sleep deprivation could accelerate tumor growth. Then, we performed transcriptome sequencing to infer the underlying mechanism. RNA sequencing found inflammation related pathways were activated in the sleep deprivation model. Moreover, we identified CXCL13 as a key mediator of sleep deprivation induced prostate progression. And inhibition of CXCR5, the receptor of CXCL13, reduced its tumor promoting effects. Molecular mechanism studies showed that CXCL13 enhanced cancer cell proliferation via activating JNK signaling pathway. In summary, our findings suggest that sleep deprivation may accelerate prostate cancer progression by activating the CXCL13/CXCR5/JNK signaling axis. These results provide preliminary insights into a potential therapeutic direction.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"280 ","pages":"Article 156379"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146070985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-29DOI: 10.1016/j.prp.2026.156385
Yuhang Wang , Han Zhang , Jiaqi Liu , Rimei Lin , Yingyu Huang , Xinrui Liu , Yunqi Dong , Hongkui Lu , Yutong Wei , Haoze Lv , Xinyu Liu , Cong Sun
Background and objectives
Sepsis-Induced Myocardial Injury (SIMI) poses a serious threat to patients' lives. Although curcumin (Cur) has potential therapeutic effects on SIMI, its clinical application is hindered by the limitation of low bioavailability. The emergence of nanodelivery systems provides novel strategies to address this issue. This study aimed to investigate the therapeutic effects of curcumin nanoparticles (Cur-NPs) on septic myocarditis (SIMI) and its potential molecular mechanisms.
Materials and methods
Cur-NPs were prepared using the ion cross-linking method, and a septicemia mouse model was established by intraperitoneal injection of lipopolysaccharide (LPS). Immunofluorescence, Western blot (WB), real-time quantitative PCR (RT-qPCR), and other molecular biology techniques were employed to systematically explore the molecular mechanisms underlying the therapeutic effects of Cur-NPs on SIMI.
Results
Cur-NPs significantly alleviated myocardial tissue damage induced by septicemia and effectively mitigated inflammatory responses and mitochondrial damage. Mechanistic studies revealed that Cur-NPs upregulated the expression levels of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2), Heme Oxygenase-1 (HO-1), Solute Carrier Family 7 Member 11 (SLC7A11), Glutathione Peroxidase 4 (GPX4), Ferroptosis-suppressor-protein 1 (FSP1), and ferritin, while downregulating the expression of Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4), LysoPHosPHatidylcholine Acyltransferase 3 (LPCAT3), and 4-hydroxynonenal (4-HNE), thereby inhibiting ferroptosis in cardiomyocytes.
Conclusions
Cur-NPs can effectively alleviate SIMI by dual regulation of the Nrf2/HO-1/xCT/GPX4 pathway and the ACSL4/LPCAT3 pathway, providing a promising new approach for the clinical treatment of SIMI.
{"title":"Curcumin nanoparticles attenuate sepsis-induced myocardial injury by modulating the Nrf2/HO-1/SLC7A11/GPX4 and ACSL4/LPCAT3 pathways","authors":"Yuhang Wang , Han Zhang , Jiaqi Liu , Rimei Lin , Yingyu Huang , Xinrui Liu , Yunqi Dong , Hongkui Lu , Yutong Wei , Haoze Lv , Xinyu Liu , Cong Sun","doi":"10.1016/j.prp.2026.156385","DOIUrl":"10.1016/j.prp.2026.156385","url":null,"abstract":"<div><h3>Background and objectives</h3><div>Sepsis-Induced Myocardial Injury (SIMI) poses a serious threat to patients' lives. Although curcumin (Cur) has potential therapeutic effects on SIMI, its clinical application is hindered by the limitation of low bioavailability. The emergence of nanodelivery systems provides novel strategies to address this issue. This study aimed to investigate the therapeutic effects of curcumin nanoparticles (Cur-NPs) on septic myocarditis (SIMI) and its potential molecular mechanisms.</div></div><div><h3>Materials and methods</h3><div>Cur-NPs were prepared using the ion cross-linking method, and a septicemia mouse model was established by intraperitoneal injection of lipopolysaccharide (LPS). Immunofluorescence, Western blot (WB), real-time quantitative PCR (RT-qPCR), and other molecular biology techniques were employed to systematically explore the molecular mechanisms underlying the therapeutic effects of Cur-NPs on SIMI.</div></div><div><h3>Results</h3><div>Cur-NPs significantly alleviated myocardial tissue damage induced by septicemia and effectively mitigated inflammatory responses and mitochondrial damage. Mechanistic studies revealed that Cur-NPs upregulated the expression levels of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2), Heme Oxygenase-1 (HO-1), Solute Carrier Family 7 Member 11 (SLC7A11), Glutathione Peroxidase 4 (GPX4), Ferroptosis-suppressor-protein 1 (FSP1), and ferritin, while downregulating the expression of Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4), LysoPHosPHatidylcholine Acyltransferase 3 (LPCAT3), and 4-hydroxynonenal (4-HNE), thereby inhibiting ferroptosis in cardiomyocytes.</div></div><div><h3>Conclusions</h3><div>Cur-NPs can effectively alleviate SIMI by dual regulation of the Nrf2/HO-1/xCT/GPX4 pathway and the ACSL4/LPCAT3 pathway, providing a promising new approach for the clinical treatment of SIMI.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"280 ","pages":"Article 156385"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-26DOI: 10.1016/j.prp.2026.156369
Hailah M. Almohaimeed , Hadeel Abdulrahman Waggas , Osama Mohammed Abdulaziz Altowaijri , Jawaher A. Abdulhakim , Zuhair M. Mohammedsaleh , Amany I. Almars , Aniruddha Chatterjee , Bikram Dhara , Daniel Ejim Uti
Exosomes are small vesicles which cells use to communicate with one another by way of transporting proteins, lipids and nucleic acids. They are promising vectors that can be applied in the delivery of drugs and genes to locations because of their natural compatibility with the body, stability, and capability to go through biological barriers. Recent advances in the field of exosome & synthetic biology resulted in new engineering strategies expanding their applicability to therapeutic applications. Scientists can target their surfaces with ligands, antibodies, or peptides to enhance accuracy of targeting, and through the development of more sophisticated loading methods- remote loading, stimuli responsive systems- nucleic acids and small molecules can be delivered effectively. Genetically engineered exosomes can deliver CRISPR/Cas9 available in biological therapy to modify immune responses and invent novel cancer-treatment options. However, high-level production, safety of the immune issues and regulatory approval are still challenges that should be overcome. The review explains the newest approaches and the issues that are yet to be resolved and emphasizes the potential that engineered exosomes can offer as versatile platforms to facilitate precision medicine and treatment of diseases.
{"title":"Exosome precision engineering: A comprehensive method for targeted gene and drug delivery","authors":"Hailah M. Almohaimeed , Hadeel Abdulrahman Waggas , Osama Mohammed Abdulaziz Altowaijri , Jawaher A. Abdulhakim , Zuhair M. Mohammedsaleh , Amany I. Almars , Aniruddha Chatterjee , Bikram Dhara , Daniel Ejim Uti","doi":"10.1016/j.prp.2026.156369","DOIUrl":"10.1016/j.prp.2026.156369","url":null,"abstract":"<div><div>Exosomes are small vesicles which cells use to communicate with one another by way of transporting proteins, lipids and nucleic acids. They are promising vectors that can be applied in the delivery of drugs and genes to locations because of their natural compatibility with the body, stability, and capability to go through biological barriers. Recent advances in the field of exosome & synthetic biology resulted in new engineering strategies expanding their applicability to therapeutic applications. Scientists can target their surfaces with ligands, antibodies, or peptides to enhance accuracy of targeting, and through the development of more sophisticated loading methods- remote loading, stimuli responsive systems- nucleic acids and small molecules can be delivered effectively. Genetically engineered exosomes can deliver CRISPR/Cas9 available in biological therapy to modify immune responses and invent novel cancer-treatment options. However, high-level production, safety of the immune issues and regulatory approval are still challenges that should be overcome. The review explains the newest approaches and the issues that are yet to be resolved and emphasizes the potential that engineered exosomes can offer as versatile platforms to facilitate precision medicine and treatment of diseases.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"280 ","pages":"Article 156369"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-29DOI: 10.1016/j.prp.2026.156382
Ru Nie , Yunlong Duan , Xiaoting Cao , Mingquan Pang , Zhixin Wang , Haining Fan
Hepatic ischemia–reperfusion injury (HIRI) remains a major clinical challenge in liver surgery, transplantation, and trauma, contributing to graft dysfunction and increased morbidity. This review summarizes the complex pathophysiology of HIRI, including metabolic derangements during ischemia, bursts of oxidative stress on reperfusion, and sterile inflammation driven by reactive oxygen species (ROS) and immune-cell activation. It also examines regulated cell death pathways—apoptosis, pyroptosis, necroptosis, and ferroptosis—that interact to create self-reinforcing cycles and further amplify tissue injury.Building on these mechanistic insights, the review highlights emerging therapeutic strategies centered on mesenchymal stem cells (MSCs) and MSC-derived products, including extracellular vesicles (EVs), exosomes, and conditioned medium. MSCs confer protection through immunomodulatory effects, such as promoting macrophage polarization toward anti-inflammatory phenotypes, as well as through cytoprotective mechanisms including antioxidant secretion and mitochondrial transfer. In addition, MSCs support tissue repair by enhancing regenerative responses. Preclinical studies consistently show that MSC-based interventions reduce oxidative stress, inflammation, and cell death. Early clinical trials in liver transplantation further suggest that MSC therapy is safe and may reduce ischemia-associated complications.Finally, this review discusses key translational barriers, including inefficient homing, donor-to-donor variability, and the need for standardized manufacturing and potency assessment. Future directions include MSC preconditioning, EV engineering, and combination approaches with machine perfusion technologies. By integrating mechanistic understanding with therapeutic advances, this review underscores the potential of MSC-based therapies to reshape HIRI management and highlights broader opportunities for regenerative medicine in organ injury.
{"title":"Pathological mechanisms of hepatic ischemia-reperfusion injury and stem cell–based therapeutic strategies: Mechanistic insights and translational perspectives","authors":"Ru Nie , Yunlong Duan , Xiaoting Cao , Mingquan Pang , Zhixin Wang , Haining Fan","doi":"10.1016/j.prp.2026.156382","DOIUrl":"10.1016/j.prp.2026.156382","url":null,"abstract":"<div><div>Hepatic ischemia–reperfusion injury (HIRI) remains a major clinical challenge in liver surgery, transplantation, and trauma, contributing to graft dysfunction and increased morbidity. This review summarizes the complex pathophysiology of HIRI, including metabolic derangements during ischemia, bursts of oxidative stress on reperfusion, and sterile inflammation driven by reactive oxygen species (ROS) and immune-cell activation. It also examines regulated cell death pathways—apoptosis, pyroptosis, necroptosis, and ferroptosis—that interact to create self-reinforcing cycles and further amplify tissue injury.Building on these mechanistic insights, the review highlights emerging therapeutic strategies centered on mesenchymal stem cells (MSCs) and MSC-derived products, including extracellular vesicles (EVs), exosomes, and conditioned medium. MSCs confer protection through immunomodulatory effects, such as promoting macrophage polarization toward anti-inflammatory phenotypes, as well as through cytoprotective mechanisms including antioxidant secretion and mitochondrial transfer. In addition, MSCs support tissue repair by enhancing regenerative responses. Preclinical studies consistently show that MSC-based interventions reduce oxidative stress, inflammation, and cell death. Early clinical trials in liver transplantation further suggest that MSC therapy is safe and may reduce ischemia-associated complications.Finally, this review discusses key translational barriers, including inefficient homing, donor-to-donor variability, and the need for standardized manufacturing and potency assessment. Future directions include MSC preconditioning, EV engineering, and combination approaches with machine perfusion technologies. By integrating mechanistic understanding with therapeutic advances, this review underscores the potential of MSC-based therapies to reshape HIRI management and highlights broader opportunities for regenerative medicine in organ injury.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"280 ","pages":"Article 156382"},"PeriodicalIF":3.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-21DOI: 10.1016/j.prp.2026.156449
Jiting Zhao, Di Huang, Zhen Sun, Defei Yin, Yang Liu, Hui Jiang, Zhanjun Qiu, Wei Wang, Jianguang Sun
Acute pancreatitis (AP) is a common and critical gastrointestinal disorder with significant morbidity and mortality, yet current therapeutic options remain limited. Recent advances have illuminated the central role of regulated cell death (RCD) - including apoptosis, necroptosis, pyroptosis, and ferroptosis - as a pivotal driver of pancreatic acinar cell injury and the ensuing inflammatory cascade in AP. Consequently, targeting RCD has emerged as a promising therapeutic strategy. Natural products derived from Traditional Chinese Medicine (TCM) present a particularly rich source of potential therapeutic agents due to their multi-target capabilities, high efficacy, and favorable safety profiles. This review comprehensively synthesizes evidence from the past decade to elucidate the mechanisms by which specific TCM natural products-including Emodin, Baicalin, and Wedelolactone-ameliorate AP through the precise modulation of distinct RCD pathways. We systematically detail the underlying molecular mechanisms, with a special emphasis on their multi-target pharmacology in disrupting the vicious cycle of cell death and inflammation. Finally, the review discusses the current challenges in drug development and proposes future directions for translating these promising findings into clinically viable TCM-inspired therapies for AP.
{"title":"Targeting multiple regulated cell death pathways in acute pancreatitis: The multi-target potential of natural products from Traditional Chinese Medicine.","authors":"Jiting Zhao, Di Huang, Zhen Sun, Defei Yin, Yang Liu, Hui Jiang, Zhanjun Qiu, Wei Wang, Jianguang Sun","doi":"10.1016/j.prp.2026.156449","DOIUrl":"https://doi.org/10.1016/j.prp.2026.156449","url":null,"abstract":"<p><p>Acute pancreatitis (AP) is a common and critical gastrointestinal disorder with significant morbidity and mortality, yet current therapeutic options remain limited. Recent advances have illuminated the central role of regulated cell death (RCD) - including apoptosis, necroptosis, pyroptosis, and ferroptosis - as a pivotal driver of pancreatic acinar cell injury and the ensuing inflammatory cascade in AP. Consequently, targeting RCD has emerged as a promising therapeutic strategy. Natural products derived from Traditional Chinese Medicine (TCM) present a particularly rich source of potential therapeutic agents due to their multi-target capabilities, high efficacy, and favorable safety profiles. This review comprehensively synthesizes evidence from the past decade to elucidate the mechanisms by which specific TCM natural products-including Emodin, Baicalin, and Wedelolactone-ameliorate AP through the precise modulation of distinct RCD pathways. We systematically detail the underlying molecular mechanisms, with a special emphasis on their multi-target pharmacology in disrupting the vicious cycle of cell death and inflammation. Finally, the review discusses the current challenges in drug development and proposes future directions for translating these promising findings into clinically viable TCM-inspired therapies for AP.</p>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"282 ","pages":"156449"},"PeriodicalIF":3.2,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-20DOI: 10.1016/j.prp.2026.156448
Yan Jiang, Wei-Ling Yang, Jin-Mei Huang, Yong-Jun Huang, Yuan-Xun Gong
Chronic diabetic wounds represent a major global health challenge due to their persistent and difficult-to-heal nature, imposing substantial burdens on patients. Moist exposed burn ointment (MEBO), a traditional Chinese medicine preparation, has shown therapeutic potential in treating diabetic wounds; however, its underlying mechanisms remain to be fully elucidated. In this study, MEBO and recombinant bovine basic fibroblast growth factor (rb-bFGF), used as a positive control, were applied to diabetic rat wound models. Wound pathology, ultrastructures, and protein expression profiles were subsequently evaluated. The results demonstrated that MEBO reduced the expression of the inflammatory factors iNOS and IL-6, thereby alleviating inflammatory cell infiltration, while simultaneously increasing the expression of IL-10 and Arg1. Furthermore, MEBO enhanced the expression of ADAM-10 and p-AKT, promoting cell regeneration and increasing collagen deposition. It also elevated Beclin1 expression while reducing GRP78 and CTSK levels, suggesting improved subcellular structural integrity through the regulation of autophagy-related pathways. Notably, MEBO modulated angiogenesis via CD31 expression, thereby accelerating the wound healing process. In conclusion, MEBO significantly promotes wound healing in diabetic rats by regulating inflammatory responses, enhancing cell regeneration, regulating autophagy, facilitating collagen deposition, and promoting angiogenesis.
{"title":"Moist exposed burn ointment (MEBO) promotes healing of chronic diabetic wounds in rats by regulating inflammatory factors and autophagy.","authors":"Yan Jiang, Wei-Ling Yang, Jin-Mei Huang, Yong-Jun Huang, Yuan-Xun Gong","doi":"10.1016/j.prp.2026.156448","DOIUrl":"https://doi.org/10.1016/j.prp.2026.156448","url":null,"abstract":"<p><p>Chronic diabetic wounds represent a major global health challenge due to their persistent and difficult-to-heal nature, imposing substantial burdens on patients. Moist exposed burn ointment (MEBO), a traditional Chinese medicine preparation, has shown therapeutic potential in treating diabetic wounds; however, its underlying mechanisms remain to be fully elucidated. In this study, MEBO and recombinant bovine basic fibroblast growth factor (rb-bFGF), used as a positive control, were applied to diabetic rat wound models. Wound pathology, ultrastructures, and protein expression profiles were subsequently evaluated. The results demonstrated that MEBO reduced the expression of the inflammatory factors iNOS and IL-6, thereby alleviating inflammatory cell infiltration, while simultaneously increasing the expression of IL-10 and Arg1. Furthermore, MEBO enhanced the expression of ADAM-10 and p-AKT, promoting cell regeneration and increasing collagen deposition. It also elevated Beclin1 expression while reducing GRP78 and CTSK levels, suggesting improved subcellular structural integrity through the regulation of autophagy-related pathways. Notably, MEBO modulated angiogenesis via CD31 expression, thereby accelerating the wound healing process. In conclusion, MEBO significantly promotes wound healing in diabetic rats by regulating inflammatory responses, enhancing cell regeneration, regulating autophagy, facilitating collagen deposition, and promoting angiogenesis.</p>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"282 ","pages":"156448"},"PeriodicalIF":3.2,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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