BACKGROUND Esophageal squamous-cell carcinoma(ESCC)is a highly aggressive cancer,predominantly affecting populations in Eastern Asia and parts of Africa.Its pathogenesis is influenced by both genetic and environmental...BACKGROUND Esophageal squamous-cell carcinoma(ESCC)is a highly aggressive cancer,predominantly affecting populations in Eastern Asia and parts of Africa.Its pathogenesis is influenced by both genetic and environmental factors.Despite recent therapeutic advances,survival rates remain dismal,underscoring an urgent need for novel therapeutic targets.AIM To investigate the role of hypoxia-inducible factor 1-alpha(HIF1A)in the progression of ESCC and its impact on the metabolic enzyme lactate dehydrogenase A(LDHA),which is crucial for the glycolytic pathway in hypoxic tumor environments.METHODS Utilizing transcriptomic data from multiple public databases,we analyzed differential gene expression and conducted gene ontology and transcription factor network analyses.The regulatory impact of HIF1A on LDHA was specifically examined through integrative analysis with HIF1A ChIP-seq data and confirmed via siRNA-mediated knockdown experiments in ESCC cell lines.RESULTS Our findings reveal a significant upregulation of HIF1A in ESCC tissues,associated with poor prognosis.HIF1A directly regulates LDHA,enhancing glycolysis under hypoxic conditions and contributing to tumor aggressiveness.Knockdown of HIF1A in cell lines not only reduced LDHA expression but also altered key pathways related to cell cycle and apoptosis.CONCLUSION The critical role of the HIF1A-LDHA axis in ESCC highlights its potential as a therapeutic target,underscoring the need for future clinical trials to validate the efficacy of HIF1A inhibitors in enhancing treatment outcomes.展开更多
The mechanism of cell damage during acute pancreatitis (AP) has not been fully elucidated, and there is still a lack of specific or effective treatments. Increasing evidence has implicated mitochondrial dysfunction as...The mechanism of cell damage during acute pancreatitis (AP) has not been fully elucidated, and there is still a lack of specific or effective treatments. Increasing evidence has implicated mitochondrial dysfunction as a key event in the pathophysiology of AP. Mitochondrial dysfunction is closely related to calcium (Ca^(2+)) overload, intracellular adenosine triphosphate depletion, mitochondrial permeability transition pore openings, loss of mitochondrial membrane potential, mitophagy damage and inflammatory responses. Mitochondrial dysfunction is an early triggering event in the initiation and development of AP,and this organelle damage may precede the release of inflammatory cytokines, intracellular trypsin activation and vacuole formation of pancreatic acinar cells. This review provides further insight into the role of mitochondria in both physiological and pathophysiological aspects of AP, aiming to improve our understanding of the underlying mechanism which may lead to the development of therapeutic and preventive strategies for AP.展开更多
Given the alarmingly increasing rates of glaucoma worldwide and the lack of satisfactory treatments,there is a dire need to explore more feasible treatment options.Magnesium(Mg)is an essential element in maintaining t...Given the alarmingly increasing rates of glaucoma worldwide and the lack of satisfactory treatments,there is a dire need to explore more feasible treatment options.Magnesium(Mg)is an essential element in maintaining the functional and structural integrity of vital ocular tissues,but Mg and its alloys are rarely mentioned in ophthalmic applications.Our previous research found that hydroxyapatite-coated Mg(Mg@HA)shows the best biocompatibility and bioactivity,and exhibits the effect of inhibiting fibrosis after filtration surgery in the rabbit model,which is expected to be a promising material for glaucoma drainage device.In this study,we further demonstrated the anti-fibrosis effect of Mg@HA from the molecular signal level and the efficacy of implantation in the rabbit filtration surgery model.In vitro experiments showed the surface modification of Mg affects the adhesion behavior and the reorganization of cytoskeleton of Human Western blot analysis and immunofluorescence found that Mg@HA regulates the adhesion and motility of human Tenon’s capsule fibroblasts mainly by down-regulating the phosphorylation of Smad2 and Smad3 in the canonical transforming growth factor-beta(TGF-β)signaling pathway.By observing and recording the condition of filtering blebs and intraocular pressure after surgery,the effectiveness of Mg@HA applied in the rabbit filtration surgery model was further evaluated.In conclusion,the application of hydroxyapatite-coated Mg in the eye has good biocompatibility and has the potential to resist postoperative glaucoma filtration fibrosis,which may be mediated by the regulation of the TGFβ/Smad signaling pathway.展开更多
文摘BACKGROUND Esophageal squamous-cell carcinoma(ESCC)is a highly aggressive cancer,predominantly affecting populations in Eastern Asia and parts of Africa.Its pathogenesis is influenced by both genetic and environmental factors.Despite recent therapeutic advances,survival rates remain dismal,underscoring an urgent need for novel therapeutic targets.AIM To investigate the role of hypoxia-inducible factor 1-alpha(HIF1A)in the progression of ESCC and its impact on the metabolic enzyme lactate dehydrogenase A(LDHA),which is crucial for the glycolytic pathway in hypoxic tumor environments.METHODS Utilizing transcriptomic data from multiple public databases,we analyzed differential gene expression and conducted gene ontology and transcription factor network analyses.The regulatory impact of HIF1A on LDHA was specifically examined through integrative analysis with HIF1A ChIP-seq data and confirmed via siRNA-mediated knockdown experiments in ESCC cell lines.RESULTS Our findings reveal a significant upregulation of HIF1A in ESCC tissues,associated with poor prognosis.HIF1A directly regulates LDHA,enhancing glycolysis under hypoxic conditions and contributing to tumor aggressiveness.Knockdown of HIF1A in cell lines not only reduced LDHA expression but also altered key pathways related to cell cycle and apoptosis.CONCLUSION The critical role of the HIF1A-LDHA axis in ESCC highlights its potential as a therapeutic target,underscoring the need for future clinical trials to validate the efficacy of HIF1A inhibitors in enhancing treatment outcomes.
基金supported by a grant from the Fund of Chengdu Medical College (CYZYB22-03)。
文摘The mechanism of cell damage during acute pancreatitis (AP) has not been fully elucidated, and there is still a lack of specific or effective treatments. Increasing evidence has implicated mitochondrial dysfunction as a key event in the pathophysiology of AP. Mitochondrial dysfunction is closely related to calcium (Ca^(2+)) overload, intracellular adenosine triphosphate depletion, mitochondrial permeability transition pore openings, loss of mitochondrial membrane potential, mitophagy damage and inflammatory responses. Mitochondrial dysfunction is an early triggering event in the initiation and development of AP,and this organelle damage may precede the release of inflammatory cytokines, intracellular trypsin activation and vacuole formation of pancreatic acinar cells. This review provides further insight into the role of mitochondria in both physiological and pathophysiological aspects of AP, aiming to improve our understanding of the underlying mechanism which may lead to the development of therapeutic and preventive strategies for AP.
基金supported by the National Natural Science Foundation of China(Grant No.81670860 and 81700836)Natural Science Foundation of Chongqing(Grant No.cstc2018jcyjAX0034 and cstc2018jcyjAX0016).
文摘Given the alarmingly increasing rates of glaucoma worldwide and the lack of satisfactory treatments,there is a dire need to explore more feasible treatment options.Magnesium(Mg)is an essential element in maintaining the functional and structural integrity of vital ocular tissues,but Mg and its alloys are rarely mentioned in ophthalmic applications.Our previous research found that hydroxyapatite-coated Mg(Mg@HA)shows the best biocompatibility and bioactivity,and exhibits the effect of inhibiting fibrosis after filtration surgery in the rabbit model,which is expected to be a promising material for glaucoma drainage device.In this study,we further demonstrated the anti-fibrosis effect of Mg@HA from the molecular signal level and the efficacy of implantation in the rabbit filtration surgery model.In vitro experiments showed the surface modification of Mg affects the adhesion behavior and the reorganization of cytoskeleton of Human Western blot analysis and immunofluorescence found that Mg@HA regulates the adhesion and motility of human Tenon’s capsule fibroblasts mainly by down-regulating the phosphorylation of Smad2 and Smad3 in the canonical transforming growth factor-beta(TGF-β)signaling pathway.By observing and recording the condition of filtering blebs and intraocular pressure after surgery,the effectiveness of Mg@HA applied in the rabbit filtration surgery model was further evaluated.In conclusion,the application of hydroxyapatite-coated Mg in the eye has good biocompatibility and has the potential to resist postoperative glaucoma filtration fibrosis,which may be mediated by the regulation of the TGFβ/Smad signaling pathway.
