BACKGROUND Liver injury is common in severe acute pancreatitis(SAP).Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes,which induces lipid peroxidation and mitochondrial iron deposition and ...BACKGROUND Liver injury is common in severe acute pancreatitis(SAP).Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes,which induces lipid peroxidation and mitochondrial iron deposition and ultimately leads to ferroptosis.Our previous study found that milk fat globule epidermal growth factor 8(MFG-E8)alleviates acinar cell damage during SAP via binding toαvβ3/5 integrins.MFG-E8 also seems to mitigate pancreatic fibrosis via inhibiting chaperone-mediated autophagy.AIM To speculate whether MFG-E8 could also alleviate SAP induced liver injury by restoring the abnormal autophagy flux.METHODS SAP was induced in mice by 2 hly intraperitoneal injections of 4.0 g/kg L-arginine or 7 hly injections of 50μg/kg cerulein plus lipopolysaccharide.mfge8-knockout mice were used to study the effect of MFG-E8 deficiency on SAPinduced liver injury.Cilengitide,a specificαvβ3/5 integrin inhibitor,was used to investigate the possible mechanism of MFG-E8.RESULTS The results showed that MFG-E8 deficiency aggravated SAP-induced liver injury in mice,enhanced autophagy flux in hepatocyte,and worsened the degree of ferroptosis.Exogenous MFG-E8 reduced SAP-induced liver injury in a dose-dependent manner.Mechanistically,MFG-E8 mitigated excessive autophagy and inhibited ferroptosis in liver cells.Cilengitide abolished MFG-E8’s beneficial effects in SAP-induced liver injury.CONCLUSION MFG-E8 acts as an endogenous protective mediator in SAP-induced liver injury.MFG-E8 alleviates the excessive autophagy and inhibits ferroptosis in hepatocytes by binding to integrinαVβ3/5.展开更多
Background: In the global burden of non-communicable diseases, the top slot among them all is occupied by various cardiovascular diseases (CVD), which also claim primacy in mortality rates. Generally speaking, the pat...Background: In the global burden of non-communicable diseases, the top slot among them all is occupied by various cardiovascular diseases (CVD), which also claim primacy in mortality rates. Generally speaking, the pathophysiological pathway frequently involves either (or a combination of) elevated serum cholesterol levels, predominantly attributed to dietary patterns characterized by extremely high levels of saturated and trans-fat consumption. Day-to-day nutritional epidemiology among university students suggests that they represent a crucial demographic for the study of preventive interventions. Objective: This in-depth study and investigation were specifically aimed to quantitatively assess and compare prevailing patterns of dietary fat consumption between female students enrolled in health sciences and non-health sciences programs at major universities in Riyadh, Saudi Arabia. Methodology: This cross-sectional study was comprised of 434 Saudi female university students (age range: 18 - 25 years), utilizing a validated Block Dietary Fat Screener accompanied by anthropometric measurements and comprehensive demographic data collection. The sampling methodology consisted of a snowball technique that was spread across three major academic institutions in Riyadh. Results: Statistical analysis revealed a significant association between academic specialization and patterns of dietary fat consumption (p = 0.012). Paradoxically, students of health science exhibited a higher prevalence of very high fat intake (41.9%) compared with their non-health sciences counterparts (27.6%). Surprisingly, anthropometric stratification revealed that it was the underweight students who demonstrated very high levels of fat consumption. A notable socioeconomic gradient was observed, with students from households earning 15,000 - 20,000 SR monthly showing the highest prevalence of very high-fat consumption (47.1%), although this association did not achieve statistical significance (p = 0.104). Conclusion: These findings challenge the conventional assumption that health sciences education correlates with superior dietary behaviors. The data suggests a critical need for enhanced education in nutrition, as well as intervention using various behavioral programs across all academic disciplines, particularly those addressing the disconnect between nutritional knowledge and dietary practices among students of health sciences. Future longitudinal studies are warranted in order to elucidate the temporal relationship between academic specialization and dietary behaviors.展开更多
Milk fat globule epithelial growth factor VIII(MFG-E8) is a novel adhesion protein mainly produced by macrophages and dendritic cells; it is expressed in most of the human tissues and functions to prompt cancer progre...Milk fat globule epithelial growth factor VIII(MFG-E8) is a novel adhesion protein mainly produced by macrophages and dendritic cells; it is expressed in most of the human tissues and functions to prompt cancer progression and survival. MFG-E8 contains a signal sequence for secretion, two epidermal growth factor(EGF)-like domains at the NH2 terminus and two discoidin domains with blood-clotting factor V/factor Ⅷ(C1 and C2) at the COOH terminus. The second EGF domain contains an arginine-glycine-aspartic(RGD) integrin-binding motif that engages α_vβ_5 integrins to facilitate cell adhesion and induce integrinmediated signal transduction. Integrin α_vβ_3 associates with VEGF receptor 2, engagement of integrins can promote angiogenesis, which plays key roles in growth, proliferation, and survival of cancer cells. VEGF stimulates the expression of α_vβ_3 and α_vβ_5 integrins on angiogenic vasculature, thereby potentiating effects of VEGF receptor engagement. Mice expressing a mutant form of α_vβ_3 integrin are unable to undergo tyrosine phosphorylation, confirming the important role that this integrin plays in pathological angiogenesis and providing important mechanistic insights. The C-terminus discoidin-like domains promote binding to membrane phospholipids, functioning close to VEGF like angiogenesis. MFG-E8 is an opsonin for apoptotic cells, and it acts as a bridging protein between apoptotic cells and phagocytes. It also influences cell immunities by altering CD4^+ and/or CD8^+ cells. Antibody or small peptide works with MFG-E8 at different functional sites or interacts with EGF-like domains and/or discoidin-like domains may play an important role in anti-angiogenesis or immune restoration. Altering the structures and/or functions of MFG-E8 and/or its domains is promising for development of novel anti-cancer strategies.展开更多
Objective: The use of animal models of aortic stenosis(AS) remains essential to further elucidate its pathophysiology and to evaluate new therapeutic strategies. The waved-2 mouse AS model has been proposed;data have ...Objective: The use of animal models of aortic stenosis(AS) remains essential to further elucidate its pathophysiology and to evaluate new therapeutic strategies. The waved-2 mouse AS model has been proposed;data have indicated that while aortic regurgitation(AR) is effectively induced, development of AS is rare.We aimed to evaluate the effect of high-fat diet(HFD) and vitamin D_3 supplementation in this model.Methods: HFD and subcutaneous vitamin D_3 injections were initiated at the age of 6 weeks until the age of 6(n = 16, 6-month treatment group) and 9(n = 11, 9-month treatment group) months. Twelve waved-2 mice without supplementation were used as control. Echocardiography was performed at 3, 6 and 9 months. Blood serum analysis(calcium, 1,25(OH)_2D_3 and cholesterol), histology and immunohistochemistry(CD-31, CD-68 and osteopontin) were evaluated at the end of the experiment(6 or 9 months).Results: Total cholesterol and 1,25(OH)_2D_3 were significantly increased relative to the control group. HFD and vitamin D_3 supplementation did result in improvements to the model, since AS was only detected in 6(15.3%) mice(2 in the 3 groups) and AR was developed in the remaining animals. Echocardiographic parameters, fibrosis, thickness, inflammation and valvular calcification, were not significantly different between the 6-month treatment and control groups. Similar results were also observed in the 9-month treatment group.Conclusion: These results suggest that HFD and vitamin D_3 supplementation have no effect in the waved-2 mouse model. This model essentially mimics AR and rarely AS. Further studies are needed to find a reliable animal model of AS.展开更多
Kruppel样因子(Kruppel like factors,KLF)基因家族是进化保守的锌指类DNA结合转录调控因子的一个亚家族,目前在哺乳动物中已鉴定到18个成员,其作为转录激活因子或抑制因子调控下游靶基因的表达。研究表明,KLF基因家族在细胞、组织和全...Kruppel样因子(Kruppel like factors,KLF)基因家族是进化保守的锌指类DNA结合转录调控因子的一个亚家族,目前在哺乳动物中已鉴定到18个成员,其作为转录激活因子或抑制因子调控下游靶基因的表达。研究表明,KLF基因家族在细胞、组织和全身水平的代谢控制中发挥重要作用,参与脂肪生成、肌肉发育等多种生理进程。文章系统综述了鸡KLF基因家族的基因组结构、蛋白质特性、进化特征和潜在的生物学功能,并总结了其对鸡肌肉发育、肌内脂肪沉积和腹脂沉积等相关重要经济性状的调控作用,为深入了解KLF基因家族对重要经济性状形成的调控机制提供文献支撑,有助于推动高效优质鸡新品种(系)的培育。展开更多
基金Supported by the National Natural Science Foundation of China,No.82100685the Scientific Research Fund of Xi’an Health Commission,No.2021yb08+1 种基金Scientific Research Fund of Xi’an Central Hospital,No.2022QN07Innovation Capability Support Plan of Xi’an Science and Technology Bureau,No.23YXYJ0097.
文摘BACKGROUND Liver injury is common in severe acute pancreatitis(SAP).Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes,which induces lipid peroxidation and mitochondrial iron deposition and ultimately leads to ferroptosis.Our previous study found that milk fat globule epidermal growth factor 8(MFG-E8)alleviates acinar cell damage during SAP via binding toαvβ3/5 integrins.MFG-E8 also seems to mitigate pancreatic fibrosis via inhibiting chaperone-mediated autophagy.AIM To speculate whether MFG-E8 could also alleviate SAP induced liver injury by restoring the abnormal autophagy flux.METHODS SAP was induced in mice by 2 hly intraperitoneal injections of 4.0 g/kg L-arginine or 7 hly injections of 50μg/kg cerulein plus lipopolysaccharide.mfge8-knockout mice were used to study the effect of MFG-E8 deficiency on SAPinduced liver injury.Cilengitide,a specificαvβ3/5 integrin inhibitor,was used to investigate the possible mechanism of MFG-E8.RESULTS The results showed that MFG-E8 deficiency aggravated SAP-induced liver injury in mice,enhanced autophagy flux in hepatocyte,and worsened the degree of ferroptosis.Exogenous MFG-E8 reduced SAP-induced liver injury in a dose-dependent manner.Mechanistically,MFG-E8 mitigated excessive autophagy and inhibited ferroptosis in liver cells.Cilengitide abolished MFG-E8’s beneficial effects in SAP-induced liver injury.CONCLUSION MFG-E8 acts as an endogenous protective mediator in SAP-induced liver injury.MFG-E8 alleviates the excessive autophagy and inhibits ferroptosis in hepatocytes by binding to integrinαVβ3/5.
文摘Background: In the global burden of non-communicable diseases, the top slot among them all is occupied by various cardiovascular diseases (CVD), which also claim primacy in mortality rates. Generally speaking, the pathophysiological pathway frequently involves either (or a combination of) elevated serum cholesterol levels, predominantly attributed to dietary patterns characterized by extremely high levels of saturated and trans-fat consumption. Day-to-day nutritional epidemiology among university students suggests that they represent a crucial demographic for the study of preventive interventions. Objective: This in-depth study and investigation were specifically aimed to quantitatively assess and compare prevailing patterns of dietary fat consumption between female students enrolled in health sciences and non-health sciences programs at major universities in Riyadh, Saudi Arabia. Methodology: This cross-sectional study was comprised of 434 Saudi female university students (age range: 18 - 25 years), utilizing a validated Block Dietary Fat Screener accompanied by anthropometric measurements and comprehensive demographic data collection. The sampling methodology consisted of a snowball technique that was spread across three major academic institutions in Riyadh. Results: Statistical analysis revealed a significant association between academic specialization and patterns of dietary fat consumption (p = 0.012). Paradoxically, students of health science exhibited a higher prevalence of very high fat intake (41.9%) compared with their non-health sciences counterparts (27.6%). Surprisingly, anthropometric stratification revealed that it was the underweight students who demonstrated very high levels of fat consumption. A notable socioeconomic gradient was observed, with students from households earning 15,000 - 20,000 SR monthly showing the highest prevalence of very high-fat consumption (47.1%), although this association did not achieve statistical significance (p = 0.104). Conclusion: These findings challenge the conventional assumption that health sciences education correlates with superior dietary behaviors. The data suggests a critical need for enhanced education in nutrition, as well as intervention using various behavioral programs across all academic disciplines, particularly those addressing the disconnect between nutritional knowledge and dietary practices among students of health sciences. Future longitudinal studies are warranted in order to elucidate the temporal relationship between academic specialization and dietary behaviors.
基金Supported by a grant from Medical Technology Research Center for Health Development of China National Health and Family Planning Commission(No.W2012FZ007)
文摘Milk fat globule epithelial growth factor VIII(MFG-E8) is a novel adhesion protein mainly produced by macrophages and dendritic cells; it is expressed in most of the human tissues and functions to prompt cancer progression and survival. MFG-E8 contains a signal sequence for secretion, two epidermal growth factor(EGF)-like domains at the NH2 terminus and two discoidin domains with blood-clotting factor V/factor Ⅷ(C1 and C2) at the COOH terminus. The second EGF domain contains an arginine-glycine-aspartic(RGD) integrin-binding motif that engages α_vβ_5 integrins to facilitate cell adhesion and induce integrinmediated signal transduction. Integrin α_vβ_3 associates with VEGF receptor 2, engagement of integrins can promote angiogenesis, which plays key roles in growth, proliferation, and survival of cancer cells. VEGF stimulates the expression of α_vβ_3 and α_vβ_5 integrins on angiogenic vasculature, thereby potentiating effects of VEGF receptor engagement. Mice expressing a mutant form of α_vβ_3 integrin are unable to undergo tyrosine phosphorylation, confirming the important role that this integrin plays in pathological angiogenesis and providing important mechanistic insights. The C-terminus discoidin-like domains promote binding to membrane phospholipids, functioning close to VEGF like angiogenesis. MFG-E8 is an opsonin for apoptotic cells, and it acts as a bridging protein between apoptotic cells and phagocytes. It also influences cell immunities by altering CD4^+ and/or CD8^+ cells. Antibody or small peptide works with MFG-E8 at different functional sites or interacts with EGF-like domains and/or discoidin-like domains may play an important role in anti-angiogenesis or immune restoration. Altering the structures and/or functions of MFG-E8 and/or its domains is promising for development of novel anti-cancer strategies.
基金supported by the French Government,managed by the National Research Agency(ANR)under the program‘‘Investissements d’avenir" with the reference ANR-16-RHUS-0003(RHU project ‘‘Search Treatment and Improve Outcome of Patients with Aortic Stenosis"(STOP-AS)-Hélène Eltchaninoff)Bérénice Colleville’s doctoral program was funded by the Fédération Hospitalo-Universitaire ‘‘Early markers of cardiovascular REMODeling in Valvulopathy and Heart Failure"(REMOD-VHF)and the Rouen Normandy University
文摘Objective: The use of animal models of aortic stenosis(AS) remains essential to further elucidate its pathophysiology and to evaluate new therapeutic strategies. The waved-2 mouse AS model has been proposed;data have indicated that while aortic regurgitation(AR) is effectively induced, development of AS is rare.We aimed to evaluate the effect of high-fat diet(HFD) and vitamin D_3 supplementation in this model.Methods: HFD and subcutaneous vitamin D_3 injections were initiated at the age of 6 weeks until the age of 6(n = 16, 6-month treatment group) and 9(n = 11, 9-month treatment group) months. Twelve waved-2 mice without supplementation were used as control. Echocardiography was performed at 3, 6 and 9 months. Blood serum analysis(calcium, 1,25(OH)_2D_3 and cholesterol), histology and immunohistochemistry(CD-31, CD-68 and osteopontin) were evaluated at the end of the experiment(6 or 9 months).Results: Total cholesterol and 1,25(OH)_2D_3 were significantly increased relative to the control group. HFD and vitamin D_3 supplementation did result in improvements to the model, since AS was only detected in 6(15.3%) mice(2 in the 3 groups) and AR was developed in the remaining animals. Echocardiographic parameters, fibrosis, thickness, inflammation and valvular calcification, were not significantly different between the 6-month treatment and control groups. Similar results were also observed in the 9-month treatment group.Conclusion: These results suggest that HFD and vitamin D_3 supplementation have no effect in the waved-2 mouse model. This model essentially mimics AR and rarely AS. Further studies are needed to find a reliable animal model of AS.
基金National Natural Science Foundation of China(No.81600249,82470055)Natural Science Foundation of Hunan Province(No.2022JJ30823)+1 种基金General Funding Project of Hunan Provincial Health Commission(No.202103010961,W20243119)Changsha Natural Science Foundation,China(No.kq2202392,kq2502197)。
文摘Kruppel样因子(Kruppel like factors,KLF)基因家族是进化保守的锌指类DNA结合转录调控因子的一个亚家族,目前在哺乳动物中已鉴定到18个成员,其作为转录激活因子或抑制因子调控下游靶基因的表达。研究表明,KLF基因家族在细胞、组织和全身水平的代谢控制中发挥重要作用,参与脂肪生成、肌肉发育等多种生理进程。文章系统综述了鸡KLF基因家族的基因组结构、蛋白质特性、进化特征和潜在的生物学功能,并总结了其对鸡肌肉发育、肌内脂肪沉积和腹脂沉积等相关重要经济性状的调控作用,为深入了解KLF基因家族对重要经济性状形成的调控机制提供文献支撑,有助于推动高效优质鸡新品种(系)的培育。
