Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects ...Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.展开更多
Objectives:The Kirsten rat sarcoma virus(KRAS)G12D oncogenic mutation poses a significant challenge in treating solid tumors due to the lack of specific and effective therapeutic interventions.This study aims to explore...Objectives:The Kirsten rat sarcoma virus(KRAS)G12D oncogenic mutation poses a significant challenge in treating solid tumors due to the lack of specific and effective therapeutic interventions.This study aims to explore innovative approaches in T cell receptor(TCR)engineering and characterization to target the KRAS G12D7-16 mutation,providing potential strategies for overcoming this therapeutic challenge.Methods:In this innovative study,we engineered and characterized two T cell receptors(TCRs),KDA11-01 and KDA11-02 with high affinity for the KRAS G12D7-16 mutation.These TCRs were isolated from tumor-infiltrating lymphocytes(TILs)derived from tumor tissues of patients with the KRAS G12D mutation.We assessed their specificity and anti-tumor activity in vitro using various cancer cell lines.Results:KDA11-01 and KDA11-02 demonstrated exceptional specificity for the HLA-A*11:01-restricted KRAS G12D7-16 epitope,significantly inducing IFN-γrelease and eliminating tumor cells without cross-reactivity or alloreactivity.Conclusions:The successful development of KDA11-01 and KDA11-02 introduces a novel and precise TCR-based therapeutic strategy against KRAS G12D mutation,showing potential for significant advancements in cancer immunotherapy.展开更多
In Africa, the prevalence of diabetes is escalating and remains a concern due to the numerous complications it causes. Vascular damage associated with diabetes leads to a prothrombotic state observed in diabetic indiv...In Africa, the prevalence of diabetes is escalating and remains a concern due to the numerous complications it causes. Vascular damage associated with diabetes leads to a prothrombotic state observed in diabetic individuals. Diabetes is a complex and multifactorial disease involving genetic components. With the aim of preventing complications and contributing to an efficient management of diabetes, we investigated genes likely to lead to a risk of thrombosis, in particular the C677T of MTHFR, G20210A of prothrombin, and R506Q of factor V Leiden in type 2 diabetics in Abidjan receiving ambulatory care. A descriptive cross-sectional study was carried out on consenting type 2 diabetic patients. Mutation detection was carried out using the PCR-RFLP method employing restriction enzymes. Hemostasis tests (fibrinogen, D-dimers, fibrin monomers, and von Willebrand factor) were performed using citrate tubes on the Stage? Star Max automated system. Plasminogen activator inhibitor was assayed by ELISA method, and biochemical parameters were determined using the COBAS C311. The study population consisted of 45 diabetic patients, 51.1% of whom presented vascular complications, mainly neuropathy. Disturbances in hemostasis parameters were observed, with 15.5% of patients showing an increase in fibrin monomers. Mutation analysis revealed an absence of factor V mutation (factor V Leiden) and of G20210A mutation of the prothrombin gene. However, 15.6% of subjects had a heterozygous C677T mutation of MTHFR, with 57% of them being anemic. The exploration of biological and genetic factors associated with thrombotic risk is of significant interest in the optimal management of African type 2 diabetics.展开更多
The purpose of this clinical trial was to delineate some of the negative consequences of high BMI on health and explore the possibility of a solution. We analysed the blood test results of nine overweight adults with ...The purpose of this clinical trial was to delineate some of the negative consequences of high BMI on health and explore the possibility of a solution. We analysed the blood test results of nine overweight adults with sedentary lifestyles, and an average BMI of 32.23. Results revealed a statistically significant reduction of visceral adipose tissue, very-low density lipoprotein (VLDL), and triglycerides. Testosterone, leptin, IGF-1 and Free T3 increased within the normal range, juxtaposed by cortisol and ghrelin that declined, but without dipping into abnormality. These findings have important implications during the COVID-19 pandemic, where optimal immunity is deemed necessary in limiting susceptibility to the virus. Recent research indicates that weight gain often escalates vulnerability to respiratory track disturbances, cardiovascular disease (CVD) and diabetes. Consequently, pre-existing conditions increase COVID-19 mortality rates. CVD and diabetes emerge out of hormonal imbalances that involve Free T3, leptin, ghrelin, testosterone, and cortisol. Physical training is decidedly the most acclaimed solution, yet, the least implemented one, due to procrastination, or demoralization after investing constant exhaustive effort with no immediately visible physical change. COVID-19 confinement exacerbates the tendency for inactivity, and promotes stress-eating behaviours. Moreover, strenuous exercise, necessary for visceral fat reduction, results in a negative cortisol/testosterone relationship that provokes caloric consumption and inflammation. Offering an alternative to exercise that effectively improves health, boosts metabolism, and controls appetite, may serve as a proactive, and preventive method that can safeguard health.展开更多
Objectives Both apolipoprotein(Apo)C-Ⅲgene polymorphism and alcohol consumption have been associated with increased serum triglyceride(TG) levels,but their interactions on serum TG levels are not well known.The prese...Objectives Both apolipoprotein(Apo)C-Ⅲgene polymorphism and alcohol consumption have been associated with increased serum triglyceride(TG) levels,but their interactions on serum TG levels are not well known.The present study was undertaken to detect the interactions of the ApoC-Ⅲ3238C】G(rs5128) polymorphism and alcohol consumption on serum TG levels.Methods A total of 516 unrelated nondrinkers and 514 drinkers aged 15-89 were randomly selected from our previous stratified randomized cluster samples. Genotyping of the ApoC-Ⅲ3238C】G was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis,and then confirmed by direct sequencing.Interactions of the ApoC-Ⅲ3238C】G genotype and alcohol consumption was assessed by using a cross-product term between genotypes and the afore-mentioned factor.Results Serum total cholesterol(TC), TG,high-density lipoprotein cholesterol(HDL-C),ApoA-I and ApoB levels were higher in drinkers than in nondrinkers (P【0.05-0.001).There was no significant difference in the genotypic and allelic frequencies between the two groups. Serum TG levels in nondrinkers were higher in CG genotype than in CC genotype(P【0,01).Serum TC,TG,low-density lipoprotein cholesterol(LDL-C) and ApoB levels in drinkers were higher in GG genotype than in CC or CG genotype(P【0.01 for all).Serum HDL-C levels in drinkers were higher in CG genotype than in CC genotype(P【0.01).Serum TC, TG,HDL-C and ApoA-I levels in CC genotype,TC,HDL-C, ApoA-I levels and the ratio of ApoA-I to ApoB in CG genotype, and TC,TG,LDL-C,ApoA-I and ApoB levels in GG genotype were higher in drinkers than in nondrinkers(P【0.05-0.01).But the ratio of ApoA-I to ApoB in GG genotype was lower in drinkers than in nondrinkers(P【0.01). Multivariate logistic regression analysis showed that the levels of TC,TG and ApoB were correlated with genotype in non drinkers(P【0.05 for all).The levels of TC,LDL-C and ApoB were associated with genotype in drinkers(P【0.01 for all). Serum lipid parameters were also correlated with age,sex,alcohol consumption,cigarette smoking,blood pressure,body weight,and body mass index in both groups.Conclusions This study suggests that the ApoC-Ⅲ3238CG heterozygotes benefited more from alcohol consumption than CC and GG homozygotes in increasing serum levels of HDL-C,ApoA-I, and the ratio of ApoA-I to ApoB,and lowering serum levels of TC and TG.展开更多
Tors are mound-like rock landforms,resistant to erosion,that may sometimes reach the size of several storeys of house by volume.They may develop in different climate regions and different rock types,led by granitic ro...Tors are mound-like rock landforms,resistant to erosion,that may sometimes reach the size of several storeys of house by volume.They may develop in different climate regions and different rock types,led by granitic rocks.In this study,tors developed in granitic rocks around Yaylal?village linked to Kürtün county in Gümü?hane were investigated.The study area is located in the eastern part of the Giresun mountain range in northeastern Turkey,2000-2300 m above sea level.The aim of the study is to determine the natural environmental characteristics in tor formation and to reveal the effect of bedrock on tor formation.During field studies,18 tors were selected by noting location,size and structural features,and dimensions were measured.Thin sections were first made from the rock samples taken from the tors and then the mineralogical composition was investigated by modal analysis method.As a result of this analysis,it was determined that the bedrock forming the tors is granite.During the field observations,it was determined that the intersecting vertical joints supported the formation of castle-like tors,while the horizontal joints supported the formation of pita pileshaped tors.There are also pseudokarstic shapes resembling kamenitza and karst pavement.In conclusion,joint sets causing local resistance differences directed the formation of tors,while excess slope affected surface erosion and suitability of climate conditions-controlled weathering rate.展开更多
基金supported by the National Key Research and Development Program of China(Grant No.2019YFC1605000)National Natural Science Foundation of China(Grant No.31871806)the Beijing Livestock Industry Innovation Team(BAIC05-2023)。
文摘Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.
基金funded by the key R&D Project of Hubei Province(Social Development),China(2022BCA018)the Cooperative Innovation Center of Industrial Fermentation(Ministry of Education&Hubei Province),China(2022KF16)to Kanghong Hu.
文摘Objectives:The Kirsten rat sarcoma virus(KRAS)G12D oncogenic mutation poses a significant challenge in treating solid tumors due to the lack of specific and effective therapeutic interventions.This study aims to explore innovative approaches in T cell receptor(TCR)engineering and characterization to target the KRAS G12D7-16 mutation,providing potential strategies for overcoming this therapeutic challenge.Methods:In this innovative study,we engineered and characterized two T cell receptors(TCRs),KDA11-01 and KDA11-02 with high affinity for the KRAS G12D7-16 mutation.These TCRs were isolated from tumor-infiltrating lymphocytes(TILs)derived from tumor tissues of patients with the KRAS G12D mutation.We assessed their specificity and anti-tumor activity in vitro using various cancer cell lines.Results:KDA11-01 and KDA11-02 demonstrated exceptional specificity for the HLA-A*11:01-restricted KRAS G12D7-16 epitope,significantly inducing IFN-γrelease and eliminating tumor cells without cross-reactivity or alloreactivity.Conclusions:The successful development of KDA11-01 and KDA11-02 introduces a novel and precise TCR-based therapeutic strategy against KRAS G12D mutation,showing potential for significant advancements in cancer immunotherapy.
文摘In Africa, the prevalence of diabetes is escalating and remains a concern due to the numerous complications it causes. Vascular damage associated with diabetes leads to a prothrombotic state observed in diabetic individuals. Diabetes is a complex and multifactorial disease involving genetic components. With the aim of preventing complications and contributing to an efficient management of diabetes, we investigated genes likely to lead to a risk of thrombosis, in particular the C677T of MTHFR, G20210A of prothrombin, and R506Q of factor V Leiden in type 2 diabetics in Abidjan receiving ambulatory care. A descriptive cross-sectional study was carried out on consenting type 2 diabetic patients. Mutation detection was carried out using the PCR-RFLP method employing restriction enzymes. Hemostasis tests (fibrinogen, D-dimers, fibrin monomers, and von Willebrand factor) were performed using citrate tubes on the Stage? Star Max automated system. Plasminogen activator inhibitor was assayed by ELISA method, and biochemical parameters were determined using the COBAS C311. The study population consisted of 45 diabetic patients, 51.1% of whom presented vascular complications, mainly neuropathy. Disturbances in hemostasis parameters were observed, with 15.5% of patients showing an increase in fibrin monomers. Mutation analysis revealed an absence of factor V mutation (factor V Leiden) and of G20210A mutation of the prothrombin gene. However, 15.6% of subjects had a heterozygous C677T mutation of MTHFR, with 57% of them being anemic. The exploration of biological and genetic factors associated with thrombotic risk is of significant interest in the optimal management of African type 2 diabetics.
文摘The purpose of this clinical trial was to delineate some of the negative consequences of high BMI on health and explore the possibility of a solution. We analysed the blood test results of nine overweight adults with sedentary lifestyles, and an average BMI of 32.23. Results revealed a statistically significant reduction of visceral adipose tissue, very-low density lipoprotein (VLDL), and triglycerides. Testosterone, leptin, IGF-1 and Free T3 increased within the normal range, juxtaposed by cortisol and ghrelin that declined, but without dipping into abnormality. These findings have important implications during the COVID-19 pandemic, where optimal immunity is deemed necessary in limiting susceptibility to the virus. Recent research indicates that weight gain often escalates vulnerability to respiratory track disturbances, cardiovascular disease (CVD) and diabetes. Consequently, pre-existing conditions increase COVID-19 mortality rates. CVD and diabetes emerge out of hormonal imbalances that involve Free T3, leptin, ghrelin, testosterone, and cortisol. Physical training is decidedly the most acclaimed solution, yet, the least implemented one, due to procrastination, or demoralization after investing constant exhaustive effort with no immediately visible physical change. COVID-19 confinement exacerbates the tendency for inactivity, and promotes stress-eating behaviours. Moreover, strenuous exercise, necessary for visceral fat reduction, results in a negative cortisol/testosterone relationship that provokes caloric consumption and inflammation. Offering an alternative to exercise that effectively improves health, boosts metabolism, and controls appetite, may serve as a proactive, and preventive method that can safeguard health.
文摘Objectives Both apolipoprotein(Apo)C-Ⅲgene polymorphism and alcohol consumption have been associated with increased serum triglyceride(TG) levels,but their interactions on serum TG levels are not well known.The present study was undertaken to detect the interactions of the ApoC-Ⅲ3238C】G(rs5128) polymorphism and alcohol consumption on serum TG levels.Methods A total of 516 unrelated nondrinkers and 514 drinkers aged 15-89 were randomly selected from our previous stratified randomized cluster samples. Genotyping of the ApoC-Ⅲ3238C】G was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis,and then confirmed by direct sequencing.Interactions of the ApoC-Ⅲ3238C】G genotype and alcohol consumption was assessed by using a cross-product term between genotypes and the afore-mentioned factor.Results Serum total cholesterol(TC), TG,high-density lipoprotein cholesterol(HDL-C),ApoA-I and ApoB levels were higher in drinkers than in nondrinkers (P【0.05-0.001).There was no significant difference in the genotypic and allelic frequencies between the two groups. Serum TG levels in nondrinkers were higher in CG genotype than in CC genotype(P【0,01).Serum TC,TG,low-density lipoprotein cholesterol(LDL-C) and ApoB levels in drinkers were higher in GG genotype than in CC or CG genotype(P【0.01 for all).Serum HDL-C levels in drinkers were higher in CG genotype than in CC genotype(P【0.01).Serum TC, TG,HDL-C and ApoA-I levels in CC genotype,TC,HDL-C, ApoA-I levels and the ratio of ApoA-I to ApoB in CG genotype, and TC,TG,LDL-C,ApoA-I and ApoB levels in GG genotype were higher in drinkers than in nondrinkers(P【0.05-0.01).But the ratio of ApoA-I to ApoB in GG genotype was lower in drinkers than in nondrinkers(P【0.01). Multivariate logistic regression analysis showed that the levels of TC,TG and ApoB were correlated with genotype in non drinkers(P【0.05 for all).The levels of TC,LDL-C and ApoB were associated with genotype in drinkers(P【0.01 for all). Serum lipid parameters were also correlated with age,sex,alcohol consumption,cigarette smoking,blood pressure,body weight,and body mass index in both groups.Conclusions This study suggests that the ApoC-Ⅲ3238CG heterozygotes benefited more from alcohol consumption than CC and GG homozygotes in increasing serum levels of HDL-C,ApoA-I, and the ratio of ApoA-I to ApoB,and lowering serum levels of TC and TG.
文摘Tors are mound-like rock landforms,resistant to erosion,that may sometimes reach the size of several storeys of house by volume.They may develop in different climate regions and different rock types,led by granitic rocks.In this study,tors developed in granitic rocks around Yaylal?village linked to Kürtün county in Gümü?hane were investigated.The study area is located in the eastern part of the Giresun mountain range in northeastern Turkey,2000-2300 m above sea level.The aim of the study is to determine the natural environmental characteristics in tor formation and to reveal the effect of bedrock on tor formation.During field studies,18 tors were selected by noting location,size and structural features,and dimensions were measured.Thin sections were first made from the rock samples taken from the tors and then the mineralogical composition was investigated by modal analysis method.As a result of this analysis,it was determined that the bedrock forming the tors is granite.During the field observations,it was determined that the intersecting vertical joints supported the formation of castle-like tors,while the horizontal joints supported the formation of pita pileshaped tors.There are also pseudokarstic shapes resembling kamenitza and karst pavement.In conclusion,joint sets causing local resistance differences directed the formation of tors,while excess slope affected surface erosion and suitability of climate conditions-controlled weathering rate.
