Mitofusin-2 （Mfn2） gene expression is positively correlated with insulin sensitivity in patients with type 2 diabetes. However, it is unclear if Mfn2 is involved in carbohydrate metabolism and lipid homeostasis. In ...Mitofusin-2 （Mfn2） gene expression is positively correlated with insulin sensitivity in patients with type 2 diabetes. However, it is unclear if Mfn2 is involved in carbohydrate metabolism and lipid homeostasis. In order to investigate the specific functions of Mfn2 in glycometabolism and lipid homeostasis in BALB/c mice, a RNA interference technique-mediated hydrodynamic injection was developed, in which short hairpin RNAs （shRNAs） were used to inhibit the Mfn2 expression in vivo. Seventy-two mice were randomly divided into two groups： the Mfn2 reduction group （Mfn2/shRNA） and the negative control group （NC）. Intraperitoneal glucose tolerance tests and intraperitoneal insulin tolerance tests were used to evaluate glycometabolism and insulin sensitivity. D-（3-3H） glucose or 3H2O was injected into the tail vein or intraperitoneally to facilitate the calculation of the rate of hepatic glucose production and fatty acid synthesis in vivo. The results showed that, in Mfn2/shRNA mice, the liver Mfn2 protein was significantly decreased, and fasting blood glucose concentrations were increased by approximately 48%, when compared with the NC mice. In parallel with the changes in fasting glucose levels, hepatic glucose production was significantly elevated in Mfn2/shRNA mice. When insulin was administrated, these mice exhibited impaired insulin tolerance. It was also found that the reduction of Mfn2 markedly decreased the rate of fatty acid synthesis in the liver, and the Mfn2/shRNA mice exhibited hypertriglyceridema. Taken together, our results indicate that Mfn2 plays an important role in maintaining glucose and lipid homeostasis, and in the development of insulin resistance in vivo.展开更多
Objective:To analysis the effect of continuous blood purification on inflammatory state, immune response and erythrocyte glycometabolism in patients with multiple injury and sepsis. Methods: A total of 78 patients wit...Objective:To analysis the effect of continuous blood purification on inflammatory state, immune response and erythrocyte glycometabolism in patients with multiple injury and sepsis. Methods: A total of 78 patients with multiple injury and sepsis were randomly divided into observation group (n=39) and control group (n=39), control group received routine therapy, observation group received continuous blood purification treatment, and then the differences in inflammatory state, immune response, erythrocyte glycometabolism and other indexes were compared between the two groups after treatment.Results: Inflammatory factor hs-CRP, TNF-α, PCT, sTREM-1 and HBP content in serum of observation group after treatment were significantly lower than those of control group;Th1 cytokines IL-2 and IFN-γ content in serum were lower than those of control group while Th2 cytokines IL-4 and IL-10 content were higher than those of control group;PFK and EGSH content in erythrocyte solution were higher than those of control group while G-6PD, AR and ELPO content were lower than those of control group;fluorescence intensity of CD11a, CD54, CD106 and CD49d in peripheral blood were significantly lower than those of control group.Conclusions: Continuous blood purification can significantly reduce the systemic inflammatory response in patients with multiple injury and sepsis, and promote the immune function and erythrocyte metabolism to return to normal.展开更多
Objec ve To observe the effi cacy of electroacupuncture on glycometabolism disturbance in metabolism syndrome. Methods With matched-pairs design,80 pa ents mee ng with the diagnos c criteria for glycometabolism abnorm...Objec ve To observe the effi cacy of electroacupuncture on glycometabolism disturbance in metabolism syndrome. Methods With matched-pairs design,80 pa ents mee ng with the diagnos c criteria for glycometabolism abnormali es were randomized into the group combining acupuncture and medica on（group A） and the western medicine group（group B）,and 40 pa ents were included in each group. Electroacupuncture was carried out on back-shu points,Zúsānlǐ（足三里 ST 36）,Zhōngwǎn（中脘 CV 12）,Sānyīnjiāo（三阴交 SP 6） and other acupoints for group A,needles were retained for 20 min except back-shu points,once a day,con nuous ten mes as a treatment course,the next treatment course was started a er an interval for 3–5 days,and totally 3 treatment courses were carried out; furthermore,the pa ents were orally administered with Glucotrol XL and felodipine,5 mg each,once a day. The pa ents in group B were treated simply with drugs（the medica on was the same to that for the group A）. Body mass index（BMI）,related biochemical indices and blood pressure of the pa ents were measured before and a er the interven on,respec vely. Results BMI,blood-fas ng glucose,blood glucose 2 h after meal,fasting insulin,insulin resistance index,systolic pressure and diastolic pressure in group A all significantly improved in comparison to those before the electroacupuncture intervention（P0.01）. The difference in BMI in group B before and after the treatments was not statistically significant（P0.05）,and other indices all showed significant improvements（P0.01）. The improvements in the indices as mentioned above in the group A after treatment were significantly better than those in the group B（P0.01）. Conclusion Electroacupuncture intervention can significantly reduce weight,combina on of acupuncture and medica on shows be er effi cacy in reducing blood glucose,improving insulin sensi vity and insulin resistance in comparison to simple administra on with medica ons.展开更多
Validamycin,as a broadly applied antibiotic,has been used to control rice sheath blight disease.Furthermore,validamycin was considered as an insecticide to control agricultural pests.Insight into the mechanism of vali...Validamycin,as a broadly applied antibiotic,has been used to control rice sheath blight disease.Furthermore,validamycin was considered as an insecticide to control agricultural pests.Insight into the mechanism of validamycin’s action on insects can provide molecular targets for the control of agricultural pests.In this study,a toxicological test analysis revealed that Spodoptera litura larval growth and development was significantly inhibited and the pupation rate was significantly reduced with the increase of the concentration of validamycin.According to the NMR-based metabolomic analysis,a total of 15 metabolites involved in glycolysis and tricarboxylic acid cycle(TCA)pathways were identified.Additionally,trehalase activities,glucose and chitin contents were significantly downregulated,but the trehalose content was upregulated after exposure to validamycin.Reverse transcription quantitative PCR analysis revealed that the expression level of genes involved in glycolysis,TCA and chitin synthesis were upregulated after treating with validamycin.Further chitin staining also confirmed that chitin content was downregulated at 12 h after validamycin treatment.Our results indicated that validamycin worked via two different molecular mechanisms,one through inhibiting glycometabolism and the other by inhibiting chitin synthesis in S.litura.The information lays a theoretical foundation for further control of S.litura.展开更多
The aim of the present study was to investigate the protein-sparing effect of carbohydrate in diets for juvenile turbot(Scophthalmus maximus) reared at five salinities(12,18,24,30,and 36).The fish were fed three isoca...The aim of the present study was to investigate the protein-sparing effect of carbohydrate in diets for juvenile turbot(Scophthalmus maximus) reared at five salinities(12,18,24,30,and 36).The fish were fed three isocaloric and isolipidic diets for 60 days.The results show that specific growth rate(SGR)and feed conversion efficiency(FCE) were higher in fish reared at salinities of 18 and 36,but lower at 12.Fish fed with diet C25P40(25%carbohydrate and 40%protein) had lower SGR and FCE values compared with those fed with the C5P52(5%carbohydrate and 52%protein) and C15P46(15%carbohydrate and 46%protein) diets;however,there was no statistical difference between diet C5P52 and C15P46.SGR and FCE values were unaffected by diet composition in fish reared at salinity 36.Hepatic lipogenic enzyme activities were higher in fish reared at 18 and 36,but lower at 12,while glucokinase(GK) activity was higher in fish reared at 12,and lower at 18 and 36.Dietary starch enhanced GK activity while depressing lipogenic enzyme activity.However,lipogenic enzyme activity increased with increasing dietary starch in fish reared at 36.It is recommended that salinity should be maintained > 12 in the farming of juvenile turbot.In addition,an increase in gelatinized starch from 5%to 15%could spare 6%dietary protein in fish reared at salinities of 18-30,while higher salinity(36) could improve dietary carbohydrate use and enhance the protein-sparing effect,which is linked with the induction of lipogenic capacities.展开更多
Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine. Multifold advantages such as simplicity of breeding, low cost of fe...Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine. Multifold advantages such as simplicity of breeding, low cost of feeding and facility of operating make the tree shrew an ideal non-human primate model proxy. Additional features like vulnerability to stress and spontaneous diabetic characteristics also indicate that the tree shrew could be a potential new animal model of human diseases. However, basal physiological indexes of tree shrew, especially those related to human disease, have not been systematically reported. Accordingly, we established important basal physiological indexes of domesticated tree shrews including several factors: (1) body weight, (2) core body temperature and rhythm, (3) diet metabolism, (4) locomotor rhythm, (5) electroencephalogram, (6) glycometabolism and (7) serum and urinary hormone level and urinary cortisol rhythm. We compared the physiological parameters of domesticated tree shrew with that of rats and macaques. Results showed that (a) the core body temperature of the tree shrew was 39.59±0.05 °C, which was higher than that of rats and macaques; (b) Compared with wild tree shrews, with two activity peaks, domesticated tree shrews had only one activity peak from 17:30 to 19:30; (c) Compared with rats, tree shrews had poor carbohydrate metabolism ability; and (d) Urinary cortisol rhythm indicated there were two peaks at 8:00 and 17:00 in domesticated tree shrews, which matched activity peaks in wild tree shrews. These results provided basal physiological indexes for domesticated tree shrews and laid an important foundation for diabetes and stress-related disease models established on tree shrews.展开更多
Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine.Multifold advantages such as simplicity of breeding,low cost of feed...Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine.Multifold advantages such as simplicity of breeding,low cost of feeding and facility of operating make the tree shrew an ideal non-human primate model proxy.Additional features like vulnerability to stress and spontaneous diabetic characteristics also indicate that the tree shrew could be a potential new animal model of human diseases.However,basal physiological indexes of tree shrew,especially those related to human disease,have not been systematically reported.Accordingly,we established important basal physiological indexes of domesticated tree shrews including several factors:(1)body weight,(2)core body temperature and rhythm,(3)diet metabolism,(4)locomotor rhythm,(5)electroencephalogram,(6)glycometabolism and(7)serum and urinary hormone level and urinary cortisol rhythm.We compared the physiological parameters of domesticated tree shrew with that of rats and macaques.Results showed that(a)the core body temperature of the tree shrew was 39.59±0.05°C,which was higher than that of rats and macaques;(b)Compared with wild tree shrews,with two activity peaks,domesticated tree shrews had only one activity peak from 17:30 to 19:30;(c)Compared with rats,tree shrews had poor carbohydrate metabolism ability;and(d)Urinary cortisol rhythm indicated there were two peaks at 8:00 and 17:00 in domesticated tree shrews,which matched activity peaks in wild tree shrews.These results provided basal physiological indexes for domesticated tree shrews and laid an important foundation for diabetes and stress-related disease models established on tree shrews.展开更多
Objective: To detect the serum Betatrophin level in patients with gestational diabetes mellitus (GDM), and to explore the relationship between Betatrophin level and disorders of glucose and lipid metabolism. Methods: ...Objective: To detect the serum Betatrophin level in patients with gestational diabetes mellitus (GDM), and to explore the relationship between Betatrophin level and disorders of glucose and lipid metabolism. Methods: 119 cases of GDM women in our hospital during August 2015 to March 2018 were selected as GDM group, 100 cases pregnant women with normal blood glucose were chosen as Normal control group. Serum level of Betatrophin, glucose metabolism and lipid metabolism between two groups were compared. Pearson test was used to evaluate the relationship between Betatrophin, glucose and lipid metabolism disorders in GDM pregnant women. Results: Serum content of Betatrophin in GDM group was significantly higher than that in Normal control group, levels of HbA1c, FINS and HOMA-IR in peripheral blood were significantly higher than those in Normal control group;contents of TC, LDL-C and Apo-B in peripheral blood were higher than those in Normal control group, contents of HDL-C, Apo-A1 were lower than those in Normal control group. Correlation analysis showed that serum level of Betatrophin in GDM pregnant women was positively correlated with the disorder of glucose and lipid metabolism. Conclusion: Abnormally high expression of Betatrophin in GDM pregnant women may be an important factor in promoting disorder of glucose and lipid metabolism.展开更多
The adoptive transfer of chimeric antigen receptor-T(CAR-T)cells has shown remarkable clinical responses in hematologic malignancies.However,unsatisfactory curative results and side effects for tumor treatment are sti...The adoptive transfer of chimeric antigen receptor-T(CAR-T)cells has shown remarkable clinical responses in hematologic malignancies.However,unsatisfactory curative results and side effects for tumor treatment are still unsolved problems.Herein we develop a click CAR-T cell engineering strategy via cell glycometabolic labeling for robustly boosting their antitumor effects and safety in vivo.Briefly,paired chemical groups(N3/BCN)are separately incorporated into CAR-T cell and tumor via nondestructive intrinsic glycometabolism of exogenous Ac4GalNAz and Ac4ManNBCN,serving as an artificial ligand-receptor.Functional groups anchored on cell surface strengthen the interaction of CAR-T cell and tumor via bioorthogonal click chemistry,further enhancing specific recognition,migration and selective antitumor effects of CAR-T cells.In vivo,click CAR-T cell completely removes lymphoma cells and minimizes off-target toxicity via selective and efficient bioorthogonal targeting in blood cancer.Surprisingly,compared to unlabeled cells,artificial bioorthogonal targeting significantly promotes the accumulation,deep penetration and homing of CAR-T cells into tumor tissues,ultimately improving its curative effect for solid tumor.Click CAR-T cell engineering robustly boosts selective recognition and antitumor capabilities of CAR T cells in vitro and in vivo,thereby holding a great potential for effective clinical cell immunotherapy with avoiding adverse events in patients.展开更多
文摘Mitofusin-2 （Mfn2） gene expression is positively correlated with insulin sensitivity in patients with type 2 diabetes. However, it is unclear if Mfn2 is involved in carbohydrate metabolism and lipid homeostasis. In order to investigate the specific functions of Mfn2 in glycometabolism and lipid homeostasis in BALB/c mice, a RNA interference technique-mediated hydrodynamic injection was developed, in which short hairpin RNAs （shRNAs） were used to inhibit the Mfn2 expression in vivo. Seventy-two mice were randomly divided into two groups： the Mfn2 reduction group （Mfn2/shRNA） and the negative control group （NC）. Intraperitoneal glucose tolerance tests and intraperitoneal insulin tolerance tests were used to evaluate glycometabolism and insulin sensitivity. D-（3-3H） glucose or 3H2O was injected into the tail vein or intraperitoneally to facilitate the calculation of the rate of hepatic glucose production and fatty acid synthesis in vivo. The results showed that, in Mfn2/shRNA mice, the liver Mfn2 protein was significantly decreased, and fasting blood glucose concentrations were increased by approximately 48%, when compared with the NC mice. In parallel with the changes in fasting glucose levels, hepatic glucose production was significantly elevated in Mfn2/shRNA mice. When insulin was administrated, these mice exhibited impaired insulin tolerance. It was also found that the reduction of Mfn2 markedly decreased the rate of fatty acid synthesis in the liver, and the Mfn2/shRNA mice exhibited hypertriglyceridema. Taken together, our results indicate that Mfn2 plays an important role in maintaining glucose and lipid homeostasis, and in the development of insulin resistance in vivo.
文摘Objective:To analysis the effect of continuous blood purification on inflammatory state, immune response and erythrocyte glycometabolism in patients with multiple injury and sepsis. Methods: A total of 78 patients with multiple injury and sepsis were randomly divided into observation group (n=39) and control group (n=39), control group received routine therapy, observation group received continuous blood purification treatment, and then the differences in inflammatory state, immune response, erythrocyte glycometabolism and other indexes were compared between the two groups after treatment.Results: Inflammatory factor hs-CRP, TNF-α, PCT, sTREM-1 and HBP content in serum of observation group after treatment were significantly lower than those of control group;Th1 cytokines IL-2 and IFN-γ content in serum were lower than those of control group while Th2 cytokines IL-4 and IL-10 content were higher than those of control group;PFK and EGSH content in erythrocyte solution were higher than those of control group while G-6PD, AR and ELPO content were lower than those of control group;fluorescence intensity of CD11a, CD54, CD106 and CD49d in peripheral blood were significantly lower than those of control group.Conclusions: Continuous blood purification can significantly reduce the systemic inflammatory response in patients with multiple injury and sepsis, and promote the immune function and erythrocyte metabolism to return to normal.
基金Supported by scien fic and technological tackling project in Administra on of TCM of Health Bureau of Hebei Province:2009099
文摘Objec ve To observe the effi cacy of electroacupuncture on glycometabolism disturbance in metabolism syndrome. Methods With matched-pairs design,80 pa ents mee ng with the diagnos c criteria for glycometabolism abnormali es were randomized into the group combining acupuncture and medica on（group A） and the western medicine group（group B）,and 40 pa ents were included in each group. Electroacupuncture was carried out on back-shu points,Zúsānlǐ（足三里 ST 36）,Zhōngwǎn（中脘 CV 12）,Sānyīnjiāo（三阴交 SP 6） and other acupoints for group A,needles were retained for 20 min except back-shu points,once a day,con nuous ten mes as a treatment course,the next treatment course was started a er an interval for 3–5 days,and totally 3 treatment courses were carried out; furthermore,the pa ents were orally administered with Glucotrol XL and felodipine,5 mg each,once a day. The pa ents in group B were treated simply with drugs（the medica on was the same to that for the group A）. Body mass index（BMI）,related biochemical indices and blood pressure of the pa ents were measured before and a er the interven on,respec vely. Results BMI,blood-fas ng glucose,blood glucose 2 h after meal,fasting insulin,insulin resistance index,systolic pressure and diastolic pressure in group A all significantly improved in comparison to those before the electroacupuncture intervention（P0.01）. The difference in BMI in group B before and after the treatments was not statistically significant（P0.05）,and other indices all showed significant improvements（P0.01）. The improvements in the indices as mentioned above in the group A after treatment were significantly better than those in the group B（P0.01）. Conclusion Electroacupuncture intervention can significantly reduce weight,combina on of acupuncture and medica on shows be er effi cacy in reducing blood glucose,improving insulin sensi vity and insulin resistance in comparison to simple administra on with medica ons.
基金The work was supported by the Natural Science Foundation of Jiangxi Province(20202BAB215004)the Major Science and technology R&D Program of Jiangxi Province(20194ABC28007)+1 种基金the Educational Commission of Jiangxi Province of China(GJJ180747 and GJJ190759)Jiangxi Agriculture System(JXARS-07).
文摘Validamycin,as a broadly applied antibiotic,has been used to control rice sheath blight disease.Furthermore,validamycin was considered as an insecticide to control agricultural pests.Insight into the mechanism of validamycin’s action on insects can provide molecular targets for the control of agricultural pests.In this study,a toxicological test analysis revealed that Spodoptera litura larval growth and development was significantly inhibited and the pupation rate was significantly reduced with the increase of the concentration of validamycin.According to the NMR-based metabolomic analysis,a total of 15 metabolites involved in glycolysis and tricarboxylic acid cycle(TCA)pathways were identified.Additionally,trehalase activities,glucose and chitin contents were significantly downregulated,but the trehalose content was upregulated after exposure to validamycin.Reverse transcription quantitative PCR analysis revealed that the expression level of genes involved in glycolysis,TCA and chitin synthesis were upregulated after treating with validamycin.Further chitin staining also confirmed that chitin content was downregulated at 12 h after validamycin treatment.Our results indicated that validamycin worked via two different molecular mechanisms,one through inhibiting glycometabolism and the other by inhibiting chitin synthesis in S.litura.The information lays a theoretical foundation for further control of S.litura.
基金Supported by the Special Fund of Chinese Ministry of Agriculture for Modern Agriculture Industry System Construction(No.CARS-50)
文摘The aim of the present study was to investigate the protein-sparing effect of carbohydrate in diets for juvenile turbot(Scophthalmus maximus) reared at five salinities(12,18,24,30,and 36).The fish were fed three isocaloric and isolipidic diets for 60 days.The results show that specific growth rate(SGR)and feed conversion efficiency(FCE) were higher in fish reared at salinities of 18 and 36,but lower at 12.Fish fed with diet C25P40(25%carbohydrate and 40%protein) had lower SGR and FCE values compared with those fed with the C5P52(5%carbohydrate and 52%protein) and C15P46(15%carbohydrate and 46%protein) diets;however,there was no statistical difference between diet C5P52 and C15P46.SGR and FCE values were unaffected by diet composition in fish reared at salinity 36.Hepatic lipogenic enzyme activities were higher in fish reared at 18 and 36,but lower at 12,while glucokinase(GK) activity was higher in fish reared at 12,and lower at 18 and 36.Dietary starch enhanced GK activity while depressing lipogenic enzyme activity.However,lipogenic enzyme activity increased with increasing dietary starch in fish reared at 36.It is recommended that salinity should be maintained > 12 in the farming of juvenile turbot.In addition,an increase in gelatinized starch from 5%to 15%could spare 6%dietary protein in fish reared at salinities of 18-30,while higher salinity(36) could improve dietary carbohydrate use and enhance the protein-sparing effect,which is linked with the induction of lipogenic capacities.
基金supported by grants from the Chinese Academy of Sciences (KSCX2-EW-R-12, KSCX2-EW-J-23)the National Natural Science Foundation of China (81171294)Shanghai Science & Technology Development Foundation(12140904200)
文摘Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine. Multifold advantages such as simplicity of breeding, low cost of feeding and facility of operating make the tree shrew an ideal non-human primate model proxy. Additional features like vulnerability to stress and spontaneous diabetic characteristics also indicate that the tree shrew could be a potential new animal model of human diseases. However, basal physiological indexes of tree shrew, especially those related to human disease, have not been systematically reported. Accordingly, we established important basal physiological indexes of domesticated tree shrews including several factors: (1) body weight, (2) core body temperature and rhythm, (3) diet metabolism, (4) locomotor rhythm, (5) electroencephalogram, (6) glycometabolism and (7) serum and urinary hormone level and urinary cortisol rhythm. We compared the physiological parameters of domesticated tree shrew with that of rats and macaques. Results showed that (a) the core body temperature of the tree shrew was 39.59±0.05 °C, which was higher than that of rats and macaques; (b) Compared with wild tree shrews, with two activity peaks, domesticated tree shrews had only one activity peak from 17:30 to 19:30; (c) Compared with rats, tree shrews had poor carbohydrate metabolism ability; and (d) Urinary cortisol rhythm indicated there were two peaks at 8:00 and 17:00 in domesticated tree shrews, which matched activity peaks in wild tree shrews. These results provided basal physiological indexes for domesticated tree shrews and laid an important foundation for diabetes and stress-related disease models established on tree shrews.
基金This work was supported by grants from the Chinese Academy of Sciences(KSCX2-EW-R-12,KSCX2-EW-J-23)the National Natural Science Foundation of China(81171294)Shanghai Science&Technology Development Foundation(12140904200).
文摘Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine.Multifold advantages such as simplicity of breeding,low cost of feeding and facility of operating make the tree shrew an ideal non-human primate model proxy.Additional features like vulnerability to stress and spontaneous diabetic characteristics also indicate that the tree shrew could be a potential new animal model of human diseases.However,basal physiological indexes of tree shrew,especially those related to human disease,have not been systematically reported.Accordingly,we established important basal physiological indexes of domesticated tree shrews including several factors:(1)body weight,(2)core body temperature and rhythm,(3)diet metabolism,(4)locomotor rhythm,(5)electroencephalogram,(6)glycometabolism and(7)serum and urinary hormone level and urinary cortisol rhythm.We compared the physiological parameters of domesticated tree shrew with that of rats and macaques.Results showed that(a)the core body temperature of the tree shrew was 39.59±0.05°C,which was higher than that of rats and macaques;(b)Compared with wild tree shrews,with two activity peaks,domesticated tree shrews had only one activity peak from 17:30 to 19:30;(c)Compared with rats,tree shrews had poor carbohydrate metabolism ability;and(d)Urinary cortisol rhythm indicated there were two peaks at 8:00 and 17:00 in domesticated tree shrews,which matched activity peaks in wild tree shrews.These results provided basal physiological indexes for domesticated tree shrews and laid an important foundation for diabetes and stress-related disease models established on tree shrews.
文摘Objective: To detect the serum Betatrophin level in patients with gestational diabetes mellitus (GDM), and to explore the relationship between Betatrophin level and disorders of glucose and lipid metabolism. Methods: 119 cases of GDM women in our hospital during August 2015 to March 2018 were selected as GDM group, 100 cases pregnant women with normal blood glucose were chosen as Normal control group. Serum level of Betatrophin, glucose metabolism and lipid metabolism between two groups were compared. Pearson test was used to evaluate the relationship between Betatrophin, glucose and lipid metabolism disorders in GDM pregnant women. Results: Serum content of Betatrophin in GDM group was significantly higher than that in Normal control group, levels of HbA1c, FINS and HOMA-IR in peripheral blood were significantly higher than those in Normal control group;contents of TC, LDL-C and Apo-B in peripheral blood were higher than those in Normal control group, contents of HDL-C, Apo-A1 were lower than those in Normal control group. Correlation analysis showed that serum level of Betatrophin in GDM pregnant women was positively correlated with the disorder of glucose and lipid metabolism. Conclusion: Abnormally high expression of Betatrophin in GDM pregnant women may be an important factor in promoting disorder of glucose and lipid metabolism.
基金the National Natural Science Foundation of China(Grant No.81971749,81601552,31571013)Guangdong Natural Science Foundation of Research Team(2016A030312006)Shenzhen Science and Technology Program(JCYJ20170818163739458,JCYJ20170306160217433,CYZZ20170331150956189).
文摘The adoptive transfer of chimeric antigen receptor-T(CAR-T)cells has shown remarkable clinical responses in hematologic malignancies.However,unsatisfactory curative results and side effects for tumor treatment are still unsolved problems.Herein we develop a click CAR-T cell engineering strategy via cell glycometabolic labeling for robustly boosting their antitumor effects and safety in vivo.Briefly,paired chemical groups(N3/BCN)are separately incorporated into CAR-T cell and tumor via nondestructive intrinsic glycometabolism of exogenous Ac4GalNAz and Ac4ManNBCN,serving as an artificial ligand-receptor.Functional groups anchored on cell surface strengthen the interaction of CAR-T cell and tumor via bioorthogonal click chemistry,further enhancing specific recognition,migration and selective antitumor effects of CAR-T cells.In vivo,click CAR-T cell completely removes lymphoma cells and minimizes off-target toxicity via selective and efficient bioorthogonal targeting in blood cancer.Surprisingly,compared to unlabeled cells,artificial bioorthogonal targeting significantly promotes the accumulation,deep penetration and homing of CAR-T cells into tumor tissues,ultimately improving its curative effect for solid tumor.Click CAR-T cell engineering robustly boosts selective recognition and antitumor capabilities of CAR T cells in vitro and in vivo,thereby holding a great potential for effective clinical cell immunotherapy with avoiding adverse events in patients.
