The rapid development and widespread use of ZnO nanoparticles(nZnO) in various industries have raised concerns about their potential environmental impact.Therefore,understanding the fate and role of nZnO in the natura...The rapid development and widespread use of ZnO nanoparticles(nZnO) in various industries have raised concerns about their potential environmental impact.Therefore,understanding the fate and role of nZnO in the natural environment is crucial for mitigating their hazardous effects on the environment and human safety.The purpose of the present study was to provide scientific support for understanding and eliminating the joint risk of nanoparticle and heavy metal pollution in the soil environment by revealing the co-transport characteristics of Cd(Ⅱ) and ZnO nanoparticles(nZnO) in soil under different ionic strength(IS) and pH.The impacts of different IS and pH on the co-transport of Cd(Ⅱ) and nZnO in a20 cm long with an inner diameter of 2.5 cm acrylic column packed with 10 cm high soil samples were investigated in the present study.In the above system,a500 μg L^(-1) Cd(Ⅱ) loaded nZnO suspension pulse with varying IS or pH was introduced into the soil column for leaching over 5 PVs,followed up by 5 PVs background solutions without nZnO.The IS was 1,10,or 50 mM NaCl,with pH6,or the pH was 6,7 or 8 with 1 mM NaCl.Meanwhile,Sedimentation experiments for nZnO,adsorption of Cd(Ⅱ) on soil,and nZnO,DLVO theory calculation for the same background condition were conducted.The presence of nZnO significantly increased the mobility of Cd(Ⅱ) as a result of its strong adsorption capacity for nZnO-associated Cd(Ⅱ).However,with the increase of IS,the co-transport of nZnO and Cd(Ⅱ) was decreased and the retention of nZnO in the soil column due to more nZnO attended to aggregate and sediment during the transport and the decrease in the adsorption capacity of nZnO for Cd(Ⅱ) by competition of Na^(+).When pH was 6,7,and 8,the co-transport of nZnO and Cd(Ⅱ) increased with higher pH due to the lower electrostatic attraction between nZnO and soil under higher pH.Meanwhile,the DLVO theory was fitted to describe the above co-transport process of nZnO and Cd(Ⅱ).More attention should be paid to the presence of nZnO on the migration of Cd(Ⅱ) in the natural soil to control the potential risk of nanoparticles and heavy metals to the environment.The risk of co-transport of nZnO and Cd(Ⅱ) might be controlled by adjusting IS and pH in the soil solution.展开更多
BACKGROUND Type 1 diabetes(T1D) is associated with major chronic microvascular complications which contribute significantly to diabetes associated morbidity.The protein primarily responsible for glucose reabsorption i...BACKGROUND Type 1 diabetes(T1D) is associated with major chronic microvascular complications which contribute significantly to diabetes associated morbidity.The protein primarily responsible for glucose reabsorption in the kidney is sodium glucose co-transporter 2(SGLT2). Presently, SGLT2 inhibitors are widely used in diabetic patients to improve blood glucose levels and prevent cardiovascular and renal complications. Given the broad therapeutic application of SGLT2 inhibitors, we hypothesised that SGLT2 inhibition may exert its protective effects via alterations of the gut microbiome and tested this in a type 1 diabetic mouse model of diabetic retinopathy.AIM To determine whether the treatment with two independent SGLT2 inhibitors affects gut health in a type 1 diabetic mouse model.METHODS The SGLT2 inhibitors empagliflozin or dapagliflozin(25 mg/kg/d) or vehicle dimethylsulfoxide(DMSO) were administered to C57 BL/6 J, Akita, Kimba and Akimba mice at 10 wk of age for 8 wk via their drinking water. Serum samples were collected and the concentration of succinate and the short chain fatty acid(SCFA) butyric acid was measured using gas chromatography-mass spectrometry. Enzyme-linked immunosorbent assay(ELISA) was performed to determine the concentration of insulin and leptin. Furthermore, the norepinephrine content in kidney tissue was determined using ELISA. Pancreatic tissue was collected and stained with haematoxylin and eosin and analysed using brightfield microscopy.RESULTS Due to the presence of the Akita allele, both Akita and Akimba mice showed a reduction in insulin production compared to C57 BL/6 J and Kimba mice.Furthermore, Akita mice also showed the presence of apoptotic bodies within the pancreatic islets. The acinar cells of Akita and Akimba mice showed swelling which is indicative of acute injury or pancreatitis. After 8 wk of SGLT2 inhibition with dapagliflozin, the intermediate metabolite of gut metabolism known as succinate was significantly reduced in Akimba mice when compared to DMSO treated mice. In addition, empagliflozin resulted in suppression of succinate levels in Akimba mice. The beneficial SCFA known as butyric acid was significantly increased in Akita mice after treatment with dapagliflozin when compared to vehicle treated mice. The norepinephrine content in the kidney was significantly reduced with both dapagliflozin and empagliflozin therapy in Akita mice and was significantly reduced in Akimba mice treated with empagliflozin.In non-diabetic C57 BL/6 J and Kimba mice, serum leptin levels were significantly reduced after dapagliflozin therapy.CONCLUSION The inhibition of SGLT2 reduces the intermediate metabolite succinate, increases SCFA butyric acid levels and reduces norepinephrine content in mouse models of T1 D. Collectively, these improvements may represent an important mechanism underlying the potential benefits of SGLT2 inhibition in T1 D and its complications.展开更多
Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chlorid...Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the speciifc sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression in-creased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These ifndings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassi-um-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassi-um-chloride co-transporter 1.展开更多
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. NAFLD is considerably more frequent in patients with type 2 diabetes mellitus (T2DM) than in the general populat...Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. NAFLD is considerably more frequent in patients with type 2 diabetes mellitus (T2DM) than in the general population and is also more severe histologically in this group. Sodium-glucose co-transporter-2 (SGLT2) inhibitors, the newest class of antidiabetic agents, appear to represent a promising option for the management of NAFLD in patients with T2DM. In a number of studies, treatment with SGLT2 inhibitors resulted in a reduction in hepatic steatosis and in transaminase levels. However, existing studies are small, their follow-up period was short and none evaluated the effects of SGLT2 inhibitors on liver histology. Accordingly, larger studies are needed to verify these preliminary results and define the role of SGLT2 inhibitors in the treatment of NAFLD in patients with T2DM.展开更多
Euglycemic diabetic ketoacidosis(EDKA)is a well-known complication of sodium-glucose co-transporter 2 inhibitors,and many cases with variable onset following the initiation of these agents are reported before,with a m...Euglycemic diabetic ketoacidosis(EDKA)is a well-known complication of sodium-glucose co-transporter 2 inhibitors,and many cases with variable onset following the initiation of these agents are reported before,with a median onset of approximately 2 wk.This letter discusses a 45-year-old lady who initially presented with ischemic stroke but developed EDKA 4 d after starting empagliflozin,a rare occurrence.The patient had severe metabolic acidosis that necessitated admission into the intensive care unit.Prompt discontinuation of empagliflozin and DKA management resulted in clinical recovery.展开更多
Sodium-glucose co-transporter 2(SGLT2)inhibitors are an insulin-independent class of oral antihyperglycemic medication and from recently established therapy in chronic heart failure patients.A rare,but potentially lif...Sodium-glucose co-transporter 2(SGLT2)inhibitors are an insulin-independent class of oral antihyperglycemic medication and from recently established therapy in chronic heart failure patients.A rare,but potentially life-threatening complication of SGLT2 inhibitor use is euglycemic diabetic ketoacidosis.We described a case of a middle-aged male patient with type 2 diabetes who developed metabolic ketoacidosis after a few days of empagliflozin administration.SGLT2 inhibitor related ketoacidosis presents with euglycemia or only modestly elevated glucose blood concentrations,which causes delayed detection and treatment of ketoacidosis.There are multiple possible risk factors and mechanism that might contribute to the pathogenesis of ketoacidosis.It is implied that SGLT2 inhibitor use and prescription by non-diabetologists(cardiologists,nephrologists,family physicians,etc.)will continue to grow in the future.It is important to inform the general cardiac public about this rare but serious side effect of SGLT2 inhibitors.展开更多
The transport of colloids and radionuclides is sophisticated because of the variety of charge properties between colloidal particles and host subsurface media, which causes great difficulty in establishing a reliable ...The transport of colloids and radionuclides is sophisticated because of the variety of charge properties between colloidal particles and host subsurface media, which causes great difficulty in establishing a reliable model of radionuclides migration by taking the colloid phase into consideration. In this work,the co-transport of illite colloids(IC) and Eu(Ⅲ) in the quartz sand and iron-coated sand porous media was investigated by column experiments to address the predominant mechanism of charge properties on co-transport. Results showed that Eu(Ⅲ) transport was driven by the illite colloids and electrostatic interaction was critical in governing the co-transport patterns. The promotion of Eu(Ⅲ) transport by IC was attenuated in the iron-coated sand systems;more IC-Eu(Ⅲ) complexes were retained uniformly in the column. The pore throat shrinkage caused by electrostatic attachment between aggregated IC and iron oxides exacerbated the physical straining and size exclusion effect of IC-Eu(Ⅲ) complexes. An aggravated irreversible retention of IC-Eu(Ⅲ) was detected in iron-coated sand column due to the electrostatic attraction of IC-Eu(Ⅲ) to host media. The findings are essential for improving the understanding on the potential transport, retention and release risk of colloids associated radionuclides, and imply that the positively charged permeable reactive barrier is an effective strategy to reduce the transport risk of colloid associated radionuclides.展开更多
Three novel gem-dimethyl C-glucosides were designed as sodium-glucose co-transporter 2 (SGLT2) inhibitors, and their syntheses started from D-glucose and three 2-substituted-5-bromobenzoic acids were achieved via a ...Three novel gem-dimethyl C-glucosides were designed as sodium-glucose co-transporter 2 (SGLT2) inhibitors, and their syntheses started from D-glucose and three 2-substituted-5-bromobenzoic acids were achieved via a facile 8-step protocol, with the key step being anhydrous aluminum chloride-catalyzed Friedel-Crafts alkylation of tertiary alcohols and phenetol. These three SGLT2 inhibitors were evaluated in vivo with a mice oral glucose tolerance test (OGTT), and the anti-hyperglycemic activities of all these three compounds were comparable with that of the positive control Dapagliflozin.展开更多
Canagliflozin(CANA)is a sodium-glucose co-transporter 2 inhibitor.One of the important mechanisms of CANA is the inhibitory effect on the glucose uptake in the proximal tubule of the nephron,and the other mechanism ca...Canagliflozin(CANA)is a sodium-glucose co-transporter 2 inhibitor.One of the important mechanisms of CANA is the inhibitory effect on the glucose uptake in the proximal tubule of the nephron,and the other mechanism can be the reduction of inflammatory cytokine expression monocytes and macrophages.It is proved by FDA for the management of type 2 diabetes.In the present work,we summarized the publication and clinical evidence of the CANA on healthy individuals and those with related metabolic diseases,such as type 1 and 2 diabetes,obesity,or cardiovascular and kidney diseases.This drug has been reported to offer potential advantages in regulating body weight and reducing heart failure,hypoglycemia,and stroke risk in patients with type 2 diabetes.Some in vitro and animal experiments also show that this drug has good effects on cancer treatment.However,some case reports and experiments also show the side effect of CANA,such as amputation,fracture,and pancreatitis,while the mechanism is still unknown.Overall,CANA has a good effect on the management of type 2 diabetes by reducing the risk of kidney failure,cardiovascular diseases,and stroke.However,as a new drug,more clinical trials and experiments of CANA should be carried out in the future.展开更多
钠-葡萄糖协同转运蛋白2抑制剂(SGLT2i)作为一种新型口服降糖药,对2型糖尿病或非糖尿病患者都表现出良好的心肾保护作用,并可改善慢性肾脏病患者的心肾结局。虽然目前临床试验已将纳入人群的估算肾小球滤过率(eGFR)扩展至更低水平,但仍...钠-葡萄糖协同转运蛋白2抑制剂(SGLT2i)作为一种新型口服降糖药,对2型糖尿病或非糖尿病患者都表现出良好的心肾保护作用,并可改善慢性肾脏病患者的心肾结局。虽然目前临床试验已将纳入人群的估算肾小球滤过率(eGFR)扩展至更低水平,但仍排除了eGFR<20 mL/(min·1.73 m 2)的患者,SGLT2i的心肾保护作用能否延续至维持性透析期是临床关注的重点。此外,SGLT2i的抗炎和抗纤维化作用可能对腹膜透析(PD)患者维持腹膜功能有益。因此,SGLT2i在PD患者中的应用值得进一步探索。展开更多
基金supported by the National Key Research and Development Project of Chinathe National Natural Science Fund of China (Grant number 2018YFC1800403, 41571226)。
文摘The rapid development and widespread use of ZnO nanoparticles(nZnO) in various industries have raised concerns about their potential environmental impact.Therefore,understanding the fate and role of nZnO in the natural environment is crucial for mitigating their hazardous effects on the environment and human safety.The purpose of the present study was to provide scientific support for understanding and eliminating the joint risk of nanoparticle and heavy metal pollution in the soil environment by revealing the co-transport characteristics of Cd(Ⅱ) and ZnO nanoparticles(nZnO) in soil under different ionic strength(IS) and pH.The impacts of different IS and pH on the co-transport of Cd(Ⅱ) and nZnO in a20 cm long with an inner diameter of 2.5 cm acrylic column packed with 10 cm high soil samples were investigated in the present study.In the above system,a500 μg L^(-1) Cd(Ⅱ) loaded nZnO suspension pulse with varying IS or pH was introduced into the soil column for leaching over 5 PVs,followed up by 5 PVs background solutions without nZnO.The IS was 1,10,or 50 mM NaCl,with pH6,or the pH was 6,7 or 8 with 1 mM NaCl.Meanwhile,Sedimentation experiments for nZnO,adsorption of Cd(Ⅱ) on soil,and nZnO,DLVO theory calculation for the same background condition were conducted.The presence of nZnO significantly increased the mobility of Cd(Ⅱ) as a result of its strong adsorption capacity for nZnO-associated Cd(Ⅱ).However,with the increase of IS,the co-transport of nZnO and Cd(Ⅱ) was decreased and the retention of nZnO in the soil column due to more nZnO attended to aggregate and sediment during the transport and the decrease in the adsorption capacity of nZnO for Cd(Ⅱ) by competition of Na^(+).When pH was 6,7,and 8,the co-transport of nZnO and Cd(Ⅱ) increased with higher pH due to the lower electrostatic attraction between nZnO and soil under higher pH.Meanwhile,the DLVO theory was fitted to describe the above co-transport process of nZnO and Cd(Ⅱ).More attention should be paid to the presence of nZnO on the migration of Cd(Ⅱ) in the natural soil to control the potential risk of nanoparticles and heavy metals to the environment.The risk of co-transport of nZnO and Cd(Ⅱ) might be controlled by adjusting IS and pH in the soil solution.
基金Supported by the Royal Perth Hospital Medical Research Foundation,No.VMMRF2018。
文摘BACKGROUND Type 1 diabetes(T1D) is associated with major chronic microvascular complications which contribute significantly to diabetes associated morbidity.The protein primarily responsible for glucose reabsorption in the kidney is sodium glucose co-transporter 2(SGLT2). Presently, SGLT2 inhibitors are widely used in diabetic patients to improve blood glucose levels and prevent cardiovascular and renal complications. Given the broad therapeutic application of SGLT2 inhibitors, we hypothesised that SGLT2 inhibition may exert its protective effects via alterations of the gut microbiome and tested this in a type 1 diabetic mouse model of diabetic retinopathy.AIM To determine whether the treatment with two independent SGLT2 inhibitors affects gut health in a type 1 diabetic mouse model.METHODS The SGLT2 inhibitors empagliflozin or dapagliflozin(25 mg/kg/d) or vehicle dimethylsulfoxide(DMSO) were administered to C57 BL/6 J, Akita, Kimba and Akimba mice at 10 wk of age for 8 wk via their drinking water. Serum samples were collected and the concentration of succinate and the short chain fatty acid(SCFA) butyric acid was measured using gas chromatography-mass spectrometry. Enzyme-linked immunosorbent assay(ELISA) was performed to determine the concentration of insulin and leptin. Furthermore, the norepinephrine content in kidney tissue was determined using ELISA. Pancreatic tissue was collected and stained with haematoxylin and eosin and analysed using brightfield microscopy.RESULTS Due to the presence of the Akita allele, both Akita and Akimba mice showed a reduction in insulin production compared to C57 BL/6 J and Kimba mice.Furthermore, Akita mice also showed the presence of apoptotic bodies within the pancreatic islets. The acinar cells of Akita and Akimba mice showed swelling which is indicative of acute injury or pancreatitis. After 8 wk of SGLT2 inhibition with dapagliflozin, the intermediate metabolite of gut metabolism known as succinate was significantly reduced in Akimba mice when compared to DMSO treated mice. In addition, empagliflozin resulted in suppression of succinate levels in Akimba mice. The beneficial SCFA known as butyric acid was significantly increased in Akita mice after treatment with dapagliflozin when compared to vehicle treated mice. The norepinephrine content in the kidney was significantly reduced with both dapagliflozin and empagliflozin therapy in Akita mice and was significantly reduced in Akimba mice treated with empagliflozin.In non-diabetic C57 BL/6 J and Kimba mice, serum leptin levels were significantly reduced after dapagliflozin therapy.CONCLUSION The inhibition of SGLT2 reduces the intermediate metabolite succinate, increases SCFA butyric acid levels and reduces norepinephrine content in mouse models of T1 D. Collectively, these improvements may represent an important mechanism underlying the potential benefits of SGLT2 inhibition in T1 D and its complications.
基金supported by a grant from Guangzhou Medical University,No.2008C24
文摘Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the speciifc sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression in-creased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These ifndings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassi-um-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassi-um-chloride co-transporter 1.
文摘Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. NAFLD is considerably more frequent in patients with type 2 diabetes mellitus (T2DM) than in the general population and is also more severe histologically in this group. Sodium-glucose co-transporter-2 (SGLT2) inhibitors, the newest class of antidiabetic agents, appear to represent a promising option for the management of NAFLD in patients with T2DM. In a number of studies, treatment with SGLT2 inhibitors resulted in a reduction in hepatic steatosis and in transaminase levels. However, existing studies are small, their follow-up period was short and none evaluated the effects of SGLT2 inhibitors on liver histology. Accordingly, larger studies are needed to verify these preliminary results and define the role of SGLT2 inhibitors in the treatment of NAFLD in patients with T2DM.
文摘Euglycemic diabetic ketoacidosis(EDKA)is a well-known complication of sodium-glucose co-transporter 2 inhibitors,and many cases with variable onset following the initiation of these agents are reported before,with a median onset of approximately 2 wk.This letter discusses a 45-year-old lady who initially presented with ischemic stroke but developed EDKA 4 d after starting empagliflozin,a rare occurrence.The patient had severe metabolic acidosis that necessitated admission into the intensive care unit.Prompt discontinuation of empagliflozin and DKA management resulted in clinical recovery.
文摘Sodium-glucose co-transporter 2(SGLT2)inhibitors are an insulin-independent class of oral antihyperglycemic medication and from recently established therapy in chronic heart failure patients.A rare,but potentially life-threatening complication of SGLT2 inhibitor use is euglycemic diabetic ketoacidosis.We described a case of a middle-aged male patient with type 2 diabetes who developed metabolic ketoacidosis after a few days of empagliflozin administration.SGLT2 inhibitor related ketoacidosis presents with euglycemia or only modestly elevated glucose blood concentrations,which causes delayed detection and treatment of ketoacidosis.There are multiple possible risk factors and mechanism that might contribute to the pathogenesis of ketoacidosis.It is implied that SGLT2 inhibitor use and prescription by non-diabetologists(cardiologists,nephrologists,family physicians,etc.)will continue to grow in the future.It is important to inform the general cardiac public about this rare but serious side effect of SGLT2 inhibitors.
基金supported by the National Natural Science Foundation of China(Nos.22176077,22006060)the Fundamental Research Funds for the Central Universities(No.lzujbky-2022-sp04)Science and Technology Program of Gansu Province,China(No.20JR10RA615).
文摘The transport of colloids and radionuclides is sophisticated because of the variety of charge properties between colloidal particles and host subsurface media, which causes great difficulty in establishing a reliable model of radionuclides migration by taking the colloid phase into consideration. In this work,the co-transport of illite colloids(IC) and Eu(Ⅲ) in the quartz sand and iron-coated sand porous media was investigated by column experiments to address the predominant mechanism of charge properties on co-transport. Results showed that Eu(Ⅲ) transport was driven by the illite colloids and electrostatic interaction was critical in governing the co-transport patterns. The promotion of Eu(Ⅲ) transport by IC was attenuated in the iron-coated sand systems;more IC-Eu(Ⅲ) complexes were retained uniformly in the column. The pore throat shrinkage caused by electrostatic attachment between aggregated IC and iron oxides exacerbated the physical straining and size exclusion effect of IC-Eu(Ⅲ) complexes. An aggravated irreversible retention of IC-Eu(Ⅲ) was detected in iron-coated sand column due to the electrostatic attraction of IC-Eu(Ⅲ) to host media. The findings are essential for improving the understanding on the potential transport, retention and release risk of colloids associated radionuclides, and imply that the positively charged permeable reactive barrier is an effective strategy to reduce the transport risk of colloid associated radionuclides.
文摘Three novel gem-dimethyl C-glucosides were designed as sodium-glucose co-transporter 2 (SGLT2) inhibitors, and their syntheses started from D-glucose and three 2-substituted-5-bromobenzoic acids were achieved via a facile 8-step protocol, with the key step being anhydrous aluminum chloride-catalyzed Friedel-Crafts alkylation of tertiary alcohols and phenetol. These three SGLT2 inhibitors were evaluated in vivo with a mice oral glucose tolerance test (OGTT), and the anti-hyperglycemic activities of all these three compounds were comparable with that of the positive control Dapagliflozin.
基金Beijing Excellent Talents Training Assistance(Grant No.2017000082595G244)the Health and Research Bureau of Tongzhou District(Grant No.TWKY-2016-QN-01-58)。
文摘Canagliflozin(CANA)is a sodium-glucose co-transporter 2 inhibitor.One of the important mechanisms of CANA is the inhibitory effect on the glucose uptake in the proximal tubule of the nephron,and the other mechanism can be the reduction of inflammatory cytokine expression monocytes and macrophages.It is proved by FDA for the management of type 2 diabetes.In the present work,we summarized the publication and clinical evidence of the CANA on healthy individuals and those with related metabolic diseases,such as type 1 and 2 diabetes,obesity,or cardiovascular and kidney diseases.This drug has been reported to offer potential advantages in regulating body weight and reducing heart failure,hypoglycemia,and stroke risk in patients with type 2 diabetes.Some in vitro and animal experiments also show that this drug has good effects on cancer treatment.However,some case reports and experiments also show the side effect of CANA,such as amputation,fracture,and pancreatitis,while the mechanism is still unknown.Overall,CANA has a good effect on the management of type 2 diabetes by reducing the risk of kidney failure,cardiovascular diseases,and stroke.However,as a new drug,more clinical trials and experiments of CANA should be carried out in the future.
文摘钠-葡萄糖协同转运蛋白2抑制剂(SGLT2i)作为一种新型口服降糖药,对2型糖尿病或非糖尿病患者都表现出良好的心肾保护作用,并可改善慢性肾脏病患者的心肾结局。虽然目前临床试验已将纳入人群的估算肾小球滤过率(eGFR)扩展至更低水平,但仍排除了eGFR<20 mL/(min·1.73 m 2)的患者,SGLT2i的心肾保护作用能否延续至维持性透析期是临床关注的重点。此外,SGLT2i的抗炎和抗纤维化作用可能对腹膜透析(PD)患者维持腹膜功能有益。因此,SGLT2i在PD患者中的应用值得进一步探索。