Heart failure(HF),which falls outside of the historical macrovascular or microvascular categorizations of diabetes complications,has been overlooked for long time in diabetic patients,despite its increasing prevalence...Heart failure(HF),which falls outside of the historical macrovascular or microvascular categorizations of diabetes complications,has been overlooked for long time in diabetic patients,despite its increasing prevalence and mortality.As originally stated in the Framingham studies,diabetes is associated with an increased risk of HF.Subsequent studies not only corroborated these findings but also identified HF as the most frequent first onset of cardiovascular involvement.The paramount role of proper management of common modifiable risk factors such as hypertension,obesity,dyslipidemia and smoking,became rapidly clear.Conversely,the impact of intensive glycemic control was more contentious.A large meta-analysis of randomized controlled trials reported a lack of effect of strict glycemic control as compared to standard care on HF-related outcomes.The considerable heterogeneity of the effect estimate and the higher risk conferred by thiazolidinediones suggested that mechanism of action of antidiabetic drugs played a key role.Furthermore,the safety concerns of pioglitazone led Food and Drug Administration to release a guidance for drug manufacturers stating that cardiovascular risk should be comprehensively evaluated during drug development.Surprisingly,in just a few years,large cardiovascular outcome trials established the beneficial cardiovascular effects of sodium-glucose cotransporter 2 inhibitors.These effects were consistent regardless diabetes and ejection fraction.Therefore,scientific community started to question the glucose-lowering and diuretic properties of sodium-glucose cotransporter 2 inhibitors as the unique mechanisms for improved outcomes.A plenty of preclinical and clinical studies identified several mechanisms besides glucose-lowering effects.However,these mechanistic studies focused on animal models and patients with established HF.If the same mechanisms account for beneficial effects in patients at risk for or with pre-HF is unknown.Grubić Rotkvićet al published an interesting work adding data in early stages HF.展开更多
To achieve an unmanned rice farm,in this study,a cotransporter system was developed using a tracked rice harvester and transporter for autonomous harvesting,unloading,and transportation.Additionally,two unloading and ...To achieve an unmanned rice farm,in this study,a cotransporter system was developed using a tracked rice harvester and transporter for autonomous harvesting,unloading,and transportation.Additionally,two unloading and transportation modes—harvester waiting for unloading(HWU)and transporter fol-lowing for unloading(TFU)—were proposed,and a harvesting-unloading-transportation(HUT)strategy was defined.By breaking down the main stages of the collaborative operation,designing module-state machines(MSMs),and constructing state-transition chains,a HUT collaborative operation logic frame-work suitable for the embedded navigation controller was designed using the concept and method of the finite-state machine(FSM).This method addresses the multiple-stage,nonsequential,and complex processes in HUT collaborative operations.Simulations and field-harvesting experiments were performed to evaluate the applicability of this proposed strategy and system.The experimental results showed that the HUT collaborative operation strategy effectively integrated path planning,path-tracking control,inter-vehicle communication,collaborative operation control,and implementation control.The cotrans-porter system completed the entire process of harvesting,unloading,and transportation.The field-harvesting experiment revealed that a harvest efficiency of 0.42 hm^(2)·h^(−1) was achieved.This study can provide insight into collaborative harvesting and solutions for the harvesting process of unmanned farms.展开更多
In real soil environments,humus,colloids and other components significantly affect pollutant migration behavior.Investigating Tl(I)and kaolinite colloids’cotransport in quartz sand media containing sodium humate(HA-N...In real soil environments,humus,colloids and other components significantly affect pollutant migration behavior.Investigating Tl(I)and kaolinite colloids’cotransport in quartz sand media containing sodium humate(HA-Na)is vital for comprehending Tl(I)migration underground.This study examined the migration of Tl(I)and kaolinite colloids across varying pH levels(5,7),ionic strengths(ISs)(1,5,50 mmol/L),and kaolinite colloid concentra-tions.Results indicate that lower IS and pH promote Tl(I)migration when transported alone.In cotransport system,kaolinite promotes Tl(I)migration under acidic conditions but inhibits it under neutral conditions,except at high kaolinite concentrations,where the effect shifts from inhibition to promotion.This is primarily due to changes in the zeta potential of quartz sand,HA-Na,and kaolinite,as well as Tl(I)adsorption after HA-Na and kaolinite occupy binding sites.Competitive adsorption between cations and Tl(I)also plays a significant role.Conversely,in individual system,higher IS and pH inhibit kaolinite migration,while increased kaolinite concentration promotes it.In cotransport system,Tl(I)promotes kaolinite migration under acidic conditions but inhibits it under neutral conditions,except at low kaolinite concentrations.This relates to changes in the zeta potential between kaolinite and the medium,as well as the retention of HA-Na in the column and its adsorption onto kaolinite.Competitive adsorption and binding site saturation also have an impact.This study enhances understanding of Tl(I)migration by revealing the dual effect of kaolinite colloids under different environmental conditions,contributing to better knowledge of Tl(I)fate and transport in natural environments.展开更多
The study by Lin et al delves into the clinical impact of dapagliflozin,a repre-sentative sodium-glucose cotransporter 2(SGLT2)inhibitor,on chronic heart failure complicated by hyperuricemia.This investigation highlig...The study by Lin et al delves into the clinical impact of dapagliflozin,a repre-sentative sodium-glucose cotransporter 2(SGLT2)inhibitor,on chronic heart failure complicated by hyperuricemia.This investigation highlights dapagliflo-zin’s efficacy in lowering serum uric acid levels,enhancing cardiac function,and reducing cardiovascular events.This work not only provides a comprehensive analysis of dapagliflozin’s sustained benefits in these patients but also introduces novel insights for managing chronic heart failure exacerbated by elevated uric acid.Furthermore,this review examines the potential role of SGLT2 inhibitor in the context of gout,evaluating its mechanisms and clinical application prospects in the management of hyperuricemia,thereby further enriching the medical community’s understanding of SGLT2 inhibitor.展开更多
BACKGROUND The use of sodium-glucose cotransporter 2(SGLT2)inhibitor in heart failure(HF)patients is increasing significantly,regardless of whether they have a history of diabetes.The effects of SGLT2 inhibitor on HF ...BACKGROUND The use of sodium-glucose cotransporter 2(SGLT2)inhibitor in heart failure(HF)patients is increasing significantly,regardless of whether they have a history of diabetes.The effects of SGLT2 inhibitor on HF are likely mediated through multiple mechanisms,including suppression of the renin-angiotensin-aldosterone system(RAAS),reduction in oxidative stress leading to enhanced myocardial efficiency,and attenuation of adverse cardiac remodeling by preventing fibrosis.These pathways are fundamental to reducing mortality,improving patients'quality of life,and alleviating the burden on the United States healthcare system by decreasing HF-related hospitalizations.AIM To evaluate SGLT2 inhibitor effects on HF,focusing on hospitalization for HF(HHF),cardiovascular(CV)deaths,and all-cause mortality.METHODS A comprehensive search was conducted in PubMed for randomized controlled trials(RCTs)evaluating the effects of SGLT2 inhibitor in HF patients compared to placebo,covering the period from January 1,2014,to January 1,2025.The primary outcomes assessed were HHF,CV deaths,and all-cause mortality.RevMan Web 5.4.1 was used to assess the risk of bias heterogeneity and to perform the statistical analyses.A random-effects model was employed for all statistical evaluations.RESULTS A total of nine RCTs were included in this analysis:DELIVER,DECLARE-TIMI 58,DAPA-HF,EMPA-REG OUTCOME,EMPEROR-Reduced,EMPEROR-Preserved,SOLOIST-WHF,EMPULSE,and VERTIS-CV.For HHF,eight trials(excluding the SOLOIST-WHF;n=25906)were pooled,while CV deaths were assessed using data from eight trials(excluding the EMPULSE;n=26598).Compared to placebo,SGLT2 inhibitor significantly reduced the risk of HHF(relative risk:0.74;95%CI:0.71-0.77;P<0.00001)and CV death(odds ratio:0.88;95%CI:0.83-0.92;P=0.0006).All nine trials(n=27128)were included in the analysis of all-cause mortality.SGLT2 inhibitor were associated with a statistically significant reduction in all-cause mortality compared to placebo(OR:0.91;95%CI:0.84-0.98;P=0.02).CONCLUSION These results suggest that SGLT2 inhibitor significantly reduce the risk of hospitalization for HF,CV deaths,and all-cause mortality.展开更多
The global prevalence of diabetes has surged in recent years,with diabetic kidney disease(DKD)emerging as a major complication.Traditional therapies have had limited success in slowing progression to end-stage kidney ...The global prevalence of diabetes has surged in recent years,with diabetic kidney disease(DKD)emerging as a major complication.Traditional therapies have had limited success in slowing progression to end-stage kidney disease.However,novel therapies,particularly sodium-glucose cotransporter 2(SGLT2)inhibitors and glucagon-like peptide-1(GLP-1)receptor agonists,which were initially developed for hyperglycemia management,have transformed the treatment of obesity,heart failure,cardiovascular disease,and more recently,DKD.SGLT2 inhibitors have consistently and significantly reduced cardiovascular events,albuminuria,and glomerular filtration rate,highlighting their efficacy across diverse clinical presentations for patients with kidney impairment.Although fewer studies have specifically investigated GLP-1 receptor agonists in patients with kidney disease,existing evidence underscores their potential to slow renal disease progression,reduce albuminuria,and improve clinically relevant outcomes.However,further research is needed to better identify patients most likely to benefit from treatment.Together,these therapies represent valuable advancements for DKD,offering significant reductions in morbidity and mortality and shifting the management of the disease by becoming essential pillars for the treatment of these patients.展开更多
Type 2 diabetes markedly elevates fracture risk despite normal or high bone mineral density,a paradox reflecting qualitative skeletal deficits rather than loss of mass.Chronic hyperglycemia fosters the accumulation of...Type 2 diabetes markedly elevates fracture risk despite normal or high bone mineral density,a paradox reflecting qualitative skeletal deficits rather than loss of mass.Chronic hyperglycemia fosters the accumulation of advanced glycation end products in bone;their nonenzymatic crosslinks stiffen type I collagen,impair mineralization,and erode mechanical strength.By engaging the receptor for advanced glycation end products,these adducts activate nuclear factorκB and mitogen-activated protein kinase cascades,amplifying oxidative stress,inflammation,osteoblast dysfunction,and osteoclastogenesis.This review synthesizes epidemiological data from type 1 and type 2 diabetes,highlights the limits of densitybased skeletal assessment,and details the molecular pathology of the glycation-collagen axis.It also appraises antiglycation therapies,including formation inhibitors,crosslink breakers and receptor antagonists,with a particular focus on sodium-glucose cotransporter 2 inhibitors that couple glycemic control with modulation of the glycation pathway.By integrating recent basic and clinical advances,we propose a mechanistic framework for diabetic bone disease and outline strategies to mitigate glycationdriven skeletal fragility.展开更多
The solute carrier family 12(SLC12)of cation-chloride cotransporters(CCCs)comprises potassium chloride cotransporters(KCCs,e.g.KCC1,KCC2,KCC3,and KCC4)-mediated Cl^(-)extrusion,and sodium potassium chloride cotranspor...The solute carrier family 12(SLC12)of cation-chloride cotransporters(CCCs)comprises potassium chloride cotransporters(KCCs,e.g.KCC1,KCC2,KCC3,and KCC4)-mediated Cl^(-)extrusion,and sodium potassium chloride cotransporters(N[K]CCs,NKCC1,NKCC2,and NCC)-mediated Cl^(-)loading.The CCCs play vital roles in cell volume regulation and ion homeostasis.Gain-of-function or loss-of-function of these ion transporters can cause diseases in many tissues.In recent years,there have been considerable advances in our understanding of CCCs'control mechanisms in cell volume regulations,with many techniques developed in studying the functions and activities of CCCs.Classic approaches to directly measure CCC activity involve assays that measure the transport of potassium substitutes through the CCCs.These techniques include the ammonium pulse technique,radioactive or nonradioactive rubidium ion uptakeassay,and thallium ion-uptake assay.CCCs'activity can also be indirectly observed by measuring gaminobutyric acid(GABA)activity with patch-clamp electrophysiology and intracellular chloride concentration with sensitive microelectrodes,radiotracer^(36)Cl^(-),and fluorescent dyes.Other techniques include directly looking at kinase regulatory sites phosphorylation,flame photometry,22Nat uptake assay,structural biology,molecular modeling,and high-throughput drug screening.This review summarizes the role of CCCs in genetic disorders and cell volume regulation,current methods applied in studying CCCs biology,and compounds developed that directly or indirectly target the CCCs for disease treatments.展开更多
The circadian system plays an immense role in controlling physiological processes in our body.The suprachiasmatic nucleus (SCN) supervises this system,regulating and harmonising the circadian rhythms in our body.Most ...The circadian system plays an immense role in controlling physiological processes in our body.The suprachiasmatic nucleus (SCN) supervises this system,regulating and harmonising the circadian rhythms in our body.Most neurons present in the SCN are GABAergic neurons.Although GABA is considered the main inhibitory neurotransmitter of the CNS,recent studies have shown that excitatory responses were recorded in this area.These responses are enabled by an increase in intracellular chloride ions[Cl;];levels.The chloride (Cl;) levels in GABAergic neurons are controlled by two solute carrier 12 (SLC12)cation-chloride-cotransporters (CCCs):Na^(+)/K^(+)/Cl^(-)co-transporter (NKCC1) and K^(+)/Cl^(-)cotransporter (KCC2),that respectively cause an influx and efflux of Cl^(-).Recent works have found altered expression and/or activity of either of these co-transporters in SCN neurons and have been associated with circadian rhythms.In this review,we summarize and discuss the role of CCCs in circadian rhythms,and highlight these recent advances which attest to CCC’s growing potential as strong research and therapeutic targets.展开更多
Sodium-glucose cotransporter 2(SGLT2) inhibition induces glucosuria and decreases blood glucose levels in diabetic patients and lowers hypoglycemic risk. SGLT1 is expressed in the kidney and intestine; SGLT1 inhibitio...Sodium-glucose cotransporter 2(SGLT2) inhibition induces glucosuria and decreases blood glucose levels in diabetic patients and lowers hypoglycemic risk. SGLT1 is expressed in the kidney and intestine; SGLT1 inhibition causes abdominal symptoms such as diarrhea and reduces incretin secretion. Therefore, SGLT2 selectivity is important. Ipragliflozin is highly selective for SGLT2. In type 2 diabetes mellitus(T2DM), urinaryglucose excretion increased to 90 g/24 h after 28 d of treatment with ipragliflozin 300 mg/d. Twelve weeks of ipragliflozin 50 mg/d vs placebo reduced glycated hemoglobin and body weight by 0.65% and 0.66 kg, respectively, in Western T2 DM patients, and by 1.3% and 1.89 kg, respectively, in Japanese patients. Ipragliflozin(highly selective SGLT2 inhibitor) improves glycemic control and reduces body weight and lowers hypoglycemic risk and abdominal symptoms. Ipragliflozin can be a novel anti-diabetic and antiobesity agent.展开更多
Three major cardiovascular outcome trials(CVOTs)with a new class of antidiabetic drugs-sodium-glucose cotransporter 2(SGLT2)inhibitors(EMPAREG OUTCOME trial with empagliflozin,CANVAS Program with canagliflozin,DECLARE...Three major cardiovascular outcome trials(CVOTs)with a new class of antidiabetic drugs-sodium-glucose cotransporter 2(SGLT2)inhibitors(EMPAREG OUTCOME trial with empagliflozin,CANVAS Program with canagliflozin,DECLARE-TIMI 58 with dapagliflozin)unexpectedly showed that cardiovascular outcomes could be improved possibly due to a reduction in heart failure risk,which seems to be the most sensitive outcome of SGLT2 inhibition.No other CVOT to date has shown any significant benefit on heart failure events.Even more impressive findings came recently from the DAPA-HF trial in patients with confirmed and well-treated heart failure:Dapagliflozin was shown to reduce heart failure risk for patients with heart failure with reduced ejection fraction regardless of diabetes status.Nevertheless,despite their possible wide clinical implications,there is much doubt about the mechanisms of action and a lot of questions to unravel,especially now when their benefits translated to nondiabetic patients,rising doubts about the validity of some current mechanistic assumptions.The time frame of their cardiovascular benefits excludes glucoselowering and antiatherosclerotic-mediated effects and multiple other mechanisms,direct cardiac as well as systemic,are suggested to explain their early cardiorenal benefits.These are:Anti-inflammatory,antifibrotic,antioxidative,antiapoptotic properties,then renoprotective and hemodynamic effects,attenuation of glucotoxicity,reduction of uric acid levels and epicardial adipose tissue,modification of neurohumoral system and cardiac fuel energetics,sodiumhydrogen exchange inhibition.The most logic explanation seems that SGLT2 inhibitors timely target various mechanisms underpinning heart failure pathogenesis.All the proposed mechanisms of their action could interfere with evolution of heart failure and are discussed separately within the main text.展开更多
Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in the Western world. It is more prevalent in male gender, and with increasing age, obesity, and insulin resistance. Besides w...Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in the Western world. It is more prevalent in male gender, and with increasing age, obesity, and insulin resistance. Besides weight loss, there are limited treatment options. The use of anti-diabetic medications has been studied with mixed results. In this review, we discuss the use of anti-diabetic medications in the management of NAFLD with a specific focus on sodium-glucose cotransporter 2 inhibitors. We shed light on the evidence supporting their use in detail and discuss limitations and future directions.展开更多
AIM: To investigate the role of Na<sup>+</sup>/K<sup>+</sup>/2Cl<sup>-</sup> cotransporter 1 (NKCC1) in the regulation of genes involved in cell cycle progression and the clinicopat...AIM: To investigate the role of Na<sup>+</sup>/K<sup>+</sup>/2Cl<sup>-</sup> cotransporter 1 (NKCC1) in the regulation of genes involved in cell cycle progression and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC).展开更多
BACKGROUND Landmark trials have established the benefits of sodium-glucose cotransporter-2 inhibitors(SGLT2-Is)in cardiovascular disease including heart failure with reduced and preserved ejection fraction and renal d...BACKGROUND Landmark trials have established the benefits of sodium-glucose cotransporter-2 inhibitors(SGLT2-Is)in cardiovascular disease including heart failure with reduced and preserved ejection fraction and renal diseases regardless of the presence of diabetes mellitus.However,studies evaluating the role of SGLT2-Is in metabolic syndrome(MetS)are limited.AIM This study primarily aimed to evaluate the impact of SGLT2-Is on the components of MetS.METHODS Two independent reviewers and an experienced librarian searched Medline,Scopus and the Cochrane central from inception to December 9,2021 to identify placebo controlled randomized controlled trials that evaluated the impact of SGLT2-Is on the components of MetS as an endpoint.Pre-and post-treatment data of each component were obtained.A meta-analysis was performed using the RevMan(version 5.3;Copenhagen:The Nordic Cochrane Center,The Cochrane Collaboration).RESULTS Treatment with SGLT2-Is resulted in a decrease in fasting plasma glucose(–18.07 mg/dL;95%CI:-25.32 to–10.82),systolic blood pressure(–1.37 mmHg;95%CI:-2.08 to–0.65),and waist circumference(–1.28 cm;95%CI:-1.39 to–1.18)compared to placebo.The impact on highdensity lipoprotein cholesterol was similar to placebo(0.01 mg/dL;95%CI:-0.05 to 0.07).CONCLUSION SGLT2-Is have a promising role in the management of MetS.展开更多
BACKGROUND Sodium taurocholate cotransport polypeptide(NTCP)deficiency disease is a genetic metabolic disorder due to mutations in the SLC10A1 gene and impaired bile acid salt uptake by the basolateral membrane transp...BACKGROUND Sodium taurocholate cotransport polypeptide(NTCP)deficiency disease is a genetic metabolic disorder due to mutations in the SLC10A1 gene and impaired bile acid salt uptake by the basolateral membrane transport protein NTCP in hepatocytes.A variety of clinical manifestations and genetic mutation loci have been reported for this disease.However,specific therapeutic measures are lacking,and the long-term effects are unknown.CASE SUMMARY An infant with elevated bile acids and behavioral neurodevelopmental delay failed to respond to bile acid-lowering therapy.Genetic testing for metabolic liver disease revealed that the child had NTCP deficiency due to the SLC10A1 mutation:c.422dupA(p.Y141X),which is a novel mutation site.The current followup revealed a gradual decrease in bile acid levels after 1 year of age,but the child still had behavioral neurodevelopmental delays.CONCLUSION The clinical manifestations,genetic characteristics,treatment and long-term prognosis due to NTCP deficiency remain poorly defined and need to be further confirmed by more studies and reports.展开更多
Sodium taurocholate cotransporting polypeptide(NTCP)is identified as the functional receptor for HBV entry,which is responsible for upregulated HBV transcription in the HBV life cycle.Besides,NTCP is also implicated i...Sodium taurocholate cotransporting polypeptide(NTCP)is identified as the functional receptor for HBV entry,which is responsible for upregulated HBV transcription in the HBV life cycle.Besides,NTCP is also implicated in the progression of HBV-induced hepatocellular carcinoma(HCC).Thereby,NTCP-targeting entry inhibitors are proposed to suppress HBV infection and replication in HBV-induced hepatoma therapy.Herein,we integrated in silico screening and chemical synthesis to obtain a small-molecule NTCP inhibitor B7,which exhibited moderate anti-proliferative activities against HepG2 cells and anti-HBV activity in vitro.Additionally,CETSA assay,molecular docking,and MD simulation validated that B7 could bind to NTCP.Furthermore,western blot analysis demonstrated that B7 induced apoptosis with an increased expression of Bax and caspase 3 cleaving as well as a decreasing expression of Bcl-2 in HepG2 cells.Taken together,our study identified B7 as a novel NTCP inhibitor with anti-proliferation activities which might provide a new opportunity for HCC therapy.展开更多
Sodium-glucose cotransporter 2(SGLT2)inhibitors have gained momentum as the latest class of antidiabetic agents for improving glycemic control.Large-scale clinical trials have reported that SGLT2 inhibitors reduced ca...Sodium-glucose cotransporter 2(SGLT2)inhibitors have gained momentum as the latest class of antidiabetic agents for improving glycemic control.Large-scale clinical trials have reported that SGLT2 inhibitors reduced cardiovascular outcomes,especially hospitalization for heart failure in patients with type 2 diabetes mellitus who have high risks of cardiovascular disease.Accumulating evidence has indicated that beneficial effects can be observed regardless of the presence or absence of type 2 diabetes mellitus.Accordingly,the Food and Drug Administration approved these agents specifically for treating patients with heart failure and a reduced ejection fraction.It has been concluded that canagliflozin,dapagliflozin,empagliflozin,or ertugliflozin can be recommended for preventing hospitalization associated with heart failure in patients with type 2 diabetes and established cardiovascular disease or those at high cardiovascular risk.In the present review,we explore the available evidence on SGLT2 inhibitors in terms of the cardioprotective effects,potential mechanisms,and ongoing clinical trials that may further clarify the cardiovascular effects of the agents.展开更多
Solid organ transplantation offers life-saving treatment for patients with endorgan dysfunction.Patient survival and quality of life have improved over the past few decades as a result of pharmacological development,e...Solid organ transplantation offers life-saving treatment for patients with endorgan dysfunction.Patient survival and quality of life have improved over the past few decades as a result of pharmacological development,expansion of the donor pool,technological advances and standardization of practices related to transplantation.Still,transplantation is associated with cardiovascular complications,of which post-transplant diabetes mellitus(PTDM)is one of the most important.PTDM increases mortality,which is best documented in patients who have received kidney and heart transplants.PTDM results from traditional risk factors seen in patients with type 2 diabetes mellitus,but also from specific posttransplant risk factors such as metabolic side effects of immunosuppressive drugs,post-transplant viral infections and hypomagnesemia.Oral hypoglycaemic agents are the first choice for the treatment of type 2 diabetes mellitus in non-transplanted patients.However,the evidence on the safety and efficacy of oral hypoglycaemic agents in transplant recipients is limited.The favourable risk/benefit ratio,which is suggested by large-scale and long-term studies on new glucoselowering drug classes such as glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors,makes studies warranted to assess the potential role of these agents in the management of PTDM.展开更多
AIM: To investigate whether Na<sup>+</sup>-K<sup>+</sup>-2Cl<sup>-</sup> cotransporter (NKCC2) is expressed in the mouse distal colonic epithelia and whether it is regulated by vaso...AIM: To investigate whether Na<sup>+</sup>-K<sup>+</sup>-2Cl<sup>-</sup> cotransporter (NKCC2) is expressed in the mouse distal colonic epithelia and whether it is regulated by vasopressin in the colon.展开更多
AIM To determine the expression and localization of the electrogenic Na^+/HCO_3^- cotransporter(NBC1) in rat pancreas during development. METHODS The rat pancreas from postnatal and embryos removed from the uterus of ...AIM To determine the expression and localization of the electrogenic Na^+/HCO_3^- cotransporter(NBC1) in rat pancreas during development. METHODS The rat pancreas from postnatal and embryos removed from the uterus of pregnant rats that had been sacrificed by CO2 asphyxiation were used. Rat pancreas from embryonic day(E) 15.5 and E18.5 rat embryos was isolated under a stereomicroscope. Rat pancreas from postnatal(P) days 0, 7, 14, 21 and adult was directly isolated by the unaided eye. The RT-PCR analysis of the NBC1 specific region on rat pancreastissues from different developmental stages. The two antibodies which target the NBC1 common COOHterminal region and NH2-terminal region detected a clear band of about 145 k Da in the Western blot analysis. The localization of NBC1 was examined by immuno-fluorescence detection. RESULTS The results revealed the first peak of NBC1 expression at E18.5 and the second peak at P14. Meanwhile, the low NBC1 expression occurred at P7 and adult stages. Our results demonstrated, for the first time, the presence of NBC1 in the plasma membrane of β and α cells, as well as in the basolateral membrane of acinar cells of the rat pancreas at different stages of development. CONCLUSION The data strongly suggests that NBC1 is diversely expressed in the pancreas at different developmental stages, where it may exert its functions in pancreatic development especially islet cell growth through HCO_3^- transport and pH regulation.展开更多
文摘Heart failure(HF),which falls outside of the historical macrovascular or microvascular categorizations of diabetes complications,has been overlooked for long time in diabetic patients,despite its increasing prevalence and mortality.As originally stated in the Framingham studies,diabetes is associated with an increased risk of HF.Subsequent studies not only corroborated these findings but also identified HF as the most frequent first onset of cardiovascular involvement.The paramount role of proper management of common modifiable risk factors such as hypertension,obesity,dyslipidemia and smoking,became rapidly clear.Conversely,the impact of intensive glycemic control was more contentious.A large meta-analysis of randomized controlled trials reported a lack of effect of strict glycemic control as compared to standard care on HF-related outcomes.The considerable heterogeneity of the effect estimate and the higher risk conferred by thiazolidinediones suggested that mechanism of action of antidiabetic drugs played a key role.Furthermore,the safety concerns of pioglitazone led Food and Drug Administration to release a guidance for drug manufacturers stating that cardiovascular risk should be comprehensively evaluated during drug development.Surprisingly,in just a few years,large cardiovascular outcome trials established the beneficial cardiovascular effects of sodium-glucose cotransporter 2 inhibitors.These effects were consistent regardless diabetes and ejection fraction.Therefore,scientific community started to question the glucose-lowering and diuretic properties of sodium-glucose cotransporter 2 inhibitors as the unique mechanisms for improved outcomes.A plenty of preclinical and clinical studies identified several mechanisms besides glucose-lowering effects.However,these mechanistic studies focused on animal models and patients with established HF.If the same mechanisms account for beneficial effects in patients at risk for or with pre-HF is unknown.Grubić Rotkvićet al published an interesting work adding data in early stages HF.
基金the National Key Research and Development Program of China(2021YFD2000600)the National Natural Science Foundation of China(32071914)+1 种基金the Modern Agricultural Industry Technology System of China(CARS-170405)the Key Research and Development Program(Science and Technology Demonstration Project)project of Shandong Province(2022SFGC0202).
文摘To achieve an unmanned rice farm,in this study,a cotransporter system was developed using a tracked rice harvester and transporter for autonomous harvesting,unloading,and transportation.Additionally,two unloading and transportation modes—harvester waiting for unloading(HWU)and transporter fol-lowing for unloading(TFU)—were proposed,and a harvesting-unloading-transportation(HUT)strategy was defined.By breaking down the main stages of the collaborative operation,designing module-state machines(MSMs),and constructing state-transition chains,a HUT collaborative operation logic frame-work suitable for the embedded navigation controller was designed using the concept and method of the finite-state machine(FSM).This method addresses the multiple-stage,nonsequential,and complex processes in HUT collaborative operations.Simulations and field-harvesting experiments were performed to evaluate the applicability of this proposed strategy and system.The experimental results showed that the HUT collaborative operation strategy effectively integrated path planning,path-tracking control,inter-vehicle communication,collaborative operation control,and implementation control.The cotrans-porter system completed the entire process of harvesting,unloading,and transportation.The field-harvesting experiment revealed that a harvest efficiency of 0.42 hm^(2)·h^(−1) was achieved.This study can provide insight into collaborative harvesting and solutions for the harvesting process of unmanned farms.
基金supported by the National Natural Science Foundation of China(Nos.52070029 and 51878092)the National Key Research and Development Program of China(No.2023YFC3904103).
文摘In real soil environments,humus,colloids and other components significantly affect pollutant migration behavior.Investigating Tl(I)and kaolinite colloids’cotransport in quartz sand media containing sodium humate(HA-Na)is vital for comprehending Tl(I)migration underground.This study examined the migration of Tl(I)and kaolinite colloids across varying pH levels(5,7),ionic strengths(ISs)(1,5,50 mmol/L),and kaolinite colloid concentra-tions.Results indicate that lower IS and pH promote Tl(I)migration when transported alone.In cotransport system,kaolinite promotes Tl(I)migration under acidic conditions but inhibits it under neutral conditions,except at high kaolinite concentrations,where the effect shifts from inhibition to promotion.This is primarily due to changes in the zeta potential of quartz sand,HA-Na,and kaolinite,as well as Tl(I)adsorption after HA-Na and kaolinite occupy binding sites.Competitive adsorption between cations and Tl(I)also plays a significant role.Conversely,in individual system,higher IS and pH inhibit kaolinite migration,while increased kaolinite concentration promotes it.In cotransport system,Tl(I)promotes kaolinite migration under acidic conditions but inhibits it under neutral conditions,except at low kaolinite concentrations.This relates to changes in the zeta potential between kaolinite and the medium,as well as the retention of HA-Na in the column and its adsorption onto kaolinite.Competitive adsorption and binding site saturation also have an impact.This study enhances understanding of Tl(I)migration by revealing the dual effect of kaolinite colloids under different environmental conditions,contributing to better knowledge of Tl(I)fate and transport in natural environments.
文摘The study by Lin et al delves into the clinical impact of dapagliflozin,a repre-sentative sodium-glucose cotransporter 2(SGLT2)inhibitor,on chronic heart failure complicated by hyperuricemia.This investigation highlights dapagliflo-zin’s efficacy in lowering serum uric acid levels,enhancing cardiac function,and reducing cardiovascular events.This work not only provides a comprehensive analysis of dapagliflozin’s sustained benefits in these patients but also introduces novel insights for managing chronic heart failure exacerbated by elevated uric acid.Furthermore,this review examines the potential role of SGLT2 inhibitor in the context of gout,evaluating its mechanisms and clinical application prospects in the management of hyperuricemia,thereby further enriching the medical community’s understanding of SGLT2 inhibitor.
文摘BACKGROUND The use of sodium-glucose cotransporter 2(SGLT2)inhibitor in heart failure(HF)patients is increasing significantly,regardless of whether they have a history of diabetes.The effects of SGLT2 inhibitor on HF are likely mediated through multiple mechanisms,including suppression of the renin-angiotensin-aldosterone system(RAAS),reduction in oxidative stress leading to enhanced myocardial efficiency,and attenuation of adverse cardiac remodeling by preventing fibrosis.These pathways are fundamental to reducing mortality,improving patients'quality of life,and alleviating the burden on the United States healthcare system by decreasing HF-related hospitalizations.AIM To evaluate SGLT2 inhibitor effects on HF,focusing on hospitalization for HF(HHF),cardiovascular(CV)deaths,and all-cause mortality.METHODS A comprehensive search was conducted in PubMed for randomized controlled trials(RCTs)evaluating the effects of SGLT2 inhibitor in HF patients compared to placebo,covering the period from January 1,2014,to January 1,2025.The primary outcomes assessed were HHF,CV deaths,and all-cause mortality.RevMan Web 5.4.1 was used to assess the risk of bias heterogeneity and to perform the statistical analyses.A random-effects model was employed for all statistical evaluations.RESULTS A total of nine RCTs were included in this analysis:DELIVER,DECLARE-TIMI 58,DAPA-HF,EMPA-REG OUTCOME,EMPEROR-Reduced,EMPEROR-Preserved,SOLOIST-WHF,EMPULSE,and VERTIS-CV.For HHF,eight trials(excluding the SOLOIST-WHF;n=25906)were pooled,while CV deaths were assessed using data from eight trials(excluding the EMPULSE;n=26598).Compared to placebo,SGLT2 inhibitor significantly reduced the risk of HHF(relative risk:0.74;95%CI:0.71-0.77;P<0.00001)and CV death(odds ratio:0.88;95%CI:0.83-0.92;P=0.0006).All nine trials(n=27128)were included in the analysis of all-cause mortality.SGLT2 inhibitor were associated with a statistically significant reduction in all-cause mortality compared to placebo(OR:0.91;95%CI:0.84-0.98;P=0.02).CONCLUSION These results suggest that SGLT2 inhibitor significantly reduce the risk of hospitalization for HF,CV deaths,and all-cause mortality.
基金Supported by Industrial Technological Initiation Scholarship of National Council for Scientific and Technological Development,CNPq,Brazil,No.0932204294929829 and No.7414780530977345the Scientific Initiation Scholarship Programme(PIBIC)of National Council for Scientific and Technological Development,CNPq,Brazil,No.5763023359532159,No.6472982965854452,and No.7340128440641417the CNPq Research Productivity Fellow,No.4357511882624145.
文摘The global prevalence of diabetes has surged in recent years,with diabetic kidney disease(DKD)emerging as a major complication.Traditional therapies have had limited success in slowing progression to end-stage kidney disease.However,novel therapies,particularly sodium-glucose cotransporter 2(SGLT2)inhibitors and glucagon-like peptide-1(GLP-1)receptor agonists,which were initially developed for hyperglycemia management,have transformed the treatment of obesity,heart failure,cardiovascular disease,and more recently,DKD.SGLT2 inhibitors have consistently and significantly reduced cardiovascular events,albuminuria,and glomerular filtration rate,highlighting their efficacy across diverse clinical presentations for patients with kidney impairment.Although fewer studies have specifically investigated GLP-1 receptor agonists in patients with kidney disease,existing evidence underscores their potential to slow renal disease progression,reduce albuminuria,and improve clinically relevant outcomes.However,further research is needed to better identify patients most likely to benefit from treatment.Together,these therapies represent valuable advancements for DKD,offering significant reductions in morbidity and mortality and shifting the management of the disease by becoming essential pillars for the treatment of these patients.
基金Supported by Clinical Medical Research Fund of the Zhejiang Medical Association,No.2025ZYC-Z32Henan Provincial Key Research and Development Program,No.231111311000+1 种基金Henan Provincial Science and Technology Research Project,No.232102310411Clinical Medical Research Fund of the Zhejiang Medical Association,2024ZYC-Z30.
文摘Type 2 diabetes markedly elevates fracture risk despite normal or high bone mineral density,a paradox reflecting qualitative skeletal deficits rather than loss of mass.Chronic hyperglycemia fosters the accumulation of advanced glycation end products in bone;their nonenzymatic crosslinks stiffen type I collagen,impair mineralization,and erode mechanical strength.By engaging the receptor for advanced glycation end products,these adducts activate nuclear factorκB and mitogen-activated protein kinase cascades,amplifying oxidative stress,inflammation,osteoblast dysfunction,and osteoclastogenesis.This review synthesizes epidemiological data from type 1 and type 2 diabetes,highlights the limits of densitybased skeletal assessment,and details the molecular pathology of the glycation-collagen axis.It also appraises antiglycation therapies,including formation inhibitors,crosslink breakers and receptor antagonists,with a particular focus on sodium-glucose cotransporter 2 inhibitors that couple glycemic control with modulation of the glycation pathway.By integrating recent basic and clinical advances,we propose a mechanistic framework for diabetic bone disease and outline strategies to mitigate glycationdriven skeletal fragility.
基金We are very grateful for the financial support from the National Natural Science Foundation of China(Grant Nos.:82170406,81970238,and 32111530119)Shanghai Municipal Science and Technology Major Project,China(Grant No.:2018SHZDZX01)+1 种基金The Royal Society UK(Grant No.:IEC\NSFC\201094)the Commonwealth Scholarship Commission UK(Grant No.:NGCA-2020-43).
文摘The solute carrier family 12(SLC12)of cation-chloride cotransporters(CCCs)comprises potassium chloride cotransporters(KCCs,e.g.KCC1,KCC2,KCC3,and KCC4)-mediated Cl^(-)extrusion,and sodium potassium chloride cotransporters(N[K]CCs,NKCC1,NKCC2,and NCC)-mediated Cl^(-)loading.The CCCs play vital roles in cell volume regulation and ion homeostasis.Gain-of-function or loss-of-function of these ion transporters can cause diseases in many tissues.In recent years,there have been considerable advances in our understanding of CCCs'control mechanisms in cell volume regulations,with many techniques developed in studying the functions and activities of CCCs.Classic approaches to directly measure CCC activity involve assays that measure the transport of potassium substitutes through the CCCs.These techniques include the ammonium pulse technique,radioactive or nonradioactive rubidium ion uptakeassay,and thallium ion-uptake assay.CCCs'activity can also be indirectly observed by measuring gaminobutyric acid(GABA)activity with patch-clamp electrophysiology and intracellular chloride concentration with sensitive microelectrodes,radiotracer^(36)Cl^(-),and fluorescent dyes.Other techniques include directly looking at kinase regulatory sites phosphorylation,flame photometry,22Nat uptake assay,structural biology,molecular modeling,and high-throughput drug screening.This review summarizes the role of CCCs in genetic disorders and cell volume regulation,current methods applied in studying CCCs biology,and compounds developed that directly or indirectly target the CCCs for disease treatments.
基金supported by a Commonwealth Ph D Scholarship(S.S.J.)NSFC grants to Y.W.(31771188,31471027)+1 种基金the University of Exeter Medical School start-up fund(J.Z.)NIH Grants R01 NS109358(J.Z.)。
文摘The circadian system plays an immense role in controlling physiological processes in our body.The suprachiasmatic nucleus (SCN) supervises this system,regulating and harmonising the circadian rhythms in our body.Most neurons present in the SCN are GABAergic neurons.Although GABA is considered the main inhibitory neurotransmitter of the CNS,recent studies have shown that excitatory responses were recorded in this area.These responses are enabled by an increase in intracellular chloride ions[Cl;];levels.The chloride (Cl;) levels in GABAergic neurons are controlled by two solute carrier 12 (SLC12)cation-chloride-cotransporters (CCCs):Na^(+)/K^(+)/Cl^(-)co-transporter (NKCC1) and K^(+)/Cl^(-)cotransporter (KCC2),that respectively cause an influx and efflux of Cl^(-).Recent works have found altered expression and/or activity of either of these co-transporters in SCN neurons and have been associated with circadian rhythms.In this review,we summarize and discuss the role of CCCs in circadian rhythms,and highlight these recent advances which attest to CCC’s growing potential as strong research and therapeutic targets.
文摘Sodium-glucose cotransporter 2(SGLT2) inhibition induces glucosuria and decreases blood glucose levels in diabetic patients and lowers hypoglycemic risk. SGLT1 is expressed in the kidney and intestine; SGLT1 inhibition causes abdominal symptoms such as diarrhea and reduces incretin secretion. Therefore, SGLT2 selectivity is important. Ipragliflozin is highly selective for SGLT2. In type 2 diabetes mellitus(T2DM), urinaryglucose excretion increased to 90 g/24 h after 28 d of treatment with ipragliflozin 300 mg/d. Twelve weeks of ipragliflozin 50 mg/d vs placebo reduced glycated hemoglobin and body weight by 0.65% and 0.66 kg, respectively, in Western T2 DM patients, and by 1.3% and 1.89 kg, respectively, in Japanese patients. Ipragliflozin(highly selective SGLT2 inhibitor) improves glycemic control and reduces body weight and lowers hypoglycemic risk and abdominal symptoms. Ipragliflozin can be a novel anti-diabetic and antiobesity agent.
文摘Three major cardiovascular outcome trials(CVOTs)with a new class of antidiabetic drugs-sodium-glucose cotransporter 2(SGLT2)inhibitors(EMPAREG OUTCOME trial with empagliflozin,CANVAS Program with canagliflozin,DECLARE-TIMI 58 with dapagliflozin)unexpectedly showed that cardiovascular outcomes could be improved possibly due to a reduction in heart failure risk,which seems to be the most sensitive outcome of SGLT2 inhibition.No other CVOT to date has shown any significant benefit on heart failure events.Even more impressive findings came recently from the DAPA-HF trial in patients with confirmed and well-treated heart failure:Dapagliflozin was shown to reduce heart failure risk for patients with heart failure with reduced ejection fraction regardless of diabetes status.Nevertheless,despite their possible wide clinical implications,there is much doubt about the mechanisms of action and a lot of questions to unravel,especially now when their benefits translated to nondiabetic patients,rising doubts about the validity of some current mechanistic assumptions.The time frame of their cardiovascular benefits excludes glucoselowering and antiatherosclerotic-mediated effects and multiple other mechanisms,direct cardiac as well as systemic,are suggested to explain their early cardiorenal benefits.These are:Anti-inflammatory,antifibrotic,antioxidative,antiapoptotic properties,then renoprotective and hemodynamic effects,attenuation of glucotoxicity,reduction of uric acid levels and epicardial adipose tissue,modification of neurohumoral system and cardiac fuel energetics,sodiumhydrogen exchange inhibition.The most logic explanation seems that SGLT2 inhibitors timely target various mechanisms underpinning heart failure pathogenesis.All the proposed mechanisms of their action could interfere with evolution of heart failure and are discussed separately within the main text.
文摘Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in the Western world. It is more prevalent in male gender, and with increasing age, obesity, and insulin resistance. Besides weight loss, there are limited treatment options. The use of anti-diabetic medications has been studied with mixed results. In this review, we discuss the use of anti-diabetic medications in the management of NAFLD with a specific focus on sodium-glucose cotransporter 2 inhibitors. We shed light on the evidence supporting their use in detail and discuss limitations and future directions.
基金Supported by Grants-in-Aid for Young Scientists(B),NO.22791295,NO.23791557,and NO.24791440a Grant-in-Aid for Scientific Research(C),NO.22591464 and NO.24591957,from the Japan Society for the Promotion of Science
文摘AIM: To investigate the role of Na<sup>+</sup>/K<sup>+</sup>/2Cl<sup>-</sup> cotransporter 1 (NKCC1) in the regulation of genes involved in cell cycle progression and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC).
文摘BACKGROUND Landmark trials have established the benefits of sodium-glucose cotransporter-2 inhibitors(SGLT2-Is)in cardiovascular disease including heart failure with reduced and preserved ejection fraction and renal diseases regardless of the presence of diabetes mellitus.However,studies evaluating the role of SGLT2-Is in metabolic syndrome(MetS)are limited.AIM This study primarily aimed to evaluate the impact of SGLT2-Is on the components of MetS.METHODS Two independent reviewers and an experienced librarian searched Medline,Scopus and the Cochrane central from inception to December 9,2021 to identify placebo controlled randomized controlled trials that evaluated the impact of SGLT2-Is on the components of MetS as an endpoint.Pre-and post-treatment data of each component were obtained.A meta-analysis was performed using the RevMan(version 5.3;Copenhagen:The Nordic Cochrane Center,The Cochrane Collaboration).RESULTS Treatment with SGLT2-Is resulted in a decrease in fasting plasma glucose(–18.07 mg/dL;95%CI:-25.32 to–10.82),systolic blood pressure(–1.37 mmHg;95%CI:-2.08 to–0.65),and waist circumference(–1.28 cm;95%CI:-1.39 to–1.18)compared to placebo.The impact on highdensity lipoprotein cholesterol was similar to placebo(0.01 mg/dL;95%CI:-0.05 to 0.07).CONCLUSION SGLT2-Is have a promising role in the management of MetS.
基金Yunnan Science Foundation Project,No.2019-81960102.
文摘BACKGROUND Sodium taurocholate cotransport polypeptide(NTCP)deficiency disease is a genetic metabolic disorder due to mutations in the SLC10A1 gene and impaired bile acid salt uptake by the basolateral membrane transport protein NTCP in hepatocytes.A variety of clinical manifestations and genetic mutation loci have been reported for this disease.However,specific therapeutic measures are lacking,and the long-term effects are unknown.CASE SUMMARY An infant with elevated bile acids and behavioral neurodevelopmental delay failed to respond to bile acid-lowering therapy.Genetic testing for metabolic liver disease revealed that the child had NTCP deficiency due to the SLC10A1 mutation:c.422dupA(p.Y141X),which is a novel mutation site.The current followup revealed a gradual decrease in bile acid levels after 1 year of age,but the child still had behavioral neurodevelopmental delays.CONCLUSION The clinical manifestations,genetic characteristics,treatment and long-term prognosis due to NTCP deficiency remain poorly defined and need to be further confirmed by more studies and reports.
基金supported by National Science and Technology Major Project of the Ministry of Science and Technology of China(No.2018ZX09735005)the National Natural Science Foundation of China(Nos.81922064,81874290,81673290,81803347 and 81903502)+1 种基金the Natural Science Foundation of Guangdong Province(No.2018A030313707)Post-Doctor Research Project,West China Hospital,Sichuan University(No.2019HXBH034)。
文摘Sodium taurocholate cotransporting polypeptide(NTCP)is identified as the functional receptor for HBV entry,which is responsible for upregulated HBV transcription in the HBV life cycle.Besides,NTCP is also implicated in the progression of HBV-induced hepatocellular carcinoma(HCC).Thereby,NTCP-targeting entry inhibitors are proposed to suppress HBV infection and replication in HBV-induced hepatoma therapy.Herein,we integrated in silico screening and chemical synthesis to obtain a small-molecule NTCP inhibitor B7,which exhibited moderate anti-proliferative activities against HepG2 cells and anti-HBV activity in vitro.Additionally,CETSA assay,molecular docking,and MD simulation validated that B7 could bind to NTCP.Furthermore,western blot analysis demonstrated that B7 induced apoptosis with an increased expression of Bax and caspase 3 cleaving as well as a decreasing expression of Bcl-2 in HepG2 cells.Taken together,our study identified B7 as a novel NTCP inhibitor with anti-proliferation activities which might provide a new opportunity for HCC therapy.
文摘Sodium-glucose cotransporter 2(SGLT2)inhibitors have gained momentum as the latest class of antidiabetic agents for improving glycemic control.Large-scale clinical trials have reported that SGLT2 inhibitors reduced cardiovascular outcomes,especially hospitalization for heart failure in patients with type 2 diabetes mellitus who have high risks of cardiovascular disease.Accumulating evidence has indicated that beneficial effects can be observed regardless of the presence or absence of type 2 diabetes mellitus.Accordingly,the Food and Drug Administration approved these agents specifically for treating patients with heart failure and a reduced ejection fraction.It has been concluded that canagliflozin,dapagliflozin,empagliflozin,or ertugliflozin can be recommended for preventing hospitalization associated with heart failure in patients with type 2 diabetes and established cardiovascular disease or those at high cardiovascular risk.In the present review,we explore the available evidence on SGLT2 inhibitors in terms of the cardioprotective effects,potential mechanisms,and ongoing clinical trials that may further clarify the cardiovascular effects of the agents.
文摘Solid organ transplantation offers life-saving treatment for patients with endorgan dysfunction.Patient survival and quality of life have improved over the past few decades as a result of pharmacological development,expansion of the donor pool,technological advances and standardization of practices related to transplantation.Still,transplantation is associated with cardiovascular complications,of which post-transplant diabetes mellitus(PTDM)is one of the most important.PTDM increases mortality,which is best documented in patients who have received kidney and heart transplants.PTDM results from traditional risk factors seen in patients with type 2 diabetes mellitus,but also from specific posttransplant risk factors such as metabolic side effects of immunosuppressive drugs,post-transplant viral infections and hypomagnesemia.Oral hypoglycaemic agents are the first choice for the treatment of type 2 diabetes mellitus in non-transplanted patients.However,the evidence on the safety and efficacy of oral hypoglycaemic agents in transplant recipients is limited.The favourable risk/benefit ratio,which is suggested by large-scale and long-term studies on new glucoselowering drug classes such as glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors,makes studies warranted to assess the potential role of these agents in the management of PTDM.
基金Supported by National Natural Science Foundation of China,No.31271290 and No.31000514Scientific Research Key Program of Beijing Municipal Commission of Education No.KZ201310025020+1 种基金Beijing Postdoctoral Research FoundationBeijing Natural Science Foundation No.7142025
文摘AIM: To investigate whether Na<sup>+</sup>-K<sup>+</sup>-2Cl<sup>-</sup> cotransporter (NKCC2) is expressed in the mouse distal colonic epithelia and whether it is regulated by vasopressin in the colon.
基金Supported by Development of Medical Science and Technology Project of Jiangsu Province,No.YKK13205
文摘AIM To determine the expression and localization of the electrogenic Na^+/HCO_3^- cotransporter(NBC1) in rat pancreas during development. METHODS The rat pancreas from postnatal and embryos removed from the uterus of pregnant rats that had been sacrificed by CO2 asphyxiation were used. Rat pancreas from embryonic day(E) 15.5 and E18.5 rat embryos was isolated under a stereomicroscope. Rat pancreas from postnatal(P) days 0, 7, 14, 21 and adult was directly isolated by the unaided eye. The RT-PCR analysis of the NBC1 specific region on rat pancreastissues from different developmental stages. The two antibodies which target the NBC1 common COOHterminal region and NH2-terminal region detected a clear band of about 145 k Da in the Western blot analysis. The localization of NBC1 was examined by immuno-fluorescence detection. RESULTS The results revealed the first peak of NBC1 expression at E18.5 and the second peak at P14. Meanwhile, the low NBC1 expression occurred at P7 and adult stages. Our results demonstrated, for the first time, the presence of NBC1 in the plasma membrane of β and α cells, as well as in the basolateral membrane of acinar cells of the rat pancreas at different stages of development. CONCLUSION The data strongly suggests that NBC1 is diversely expressed in the pancreas at different developmental stages, where it may exert its functions in pancreatic development especially islet cell growth through HCO_3^- transport and pH regulation.
