Hepatocellular carcinoma(HCC)is a malignant tumour with high prevalence and mortality rate worldwide.Metabolic reprogramming of cancer cells may be a major factor in the process of this disease.Glucose transporter pro...Hepatocellular carcinoma(HCC)is a malignant tumour with high prevalence and mortality rate worldwide.Metabolic reprogramming of cancer cells may be a major factor in the process of this disease.Glucose transporter proteins(GLUTs)are members of the major facilitator superfamily of membrane transporters,playing a pivotal role in the metabolic reprogramming and tumour progression in HCC.This review discusses the advances in the study of GLUTs in HCC,in-cluding the expression patterns,functions and possibilities of GLUTs.In HCC,the expression levels of GLUTs are closely associated with tumour aggressiveness,metabolic reprogramming and prognosis.A series of inhibitors have been de-monstrated efficacy in inhibiting HCC cell growth and glucose uptake in in vitro and in vivo models.These inhibitors offer a novel approach to HCC treatment by reducing the glucose metabolism of tumour cells,thereby impeding tumour growth,and concurrently enhancing the sensitivity to chemotherapeutic agents.This reminds us of the urgent need to elucidate GLUTs’roles in HCC and to determine the most effective ways to translate these findings into clinical practice.展开更多
Background The delivery of glucose from the blood to the brain involves its passage across the endothelial cells of the blood-brain barrier （BBB）, which is mediated by the facilitative glucose transporter protein 1 ...Background The delivery of glucose from the blood to the brain involves its passage across the endothelial cells of the blood-brain barrier （BBB）, which is mediated by the facilitative glucose transporter protein 1 （GLUT1）, end then across the neural cell membranes, which is mediated by GLUT3. This study aimed to evaluate the dynamic influence of hyperglycemia on the expression of these GLUTs by measuring their expression in the brain at different blood glucose levels in e rat model of diabetes. This might help to determine the proper blood glucose threshold level in the treatment of diabetic apoplexy. Methods Diabetes mellitus was induced with streptozotocin （STZ） in 30 rats. The rats were randomly divided into 3 groups： diabetic group without blood glucose control （group DM1）, diabetic rats treated with low dose insulin （group DM2） end diabetic rats treated with high dose insulin （group DM3）. The mRNA end protein levels of GLUT1 end GLUT3 were essayed by reverse trenscriptese-polymerese chain reaction （RT-PCR） end immunohistochemistry, respectively. Results Compared with normal control rats, the G/UT1 mRNA was reduced by 46.08%, 29.80%, 19.22% （P〈0.01） in DM1, DM2, end DM3 group, respectively; end the GLUT3 mRNA was reduced by 75.00%, 46.75%, end 17.89% （P〈0.01） in DM1, DM2, end DM3 group, respectively. The abundance of GLUT1 end GLUT3 proteins had negative correlation with the blood glucose level （P〈0.01）. The density of microvessels in the brain of diabetic rats did not change significantly compared with normal rats. Conclusions Chronic hyperglycemia downreguletes G/UT1 end GLUT3 expression at both mRNA end protein levels in the rat brain, which is not due to the decrease of the density of microvessels. The downreguletion of G/UT1 end GLUT3 expression might be the adaptive reaction of the body to prevent excessive glucose entering the cell that may lead to cell damage.展开更多
Objective: To investigate the changes in glucose transporter-4(Glut-4) mRNA expression in skeletal muscle before and after the thoracic operation and to observe the changes in Glut-4 mRNA expression by preoperative in...Objective: To investigate the changes in glucose transporter-4(Glut-4) mRNA expression in skeletal muscle before and after the thoracic operation and to observe the changes in Glut-4 mRNA expression by preoperative infusion of glucose. Methods: Twelve cases of elective thoracic operation were randomly divided into two groups, namely ordinary group Ⅰ and glucose infusion group Ⅱ. One gram of intercostal muscle was taken while thorax being opened and closed from patients under general anesthesia. Total RNA of the muscle cells was extracted by TRIzol one-step assay. Reverse transcription-competitive polymerase chain reaction (RT-PCR) was used to determine the Glut-4 mRNA amplification products with β-actin mRNA as an internal control. The Glut-4 mRNA expression was expressed by targeted gene /β-actin ×100%. The plasma glucose and insulin levels were determined at the same time.Results: Glut-4 mRNA expression was significantly reduced(P<0.05) and plasma glucose level increased (P<0.05), while thorax was being closed as compared with those while being opened. However, Glut-4 mRNA expression in glucose infusion group Ⅱ was significantly higher than ordinary group Ⅰ (P<0.01) and plasma glucose level in group Ⅱ was lower than group Ⅰ(P<0.05) when thorax was being closed. Conclusion: The results indicate that the synthesis of Glut-4 is suppressed by the surgical stress of thoracic operation under general anesthesia. We found that preoperative infusion glucose can increase Glut-4 mRNA expression at the same surgical stress and relieve postoperative insulin resistance.展开更多
Objective:To determine the effect of steroidogenic acute regulatory protein(StAR) overexpression on the levels of adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1) and ATP-binding cassette transporter...Objective:To determine the effect of steroidogenic acute regulatory protein(StAR) overexpression on the levels of adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1) and ATP-binding cassette transporter G1(ABCG1) in an endothelial cell line(bEnd.3).Methods:The StAR gene was induced in bEnd.3 cells with adenovirus infection.The infection efficiency was detected by fluorescence activated cell sorter(FACS) and fluorescence microscopy.The expressions of StAR gene and protein levels were detected by real-time polymerase chain reaction(PCR) and Western blot.The gene and protein levels of ABCA1 and ABCG1 were detected by real-time PCR and Western blot after StAR overexpression.Results:The result shows that StAR was successfully overexpressed in bEnd.3 cells by adenovirus infection.The mRNA and protein expressions of ABCA1 and ABCG1 were greatly increased by StAR overexpression in bEnd.3 cells.Conclusion:Overexpression of StAR increases ABCA1 and ABCG1 expressions in endothelial cells.展开更多
The sympathetic nervous system plays a cardinal role in regulating cardiac function through releasing the neurotransmitter norepinephrine (NE). In comparison with central nervous system, the molecular mechanism of NE ...The sympathetic nervous system plays a cardinal role in regulating cardiac function through releasing the neurotransmitter norepinephrine (NE). In comparison with central nervous system, the molecular mechanism of NE uptake in myocardium is not clear. In present study, we proved that in rat the CNS type of NE transporter (NET) was also expressed in middle cervical-stellate ganglion complex (MC-SG complex) which is considered to control the activity of heart, but not expressed in myocardium. The results also showed that NET expression level in right ganglion was significantly higher than in the left, rendering the greater capacity of NE uptake in right ventricle, a fact which may contribute to the maintenance of right ventricular function under pathologic state.展开更多
GABA transporter 1(GAT1) takes important roles in multiple physiological processes through the uptake and release of GABA, but the regulation of GAT1 gene expression in different tissues is rarely known. To address th...GABA transporter 1(GAT1) takes important roles in multiple physiological processes through the uptake and release of GABA, but the regulation of GAT1 gene expression in different tissues is rarely known. To address the question, first, 5’ Rapid amplification of cDNA end (RACE) was used to determine GAT1 transcriptional starting sites in neonatal mouse cerebral cortex and intestine, adult mouse brain and adult rat testis. The products of 5’RACE were confirmed by DNA sequencing. We found that the transcript of GAT1 in neonatal mouse cerebral cortex and adult mouse brain starts at the same site (inside of exon 1), while in mouse intestine, GAT1 starts transcription in intron 1, and in rat testis, the transcript of GAT1 has an additional untranslation exon to the 5’ direction.展开更多
AIM: To study the effect of copper transporting P-type ATPase in copper metabolism of hepatocyte and pathogenesis of Wilson disease (WD). METHODS: WD copper transporting properties in some organelles of the cultured h...AIM: To study the effect of copper transporting P-type ATPase in copper metabolism of hepatocyte and pathogenesis of Wilson disease (WD). METHODS: WD copper transporting properties in some organelles of the cultured hepatocytes were studied from WD patients and normal controls.These cultured hepatocytes were incubated in the media of copper 15 mg x L(-1) only, copper 15 mg x L(-1) with vincristine (agonist of P-type ATPase) 0.5mg x L(-1), or copper 15 mg x L(-1) with vanadate (antagonist of P-type ATPase) 18.39 mg x L(-1) separately. Microsome (endoplasmic reticulum and Golgi apparatus), lysosome, mitochondria, and cytosol were isolated by differential centrifugation. Copper contents in these organelles were measured with atomic absorption spectrophotometer, and the influence in copper transportion of these organelles by vanadate and vincristine were comparatively analyzed between WD patients and controls. WD copper transporting P-type ATPase was detected by SDS-PAGE in conjunction with Western blot in liver samples of WD patients and controls. RESULTS: The specific WD proteins (M(r)155,000 lanes) were expressed in human hepatocytes, including the control and WD patients. After incubation with medium containing copper for 2 h or 24 h, the microsome copper concentration in WD patients was obviously lower than that of controls, and the addition of vanadate or vincristine would change the copper transporting of microsomes obviously. When incubated with vincristine, levels of copper in microsome were significantly increased, while incubated with vanadate, the copper concentrations in microsome were obviously decreased. The results indicated that there were WD proteins, the copper transportion P-type ATPase in the microsome of hepatocytes. WD patients possessed abnormal copper transporting function of WD protein in the microsome, and the agonist might correct the defect of copper transportion by promoting the activity of copper transportion P-type ATPase. CONCLUSION: Copper transportion P-type ATPase plays an important role in hepatocytic copper metabolism. Dysfunction of hepatocytic WD protein copper transportion might be one of the most important factors for WD.展开更多
MOLECULAR PHYSIOLLGY OF HEPATOCELLULAR TRANSPORT PROTEINS Basolaferal transport systems Na+-dependent bile salt uptake Uptake of bile salts into the liver was first isolated perfused rat liver[1],isolated hepatocyte...MOLECULAR PHYSIOLLGY OF HEPATOCELLULAR TRANSPORT PROTEINS Basolaferal transport systems Na+-dependent bile salt uptake Uptake of bile salts into the liver was first isolated perfused rat liver[1],isolated hepatocyte cultures and basolateral plasma membrane vesicles [2,4].展开更多
HKT transport protein is an ion transporter thai exists on plasmalemma and a ubiquitous transmembrane protein responsible for Na ＋ transport and K＋ - Na ＋ symport. HKT transport protein is regulated by the expressi...HKT transport protein is an ion transporter thai exists on plasmalemma and a ubiquitous transmembrane protein responsible for Na ＋ transport and K＋ - Na ＋ symport. HKT transport protein is regulated by the expression of ItKT family genes. The overexpression of HKT family genes can improve activity of Na＋ transport and K＋ - Na＋ s.vmport proteins in plants, lead to Na ＋ recycle, reduce Na ＋ concentration in vivo, maintain K ＋/Na＋ ratio, and ensure normal physiological functions of eells, thereby improving salt toleranee of plants. This paper introduced the discovery and claning of HKT family genes, revealed interactions between HKT family genes and SOS, NHX genes, and summarized the relationship between the structure, function of HKT protein and salt tolerance of plants to clarify the function and mechanism of action of HKT transport protein, aiming at laying the foundation for genetic engineering of plants for salt tolerauee and providing basis for breeding haloduric transgenie plant.展开更多
In order to illustrate the ion transport mechanism of chloride channel（Cl C） protein,a type of Cl C protein,Cl C-ec1,from Escherichia coli is embedded into an explicit membranewater system by using software VMD. The...In order to illustrate the ion transport mechanism of chloride channel（Cl C） protein,a type of Cl C protein,Cl C-ec1,from Escherichia coli is embedded into an explicit membranewater system by using software VMD. Then a parallel molecular dynamics（MD） simulation is employed to equilibrate the Cl C-ec1 structure for 27.5 ns at temperature 298.15 K. Based on this equilibrated structure,we compute the channel geometric size variation and electrostatic potential distribution along the channel. Meanwhile,Cl^- transport process is simulated using oriented random walk method under variable external potential. The simulation result shows that Cl^- transport velocity depends on the width of the narrowest channel region. Mutation of negative glutamate E148 can produce positive potential,which is beneficial for Cl^- transport,around external Cl^- binding region in the channel. The simulated current-voltage curves about Cl^- transporting in Cl C-ec1 protein agree with Jayaram＇s experimental results.展开更多
Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in hig...Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.展开更多
BACKGROUND Fanconi–Bickel syndrome(FBS)is a rare autosomal recessive disorder caused by mutation of the SLC2A2 gene,which encodes glucose transporter protein 2(GLUT2).CASE SUMMARY We report a 7-mo-old girl with cytom...BACKGROUND Fanconi–Bickel syndrome(FBS)is a rare autosomal recessive disorder caused by mutation of the SLC2A2 gene,which encodes glucose transporter protein 2(GLUT2).CASE SUMMARY We report a 7-mo-old girl with cytomegalovirus infection presenting hepatomegaly,jaundice,liver transaminase elevation,fasting hypoglycemia,hyperglycosuria,proteinuria,hypophosphatemia,rickets,and growth retardation.After prescription of ganciclovir,the levels of bilirubin and alanine aminotransferase decreased to normal,while she still had aggravating hepatomegaly and severe hyperglycosuria.Then,whole exome sequencing was conducted and revealed a homozygous c.416delC mutation in exon 4 of SLC2A2 inherited from her parents,which was predicted to change alanine 139 to valine(p.A139Vfs*3),indicating a diagnosis of FBS.During the follow-up,the entire laboratory test returned to normal with extra supplement of vitamin D and corn starch.Her weight increased to normal range at 3 years old without hepatomegaly.However,she still had short stature.Although there was heterogeneity between phenotype and genotype,Chinese children had typical clinical manifestations.No hot spot mutation or association between severity and mutations was found,but nonsense and missense mutations were more common.Data of long-term follow-up were rare,leading to insufficient assessment of the prognosis in Chinese children.CONCLUSION FBS is a rare genetic metabolic disease causing impaired glucose liver homeostasis and proximal renal tubular dysfunction.Results of urine and blood testing suggesting abnormal glucose metabolism could be the clues for FBS in neonates and infants.Genetic sequencing is indispensable for diagnosis.Since the diversity of disease severity,early identification and long-term follow-up could help improve patients’quality of life and decrease mortality.展开更多
OBJECTIVE: To investigate the antiepileptic effects of Chaihushugan decoction(CHSGD) in rats with pentylenetetrazole(PTZ)-induced seizures and to discuss the impact of CHSGD on glutamate metabolism, a hypothesized und...OBJECTIVE: To investigate the antiepileptic effects of Chaihushugan decoction(CHSGD) in rats with pentylenetetrazole(PTZ)-induced seizures and to discuss the impact of CHSGD on glutamate metabolism, a hypothesized underlying mechanism of seizure reduction.METHODS: Fifty Wistar rats were divided randomly into either control(n = 10) or experimental(n = 40)groups. Rats in the control group were administered physiological saline intraperitoneally. A subconvulsive dose of PTZ(35 mg/kg) was administered intraperitoneally to rats in the experimental group to induce seizures. The fully PTZ-kindled rats were then randomly divided into five subgroups(n = 8 each) based on the following treatment categories: physiological saline, VPA(200 mg/kg), CHSGD(2.5 g/kg), CHSGD(5 g/kg), or CHSGD(10 g/kg),administered orally once per day, respectively. On day 28 following initiation of drug treatment, seizures were monitored. The rats were then sacrificed, and hippocampal dissections were performed for subsequent studies.RESULTS: CHSGD significantly prolonged the latency of myoclonic, clonic, and tonic seizures, while decreasing overall seizure rates in the kindled rats.The measured concentrations of 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose(2-NBDG) and glutamate were significantly lower in the hippocampi of kindled rats in groups treated with CHSGD compared with those treated with PTZ alone. In addition, CHSGD was found to up-regulate both the expression of glutamate transporter-1(GLT-1) protein and the activity of glutamine synthetase(GS) in the hippocampi of kindled rats.CONCLUSION: These results suggest that CHSGD has antiepileptic effects on PTZ-induced seizures.The results further suggest an increase in glutamate metabolism at the synaptic cleft is a putative underlying mechanism of seizure reduction.展开更多
Heat as a stressor of poultry has been studied extensively for many decades; it affects poultry production on a worldwide basis and has significant impact on well-being and production. More recently, the involvement o...Heat as a stressor of poultry has been studied extensively for many decades; it affects poultry production on a worldwide basis and has significant impact on well-being and production. More recently, the involvement of heat stress in inducing oxidative stress has received much interest. Oxidative stress is defined as the presence of reactive species in excess of the available antioxidant capacity of animal cells. Reactive species can modify several biologically cellular macromolecules and can interfere with cell signaling pathways. Furthermore, during the last decade, there has been an ever-increasing interest in the use of a wide array of natural feed-delivered phytochemicals that have potential antioxidant properties for poultry. In light of this, the current review aims to（1） summarize the mechanisms through which heat stress triggers excessive superoxide radical production in the mitochondrion and progresses into oxidative stress,（2） illustrate that this pathophysiology is dependent on the intensity and duration of heat stress,（3） present different nutritional strategies for mitigation of mitochondrial dysfunction, with particular focus on antioxidant phytochemicals.Oxidative stress that occurs with heat exposure can be manifest in all parts of the body; however, mitochondrial dysfunction underlies oxidative stress. In the initial phase of acute heat stress, mitochondrial substrate oxidation and electron transport chain activity are increased resulting in excessive superoxide production. During the later stage of acute heat stress, down-regulation of avian uncoupling protein worsens the oxidative stress situation causing mitochondrial dysfunction and tissue damage. Typically, antioxidant enzyme activities are upregulated. Chronic heat stress, however, leads to downsizing of mitochondrial metabolic oxidative capacity, up-regulation of avian uncoupling protein, a clear alteration in the pattern of antioxidant enzyme activities, and depletion of antioxidant reserves.Some phytochemicals, such as various types of flavonoids and related compounds, were shown to be beneficial in chronic heat-stressed poultry, but were less or not effective in non-heat-stressed counterparts. This supports the contention that antioxidant phytochemicals have potential under challenging conditions. Though substantial progress has been made in our understanding of the association between heat stress and oxidative stress, the means by which phytochemicals can alleviate oxidative stress have been sparsely explored.展开更多
Rice is moderately sensitive to salinity,and the response to salt stress is a complex process,including the perception and transduction of salt stress signal,the activation of specific transcriptional factors and the ...Rice is moderately sensitive to salinity,and the response to salt stress is a complex process,including the perception and transduction of salt stress signal,the activation of specific transcriptional factors and the expression of downstream stress-responsive genes.The functions of Na+ transporters which are involved in the maintenance and reconstruction of the ion homeostasis,transcriptional regulators and osmotic regulation genes were reviewed.Salt tolerance of plants are enhanced by Na+ vacuolar compartmentation or efflux or high levels of osmoprotectants accumulation in cytoplasm.展开更多
Excessive secretion of human islet amyloid polypeptide(hIAPP)is an important pathological basis of diabetic encephalopathy(DE).In this study,we aimed to investigate the potential implications of hIAPP in DE pathogenes...Excessive secretion of human islet amyloid polypeptide(hIAPP)is an important pathological basis of diabetic encephalopathy(DE).In this study,we aimed to investigate the potential implications of hIAPP in DE pathogenesis.Brain magnetic resonance imaging and cognitive scales were applied to evaluate white matter damage and cognitive function.We found that the concentration of serum hIAPP was positively correlated with white matter damage but negatively correlated with cognitive scores in patients with type 2 diabetes mellitus.In vitro assays revealed that oligodendrocytes,compared with neurons,were more prone to acidosis under exogenous hIAPP stimulation.Moreover,western blotting and co-immunoprecipitation indicated that hIAPP interfered with the binding process of monocarboxylate transporter(MCT)1 to its accessory protein CD147 but had no effect on the binding of MCT2 to its accessory protein gp70.Proteomic differential analysis of proteins co-immunoprecipitated with CD147 in oligodendrocytes revealed Yeast Rab GTPase-Interacting protein 2(YIPF2,which modulates the transfer of CD147 to the cell membrane)as a significant target.Furthermore,YIPF2 inhibition significantly improved hIAPP-induced acidosis in oligodendrocytes and alleviated cognitive dysfunction in DE model mice.These findings suggest that increased CD147 translocation by inhibition of YIPF2 optimizes MCT1 and CD147 binding,potentially ameliorating hIAPP-induced acidosis and the consequent DE-related demyelination.展开更多
Excessive uptake of purine and glucose can lead to hyperglycemia and hyperuricemia,mediated by specific intestinal transport proteins.Currently,there is a deficiency in targeted regulation of these proteins.In this st...Excessive uptake of purine and glucose can lead to hyperglycemia and hyperuricemia,mediated by specific intestinal transport proteins.Currently,there is a deficiency in targeted regulation of these proteins.In this study,we introduce an oral approach for targeted modulation using electrospun core–shell short-fibers that settle on the intestinal mucosa.These fibers,designed for the controlled in situ release of phlorizin—a multi-transporter inhibitor—are crafted through a refined electrospinning-homogenizing process using polylactic acid and gelatin.Phlorizin is conjugated via a phenyl borate ester bond.Furthermore,a calcium alginate shell ensures intestinal disintegration triggered by pH changes.These fibers adhere to the mucosa due to their unique structure,and phlorizin is released in situ post-ingestion through glucose-sensitive cleavage of the phenyl borate ester bond,enabling dual-target inhibition of intestinal transporter proteins.Both in vitro and in vivo studies confirm that the short-fibers possess intestine-settling and glucose-responsive properties,facilitating precise control over transport proteins.Using models of hyperuricemia and diabetes in mice,treatment with short-fibers results in reduc-tions of 49.6%in blood uric acid and 17.8%in glucose levels,respectively.Additionally,16S rRNA sequencing indicates an improved intestinal flora composition.In conclusion,we have developed an innovative oral strategy for the prevention of hyperglycemia and hyperuricemia.展开更多
OBJECTIVE: To investigate the distribution, changes and a possible role for retinal dopamine transporter (DAT) in experimental myopia in chickens. METHODS: Two-day-old chickens were divided into four groups. Chicken e...OBJECTIVE: To investigate the distribution, changes and a possible role for retinal dopamine transporter (DAT) in experimental myopia in chickens. METHODS: Two-day-old chickens were divided into four groups. Chicken eyes were fitted with lenses of -10D,-20D and translucent goggles unilaterally. Normal eyes were used as controls. After 3 wk, all chickens were given an intramuscular injection of (125)I-beta-CIT 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane and sacrificed two hours post injection. Retinal pigment epithelium (RPE) and the neural retina were obtained together or RPE was dissected out from the neural retina. Radioactive DAT from each specimen was assayed by gamma-counter. RESULTS: Retinal DAT was detected in RPE specimens rather than in the neural retina in all eyes. Radioactive DAT in myopic eyes was higher, compared with control eyes. CONCLUSIONS: Retinal DAT is mainly located in the RPE and may be involved in the formation of lens induced myopia (LIM) and form deprivation myopia (FDM). These methods may provide a new approach for further studying the role of the dopamine system in experimental myopia.展开更多
Nephronophthisis(NPHP)is an autosomal recessive kidney disease and is the most prevalent monogenic cause of end-stage renal disease in childhood.The tetratricopeptide repeat domain 21B(TTC21B)gene encodes the ciliary ...Nephronophthisis(NPHP)is an autosomal recessive kidney disease and is the most prevalent monogenic cause of end-stage renal disease in childhood.The tetratricopeptide repeat domain 21B(TTC21B)gene encodes the ciliary protein intraflagellar transport protein 139(IFT139)and has been recently implicated in heterogeneous diseases,including nephronophthisis type 12(NPHP12),short-rib thoracic dysplasia 4(SRTD4).展开更多
To the Editor:Exportin-1(XPO1)is the most extensively studied nuclear transport protein and is highly expressed in malignant solid tumors,including small cell lung cancer(SCLC).XPO1 may play a significant role in drug...To the Editor:Exportin-1(XPO1)is the most extensively studied nuclear transport protein and is highly expressed in malignant solid tumors,including small cell lung cancer(SCLC).XPO1 may play a significant role in drug resistance and poor prognosis.Given the development and promising perspective of XPO1 in the oncological field,we summarized the current understanding of XPO1 in malignant solid tumors,particularly SCLC.In addition,we discussed the therapeutic potential of XPO1 inhibitors,combination strategies,and future challenges.展开更多
文摘Hepatocellular carcinoma(HCC)is a malignant tumour with high prevalence and mortality rate worldwide.Metabolic reprogramming of cancer cells may be a major factor in the process of this disease.Glucose transporter proteins(GLUTs)are members of the major facilitator superfamily of membrane transporters,playing a pivotal role in the metabolic reprogramming and tumour progression in HCC.This review discusses the advances in the study of GLUTs in HCC,in-cluding the expression patterns,functions and possibilities of GLUTs.In HCC,the expression levels of GLUTs are closely associated with tumour aggressiveness,metabolic reprogramming and prognosis.A series of inhibitors have been de-monstrated efficacy in inhibiting HCC cell growth and glucose uptake in in vitro and in vivo models.These inhibitors offer a novel approach to HCC treatment by reducing the glucose metabolism of tumour cells,thereby impeding tumour growth,and concurrently enhancing the sensitivity to chemotherapeutic agents.This reminds us of the urgent need to elucidate GLUTs’roles in HCC and to determine the most effective ways to translate these findings into clinical practice.
文摘Background The delivery of glucose from the blood to the brain involves its passage across the endothelial cells of the blood-brain barrier （BBB）, which is mediated by the facilitative glucose transporter protein 1 （GLUT1）, end then across the neural cell membranes, which is mediated by GLUT3. This study aimed to evaluate the dynamic influence of hyperglycemia on the expression of these GLUTs by measuring their expression in the brain at different blood glucose levels in e rat model of diabetes. This might help to determine the proper blood glucose threshold level in the treatment of diabetic apoplexy. Methods Diabetes mellitus was induced with streptozotocin （STZ） in 30 rats. The rats were randomly divided into 3 groups： diabetic group without blood glucose control （group DM1）, diabetic rats treated with low dose insulin （group DM2） end diabetic rats treated with high dose insulin （group DM3）. The mRNA end protein levels of GLUT1 end GLUT3 were essayed by reverse trenscriptese-polymerese chain reaction （RT-PCR） end immunohistochemistry, respectively. Results Compared with normal control rats, the G/UT1 mRNA was reduced by 46.08%, 29.80%, 19.22% （P〈0.01） in DM1, DM2, end DM3 group, respectively; end the GLUT3 mRNA was reduced by 75.00%, 46.75%, end 17.89% （P〈0.01） in DM1, DM2, end DM3 group, respectively. The abundance of GLUT1 end GLUT3 proteins had negative correlation with the blood glucose level （P〈0.01）. The density of microvessels in the brain of diabetic rats did not change significantly compared with normal rats. Conclusions Chronic hyperglycemia downreguletes G/UT1 end GLUT3 expression at both mRNA end protein levels in the rat brain, which is not due to the decrease of the density of microvessels. The downreguletion of G/UT1 end GLUT3 expression might be the adaptive reaction of the body to prevent excessive glucose entering the cell that may lead to cell damage.
文摘Objective: To investigate the changes in glucose transporter-4(Glut-4) mRNA expression in skeletal muscle before and after the thoracic operation and to observe the changes in Glut-4 mRNA expression by preoperative infusion of glucose. Methods: Twelve cases of elective thoracic operation were randomly divided into two groups, namely ordinary group Ⅰ and glucose infusion group Ⅱ. One gram of intercostal muscle was taken while thorax being opened and closed from patients under general anesthesia. Total RNA of the muscle cells was extracted by TRIzol one-step assay. Reverse transcription-competitive polymerase chain reaction (RT-PCR) was used to determine the Glut-4 mRNA amplification products with β-actin mRNA as an internal control. The Glut-4 mRNA expression was expressed by targeted gene /β-actin ×100%. The plasma glucose and insulin levels were determined at the same time.Results: Glut-4 mRNA expression was significantly reduced(P<0.05) and plasma glucose level increased (P<0.05), while thorax was being closed as compared with those while being opened. However, Glut-4 mRNA expression in glucose infusion group Ⅱ was significantly higher than ordinary group Ⅰ (P<0.01) and plasma glucose level in group Ⅱ was lower than group Ⅰ(P<0.05) when thorax was being closed. Conclusion: The results indicate that the synthesis of Glut-4 is suppressed by the surgical stress of thoracic operation under general anesthesia. We found that preoperative infusion glucose can increase Glut-4 mRNA expression at the same surgical stress and relieve postoperative insulin resistance.
基金Project (Nos 30871021 and 30900716) supported by the National Natural Science Foundation of China
文摘Objective:To determine the effect of steroidogenic acute regulatory protein(StAR) overexpression on the levels of adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1) and ATP-binding cassette transporter G1(ABCG1) in an endothelial cell line(bEnd.3).Methods:The StAR gene was induced in bEnd.3 cells with adenovirus infection.The infection efficiency was detected by fluorescence activated cell sorter(FACS) and fluorescence microscopy.The expressions of StAR gene and protein levels were detected by real-time polymerase chain reaction(PCR) and Western blot.The gene and protein levels of ABCA1 and ABCG1 were detected by real-time PCR and Western blot after StAR overexpression.Results:The result shows that StAR was successfully overexpressed in bEnd.3 cells by adenovirus infection.The mRNA and protein expressions of ABCA1 and ABCG1 were greatly increased by StAR overexpression in bEnd.3 cells.Conclusion:Overexpression of StAR increases ABCA1 and ABCG1 expressions in endothelial cells.
文摘The sympathetic nervous system plays a cardinal role in regulating cardiac function through releasing the neurotransmitter norepinephrine (NE). In comparison with central nervous system, the molecular mechanism of NE uptake in myocardium is not clear. In present study, we proved that in rat the CNS type of NE transporter (NET) was also expressed in middle cervical-stellate ganglion complex (MC-SG complex) which is considered to control the activity of heart, but not expressed in myocardium. The results also showed that NET expression level in right ganglion was significantly higher than in the left, rendering the greater capacity of NE uptake in right ventricle, a fact which may contribute to the maintenance of right ventricular function under pathologic state.
基金foundations from Chinese Academy of Sciences and Special Funds for Major State Basic reseaxch of China (G1999053903).
文摘GABA transporter 1(GAT1) takes important roles in multiple physiological processes through the uptake and release of GABA, but the regulation of GAT1 gene expression in different tissues is rarely known. To address the question, first, 5’ Rapid amplification of cDNA end (RACE) was used to determine GAT1 transcriptional starting sites in neonatal mouse cerebral cortex and intestine, adult mouse brain and adult rat testis. The products of 5’RACE were confirmed by DNA sequencing. We found that the transcript of GAT1 in neonatal mouse cerebral cortex and adult mouse brain starts at the same site (inside of exon 1), while in mouse intestine, GAT1 starts transcription in intron 1, and in rat testis, the transcript of GAT1 has an additional untranslation exon to the 5’ direction.
基金Supported by Key Clinical Program of Ministry of Ministry of Health(No.37091)"211 Project"of SUMS sponsored by Ministry of Health and Guangdong Provincial Natural Science Foundation,No.990064
文摘AIM: To study the effect of copper transporting P-type ATPase in copper metabolism of hepatocyte and pathogenesis of Wilson disease (WD). METHODS: WD copper transporting properties in some organelles of the cultured hepatocytes were studied from WD patients and normal controls.These cultured hepatocytes were incubated in the media of copper 15 mg x L(-1) only, copper 15 mg x L(-1) with vincristine (agonist of P-type ATPase) 0.5mg x L(-1), or copper 15 mg x L(-1) with vanadate (antagonist of P-type ATPase) 18.39 mg x L(-1) separately. Microsome (endoplasmic reticulum and Golgi apparatus), lysosome, mitochondria, and cytosol were isolated by differential centrifugation. Copper contents in these organelles were measured with atomic absorption spectrophotometer, and the influence in copper transportion of these organelles by vanadate and vincristine were comparatively analyzed between WD patients and controls. WD copper transporting P-type ATPase was detected by SDS-PAGE in conjunction with Western blot in liver samples of WD patients and controls. RESULTS: The specific WD proteins (M(r)155,000 lanes) were expressed in human hepatocytes, including the control and WD patients. After incubation with medium containing copper for 2 h or 24 h, the microsome copper concentration in WD patients was obviously lower than that of controls, and the addition of vanadate or vincristine would change the copper transporting of microsomes obviously. When incubated with vincristine, levels of copper in microsome were significantly increased, while incubated with vanadate, the copper concentrations in microsome were obviously decreased. The results indicated that there were WD proteins, the copper transportion P-type ATPase in the microsome of hepatocytes. WD patients possessed abnormal copper transporting function of WD protein in the microsome, and the agonist might correct the defect of copper transportion by promoting the activity of copper transportion P-type ATPase. CONCLUSION: Copper transportion P-type ATPase plays an important role in hepatocytic copper metabolism. Dysfunction of hepatocytic WD protein copper transportion might be one of the most important factors for WD.
基金supported by"H+Die Spitaler der Schweiz" the Swiss Agency for Development and Cooperation(DEZA)by the University Hospital Zurich/Switzerland
文摘MOLECULAR PHYSIOLLGY OF HEPATOCELLULAR TRANSPORT PROTEINS Basolaferal transport systems Na+-dependent bile salt uptake Uptake of bile salts into the liver was first isolated perfused rat liver[1],isolated hepatocyte cultures and basolateral plasma membrane vesicles [2,4].
基金Supported by Graduate Science and Technology Innovation Project of Inner Mongolia Autonomous Region(S2016013604)National Natural Science Foundation of China(31260336)
文摘HKT transport protein is an ion transporter thai exists on plasmalemma and a ubiquitous transmembrane protein responsible for Na ＋ transport and K＋ - Na ＋ symport. HKT transport protein is regulated by the expression of ItKT family genes. The overexpression of HKT family genes can improve activity of Na＋ transport and K＋ - Na＋ s.vmport proteins in plants, lead to Na ＋ recycle, reduce Na ＋ concentration in vivo, maintain K ＋/Na＋ ratio, and ensure normal physiological functions of eells, thereby improving salt toleranee of plants. This paper introduced the discovery and claning of HKT family genes, revealed interactions between HKT family genes and SOS, NHX genes, and summarized the relationship between the structure, function of HKT protein and salt tolerance of plants to clarify the function and mechanism of action of HKT transport protein, aiming at laying the foundation for genetic engineering of plants for salt tolerauee and providing basis for breeding haloduric transgenie plant.
基金Supported by the National Natural Science Foundation of China(11304123)the Scientific Research Foundation of Jianghan University(2013016)
文摘In order to illustrate the ion transport mechanism of chloride channel（Cl C） protein,a type of Cl C protein,Cl C-ec1,from Escherichia coli is embedded into an explicit membranewater system by using software VMD. Then a parallel molecular dynamics（MD） simulation is employed to equilibrate the Cl C-ec1 structure for 27.5 ns at temperature 298.15 K. Based on this equilibrated structure,we compute the channel geometric size variation and electrostatic potential distribution along the channel. Meanwhile,Cl^- transport process is simulated using oriented random walk method under variable external potential. The simulation result shows that Cl^- transport velocity depends on the width of the narrowest channel region. Mutation of negative glutamate E148 can produce positive potential,which is beneficial for Cl^- transport,around external Cl^- binding region in the channel. The simulated current-voltage curves about Cl^- transporting in Cl C-ec1 protein agree with Jayaram＇s experimental results.
基金supported by National Natural Science Foundation of China(32072212)Multi-Year Research Grant of University of Macao(MYRG2018-00169-ICMS)+5 种基金Science and Technology Development Fund of Macao(FDCT)(0098/2020/A)MICINN supporting the Ramón y Cajal grant for M.A.Prieto(RYC-201722891)Jianbo Xiao(RYC2020-030365-I)Xunta de Galicia supporting the Axudas Conecta Peme,the IN852A 2018/58 Neuro Food Project,the program EXCELENCIA-ED431F 2020/12the pre-doctoral grants of P.García-Oliveira(ED481A-2019/295)to Ibero-American Program on Science and Technology(CYTED-AQUA-CIBUS,P317RT0003).
文摘Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.
文摘BACKGROUND Fanconi–Bickel syndrome(FBS)is a rare autosomal recessive disorder caused by mutation of the SLC2A2 gene,which encodes glucose transporter protein 2(GLUT2).CASE SUMMARY We report a 7-mo-old girl with cytomegalovirus infection presenting hepatomegaly,jaundice,liver transaminase elevation,fasting hypoglycemia,hyperglycosuria,proteinuria,hypophosphatemia,rickets,and growth retardation.After prescription of ganciclovir,the levels of bilirubin and alanine aminotransferase decreased to normal,while she still had aggravating hepatomegaly and severe hyperglycosuria.Then,whole exome sequencing was conducted and revealed a homozygous c.416delC mutation in exon 4 of SLC2A2 inherited from her parents,which was predicted to change alanine 139 to valine(p.A139Vfs*3),indicating a diagnosis of FBS.During the follow-up,the entire laboratory test returned to normal with extra supplement of vitamin D and corn starch.Her weight increased to normal range at 3 years old without hepatomegaly.However,she still had short stature.Although there was heterogeneity between phenotype and genotype,Chinese children had typical clinical manifestations.No hot spot mutation or association between severity and mutations was found,but nonsense and missense mutations were more common.Data of long-term follow-up were rare,leading to insufficient assessment of the prognosis in Chinese children.CONCLUSION FBS is a rare genetic metabolic disease causing impaired glucose liver homeostasis and proximal renal tubular dysfunction.Results of urine and blood testing suggesting abnormal glucose metabolism could be the clues for FBS in neonates and infants.Genetic sequencing is indispensable for diagnosis.Since the diversity of disease severity,early identification and long-term follow-up could help improve patients’quality of life and decrease mortality.
基金Supported by Guangdong Natural Science Foundation(The effects of "Treatment from Gan"on Regulation of A-type Potassium Channels by KChIP/Kv4 in the pathomechanism of Refractory Epilepsy,No.2014A030310052)National Natural Science Foundation of China(Study on Regulation of A-type Potassium Channels by KChIP/Kv4 in the Pathomechanism of Refractory Epilepsy and the Effects of "Treatment from Gan",No.81503564)
文摘OBJECTIVE: To investigate the antiepileptic effects of Chaihushugan decoction(CHSGD) in rats with pentylenetetrazole(PTZ)-induced seizures and to discuss the impact of CHSGD on glutamate metabolism, a hypothesized underlying mechanism of seizure reduction.METHODS: Fifty Wistar rats were divided randomly into either control(n = 10) or experimental(n = 40)groups. Rats in the control group were administered physiological saline intraperitoneally. A subconvulsive dose of PTZ(35 mg/kg) was administered intraperitoneally to rats in the experimental group to induce seizures. The fully PTZ-kindled rats were then randomly divided into five subgroups(n = 8 each) based on the following treatment categories: physiological saline, VPA(200 mg/kg), CHSGD(2.5 g/kg), CHSGD(5 g/kg), or CHSGD(10 g/kg),administered orally once per day, respectively. On day 28 following initiation of drug treatment, seizures were monitored. The rats were then sacrificed, and hippocampal dissections were performed for subsequent studies.RESULTS: CHSGD significantly prolonged the latency of myoclonic, clonic, and tonic seizures, while decreasing overall seizure rates in the kindled rats.The measured concentrations of 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose(2-NBDG) and glutamate were significantly lower in the hippocampi of kindled rats in groups treated with CHSGD compared with those treated with PTZ alone. In addition, CHSGD was found to up-regulate both the expression of glutamate transporter-1(GLT-1) protein and the activity of glutamine synthetase(GS) in the hippocampi of kindled rats.CONCLUSION: These results suggest that CHSGD has antiepileptic effects on PTZ-induced seizures.The results further suggest an increase in glutamate metabolism at the synaptic cleft is a putative underlying mechanism of seizure reduction.
基金the Special Research Fund(BOF)of Ghent University(Belgium)for the financial support of Abdol ah Akbarian(grant number 01SF2711)
文摘Heat as a stressor of poultry has been studied extensively for many decades; it affects poultry production on a worldwide basis and has significant impact on well-being and production. More recently, the involvement of heat stress in inducing oxidative stress has received much interest. Oxidative stress is defined as the presence of reactive species in excess of the available antioxidant capacity of animal cells. Reactive species can modify several biologically cellular macromolecules and can interfere with cell signaling pathways. Furthermore, during the last decade, there has been an ever-increasing interest in the use of a wide array of natural feed-delivered phytochemicals that have potential antioxidant properties for poultry. In light of this, the current review aims to（1） summarize the mechanisms through which heat stress triggers excessive superoxide radical production in the mitochondrion and progresses into oxidative stress,（2） illustrate that this pathophysiology is dependent on the intensity and duration of heat stress,（3） present different nutritional strategies for mitigation of mitochondrial dysfunction, with particular focus on antioxidant phytochemicals.Oxidative stress that occurs with heat exposure can be manifest in all parts of the body; however, mitochondrial dysfunction underlies oxidative stress. In the initial phase of acute heat stress, mitochondrial substrate oxidation and electron transport chain activity are increased resulting in excessive superoxide production. During the later stage of acute heat stress, down-regulation of avian uncoupling protein worsens the oxidative stress situation causing mitochondrial dysfunction and tissue damage. Typically, antioxidant enzyme activities are upregulated. Chronic heat stress, however, leads to downsizing of mitochondrial metabolic oxidative capacity, up-regulation of avian uncoupling protein, a clear alteration in the pattern of antioxidant enzyme activities, and depletion of antioxidant reserves.Some phytochemicals, such as various types of flavonoids and related compounds, were shown to be beneficial in chronic heat-stressed poultry, but were less or not effective in non-heat-stressed counterparts. This supports the contention that antioxidant phytochemicals have potential under challenging conditions. Though substantial progress has been made in our understanding of the association between heat stress and oxidative stress, the means by which phytochemicals can alleviate oxidative stress have been sparsely explored.
基金Supported by National High Technology Research and Development Program of China(2006AAl0ZlE8)Special Fund for Developing Super Rice from Ministry of Agriculture(200906)Project of Basic Research for National Non-profit Institute of China(2009RG005)
文摘Rice is moderately sensitive to salinity,and the response to salt stress is a complex process,including the perception and transduction of salt stress signal,the activation of specific transcriptional factors and the expression of downstream stress-responsive genes.The functions of Na+ transporters which are involved in the maintenance and reconstruction of the ion homeostasis,transcriptional regulators and osmotic regulation genes were reviewed.Salt tolerance of plants are enhanced by Na+ vacuolar compartmentation or efflux or high levels of osmoprotectants accumulation in cytoplasm.
基金supported by the National Natural Science Foundation of China (82100863)Hebei Natural Science Foundation (H2020206643 and H2020206105)+3 种基金Funding project for introducing overseas students of Hebei Province (C20210346)Medical Science Research Project of Hebei Province (20211628)Hebei Province Government-funded Excellent Talents Project in Clinical Medicine (ZF2023029)Spark Scientific Research Project of the First Hospital of Hebei Medical University (XH202004).
文摘Excessive secretion of human islet amyloid polypeptide(hIAPP)is an important pathological basis of diabetic encephalopathy(DE).In this study,we aimed to investigate the potential implications of hIAPP in DE pathogenesis.Brain magnetic resonance imaging and cognitive scales were applied to evaluate white matter damage and cognitive function.We found that the concentration of serum hIAPP was positively correlated with white matter damage but negatively correlated with cognitive scores in patients with type 2 diabetes mellitus.In vitro assays revealed that oligodendrocytes,compared with neurons,were more prone to acidosis under exogenous hIAPP stimulation.Moreover,western blotting and co-immunoprecipitation indicated that hIAPP interfered with the binding process of monocarboxylate transporter(MCT)1 to its accessory protein CD147 but had no effect on the binding of MCT2 to its accessory protein gp70.Proteomic differential analysis of proteins co-immunoprecipitated with CD147 in oligodendrocytes revealed Yeast Rab GTPase-Interacting protein 2(YIPF2,which modulates the transfer of CD147 to the cell membrane)as a significant target.Furthermore,YIPF2 inhibition significantly improved hIAPP-induced acidosis in oligodendrocytes and alleviated cognitive dysfunction in DE model mice.These findings suggest that increased CD147 translocation by inhibition of YIPF2 optimizes MCT1 and CD147 binding,potentially ameliorating hIAPP-induced acidosis and the consequent DE-related demyelination.
基金supported by the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(81930051 and 22105127)+1 种基金the Shanghai Municipal Health Commission(2022XD055 and 202140128)the Shanghai Jiao Tong University School of Medicine PhD Cultivation Fund for Science and Innovation(24KCPYYB005).
文摘Excessive uptake of purine and glucose can lead to hyperglycemia and hyperuricemia,mediated by specific intestinal transport proteins.Currently,there is a deficiency in targeted regulation of these proteins.In this study,we introduce an oral approach for targeted modulation using electrospun core–shell short-fibers that settle on the intestinal mucosa.These fibers,designed for the controlled in situ release of phlorizin—a multi-transporter inhibitor—are crafted through a refined electrospinning-homogenizing process using polylactic acid and gelatin.Phlorizin is conjugated via a phenyl borate ester bond.Furthermore,a calcium alginate shell ensures intestinal disintegration triggered by pH changes.These fibers adhere to the mucosa due to their unique structure,and phlorizin is released in situ post-ingestion through glucose-sensitive cleavage of the phenyl borate ester bond,enabling dual-target inhibition of intestinal transporter proteins.Both in vitro and in vivo studies confirm that the short-fibers possess intestine-settling and glucose-responsive properties,facilitating precise control over transport proteins.Using models of hyperuricemia and diabetes in mice,treatment with short-fibers results in reduc-tions of 49.6%in blood uric acid and 17.8%in glucose levels,respectively.Additionally,16S rRNA sequencing indicates an improved intestinal flora composition.In conclusion,we have developed an innovative oral strategy for the prevention of hyperglycemia and hyperuricemia.
基金ThisworkwassupportedbytheKeyProjectofClinicalScienceoftheHealthyMinistryofChina (No 970 3 0 2 2 5 )
文摘OBJECTIVE: To investigate the distribution, changes and a possible role for retinal dopamine transporter (DAT) in experimental myopia in chickens. METHODS: Two-day-old chickens were divided into four groups. Chicken eyes were fitted with lenses of -10D,-20D and translucent goggles unilaterally. Normal eyes were used as controls. After 3 wk, all chickens were given an intramuscular injection of (125)I-beta-CIT 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane and sacrificed two hours post injection. Retinal pigment epithelium (RPE) and the neural retina were obtained together or RPE was dissected out from the neural retina. Radioactive DAT from each specimen was assayed by gamma-counter. RESULTS: Retinal DAT was detected in RPE specimens rather than in the neural retina in all eyes. Radioactive DAT in myopic eyes was higher, compared with control eyes. CONCLUSIONS: Retinal DAT is mainly located in the RPE and may be involved in the formation of lens induced myopia (LIM) and form deprivation myopia (FDM). These methods may provide a new approach for further studying the role of the dopamine system in experimental myopia.
基金supported by the National Natural Science Foundation of China(No.81873596)the Key Research and Development Program of Hubei Province,China(No.2022BCA047)the National Key Research and Development Program of China(No.2022YFC2705102 and No.2022YFC2705103).
文摘Nephronophthisis(NPHP)is an autosomal recessive kidney disease and is the most prevalent monogenic cause of end-stage renal disease in childhood.The tetratricopeptide repeat domain 21B(TTC21B)gene encodes the ciliary protein intraflagellar transport protein 139(IFT139)and has been recently implicated in heterogeneous diseases,including nephronophthisis type 12(NPHP12),short-rib thoracic dysplasia 4(SRTD4).
基金supported by grants from the Science and Technology Development Plan Project in Jilin Province(No.YD ZJ202301ZYTS515)the National Natural Science Foundation of China(No.82473000).
文摘To the Editor:Exportin-1(XPO1)is the most extensively studied nuclear transport protein and is highly expressed in malignant solid tumors,including small cell lung cancer(SCLC).XPO1 may play a significant role in drug resistance and poor prognosis.Given the development and promising perspective of XPO1 in the oncological field,we summarized the current understanding of XPO1 in malignant solid tumors,particularly SCLC.In addition,we discussed the therapeutic potential of XPO1 inhibitors,combination strategies,and future challenges.
