Asian cultivated rice shows allelic variation in sodium transporter,OsHKT1;5,correlating with shoot sodium exclusion(salinity tolerance).These changes map to intra/extracellularly-oriented loops that occur between fou...Asian cultivated rice shows allelic variation in sodium transporter,OsHKT1;5,correlating with shoot sodium exclusion(salinity tolerance).These changes map to intra/extracellularly-oriented loops that occur between four transmembrane-P loop-transmembrane(MPM)motifs in OsHKT1;5.HKT1;5 sequences from more recently evolved Oryza species(O.sativa/O.officinalis complex species)contain two expansions that involve two intracellularly oriented loops/helical regions between MPM domains,potentially governing transport characteristics,while more ancestral HKT1;5 sequences have shorter intracellular loops.We compared homology models for homoeologous OcHKT 1;5-K and OcHKT1;5-L from halophytic O.coarctata to identify complementary amino acid residues in OcHKT1;5-L that potentially enhance affinity for Na+.Using haplotyping,we showed that Asian cultivated rice accessions only have a fraction of HKT1;5 diversity available in progenitor wild rice species(O.nivara and O.rufipogon).Progenitor HKT1;5 haplotypes can thus be used as novel potential donors for enhancing cultivated rice salinity tolerance.Within Asian rice accessions,10 non-synonymous HKT1;5 haplotypic groups occur.More HKT1;5 haplotypic diversities occur in cultivated indica gene pool compared to japonica.Predominant Haplotypes 2 and 10 occur in mutually exclusive japonica and indica groups,corresponding to haplotypes in O.sativa salt-sensitive and salt-tolerant landraces,respectively.This distinct haplotype partitioning may have originated in separate ancestral gene pools of indica and japonica,or from different haplotypes selected during domestication.Predominance of specific HKT1;5 haplotypes within the 3000 rice dataset may relate to eco-physiological fitness in specific geo-climatic and/or edaphic contexts.展开更多
AIM: To quantify changes in urinary excretion of aquaporin2 water channels (u-AQP2), the sodium-potassium-chloride co-transporter (u-NKCC2) and the epithelial sodium channels (u-ENaC) during treatment with bend...AIM: To quantify changes in urinary excretion of aquaporin2 water channels (u-AQP2), the sodium-potassium-chloride co-transporter (u-NKCC2) and the epithelial sodium channels (u-ENaC) during treatment with bendrofumethiazide (BFTZ), amiloride and placebo.METHODS: In a randomized, double-blinded, placebo-controlled, 3-way crossover study we examined 23 healthy subjects on a standardized diet and fuid intake. The subjects were treated with amiloride 5 mg, BFTZ 1.25 mg or placebo twice a day for 4.5 d before each examination day. On the examination day, glomerular filtration rate was measured by the constant infusion clearance technique with 51Cr-EDTA as reference substance. To estimate the changes in water transport via AQP2 and sodium transport via NKCC2 and ENaC, u-NKCC2, the gamma fraction of ENaC (u-ENaCγ), and u-AQP2 were measured at baseline and after infusion with 3% hypertonic saline. U-NKCC2, u-ENaCγ, u-AQP2 and plasma concentrations of vasopressin (p-AVP), renin (PRC), angiotensin Ⅱ (p-ANG Ⅱ) and aldosterone (p-Aldo) were measured, by radioimmunoassay. Central blood pressure was estimated by applanation tonometry and body fuid volumes were estimated by bio-impedance spectroscopy. General linear model with repeated measures or related samples Friedman’s two-way analysis was used to compare differences. Post hoc Bonferroni correction was used for multiple comparisons of post infusion periods to baseline within each treatment group.RESULTS: At baseline there were no differences in u-NKCC2, u-ENaCγ and u-AQP2. PRC, p-Ang Ⅱ and p-Aldo were increased during active treatments (P 〈 0.001). After hypertonic saline, u-NKCC2 increased during amiloride (6% ± 34%; P = 0.081) and increased significantly during placebo (17% ± 24%; P = 0.010). U-AQP2 increased signifcantly during amiloride (31% ± 22%; P 〈 0.001) and placebo (34% ± 27%; P 〈 0.001), while u-NKCC2 and u-AQP2 did not change signifcantly during BFTZ (-7% ± 28%; P = 0.257 and 5% ± 16%; P = 0.261). U- ENaCγ increased in all three groups ( P 〈 0.050). PRC, AngⅡ and p-Aldo decreased to the same extent, while AVP increased, but to a smaller degree during BFTZ ( P = 0.048). cDBP decreased significantly during BFTZ (P 〈 0.001), but not during amiloride or placebo. There were no significant differences in body fuid volumes.CONCLUSION: After hypertonic saline, u-NKCC2 and u-AQP2 increased during amiloride, but not during BFTZ. Lower p-AVP during BFTZ potentially caused less stimulation of NKCC2 and AQP2 and subsequent lower reabsorption of water and sodium.展开更多
Barrett's esophagus (BE) is characterized by intestinal metaplasia with the differentiated epithelium replaced by another type of epithelium morphologically similar to normal intestinal epithelium. The metaplasia ...Barrett's esophagus (BE) is characterized by intestinal metaplasia with the differentiated epithelium replaced by another type of epithelium morphologically similar to normal intestinal epithelium. The metaplasia is preceded by bile and acid reflux into the esophagus. BE is a premalignant condition associated with increased risk of esophageal cancer, especially esophageal adenocarcinoma. The Caudal-related homeodomain transcription factors Caudal-related homeodomain transcription factor CDX1 and CDX2 are expressed exclusively in the small and large intestine, playing important roles in proliferation and differentiation of intestinal epithelial cells. Ectopic expression of CDX1 and CDX2 occurs in BE. The apical sodium-dependent bile acid transporter (ASBT) is expressed primarily in terminal ileum where it is a key factor for intestinal reabsorption of bile salts. In addition to upregulation of CDX1 and CDX2, ASBT expression is up-regulated in BE. Furthermore, both CDX1/CDX2 and ASBT expressions are down-regulated in high-grade esophageal dysplasia. The alteration of the above-mentioned factors calls for attention: what is the relationship between CDXs and ASBT aberrant expression in BE? In this commentary, we discuss this issue on basis of the recent study done by Ma et al .展开更多
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. NAFLD is considerably more frequent in patients with type 2 diabetes mellitus (T2DM) than in the general populat...Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. NAFLD is considerably more frequent in patients with type 2 diabetes mellitus (T2DM) than in the general population and is also more severe histologically in this group. Sodium-glucose co-transporter-2 (SGLT2) inhibitors, the newest class of antidiabetic agents, appear to represent a promising option for the management of NAFLD in patients with T2DM. In a number of studies, treatment with SGLT2 inhibitors resulted in a reduction in hepatic steatosis and in transaminase levels. However, existing studies are small, their follow-up period was short and none evaluated the effects of SGLT2 inhibitors on liver histology. Accordingly, larger studies are needed to verify these preliminary results and define the role of SGLT2 inhibitors in the treatment of NAFLD in patients with T2DM.展开更多
Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chlorid...Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the speciifc sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression in-creased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These ifndings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassi-um-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassi-um-chloride co-transporter 1.展开更多
Objective To clarify the potential mechanism of Banxia Xiexin Decoction(BXD)on colorectal cancer(CRC)from the perspective of metabolomics.Methods Forty male C57BL/6 mice were randomly divided into normal control(NC),a...Objective To clarify the potential mechanism of Banxia Xiexin Decoction(BXD)on colorectal cancer(CRC)from the perspective of metabolomics.Methods Forty male C57BL/6 mice were randomly divided into normal control(NC),azoxymethane/dextran sulfate sodium(AOM/DSS)model,low-dose BXD(L-BXD),high-dose BXD(H-BXD)and mesalamine(MS)groups according to a random number table,8 mice in each group.Colorectal cancer model was induced by AOM/DSS.BXD was administered daily at doses of 3.915(L-BXD)and 15.66 g/kg(H-BXD)by gavage for consecutive 21 days,and 100 mg/kg MS was used as positive control.Following the entire modeling cycle,colon length of mice was measured and quantity of colorectal tumors were counted.The spleen and thymus index were determined by calculating the spleen/thymus weight to body weight.Inflammatory cytokine and changes of serum metabolites were analyzed by enzyme-linked immunosorbent assay kits and ultra performance liquid chromatography-quadrupole/time-of-flight mass spectrometry(UPLC-Q/TOF-MS),respectively.Results Notably,BXD supplementation protected against weight loss,mitigated tumor formation,and diminished histologic damage in mice treated with AOM/DSS(P<0.05 or P<0.01).Moreover,BXD suppressed expression of serum inflammatory enzymes,and improved the spleen and thymus index(P<0.05).Compared with the normal group,102 kinds of differential metabolites were screened in the AOM/DSS group,including 48 potential biomarkers,involving 18 main metabolic pathways.Totally 18 potential biomarkers related to CRC were identified,and the anti-CRC mechanism of BXD was closely related to D-glutamine and D-glutamate metabolism,phenylalanine,tyrosine and tryptophan biosynthesis,arginine biosynthesis,nitrogen metabolism and so on.Conclusion BXD exerts partial protective effects on AOM/DSS-induced CRC by reducing inflammation,protecting organism immunity ability,and regulating amino acid metabolism.展开更多
Obstructive jaundice occurs in patients suffering from cholelithiasis and from neoplasms affecting the pancreas and the common bile duct.The absorption,distribution and elimination of drugs are impaired during this pa...Obstructive jaundice occurs in patients suffering from cholelithiasis and from neoplasms affecting the pancreas and the common bile duct.The absorption,distribution and elimination of drugs are impaired during this pathology.Prolonged cholestasis may alter both liver and kidney function.Lactam antibiotics,diuretics,non-steroidal anti-inflammatory drugs,several antiviral drugs as well as endogenous compounds are classified as organic anions.The hepatic and renal organic anion transport pathways play a key role in the pharmacokinetics of these compounds.It has been demonstrated that acute extrahepatic cholestasis is associated with increased renal elimination of organic anions.The present work describes the molecular mechanisms involved in the regulation of the expression and function of the renal and hepatic organic anion transporters in extrahepatic cholestasis,such as multidrug resistanceassociated protein 2,organic anion transporting polypeptide 1,organic anion transporter 3,bilitranslocase,bromosulfophthalein/bilirubin binding protein,organic anion transporter 1 and sodium dependent bile salt transporter.The modulation in the expression of renal organic anion transporters constitutes a compensatory mechanism to overcome the hepatic dysfunction in the elimination of organic anions.展开更多
AIM: To study the effect of glucose on sodium butyrate- induced proliferation inhibition and apoptosis in HT-29 cell line, and explored its possible mechanisms. METHODS: HT-29 cells were grown in RPMI-1640 medium su...AIM: To study the effect of glucose on sodium butyrate- induced proliferation inhibition and apoptosis in HT-29 cell line, and explored its possible mechanisms. METHODS: HT-29 cells were grown in RPMI-1640 medium supplemented with 10% fetal calf serum, and were allowed to adhere for 24 h, and then replaced with experimental medium. Cell survival rates were detected by MTr assay. Apoptosis was detected by TUNEL assay. Glucose transport protein 1 (GLUT1) and monocarboxylate transporter 1 (MCT1) mRNA expression was detected by RT-PCR. RESULTS: Low concentration of glucose induced apoptosis and regulated proliferation in HT-29 cell line, and glucose can obviously inhibit the effect of proliferation inhibition and apoptosis induced by sodium butyrate. Glucose also down-regulated the expression of MCT1mRNA (0.28 ± 0.07 vs 0.19± 0.10, P 〈 0.05), and decreased the expression of GLUTlmRNA slightly (0.18 ± 0.04 vs 0.13 ± 0.03, P 〈 0.05). CONCLUSION: Glucose can regulate the effect of proliferation inhibition and apoptosis induced by sodium butyrate and this influence may be associated with the intracellular concentration of glucose and sodium butyrate.展开更多
The action of micromolar concentrations of Deltamethrin on sodium net transport through the in vivo skin of the South American toad Bufo arenarum was studied. The effect of pure ethanolic insecticide solutions and com...The action of micromolar concentrations of Deltamethrin on sodium net transport through the in vivo skin of the South American toad Bufo arenarum was studied. The effect of pure ethanolic insecticide solutions and commercial formulations when applied on the mucosal surface was assayed. Deltamethrin provoked a concentration-independent inhibition; the highest inhibition was found at the lowest concentrations. At highest concentrations of the insecticide the J Na was not altered展开更多
This study examined the effects of various levels of dietary nonphytate phosphorus on laying performance and the expression patterns of phosphorus metabolism related genes in Dwarf pink-shell Jaying hens. A total of 4...This study examined the effects of various levels of dietary nonphytate phosphorus on laying performance and the expression patterns of phosphorus metabolism related genes in Dwarf pink-shell Jaying hens. A total of 405 28-week-old Dwarf pink-shell laying hens were fed the same corn-soybean basal meals but containing 0.20%, 0.25%, 0.30%, 0.35% or 0.40% nonphytate phosphorus. The results showed that feed intake, egg production, and average egg weights were quadratically correlated with dietary nonphytate phosphorus content (P 〈 0.05), and the highest egg production, feed intake and average egg weights were achieved when dietary nonphytate phosphorus was at 0.3% (P 〈 0.05). mRNA expression of intestinal sodium phosphorus co-transporter linearly decreased when dietary nonphytate phosphorus increased, mRNA and protein expression of intestinal calbindin and vitamin D receptor correlated quadratically with dietary nonphytate phosphorus, and the highest expression was found when dietary available phosphorus was at 0.2,5% to 0.3%. In conclusion, the ideal phosphorus requirement for Dwarf pink-shell layer hens is estimated to be 0.3% in a corn-soybean diet. With this level of phosphorus supplementation, calbindin and vitamin D receptor reached their highest expression.展开更多
Objective: To compare renal sodium transport, using fractional excretions of lithium(FEii)as a marker of proximal tubule sodium reabsorption, between hypertensive and non-hypertensive ouabaintreated rats and further t...Objective: To compare renal sodium transport, using fractional excretions of lithium(FEii)as a marker of proximal tubule sodium reabsorption, between hypertensive and non-hypertensive ouabaintreated rats and further to elucidate the role of ouabain in pathogenesis of hypertension. Methods:Thirty male Sprague-Dawley rats weighting 180-200 g were randomly divided into normal control group and ouabain treated group. Rats were infused with 1 ml/kg · d normal saline or 27.8 μg/kg · d ouabain intraperitoneally once a day respectively. Systolic blood pressure (SBP), heart rate and body weight were recorded weekly. Rats were sacrificed 6 weeks after treatment. Blood and 24-hour urine sample were collected to measure the serum and urinary concentration of sodium, trace lithium and creatinine. Endogenous creatinine clearance rate (Ccr), fractional excretions of sodium (FENa), fractional excretions of lithium (FELi) and fractional reabsorption of sodium in the postproximal tubules (FDRNa) were calculated.Ouabain levels of plasma and renal tissue, plasma renin activity, angiotensin Ⅱ and aldosterone concentration were determined. Results: 65% of the ouabain-treated rats achieved significantly higher SBP after 4weeks, compared with that of the saline control groups or self baseline (P<0. 01). But in the other 35%of the ouabain-treated rats, their SBP was similar with control group during the experiment (P>0. 05).The body weight, heart rate and food intake between the 3 groups were no significant differences (P>0.05). FELi and FDRNa were significantly lower in ouabain-hypertensive group compared with ouabain-nonhypertensive group and control group(P<0.01 and P<0.05). The FELi and FDRNa of ouabain-nonhypertensive groups were similar with control group(P>0.05). Ccr and FENa were comparable between the 3 groups (P>0. 05). Plasma and renal tissue ouabain levels, plasma renin activity, angiotensin Ⅱ and aldosterone contents in ouabain-hypertensive rats were comparable with ouabain-nonhypertensive rats. Conclusion: Increase of proximal tubule sodium reabsorption play an important role in the pathogenesis of ouabain-hypertensive rats. The change of renal sodium transport may result from regulation to renal Na+ ,K+-ATPase by ouabain.展开更多
The transport of sodium ions by erythrocytes and the plasma level of endogenous digitalis-like compound (EDLC) were assessed in 59 patients with essential hypertension before and after theadminstration of nifedipine a...The transport of sodium ions by erythrocytes and the plasma level of endogenous digitalis-like compound (EDLC) were assessed in 59 patients with essential hypertension before and after theadminstration of nifedipine and prazosin. 20 normal subjects were studied similarly and served as con-trol. It was found that (1) EH patients had a pronounced defect of both the active and passive trans-port of sodium ions by the erythrocytes; (2) a higher plasma level of EDLC was detected in EH pa-tients as compared with that of the control, but the changes of EDLC and soudium pump were notparallel; (3) after the administration of nifedipine and prazosin, the function of sodium pump wasmarkedly improved and the plasma level of EDLC decreased. In addition, the relationship betweenthe transport of sodium ions by erythrocytes and the pathogenesis of EH, and the effects of anti-hypertensive agents were discussed.展开更多
基金supported by the Department of Biotechnology,Government of India(Grant No.BT/PR11396/NDB/52/118/2008)and Council for Scientific and Industrial Research,India for Senior Research Fellowship(Grant No.09/656(0018)/2016-EMR-1)to Shalini PULIPATIfunding and support provided by JC Bose Fellowship(Grant No.SB/S2/JC-071/2015)from Science and Engineering Research Board,India and Bioinformatics Centre Grant funded by Department of Biotechnology,India(Grant No.BT/PR40187/BTIS/137/9/2021)。
文摘Asian cultivated rice shows allelic variation in sodium transporter,OsHKT1;5,correlating with shoot sodium exclusion(salinity tolerance).These changes map to intra/extracellularly-oriented loops that occur between four transmembrane-P loop-transmembrane(MPM)motifs in OsHKT1;5.HKT1;5 sequences from more recently evolved Oryza species(O.sativa/O.officinalis complex species)contain two expansions that involve two intracellularly oriented loops/helical regions between MPM domains,potentially governing transport characteristics,while more ancestral HKT1;5 sequences have shorter intracellular loops.We compared homology models for homoeologous OcHKT 1;5-K and OcHKT1;5-L from halophytic O.coarctata to identify complementary amino acid residues in OcHKT1;5-L that potentially enhance affinity for Na+.Using haplotyping,we showed that Asian cultivated rice accessions only have a fraction of HKT1;5 diversity available in progenitor wild rice species(O.nivara and O.rufipogon).Progenitor HKT1;5 haplotypes can thus be used as novel potential donors for enhancing cultivated rice salinity tolerance.Within Asian rice accessions,10 non-synonymous HKT1;5 haplotypic groups occur.More HKT1;5 haplotypic diversities occur in cultivated indica gene pool compared to japonica.Predominant Haplotypes 2 and 10 occur in mutually exclusive japonica and indica groups,corresponding to haplotypes in O.sativa salt-sensitive and salt-tolerant landraces,respectively.This distinct haplotype partitioning may have originated in separate ancestral gene pools of indica and japonica,or from different haplotypes selected during domestication.Predominance of specific HKT1;5 haplotypes within the 3000 rice dataset may relate to eco-physiological fitness in specific geo-climatic and/or edaphic contexts.
基金Supported by Grants from The Lundbeck FoundationAase and Ejnar Danielsens Foundation+1 种基金Helen and Ejnar Bjoernows FoundationRegion Midjutlands Research Fund
文摘AIM: To quantify changes in urinary excretion of aquaporin2 water channels (u-AQP2), the sodium-potassium-chloride co-transporter (u-NKCC2) and the epithelial sodium channels (u-ENaC) during treatment with bendrofumethiazide (BFTZ), amiloride and placebo.METHODS: In a randomized, double-blinded, placebo-controlled, 3-way crossover study we examined 23 healthy subjects on a standardized diet and fuid intake. The subjects were treated with amiloride 5 mg, BFTZ 1.25 mg or placebo twice a day for 4.5 d before each examination day. On the examination day, glomerular filtration rate was measured by the constant infusion clearance technique with 51Cr-EDTA as reference substance. To estimate the changes in water transport via AQP2 and sodium transport via NKCC2 and ENaC, u-NKCC2, the gamma fraction of ENaC (u-ENaCγ), and u-AQP2 were measured at baseline and after infusion with 3% hypertonic saline. U-NKCC2, u-ENaCγ, u-AQP2 and plasma concentrations of vasopressin (p-AVP), renin (PRC), angiotensin Ⅱ (p-ANG Ⅱ) and aldosterone (p-Aldo) were measured, by radioimmunoassay. Central blood pressure was estimated by applanation tonometry and body fuid volumes were estimated by bio-impedance spectroscopy. General linear model with repeated measures or related samples Friedman’s two-way analysis was used to compare differences. Post hoc Bonferroni correction was used for multiple comparisons of post infusion periods to baseline within each treatment group.RESULTS: At baseline there were no differences in u-NKCC2, u-ENaCγ and u-AQP2. PRC, p-Ang Ⅱ and p-Aldo were increased during active treatments (P 〈 0.001). After hypertonic saline, u-NKCC2 increased during amiloride (6% ± 34%; P = 0.081) and increased significantly during placebo (17% ± 24%; P = 0.010). U-AQP2 increased signifcantly during amiloride (31% ± 22%; P 〈 0.001) and placebo (34% ± 27%; P 〈 0.001), while u-NKCC2 and u-AQP2 did not change signifcantly during BFTZ (-7% ± 28%; P = 0.257 and 5% ± 16%; P = 0.261). U- ENaCγ increased in all three groups ( P 〈 0.050). PRC, AngⅡ and p-Aldo decreased to the same extent, while AVP increased, but to a smaller degree during BFTZ ( P = 0.048). cDBP decreased significantly during BFTZ (P 〈 0.001), but not during amiloride or placebo. There were no significant differences in body fuid volumes.CONCLUSION: After hypertonic saline, u-NKCC2 and u-AQP2 increased during amiloride, but not during BFTZ. Lower p-AVP during BFTZ potentially caused less stimulation of NKCC2 and AQP2 and subsequent lower reabsorption of water and sodium.
文摘Barrett's esophagus (BE) is characterized by intestinal metaplasia with the differentiated epithelium replaced by another type of epithelium morphologically similar to normal intestinal epithelium. The metaplasia is preceded by bile and acid reflux into the esophagus. BE is a premalignant condition associated with increased risk of esophageal cancer, especially esophageal adenocarcinoma. The Caudal-related homeodomain transcription factors Caudal-related homeodomain transcription factor CDX1 and CDX2 are expressed exclusively in the small and large intestine, playing important roles in proliferation and differentiation of intestinal epithelial cells. Ectopic expression of CDX1 and CDX2 occurs in BE. The apical sodium-dependent bile acid transporter (ASBT) is expressed primarily in terminal ileum where it is a key factor for intestinal reabsorption of bile salts. In addition to upregulation of CDX1 and CDX2, ASBT expression is up-regulated in BE. Furthermore, both CDX1/CDX2 and ASBT expressions are down-regulated in high-grade esophageal dysplasia. The alteration of the above-mentioned factors calls for attention: what is the relationship between CDXs and ASBT aberrant expression in BE? In this commentary, we discuss this issue on basis of the recent study done by Ma et al .
文摘Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. NAFLD is considerably more frequent in patients with type 2 diabetes mellitus (T2DM) than in the general population and is also more severe histologically in this group. Sodium-glucose co-transporter-2 (SGLT2) inhibitors, the newest class of antidiabetic agents, appear to represent a promising option for the management of NAFLD in patients with T2DM. In a number of studies, treatment with SGLT2 inhibitors resulted in a reduction in hepatic steatosis and in transaminase levels. However, existing studies are small, their follow-up period was short and none evaluated the effects of SGLT2 inhibitors on liver histology. Accordingly, larger studies are needed to verify these preliminary results and define the role of SGLT2 inhibitors in the treatment of NAFLD in patients with T2DM.
基金supported by a grant from Guangzhou Medical University,No.2008C24
文摘Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the speciifc sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression in-creased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These ifndings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassi-um-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassi-um-chloride co-transporter 1.
基金Supported by the Natural Science Foundation of Nanjing University of Chinese Medicine(No.XZR2020038)Science and Technology Innovation Project of Suzhou Medical and Health Care(No.SKJY2021136)Fifth Batch of Gusu Health Personnel Training Project in Suzhou(No.GSWS2020085)。
文摘Objective To clarify the potential mechanism of Banxia Xiexin Decoction(BXD)on colorectal cancer(CRC)from the perspective of metabolomics.Methods Forty male C57BL/6 mice were randomly divided into normal control(NC),azoxymethane/dextran sulfate sodium(AOM/DSS)model,low-dose BXD(L-BXD),high-dose BXD(H-BXD)and mesalamine(MS)groups according to a random number table,8 mice in each group.Colorectal cancer model was induced by AOM/DSS.BXD was administered daily at doses of 3.915(L-BXD)and 15.66 g/kg(H-BXD)by gavage for consecutive 21 days,and 100 mg/kg MS was used as positive control.Following the entire modeling cycle,colon length of mice was measured and quantity of colorectal tumors were counted.The spleen and thymus index were determined by calculating the spleen/thymus weight to body weight.Inflammatory cytokine and changes of serum metabolites were analyzed by enzyme-linked immunosorbent assay kits and ultra performance liquid chromatography-quadrupole/time-of-flight mass spectrometry(UPLC-Q/TOF-MS),respectively.Results Notably,BXD supplementation protected against weight loss,mitigated tumor formation,and diminished histologic damage in mice treated with AOM/DSS(P<0.05 or P<0.01).Moreover,BXD suppressed expression of serum inflammatory enzymes,and improved the spleen and thymus index(P<0.05).Compared with the normal group,102 kinds of differential metabolites were screened in the AOM/DSS group,including 48 potential biomarkers,involving 18 main metabolic pathways.Totally 18 potential biomarkers related to CRC were identified,and the anti-CRC mechanism of BXD was closely related to D-glutamine and D-glutamate metabolism,phenylalanine,tyrosine and tryptophan biosynthesis,arginine biosynthesis,nitrogen metabolism and so on.Conclusion BXD exerts partial protective effects on AOM/DSS-induced CRC by reducing inflammation,protecting organism immunity ability,and regulating amino acid metabolism.
基金Supported by Grants from FONCYT(PICT 2007,No.00966, PICT 2010,No.2127)CONICET(PIP 2009-2011,No.1665, PIP2012-2015,No.00014)UNR PID(2008-2011/2012-2015)
文摘Obstructive jaundice occurs in patients suffering from cholelithiasis and from neoplasms affecting the pancreas and the common bile duct.The absorption,distribution and elimination of drugs are impaired during this pathology.Prolonged cholestasis may alter both liver and kidney function.Lactam antibiotics,diuretics,non-steroidal anti-inflammatory drugs,several antiviral drugs as well as endogenous compounds are classified as organic anions.The hepatic and renal organic anion transport pathways play a key role in the pharmacokinetics of these compounds.It has been demonstrated that acute extrahepatic cholestasis is associated with increased renal elimination of organic anions.The present work describes the molecular mechanisms involved in the regulation of the expression and function of the renal and hepatic organic anion transporters in extrahepatic cholestasis,such as multidrug resistanceassociated protein 2,organic anion transporting polypeptide 1,organic anion transporter 3,bilitranslocase,bromosulfophthalein/bilirubin binding protein,organic anion transporter 1 and sodium dependent bile salt transporter.The modulation in the expression of renal organic anion transporters constitutes a compensatory mechanism to overcome the hepatic dysfunction in the elimination of organic anions.
基金Supported by the Key Technologies R&D Program of Hubei Province, No. 2004AA304B08
文摘AIM: To study the effect of glucose on sodium butyrate- induced proliferation inhibition and apoptosis in HT-29 cell line, and explored its possible mechanisms. METHODS: HT-29 cells were grown in RPMI-1640 medium supplemented with 10% fetal calf serum, and were allowed to adhere for 24 h, and then replaced with experimental medium. Cell survival rates were detected by MTr assay. Apoptosis was detected by TUNEL assay. Glucose transport protein 1 (GLUT1) and monocarboxylate transporter 1 (MCT1) mRNA expression was detected by RT-PCR. RESULTS: Low concentration of glucose induced apoptosis and regulated proliferation in HT-29 cell line, and glucose can obviously inhibit the effect of proliferation inhibition and apoptosis induced by sodium butyrate. Glucose also down-regulated the expression of MCT1mRNA (0.28 ± 0.07 vs 0.19± 0.10, P 〈 0.05), and decreased the expression of GLUTlmRNA slightly (0.18 ± 0.04 vs 0.13 ± 0.03, P 〈 0.05). CONCLUSION: Glucose can regulate the effect of proliferation inhibition and apoptosis induced by sodium butyrate and this influence may be associated with the intracellular concentration of glucose and sodium butyrate.
文摘The action of micromolar concentrations of Deltamethrin on sodium net transport through the in vivo skin of the South American toad Bufo arenarum was studied. The effect of pure ethanolic insecticide solutions and commercial formulations when applied on the mucosal surface was assayed. Deltamethrin provoked a concentration-independent inhibition; the highest inhibition was found at the lowest concentrations. At highest concentrations of the insecticide the J Na was not altered
基金financially supported by the Chinese Universities Scientific Fund
文摘This study examined the effects of various levels of dietary nonphytate phosphorus on laying performance and the expression patterns of phosphorus metabolism related genes in Dwarf pink-shell Jaying hens. A total of 405 28-week-old Dwarf pink-shell laying hens were fed the same corn-soybean basal meals but containing 0.20%, 0.25%, 0.30%, 0.35% or 0.40% nonphytate phosphorus. The results showed that feed intake, egg production, and average egg weights were quadratically correlated with dietary nonphytate phosphorus content (P 〈 0.05), and the highest egg production, feed intake and average egg weights were achieved when dietary nonphytate phosphorus was at 0.3% (P 〈 0.05). mRNA expression of intestinal sodium phosphorus co-transporter linearly decreased when dietary nonphytate phosphorus increased, mRNA and protein expression of intestinal calbindin and vitamin D receptor correlated quadratically with dietary nonphytate phosphorus, and the highest expression was found when dietary available phosphorus was at 0.2,5% to 0.3%. In conclusion, the ideal phosphorus requirement for Dwarf pink-shell layer hens is estimated to be 0.3% in a corn-soybean diet. With this level of phosphorus supplementation, calbindin and vitamin D receptor reached their highest expression.
基金Supported by the Natural Sciences Research Foundation of Shan'xi Province (2004C213)
文摘Objective: To compare renal sodium transport, using fractional excretions of lithium(FEii)as a marker of proximal tubule sodium reabsorption, between hypertensive and non-hypertensive ouabaintreated rats and further to elucidate the role of ouabain in pathogenesis of hypertension. Methods:Thirty male Sprague-Dawley rats weighting 180-200 g were randomly divided into normal control group and ouabain treated group. Rats were infused with 1 ml/kg · d normal saline or 27.8 μg/kg · d ouabain intraperitoneally once a day respectively. Systolic blood pressure (SBP), heart rate and body weight were recorded weekly. Rats were sacrificed 6 weeks after treatment. Blood and 24-hour urine sample were collected to measure the serum and urinary concentration of sodium, trace lithium and creatinine. Endogenous creatinine clearance rate (Ccr), fractional excretions of sodium (FENa), fractional excretions of lithium (FELi) and fractional reabsorption of sodium in the postproximal tubules (FDRNa) were calculated.Ouabain levels of plasma and renal tissue, plasma renin activity, angiotensin Ⅱ and aldosterone concentration were determined. Results: 65% of the ouabain-treated rats achieved significantly higher SBP after 4weeks, compared with that of the saline control groups or self baseline (P<0. 01). But in the other 35%of the ouabain-treated rats, their SBP was similar with control group during the experiment (P>0. 05).The body weight, heart rate and food intake between the 3 groups were no significant differences (P>0.05). FELi and FDRNa were significantly lower in ouabain-hypertensive group compared with ouabain-nonhypertensive group and control group(P<0.01 and P<0.05). The FELi and FDRNa of ouabain-nonhypertensive groups were similar with control group(P>0.05). Ccr and FENa were comparable between the 3 groups (P>0. 05). Plasma and renal tissue ouabain levels, plasma renin activity, angiotensin Ⅱ and aldosterone contents in ouabain-hypertensive rats were comparable with ouabain-nonhypertensive rats. Conclusion: Increase of proximal tubule sodium reabsorption play an important role in the pathogenesis of ouabain-hypertensive rats. The change of renal sodium transport may result from regulation to renal Na+ ,K+-ATPase by ouabain.
文摘The transport of sodium ions by erythrocytes and the plasma level of endogenous digitalis-like compound (EDLC) were assessed in 59 patients with essential hypertension before and after theadminstration of nifedipine and prazosin. 20 normal subjects were studied similarly and served as con-trol. It was found that (1) EH patients had a pronounced defect of both the active and passive trans-port of sodium ions by the erythrocytes; (2) a higher plasma level of EDLC was detected in EH pa-tients as compared with that of the control, but the changes of EDLC and soudium pump were notparallel; (3) after the administration of nifedipine and prazosin, the function of sodium pump wasmarkedly improved and the plasma level of EDLC decreased. In addition, the relationship betweenthe transport of sodium ions by erythrocytes and the pathogenesis of EH, and the effects of anti-hypertensive agents were discussed.