BACKGROUND The exact mechanisms underlying diabetic nephropathy(DN)remain incompletely elucidated,prompting researchers to explore new perspectives and identify novel intervention targets in this field.AIM To explore ...BACKGROUND The exact mechanisms underlying diabetic nephropathy(DN)remain incompletely elucidated,prompting researchers to explore new perspectives and identify novel intervention targets in this field.AIM To explore the role and underlying mechanisms of farnesoid X receptor(FXR)in the development of DN by regulating endoplasmic reticulum stress(ERS)molecular chaperone binding immunoglobulin protein(BiP)expression.METHODS Bioinformatics analyses identified potential FXR-binding elements in the BiP promoter.Dual-luciferase and chromatin immunoprecipitation(ChIP)assays confirmed FXR-BiP binding sites.In vitro studies used SV40 MES 13 cells under varying glucose conditions and treatments with FXR modulators[obeticholic acid(INT-747)and guggulsterones]or BiP small interfering RNA.The expression of BiP and ERS-related proteins[protein kinase R-like endoplasmic reticulum kinase(PERK),inositol-requiring enzyme 1(IRE1),activating transcription factor 6(ATF6)]was assessed alongside cell proliferation and extracellular matrix(ECM)synthesis.In vivo studies in DN mice(db/db)examined the effects of FXR activation on renal function and morphology.RESULTS FXR bound to the target sequence in the BiP promoter region,enhancing transcriptional activity,as confirmed by ChIP experiments.FXR expression decreased in SV40 MES 13 cells stimulated with high glucose and in renal tissues of DN mice compared with control.Treatment of SV40 MES 13 cells with the FXR agonist INT-747 significantly increased intracellular BiP expression,whereas silencing the FXR gene led to the downregulation of BiP levels.In vivo administration of INT-747 significantly elevated BiP levels in renal tissues,improved renal function and fibrosis in DN mice,while inhibiting the expression of ERS-related signaling proteins PERK,IRE1,and ATF6.CONCLUSION FXR promotes BiP expression by binding to its promoter,suppressing ERS pathways,and reducing mesangial cell proliferation and ECM synthesis.These findings highlight FXR as a potential therapeutic target for diabetic glomerulosclerosis.展开更多
Objective： To evaluate the regulatory effects of Banxia （Pinellia ternata, P） and Huanglian （Coptis chinensis, C） drugpair, derived from Banxiaxiexin soup, on the gastrointestinal movement of mice with functional...Objective： To evaluate the regulatory effects of Banxia （Pinellia ternata, P） and Huanglian （Coptis chinensis, C） drugpair, derived from Banxiaxiexin soup, on the gastrointestinal movement of mice with functional dyspepsia. Methods：Mice were treated with different proportions of the P and C drug pair （1：1, 3：1, and 4：1） for 10 days, and subsequentlyinjected with atropine （ATR） or neostigmine （NEO）. The effects of the different proportions of P and C were evaluatedbased on the alvine advance rate. In addition, we used the same modeling method used in the first experiment andadministered P： C at ratio of 3：1 and at different doses respectively （4.68 g/L, 2.34 g/L, and 1.17 g/L）, and tested levelsof the gastrointestinal hormones, gastrin （GAS）, vasoactive intestinal polypeptide （VIP）, and somatostatin （SS） in thesmall intestinal tissue using an enzyme-linked immunosorbent assay. Results： In the groups of NEO-induced mice, P：Cat ratios of 1：1, 3：1, and 4：1 significantly reduced the alvine advance rate compared with the NEO model group （P =0.003, P = 0.012 and P = 0.021, respectively）. In the groups of ATR-induced mice, only P：1 at ratio of 3：1 significantlyincreased the alvine advance rate compared with the ATR model group （P = 0.007）. After exposure to P： C at ratio of 3：1and at different dose, the GAS level was lower in the low-, medium-, and high-dose NEO groups than that in the NEOmodel group （P = 0.001, P = 0.004, and P = 0.003, respectively）. The VIP levels were higher in the medium-andhigh-dose NEO groups than that in the NEO model group （P = 0.004 and P = 0.002, respectively）. In addition, the SSlevel increased in the NEO medium-dose group compared with that in the NEO model group （P = 0.002）. The GAS levelwas higher in the ATR medium- and high-dose groups than in the ATR model group （P = 0.007 and P = 0.021,respectively）. The VIP level was lower in the ATR low-, medium-, and high-dose than that in the ATR model group （P =0.001, P = 0.001, and P = 0.001, respectively）. Furthermore, the SS level was lower in the ATR medium- and high-dosegroups than that in the ATR model group （P = 0.001 and P = 0.006）. Conclusion： The PC drug pair bidirectionallyadjusted the NEO- and ATR-induced functional dyspepsia in mice by modulating GAS, VIP, and SS levels in theintestine.展开更多
The optimization of hot compression technique of as-cast 0Cr23Ni13 stainless steel at high strain rate was discussed,and its corrosion resistance was evaluated after hot compression treatment experimentally.By adjusti...The optimization of hot compression technique of as-cast 0Cr23Ni13 stainless steel at high strain rate was discussed,and its corrosion resistance was evaluated after hot compression treatment experimentally.By adjusting the dynamic recrys-tallization(DRX)ratio of 0Cr23Nil3 stainless steel during hot pressing,the content of low Σ coincident site lattice(ΣCSL)grain boundaries is increased,and the grain orientation is optimized.The results show that ferrite and austenite are completely recrystallized at 1050 and 1150℃,respectively.The number of grains in the<111>and<101>directions increases significantly,the corrosion potential increases,and the corrosion current density decreases,which will signifi-cantly improve the corrosion resistance of 0Cr23Nil3 stainless steel.After the optimization of grain boundary distribution,corrosion resistance is noticeably improved due to the existence of lowΣCSL boundaries.The interference effect of lowΣCSL grain boundary on random grain boundary network becomes intense with the increase in DRX ratio,which is the fundamental measure to improve the corrosion resistance.展开更多
基金Supported by the Talent Launch Fund of Chongqing Medical University Affiliated University City HospitalChongqing Medical University Affiliated University City Hospital Youth Program,No.2021ZD05.
文摘BACKGROUND The exact mechanisms underlying diabetic nephropathy(DN)remain incompletely elucidated,prompting researchers to explore new perspectives and identify novel intervention targets in this field.AIM To explore the role and underlying mechanisms of farnesoid X receptor(FXR)in the development of DN by regulating endoplasmic reticulum stress(ERS)molecular chaperone binding immunoglobulin protein(BiP)expression.METHODS Bioinformatics analyses identified potential FXR-binding elements in the BiP promoter.Dual-luciferase and chromatin immunoprecipitation(ChIP)assays confirmed FXR-BiP binding sites.In vitro studies used SV40 MES 13 cells under varying glucose conditions and treatments with FXR modulators[obeticholic acid(INT-747)and guggulsterones]or BiP small interfering RNA.The expression of BiP and ERS-related proteins[protein kinase R-like endoplasmic reticulum kinase(PERK),inositol-requiring enzyme 1(IRE1),activating transcription factor 6(ATF6)]was assessed alongside cell proliferation and extracellular matrix(ECM)synthesis.In vivo studies in DN mice(db/db)examined the effects of FXR activation on renal function and morphology.RESULTS FXR bound to the target sequence in the BiP promoter region,enhancing transcriptional activity,as confirmed by ChIP experiments.FXR expression decreased in SV40 MES 13 cells stimulated with high glucose and in renal tissues of DN mice compared with control.Treatment of SV40 MES 13 cells with the FXR agonist INT-747 significantly increased intracellular BiP expression,whereas silencing the FXR gene led to the downregulation of BiP levels.In vivo administration of INT-747 significantly elevated BiP levels in renal tissues,improved renal function and fibrosis in DN mice,while inhibiting the expression of ERS-related signaling proteins PERK,IRE1,and ATF6.CONCLUSION FXR promotes BiP expression by binding to its promoter,suppressing ERS pathways,and reducing mesangial cell proliferation and ECM synthesis.These findings highlight FXR as a potential therapeutic target for diabetic glomerulosclerosis.
文摘Objective： To evaluate the regulatory effects of Banxia （Pinellia ternata, P） and Huanglian （Coptis chinensis, C） drugpair, derived from Banxiaxiexin soup, on the gastrointestinal movement of mice with functional dyspepsia. Methods：Mice were treated with different proportions of the P and C drug pair （1：1, 3：1, and 4：1） for 10 days, and subsequentlyinjected with atropine （ATR） or neostigmine （NEO）. The effects of the different proportions of P and C were evaluatedbased on the alvine advance rate. In addition, we used the same modeling method used in the first experiment andadministered P： C at ratio of 3：1 and at different doses respectively （4.68 g/L, 2.34 g/L, and 1.17 g/L）, and tested levelsof the gastrointestinal hormones, gastrin （GAS）, vasoactive intestinal polypeptide （VIP）, and somatostatin （SS） in thesmall intestinal tissue using an enzyme-linked immunosorbent assay. Results： In the groups of NEO-induced mice, P：Cat ratios of 1：1, 3：1, and 4：1 significantly reduced the alvine advance rate compared with the NEO model group （P =0.003, P = 0.012 and P = 0.021, respectively）. In the groups of ATR-induced mice, only P：1 at ratio of 3：1 significantlyincreased the alvine advance rate compared with the ATR model group （P = 0.007）. After exposure to P： C at ratio of 3：1and at different dose, the GAS level was lower in the low-, medium-, and high-dose NEO groups than that in the NEOmodel group （P = 0.001, P = 0.004, and P = 0.003, respectively）. The VIP levels were higher in the medium-andhigh-dose NEO groups than that in the NEO model group （P = 0.004 and P = 0.002, respectively）. In addition, the SSlevel increased in the NEO medium-dose group compared with that in the NEO model group （P = 0.002）. The GAS levelwas higher in the ATR medium- and high-dose groups than in the ATR model group （P = 0.007 and P = 0.021,respectively）. The VIP level was lower in the ATR low-, medium-, and high-dose than that in the ATR model group （P =0.001, P = 0.001, and P = 0.001, respectively）. Furthermore, the SS level was lower in the ATR medium- and high-dosegroups than that in the ATR model group （P = 0.001 and P = 0.006）. Conclusion： The PC drug pair bidirectionallyadjusted the NEO- and ATR-induced functional dyspepsia in mice by modulating GAS, VIP, and SS levels in theintestine.
基金This research was financially supported by the Science and Technology Major Project of Gansu Province(Grant No.17ZD2GB012)the City Key Research and Development Plan of Jiayuguan(Grant Nos.20-16).
文摘The optimization of hot compression technique of as-cast 0Cr23Ni13 stainless steel at high strain rate was discussed,and its corrosion resistance was evaluated after hot compression treatment experimentally.By adjusting the dynamic recrys-tallization(DRX)ratio of 0Cr23Nil3 stainless steel during hot pressing,the content of low Σ coincident site lattice(ΣCSL)grain boundaries is increased,and the grain orientation is optimized.The results show that ferrite and austenite are completely recrystallized at 1050 and 1150℃,respectively.The number of grains in the<111>and<101>directions increases significantly,the corrosion potential increases,and the corrosion current density decreases,which will signifi-cantly improve the corrosion resistance of 0Cr23Nil3 stainless steel.After the optimization of grain boundary distribution,corrosion resistance is noticeably improved due to the existence of lowΣCSL boundaries.The interference effect of lowΣCSL grain boundary on random grain boundary network becomes intense with the increase in DRX ratio,which is the fundamental measure to improve the corrosion resistance.
