1.Carthamus tinctorius L.extract ameliorates alcoholic liver disease by modulating PI3K/Akt/FoxO signaling pathway
Wen-Xuan WANG ; Xiang-Lei FU ; Man QI ; Fu-Rong FAN ; Fu-Rong ZHU ; Yuan-Chuang WANG ; Kai-Yue ZHANG ; Min LIU ; Sheng-Hui CHU
Chinese Pharmacological Bulletin 2024;40(6):1137-1145
Aim To investigate the effects of Cartham-us tinctorius L.extract(CTLE)on oxidative stress,lipid metabolism,and apoptosis levels of mice with al-cohol-induced liver injury and its mechanism of action.Methods The mouse model of alcohol-associated liver disease was established by chronic alcohol feeding and acute alcohol gavage.Mice were randomly divided into four groups.During the modeling period,the state changes of mice were observed every day,and their weight was recorded.At the end of modeling,blood and liver tissues were collected from each group of mice.The blood of mice was analyzed biochemically,and HE staining and Oil Red O staining were used to evaluate further the degree of pathological damage in the liver of mice.Quantitative real-time PCR(qPCR)and Western blot were applied to detect the mRNA and protein expression levels of p-PI3K,PI3K,p-Akt,Akt,p-mTOR,mTOR,p-FoxO1,FoxO1,p-FoxO3a,FoxO3a,p-FoxO4,FoxO4,BCL and BAX factors.Results Compared to the model group,the CTLE administration group showed improved hepatic patho-logical injury and reduced lipid deposition.The bio-chemical indexes in serum and liver,such as ALT,AST,TG,TC,and MDA levels were reduced,while GSH and SOD levels increased.Regulating the PI3K/Akt/FoxO pathway resulted in increased production of SOD,which reduced damage and apoptosis caused by reactive oxygen species(ROS).Conclusions CTLE can exert anti-oxidative stress and anti-apoptotic effects through the PI3K/Akt/FoxO pathway and attenuates alcoholic liver injury in mice,providing new ideas for the treatment of alcoholic liver disease and the develop-ment of related drugs.
2.Study on improvement effect of Danggui Shaoyao San on edema in rats with nephrotic syndrome and its mechanism
Xiao-Wen MA ; Sheng-Nan FAN ; Zai-Ping XU ; Qing-Zhen XIANG ; Zi-Hua XUAN ; Yun-Lai WANG ; Fan XU
Chinese Pharmacological Bulletin 2024;40(6):1172-1178
Aim To explore the effect of Danggui Shaoyao San on edema in rats with nephrotic syndrome and the underlying mechanism.Methods Rats were randomly divided into control group,model group,Danggui Shaoyao San group(17.2 g·kg-1·d-1),losartan group(30 mg·kg-1·d-1)and tolvaptan group(3 mg·kg-1·d-1).The rat model of nephrot-ic syndrome was established by tail vein injection of adriamycin.After four weeks of treatment,the levels of renal function and 24 h urinary protein were detected.The distribution of aquaporin 2(AQP2)and pS256-AQP2 in renal tissue was detected by immunohisto-chemistry.The levels of plasma arginine vasopressin(AVP)and angiotensin Ⅱ(Ang Ⅱ)were measured by radioimmunoassay.The expressions of renal AQP2,pS256-AQP2,angiotensin type 1 receptor(AT1R),arginine vasopressin receptor 2(V2R)protein and mRNA were measured by Western blot and RT-PCR,respectively.Results The three drugs could improve renal function,reduce proteinuria,decrease plasma AVP and Ang Ⅱ levels,and down-regulate AQP2 and pS256-AQP2 protein and mRNA expression in model rats.Danggui Shaoyao San and tolvaptan were more ef-fective than losartan in reducing plasma AVP levels.Conclusions Danggui Shaoyao San may regulate the expression of AQP2 by reducing the levels of AVP and Ang Ⅱ,and improve the edema of nephrotic syndrome rats.
3.LncRNA-CCRR regulates arrhythmia induced by myocardial infarction by affecting sodium channel ubiquitination via UBA6
Fei-Han SUN ; Dan-Ning LI ; Hua YANG ; Sheng-Jie WANG ; Hui-Shan LUO ; Jian-Jun GUO ; Li-Na XUAN ; Li-Hua SUN
Chinese Pharmacological Bulletin 2024;40(8):1437-1446
Aim To investigate the regulatory mecha-nism of arrhythmia of sodium channel ubiquitination af-ter MI and to study the electrophysiological remodeling mechanism of lncRNA-CCRR after MI for the preven-tion and treatment of arrhythmia after MI.Methods LncRNA-CCRR transgenic mice and C57BL/6 mice injected with lncRNA-CCRR overexpressed adeno-asso-ciated virus were used.Four weeks after infection,the left anterior descending branch of the coronary artery was ligated for 12 h to establish a mouse acute myocar-dial infarction model,and the incidence of arrhythmia was detected by programmed electrical stimulation.Ln-cRNA-CCRR overexpression/knockdown adeno-associ-ated virus and negative control were transfected into neonatal mouse cardiomyocytes(NMCMs),and the model was prepared by hypoxia for 12 h.LncRNA-CCRR expression was detected by FISH,Nav1.5 and UBA6 protein and Nav.1.5 mRNA expression were de-tected by Western blot and real-time quantitative poly-merase chain reaction(qRT-PCR),Nav1.5 and UBA6 expressions were detected by immunofluores-cence,and the relationship between lncRNA-CCRR and UBA6 was detected by RIP.INa current density af-ter CCRR overexpression and knockdown was detected by Whole-cell clamp patch.Results In MI mice,the expression of lncRNA-CCRR decreased,the incidence of arrhythmia increased,the expression of CCRR and Nav1.5 mRNA was down-regulated,the protein ex-pression of Nav1.5 was down-regulated,and the pro-tein expression of UBA6 was up-regulated compared with sham group.Overexpression of CCRR could re-verse the above changes.AAV-CCRR could reverse the down-regulated CCRR and Nav1.5 mRNA levels af-ter hypoxia,and improve the expression of Nav1.5 and UBA6 protein.The direct relationship between ln-cRNA-CCRR and UBA6 was identified by RIP analy-sis.The INa density increased after transfection with AAV-CCRR.The INa density decreased after transfec-tion with AAV-si-CCRR.Conclusions The expres-sion of lncRNA-CCRR decreases after MI,and ln-cRNA-CCRR can improve arrhythmia induced by MI by inhibiting UBA6 to increase the protein expression level of Nav1.5 and the density of INa.
4.Efficacy and safety of Kegel exercise combined with biofeedback electrical stimulation in the treatment of postpartum pelvic floor dysfunction
Fang SHENG ; Nanping DING ; Jie XUAN ; Zhengbin PAN
China Modern Doctor 2024;62(31):23-26
Objective To explore the efficacy and safety of Kegel exercise combined with biofeedback electrical stimulation in the treatment of postpartum pelvic floor dysfunction(PFD).Methods A total of 100 postpartum PFD patients diagnosed and treated in Shaoxing Maternal and Child Health Care Hospital from January 2022 to May 2023 were selected and divided into KEG group and combination group according to random number table method,with 50 cases in each group.Patients in KEG group were given Kegel exercise,and patients in combination group were treated with Kegel exercise combined with biofeedback electrical stimulation.The clinical efficacy,pelvic floor electrophysiological indexes,bladder neck mobility,urethral rotation angle and sexual function were compared between two groups.Results The total effective rate of combination group was significantly higher than that of KEG group(x2=4.891,P=0.026).After treatment,the anterior resting average electromyogram value(aEMG),posterior resting aEMG,slow muscle aEMG and fast muscle maximum electromyogram value(mEMG)of pelvic floor muscles and sexual satisfaction scores in two groups were significantly higher than before treatment,bladder neck mobility and urethral rotation angle in combination group were significantly lower than before treatment,the duration of vaginal contraction in combination group was significantly longer than before treatment,and the pain score of coitus in combination group was significantly lower than before treatment(P<0.05).The anterior resting aEMG,posterior resting aEMG,slow muscle aEMG and fast muscle mEMG of pelvic floor muscles and sexual satisfaction scores in combination group were significantly higher than those in KEG group,bladder neck mobility and urethral rotation angle were significantly lower than those in KEG group,the duration of vaginal contraction was significantly longer than that in KEG group,and the pain score of coitus was significantly lower than that in KEG group(P<0.05).No complications occurred in both groups after treatment.Conclusion Kegel exercise combined with biofeedback electrical stimulation can significantly improve pelvic floor muscle function,sexual function and urinary function in patients with postpartum PFD with good safety,and its efficacy is better than Kegel exercise.
5.Efficacy Evaluation and Mechanism Research of Qi-Shen-Yi-Zhi Formula in Improving the Learning and Memory Ability of Aβ1-42 Hippocampus Injection Mice
Ziqiang ZHU ; Yunqing LU ; Jiani ZHENG ; Cheng CAO ; Yang CHEN ; Jiaxiang TONG ; Xuan LI ; Sheng GUO ; Jin'ao DUAN ; Yue ZHU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(1):40-47
Objective Evaluation of the effect and mechanism research of Qi-Shen-Yi-Zhi formula on improving learning and memory ability in mice injected with Aβ1-42 in hippocampus.Methods Alzheimer's disease model mice were constructed by injecting β amyloid peptide 1-42 into hippocampus and treated with water extracts of Qi-Shen-Yi-Zhi formula.The cognitive abilities of mice were assessed using Morris water maze and Y maze tests,which measure learning and memory capabilities.HE staining was used to observe the damage and TUNEL method was used to determine apoptosis of hippocampus.Detection of the expression of oxidative factors,inflammatory factors,and related antioxidant proteins and apoptotic proteins in the hippocampal tissue of a mouse model of dementia.Results Both high-dose and low-dose groups of Qi-Shen-Yi-Zhi formula significantly improved cognitive dysfunction in mice injected with Aβ1-42 in hippocampus,and attenuated the damage and apoptosis of the hippocampus.It also inhibited oxidative stress and downregulated the expressions of inflammatory factors IL-6,IL-1β and TNF-a,increased the expression of antioxidant proteins Nrf2 and HO-1,and regulated the expressions of apoptotic proteins Caspase-9,Caspase-3,Bax and Bcl-2.Conclusion Qi-Shen-Yi-Zhi formula improves the learning and memory abilities of mice injected with Aβ1-42 in hippocampus,which might be related to the attenuation of oxidative stress and neuronal inflammation of hippocampus.
6.Researches on Effective Fraction and Mechanism of Lycium Barbarum Leaves on Improving Learning and Memory Abilities of D-Galactose-Induced Subacute Aging Mice
Jiaxiang TONG ; Yang CHEN ; Xuan LI ; Ziqiang ZHU ; Shulan SU ; Sheng GUO ; Hongjie KANG ; Jin'ao DUAN ; Yue ZHU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(1):48-60
Objective To study the effective fraction and mechanism of Lycium barbarum leaves on improving learning and memory ability of subacute aging mice induced by D-galactose injection.Methods The model of subacute aging mice was developed by injection of D-galactose subcutaneously,and different extracts of Lycium barbarum leaves were prepared.The effects of the extracts of Lycium barbarum leaves on the learning and memory ability of model mice were evaluated by Y maze experiment and new object recognition experiment.The pathomorphological changes of hippocampus in mice were observed by hematoxylin-eosin and Nissl staining.The levels of brain-derived neurotrophic factor(BDNF),nerve growth factor(NGF),glial cell line-derived neurotrophic factor(GDNF),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interferon-γ(IFN-γ)and interleukin-10(IL-10)in hippocampus of mice were detected by enzyme-linked immunosorbent assay.The activities of superoxide dismutase(SOD)and the contents of glutathione(GSH)and malondialdehyde(MDA)in hippocampus of mice were detected by related assay kits.Detection of apoptosis in the hippocampal region of mouse brain tissue using the TUNEL method.Western blotting analysis was used to detect the expressions of antioxidant proteins Nrf2,HO-1 and apoptotic proteins Caspase-3,Caspase-9 in hippocampus of mice.Results The water extraction part and 80%alcohol precipitation supernatant part of Lycium barbarum leaves significantly improved the learning and memory ability of model mice,improved the pathological damage of hippocampus in mice,increased the number of Nissl bodies in hippocampus of mice,and promoted the expression of neurotrophic factors BDNF,NGF and GDNF,and promoted the expression of neurotrophic factors BDNF,NGF and GDNF.Pro-inflammatory factors TNF-α,IL-1β and IFN-γ expression declines while anti-inflammatory factor IL-10 expression rises.The activity of SOD and the expression of GSH were increased,and the expression of MDA was decreased.Increase the expression of Nrf2 and HO-1 antioxidant proteins;reduce the expression of Caspase-3 and Caspase-9 apoptosis pathway proteins.Inhibition of apoptosis in the hippocampal region of mouse brain tissue using a model.Conclusion The water extracts and 80%alcohol precipitation supernatant extracts of Lycium barbarum leaves are the effective fractions of Lycium barbarum leaves to improve the learning and memory ability of D-galactose-induced subacute aging mice,and its mechanism might be related to the inhibition of neuronal apoptosis caused by oxidative stress and inflammation.
7.Role of complement C3 in early predicting pregnancy outcomes of frozen-thawed embryo transfer
Zhixia TANG ; Shuangying MA ; Ying ZHAGN ; Jiajia SHENG ; Juan LI ; Jingjing HE ; Henghua XUAN ; Min-Gyun HONG
The Journal of Practical Medicine 2024;40(7):924-929
Objective To investigate the role of complement C3 in early predicting pregnancy outcomes of frozen-thawed embryo transfer(F-ET).Methods A total of 378 F-ET cycles were prospectively collected and divided into group A(complement C3≤1.05,120 cycles)and group B(complement C3>1.05,258 cycles)based on the best cutoff value of complement C3 for predicting F-ET pregnancy outcomes.The outcomes of the two groups were compared,and the best cutoff value of complement C3 for predicting F-ET spontaneous abortion was analyzed in group B.Results Age was a risk factor for successful F-ET pregnancy(P<0.05),and complement C3 and embryo type were protective factors for successful F-ET pregnancy(P<0.05).The area under the receiver-operating characteristic curve(ROC)of complement C3 for predicting F-ET pregnancy outcome was 0.702,and the best cutoff value was 1.05 g/L,with a clinical pregnancy sensitivity of 87.60%and a specificity of 52.00%.The clinical pregnancy rate and embryo implantation rate in group B were both significantly higher than those in group A(67.05%vs.52.75%,P<0.05).The best cutoff value of complement C3 for predicting spontaneous abortion after F-ET was 1.32 g/L,with an area under the ROC curve of 0.760,a sensitivity of 69.00%,and a specificity of 81.20%.Conclusions Complement C3 is of significance in the early prediction of F-ET pregnancy outcome.When complement C3 exceeds the level of 1.32 g/L,it may lead to an increase in the rate of spontaneous abortion.
8.Mechanism of crocin alleviating monocrotaline-induced right ventricular injury in rats with pulmonary arterial hypertension
Yanling SHENG ; Xiaowei GONG ; Zhijuan LI ; Xuan ZHANG ; Tao TIAN ; Yadong YUAN
Chinese Journal of Pathophysiology 2024;40(2):221-229
AIM:To investigate whether crocin alleviates right ventricular injury induced by monocrotaline(MCT)in rats with pulmonary arterial hypertension(PAH),and to explore the underlying mechanisms.METHODS:Forty male SD rats were randomly divided into 4 groups:normal group,PAH group,crocin group and sildenafil group,with 10 rats in each group.The rats in PAH,crocin and sildenafil groups received subcutaneous injection of MCT(50 mg/kg)to establish the PAH model.Starting from the day of MCT injection,the rats in crocin group received crocin(200 mg/kg),the rats in sildenafil group received sildenafil(30 mg/kg),and those in PAH and normal groups were orally gavaged with an equal volume of saline once daily.After 4 weeks,measurements of right ventricular systolic pressure(RVSP),mean pulmonary artery pressure(mPAP),right ventricular hypertrophy index(RVHI)and right ventricular mass index(RVMI)were taken for the rats in each group.Tissue staining was conducted to observe pathological changes in the right ventricle,and the expression levels of inflammatory factors(IL-1β,IL-6 and TNF-α),the p38 MAPK/NF-κB inflammato-ry pathway,CCL2,CCR2,and the macrophage marker CD68 were assessed.RESULTS:Compared with PAH group,the rats in crocin and sildenafil groups exhibited significant reductions in RVSP,mPAP,RVHI and RVMI(P<0.05).Right ventricular tissue displayed no evident infiltration of inflammatory cells or proliferation of collagen fibers.The down-regulation of the p38 MAPK/NF-κB pathway and inflammatory factors(IL-1β,IL-6 and TNF-α)was significant(P<0.05).Additionally,the CCL2/CCR2 pathway and the infiltration of CD68+ macrophages were markedly decreased(P<0.05).CONCLUSION:Crocin effectively mitigates right ventricular damage in MCT-induced PAH rats,with its effica-cy comparable to that of sildenafil at the dosage utilized in this experiment.Some protective mechanisms of crocin may be attributed to its regulatory effects on inflammation.
9.Beak Sign:A New Sign of Prenatal Ultrasound in the Diagnosis of Annular Pancreas
Xuan SHENG ; Houmei HAN ; Dequan LIU ; Yang GAO ; Dan GUO ; Hong YIN
Chinese Journal of Medical Imaging 2024;32(2):162-165,167
Purpose To explore the diagnostic value of beak sign in fetal annular pancreas by analyzing the ultrasonographic features of fetal annular pancreas.Materials and Methods The ultrasound images and clinical data of 13 cases of fetal annular pancreas diagnosed by prenatal ultrasound in Shandong Provincial Maternal and Child Health Hospital from September 2019 to December 2021 and confirmed by surgery after birth were retrospectively analyzed.The degree of duodenal stenosis at the obstruction site was observed,especially whether the angle formed by the intestinal wall could identify the fetal annular pancreas,and the ultrasonic characteristics were summarized and analyzed.Results A total of 13 fetuses with annular pancreas showed double bubble sign,3 cases showed clamp sign,and 7 cases showed beak sign at the end of duodenal dilatation.All the 13 cases underwent surgical treatment after birth,including 2 cases with duodenal atresia and 1 case with atypical intestinal malrotation.All the children had good prognosis after operation.Conclusion By observing the dilated end of duodenum and the relationship with pancreatic head,prenatal ultrasound combined with beak sign and double bubble sign could improve the diagnostic accuracy of fetal annular pancreas,which has significant value in prenatal diagnosis of fetal annular pancreas.
10.Chemical constituents from Ganoderma angustisporum and their α-glucosidase inhibitory activities
Ya-Qin HUO ; Yu-Xi WANG ; Yu-Lian WEI ; Yi-Xuan ZHANG ; Hai-Sheng YUAN
Chinese Traditional Patent Medicine 2024;46(1):132-137
AIM To study the chemical constituents from Ganoderma angustisporum J.H.Xing,B.K.Cui&Y.C.Dai and their α-glucosidase inhibitory activities.METHODS The ethyl acetate extract from G.angustisporum was isolated and purified by silica gel,ODS,TLC and HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.pNPG method was used to evaluate their α-glucosidase inhibitory activities.RESULTS Seven compounds were isolated and identified as N-acetyl-L-phenylalanine ethyl ester(1),N-acetyl-L-phenylalanine methyl ester(2),4-hydroxy-17R-methylincisterol(3),6,8-di-O-methylaverufin(4),aversin(5),methyl 2-(4-hydroxyphenyl)aceate(6),5-toluene-1,3-diol(7).Compounds 1-2,4-7 showed inhibitory activities of α-glucosidase with IC50 values being(33.80±0.47),(45.45±7.95),(48.80±5.86),(39.48±2.82),(41.47±6.68),(55.38±10.12)μmol/L,and compound 1 showed good inhibitory activity.CONCLUSION Compound 1 is a new natural product.Compounds 2-7 are isolated from genus Ganoderma for the first time.Compounds 1-2,4-7 have α-glucosidase inhibitory activities.

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