1.α-Lipoic acid alleviates alcohol-induced damage in rat H9c2 cardiomyo-cytes by activating ALDH2
Yaru ZHANG ; Fang FANG ; Haoran ZHU ; Xiaorong YIN ; Lu CUI ; Yong CAO ; Cheng SHEN
Chinese Journal of Pathophysiology 2025;41(1):1-10
AIM:This study aims to investigate the protective effect of α-lipoic acid(α-LA)against alcohol-induced damage in H9c2 rat cardiomyocytes and to explore the underlying mechanisms.METHODS:An alcohol-induced injury model of H9c2 cells was established,and the cells were divided into 4 groups:control group,alcohol group,α-LA group,and alcohol+α-LA group.Additionally,H9c2 cells overexpressing aldehyde dehydrogenase 2(ALDH2)were cre-ated and further divided into 6 groups:normal control group,normal cells treated with alcohol group,normal cells treated with alcohol+α-LA group,ALDH2 overexpression group,ALDH2-overexpressing cardiomyocytes treated with alcohol group,and ALDH2-overexpressing cardiomyocytes treated with alcohol+α-LA group.Cell proliferation was assessed using 5-ethynyl-2'-deoxyuridine(EdU)staining.Reactive oxygen species(ROS)levels in each group were measured using di-hydroethidium(DHE)staining,while the expression levels of ALDH2,silent information regulator 1(SIRT1),heme oxy-genase 1(HO1)and P53 proteins were detected by Western blot analysis.RESULTS:(1)Alcohol exposure resulted in a decrease in the proliferation of H9c2 cells and an increase in intracellular oxidative stress,evidenced by elevated ROS levels and decreased expression of related proteins(ALDH2,SIRT1 and HO1).However,α-LA treatment significantly mitigated the decline in cell proliferation and the oxidative stress induced by alcohol.(2)Alcohol may induce cellular se-nescence,as demonstrated by the up-regulation of P53 expression,which were reversed by α-LA.(3)The H9c2 cells with high ALDH2 expression markedly improved the cell proliferation in the presence of alcohol,suppressed the ROS pro-duction,prevented the down-regulation of oxidative stress-related proteins(ALDH2,SIRT1 and HO1),and reversed the enhanced expression of the senescence marker P53.CONCLUSION:Treatment with α-LA may counteract oxidative stress and attenuate cellular senescence by activating ALDH2,thereby protecting cardiomyocytes from alcohol-induced damage.
2.α-Lipoic acid alleviates alcohol-induced damage in rat H9c2 cardiomyo-cytes by activating ALDH2
Yaru ZHANG ; Fang FANG ; Haoran ZHU ; Xiaorong YIN ; Lu CUI ; Yong CAO ; Cheng SHEN
Chinese Journal of Pathophysiology 2025;41(1):1-10
AIM:This study aims to investigate the protective effect of α-lipoic acid(α-LA)against alcohol-induced damage in H9c2 rat cardiomyocytes and to explore the underlying mechanisms.METHODS:An alcohol-induced injury model of H9c2 cells was established,and the cells were divided into 4 groups:control group,alcohol group,α-LA group,and alcohol+α-LA group.Additionally,H9c2 cells overexpressing aldehyde dehydrogenase 2(ALDH2)were cre-ated and further divided into 6 groups:normal control group,normal cells treated with alcohol group,normal cells treated with alcohol+α-LA group,ALDH2 overexpression group,ALDH2-overexpressing cardiomyocytes treated with alcohol group,and ALDH2-overexpressing cardiomyocytes treated with alcohol+α-LA group.Cell proliferation was assessed using 5-ethynyl-2'-deoxyuridine(EdU)staining.Reactive oxygen species(ROS)levels in each group were measured using di-hydroethidium(DHE)staining,while the expression levels of ALDH2,silent information regulator 1(SIRT1),heme oxy-genase 1(HO1)and P53 proteins were detected by Western blot analysis.RESULTS:(1)Alcohol exposure resulted in a decrease in the proliferation of H9c2 cells and an increase in intracellular oxidative stress,evidenced by elevated ROS levels and decreased expression of related proteins(ALDH2,SIRT1 and HO1).However,α-LA treatment significantly mitigated the decline in cell proliferation and the oxidative stress induced by alcohol.(2)Alcohol may induce cellular se-nescence,as demonstrated by the up-regulation of P53 expression,which were reversed by α-LA.(3)The H9c2 cells with high ALDH2 expression markedly improved the cell proliferation in the presence of alcohol,suppressed the ROS pro-duction,prevented the down-regulation of oxidative stress-related proteins(ALDH2,SIRT1 and HO1),and reversed the enhanced expression of the senescence marker P53.CONCLUSION:Treatment with α-LA may counteract oxidative stress and attenuate cellular senescence by activating ALDH2,thereby protecting cardiomyocytes from alcohol-induced damage.
3.Relationship between Doppler ultrasound parameters of uterine artery,umbilical artery,middle cerebral artery and placental vasculopathology and pregnancy outcome in preeclampsia rat model
Ruilin MA ; Yu LIU ; Guixiang XU ; Haoran SHI ; Jianjian CUI ; Zejun YANG ; Yan MAO ; Yin ZHAO
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(5):543-551
Objective·To measure the parameters of the uterine artery,umbilical artery and middle cerebral artery in a rat model of preeclampsia(PE)by Doppler ultrasound,and compare the pathological changes in placental blood vessels and pregnancy outcomes,in order to provide an effective method and reference for evaluating placental function in PE animal models.Methods·PE(n=8)and normal pregnancy(NP,n=8)groups in Sprague-Dawley(SD)rat models were established by intraperitoneal injections of N'-nitro-L-arginine methylesterhydrochloride(L-NAME)and 0.9%sodium chloride solution.Blood pressure and proteinuria indexes were detected to evaluate whether the model was successfully established.On gestational day 19(GD19),Doppler ultrasound was utilized to measure the parameters of the uterine artery,umbilical artery and the fetal middle cerebral artery in both the PE and NP groups.After termination of the pregnancies,placental function was evaluated through the pathology of placental blood vessels and the quality of the fetuses and placentas.Results·In the PE group,both blood pressure(GD15:P=0.001;GD19:P=0.001)and proteinuria(GD15:P=0.001;GD19:P=0.001)were significantly higher than those in the NP group.The pulsatility index(PI)of the umbilical artery and uterine artery was notably elevated in the PE group compared to the NP group(both P=0.000).Furthermore,the resistance index(RI)of the fetal middle cerebral artery was significantly lower than that in the PE group(P=0.000).While the number of fetal rats did not differ significantly,the quality of placental and fetal rats was notably lower in the PE group(P=0.006 and P=0.000,respectively).Immunohistochemical staining of placental tissue revealed that the number of placental micro vessel densities in the PE group was less than that in the NP group(P=0.001).Correlation analysis revealed that placental micro vessel density,fetal quality and placental quality were inversely related with the RI of the umbilical artery and the PI and RI of the uterine artery,and positively correlated with the S/D,PI and RI of the fetal middle cerebral artery(all P<0.05).Conculsion·Doppler ultrasound assessment of the uterine artery,umbilical artery and middle cerebral artery indices in L-NAME-induced PE rat models effectively reflects pregnancy outcomes and placental vascular pathology.This method is valuable for evaluating placental vascular perfusion in PE rat models,offering practicality and convenience for research involving animal models.
4.Progress of mesenchymal stem cell-derived exosomes for management of preeclampsia
Chinese Journal of Perinatal Medicine 2022;25(2):154-157
Pre-eclampsia is a common complication of pregnancy that can result in serious consequences for mother and child health, but there are currently no established therapeutic options. Mesenchymal stem cell-derived exosomes (MSC-exos) are nanoparticles carrying bioactive substances such as proteins, lipids, and nucleic acids, and serve as a medium of intercellular communication. MSC-exos are involved in many important physiological processes, including immunological regulation, cell proliferation and migration, and angiogenesis, thereby play an important role in tissue repair and potentially clinical treatment strategies. In recent years, the treatment strategies of MSC-exos have become an emerging hot topic in the management of ischemic diseases, immune dysfunction, inflammatory diseases, and other fields. We review the advantages and challenges of MSC-exos as a new acellular therapy strategy as well as the feasibility of MSC-exos in managing preeclampsia, from its biological role in the important pathogenesis of preeclampsia, such as trophoblastic and endothelial cell dysfunction, immune imbalance at the maternal-fetal interface, and oxidative stress, and summarize the progress of animal experimental research in this field.
5.Training the skills of obstetric forceps delivery for resident doctors by using simulation teaching method
Yin ZHAO ; Wei ZHUANG ; Xiaoxia LIU ; Guangyao YANG ; Weifang LIU ; Yu LIU ; Yang ZHANG ; Haoran SHI ; Li ZOU
Chinese Journal of Medical Education Research 2021;20(10):1187-1190
In this study, 15 second-year resident doctors who had standardized training of OBGYN were taken as research subjects to discuss the effect of training resident doctors with obstetrics forceps by using simulation teaching method. The simulation teaching process includes theoretical study, theoretical examination, simulation teaching of forceps skills and Assessment of forceps skills. In theoretical study section: before learning to use forceps, the students acquired the theoretical knowledge by flipped teaching micro-video mode. In theoretical examination section: the mastery of basic clinical knowledge of using forceps was evaluated through online assessment. In simulation teaching of forceps skills: students who scored 8/10 points were admitted to enter the simulation teaching process, and they had practical training of scenario simulation skills in Clinical Skills Center. In assessment of forceps skills: the mastery of forceps skills was evaluated by standardized forceps delivery procedure items. The results showed that the students in the simulation teaching group had excellent teaching assessment results, and the resident doctors had more confidence in operating forceps independently, and the teaching effect was ideal, which could further promote the simulation teaching of obstetric clinical skills.
6.Mechanism of elevated blood pressure in pediatric patients with repaired CoA
Jiemin ZENG ; Ping HUANG ; Hongying WANG ; Tingting SHI ; Haoran FENG ; Genquan YIN ; Yingkang JIN ; Gen LU
Chinese Journal of Thoracic and Cardiovascular Surgery 2021;37(10):579-585
Objective:To monitor the blood pressure in pediatric patients with coarctation of the aorta (CoA) before and 8 years after surgery, and explore the mechanism of elevated blood pressure in pediatric patients with repaired CoA.Methods:A cohort of 23 pediatric patients who underwent CoA repair between January 2010 and October 2010 in Guangzhou Women and Children's Medical Center was studied. And 20 age-, sex-match patients with isolated ventricular septal defect (VSD) who underwent surgery at the same time, 20 age-, sex-match health patients with normal echocardiographic findings were included in the study. Systolic blood pressure (SBP), diastolic blood pressure (DBP), arm-leg SBP gradient, right carotid intima-media thickness (CIMT), serum transforming growth factor-β1 (TGF-β1) were monitored at baseline(1 day before surgery) and 8-year follow-up (8 years after surgery).Results:There were no differences in SBP and DBP among patients with CoA, patients with VSD and health children at baseline ( P>0.05). But at 8-year follow-up, 2 patients with CoA exhibited hypertension. Not only that, patients with CoA had higher SBP than patients with VSD and health children at 8-year follow-up ( P<0.05). Patients with CoA had higher arm-leg SBP gradient than patients with VSD and health children at baseline ( P<0.01). But there were no differences in arm-leg SBP among patients with CoA, patients with VSD and health children at 8-year follow-up ( P>0.05). Patients with CoA had increased CIMT and higher serum levels of TGF-β1 at baseline and 8-year follow-up ( P<0.05). The preoperative levels of CIMT and serum TGF-β1 in the patients with CoA were highly positively correlated with their levels at 8-year follow-up, respectively ( P<0.01). There was a strong correlation between the levels of CIMT and serum TGF-β1 in patients with CoA, both preoperatively and postoperatively ( P<0.01). The preoperative and postoperative levels of CIMT and serum TGF-β1 in the patients with CoA were highly positively correlated with SBP at 8-year follow-up, respectively( P<0.05). Conclusion:Although surgery can successfully cure the anatomical " stenosis" , patients with CoA have elevated systolic blood pressure than normal people and patients with simple congenital heart disease (such as VSD). And some of the patients with CoA suffer from hypertension at long-term follow-up, even they are normotensive preoperatively. It may be related to vascular remodeling, in which TGF-β signaling pathway may be involved. Monitoring CIMT and TGF-β1 in patients with CoA preoperatively may be significative for prediction for the levels of SBP postoperatively.
8.A magnetism/laser-auxiliary cascaded drug delivery to pulmonary carcinoma.
Jialiang LIN ; Qingqing YIN ; Binlong CHEN ; Haoran ZHANG ; Dong MEI ; Jijun FU ; Bing HE ; Hua ZHANG ; Wenbing DAI ; Xueqing WANG ; Yiguang WANG ; Qiang ZHANG
Acta Pharmaceutica Sinica B 2020;10(8):1549-1562
Although high-efficiency targeted delivery is investigated for years, the efficiency of tumor targeting seems still a hard core to smash. To overcome this problem, we design a three-step delivery strategy based on streptavidin-biotin interaction with the help of c(RGDfK), magnetic fields and lasers. The ultrasmall superparamagnetic iron oxide nanoparticles (USIONPs) modified with c(RGDfK) and biotin are delivered at step 1, followed by streptavidin and the doxorubicin (Dox) loaded nanosystems conjugated with biotin at steps 2 and 3, respectively. The delivery systems were proved to be efficient on A549 cells. The co-localization of signal for each step revealed the targeting mechanism. The external magnetic field could further amplify the endocytosis of USPIONs based on c(RGDfK), and magnify the uptake distinctions among different test groups. Based on photoacoustic imaging, laser-heating treatment could enhance the permeability of tumor venous blood vessels and change the insufficient blood flow in cancer. Then, it was noticed that only three-step delivery with laser-heating and magnetic fields realized the highest tumor distribution of nanosystem. Finally, the magnetism/laser-auxiliary cascaded delivery exhibited the best antitumor efficacy. Generally, this study demonstrated the necessity of combining physical, biological and chemical means of targeting.
9.Outcome of surgical intervention for non-small-cell lung cancer patients with pleural carcinomatosis first detected at thoracotomy
Baoxing LIU ; Yin LI ; Haibo MA ; Jianjun QIN ; Yongkui YU ; Haoran WANG ; Shilei LIU ; Guanghui LIANG ; Ruixiang ZHANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2017;33(9):522-526
Objective To describe the effects of surgical intervention on the prognosis in non-small-cell lung cancer patients with pleural carcinomatosis detected at thoracotomy.Methods Retrospectively analyzed clinical data from 54 patients who have unexpected malignant pleural nodules and/or malignant pleural effusions first detected at thoracotomy from January 2009 and December 2013.The effects of surgical intervention on the prognosis were also discussed.Results Sixteen cases had only biopsy,whereas 38 (70.4%) cases had primary tumor resection.The median survival time of 54 patients with pleural carcinomatosis were 23 months.The overall 1 and 5-year survival rates were 64% and 18%,respectively.Primary tumor resection had significantly better outcome compared with biopsy(MST:respectively,24 vs 15 months,5-year survival rate 39% vs 6%,P <0.05).Univariate analysis showed that primary tumor resection,no smoking history,lower T and N stage has favorable survival(P < 0.05).Multivariate analysis showed that the best N stage(P =0.002) and adenocarcinoma(P =0.035) were favorable prognostic factors in these patients.Conclusion For patients with pleural careinomatosis first detected at thoracotomy,limited primary tumor resection may have survival benefits,lower T and N stage for them was associated with better survival.
10.Surgical treatment of gastric cancer in the elderly
Jun CHEN ; Zhenggang ZHU ; Min YAN ; Jianyuan XUE ; Haoran YIN ; Yanzhen LIN
International Journal of Surgery 2010;37(6):382-385
Objective To explore the clinical characteristics and surgical treatment of gastric cancer in elderly patients.Methods The clinical data of 431 patients older than 70 years with gastric cancer from 1984 to 1998 were analyzed retrospectively.Results The main clinical manifestations were upper abdominal pain,distension or upset,loss of appetite and weight.The patients with clinicalⅢ,Ⅳ stage accounted for 64.2 percent.Pathological findings showed no specificity.Radical gastrectomy was performed in 215 cases(49.9%),and palliative resection was done in 122 ones(28.3%).The operative mortality and postoperative complication rate were 5.1%and 25.5%in the patients respectively.The 5-year survival rate was 29.5%in the patients with surgery,53.2%with radical gastrectomy and 10.7%with palliative resection.There were significant differences in 5-year survival rate between the radical and palliative groups.Conclusions The majority of elderly patients are clinical Ⅲ,Ⅳ stages and their operative complication rate is high.The key to increase the survival rate and life quality of elderly patients with gastric cancer is early diagnoses,strong perioperative management and suitable radical surgery.

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