1.Role of AMPK/PGC-1αpathway in cardioprotection of hydrogen sulfide against ischemia/reperfusion injury
Jieqiong YANG ; Mingzhu HU ; Bin DU ; Junliang CHEN ; Qingfeng PANG ; Yong JI
Chinese Pharmacological Bulletin 2015;(7):951-956
Aim To explore the role of AMPK/ PGC-1α pathway in cardioprotection of hydrogen sulfide ( H2 S ) against ischemia/reperfusion ( I/R ) injury. Methods Langendorff perfusion apparatus was used to build an isolated rat myocardial I/R model. Seventy-two male SD rats were randomly divided into 6 groups (n=12):control group (Control), ischemia/reperfu-sion group ( I/R ) , DMSO group ( DMSO ) , inhibitor Compound C group ( CC) , H2 S postconditioning group ( NP) , and H2 S with Compound C group ( N +C ) . The heart rate ( HR ) , the left ventricular developed pressure ( LVDP ) , the maximum rate of increase or decrease of left ventricular pressure ( ± dp/dtmax ) and the left ventricular diastolic pressure ( LVEDP ) were registered at 20 min of baseline and 60 min of reperfu-sion separately. Triphenyl tetrazolium chloride ( TTC) staining and HE staining were used to determine the myocardial infarct size and the myocardial tissue mor-phological change of each group was observed respec-tively. Immunohistochemistry was used to determine the expression of PGC-1α. The expressions of total AMPK ( tAMPKα ) , phosphorylated AMPK ( pAMPKα) and PGC-1α were detected with Western blot anaylsis. Results There were no differences in e-quilibrium hemodyamics observed between the experi-mental groups(P>0. 05). At the end of reperfusion, compared with I/R group, NP group had obviously a-meliorated functional recovery and significantly de-creased myocardial infarct size [ ( 23. 9 ± 3. 4 )% vs (60. 9 ± 3. 8 )%, ( P <0. 05 ) ] . HE staining showed that in NP group, the myocardial injury was reduced. Meanwhile, the expression of pAMPKα and PGC-1αincreased significantly. However, Compound C re-versed the cardioprotection effects provided by hydro-gen sulfide postconditioning and reduced the expression of pAMPKαand PGC-1α. Conclusion AMPK/ PGC-1α pathway is involved in the role of hydrogen sulfide against ischemia/reperfusion injury.
2.PI3 K/Akt/Sirt1 signaling pathway mediated hydrogen sulfide postconditioning-induced protection against I/R injury
Mingzhu HU ; Bo ZHOU ; Qiong SHENG ; Bin DU ; Junliang CHEN ; Qingfeng PANG ; Yong JI
Chinese Pharmacological Bulletin 2016;(2):268-273
Aim To explore the role of PI3 K/Akt/Sirt1 pathway in cardioprotection of hydrogen sulfide ( H2 S ) postconditioning against ischemia/reperfusion ( I/R) injury. Methods Langendorff perfusion appa-ratus was used to build an isolated rat myocardial I/R model. Isolated rat hearts were subjected to 30 min global ischemia followed by 60 min reperfusion after 20 min of equilibrium. 60 male SD rats were randomly di-vided into 5 groups(n=12):control group(Control), ischemia/reperfusion group( I/R) , H2 S postcondition-ing group( H2 S) , inhibitor LY294002 group( LY) and H2 S with inhibitor group( H2 S+LY) . The left ventric-ular diastolic pressure ( LVEDP ) , the left ventricular developed pressure(LVDP), the maximum rate of in-crease or decrease of left ventricular pressure ( ± dp/dtmax ) were registered at the end of 20 min equilibri-um, 30 and 60 min of reperfusion separately. Triphe-nyl tetrazolium chloride( TTC) staining was used to de-termine the myocardial infarct size. The levels of Sirt1 and PGC-1 mRNA were tested using real-time PCR. The expressions of Sirt1 and PGC-1αwere detected with Western blot analysis. Immunohistochemical method was used to determine the location of Sirt1 . Results There were no differences in equilibrium hemodynamics observed between the experimental groups(P>0. 05). At the end of reperfusion, compared with I/R group, H2 S group had obviously ameliorated functional recov-ery and significantly decreased the myocardial infarct size(26. 9 ± 4. 9)% vs(48. 9 ± 5. 6)%(P <0. 05). Meanwhile, the expression of Sirt1 and PGC-1α in-creased significantly. However,LY294002 reversed the cardioprotective effects provided by hydrogen sulfide postconditioning and reduced the level of Sirt1 and PGC-1α, the percentage of Sirt1-positive nuclei. Con-clusion PI3 K/Akt/Sirt1 signaling pathway mediates the hydrogen sulfide postconditioning-induced protec-tion against I/R injury.
3.Curative effects of second-line regimen combined with rituximab in treatment of relapsed or refractory non-Hodgkin lymphoma
Fei GAO ; Mingzhu DU ; Guang LI ; Siqian BIAN ; Hao WANG ; Feng LIU ; Yan-Ping SONG
Journal of International Oncology 2018;45(10):610-614
Objective To investigate the clinical efficiency,safety and prognostic factors of secondline chemotherapy regimen with gemcitabine combined with rituximab in the treatment of relapsed or refractory B-cell non-Hodgkin lymphoma.Methods A total of 157 patients with relapsed or refractory B-cell nonHodgkin lymphoma were selected from July 2008 to February 2015 in Xi'an Central Hospital.Among them,87 patients were given GEMOX regimen (gemcitabine + oxaliplatin) combined with rituximab,and 70 patients were given GDP program (gemcitabine + cisplatin + dexamethasone) combined with rituximab.The chemotherapy efficacies of the two groups were evaluated.At the same time,the patients were grouped according to whether rituximab was applied or not,and the total objective response rate (ORR) difference was compared.The relevant prognostic factors affecting overall survival (OS) were found.The adverse reactions of patients after treatment were observed.Results The ORR of the GEMOX regimen combined with rituximab group was 65.5%,and the ORR of the GDP regimen combined with rituximab group was 55.7%,but the difference between the two groups was not statistically significant (x2 =1.58,P =0.210).The ORR was 75.2% in 105 patients who had not used rituximab,and the ORR was 32.7% in 52 patients who had previously received rituximab.The difference between the two groups was statistically significant (x2 =29.50,P < 0.001).Univariate analysis showed that middle-high risk or high risk of the lymphoma international prognostic index (IPI) score (x2 =69.21,P <0.001),lactate dehydrogenase (LDH) increased (x2 =16.90,P <0.001),refractory patients (x2 =14.43,P =0.001),large mass (x2 =4.57,P =0.030),and failure to achieve CR or PR after salvage chemotherapy (x2 =50.85,P < 0.001) were risk factors for OS.Cox multivariate analysis showed that middle-high risk or high risk of IPI (HR =2.138,95% CI:1.301-3.512,P =0.001),refractory patients (HR =3.157,95%CI:1.001-10.644,P =0.014),failure to achieve CR or PR after salvage chemotherapy (HR=3.017,95%CI:2.218-7.366,P<0.001),LDH increased (HR =2.236,95% CI:1.797-2.781,P =0.001),large mass (HR =1.792,95% CI:1.255-2.558,P < 0.001) were independent risk factors affecting OS.Adverse reactions to chemotherapy were neutropenia,thrombocytopenia,nausea and vomiting,liver damage and cardiotoxicity,with no treatment-related death.Conclusion The second-line chemotherapy regimen containing gemcitabine combined with rituximab has a better curative effect on relapsed or refractory B-cell non-Hodgkin lymphoma,and the safety is good.Middle-high risk or high risk of IPI,refractory patients,failure to achieve CR or PR after salvage chemotherapy,elevated LDH and large mass were independent risk factors for OS.In patients with relapsed or refractory disease after rituximab treatment,re-application of rituximab was not effective.
4.Voluntary blood donation among undergraduates in Beijing: status and influencing factors of knowledge, attitude and practice
Kexiang SHI ; Mei YOU ; Linyi CHEN ; Mingzhu XIE ; Xinyao LIAN ; Wenjun SUN ; Juan DU ; Qingbin LU
Chinese Journal of Blood Transfusion 2022;35(4):415-419
【Objective】 To explore the status quo and influencing factors of knowledge, attitude and practice of voluntary blood donation among undergraduates in Beijing. 【Methods】 A questionnaire was designed on the basis of literature, using the method of convenience sampling to survey the undergraduates from 39 universities in Beijing. The t-test, analysis of variance and χ2 test were used to compare the differences in knowledge, attitude and practice of voluntary blood donation among different groups, and logistic regression model was performed to analyze the influencing factors. 【Results】 A total of 1 075 valid questionnaires were collected from undergraduates of 39 universities in Beijing. The results showed that the proportion of the participants who had good knowledge about voluntary blood donation was 69.21% (744/1 075). No statistically significant difference was noticed on the scores of voluntary blood donation knowledge between males and females (P>0.05). The scores of voluntary blood donation knowledge of medical students were higher than those of other subjects (P<0.05). The scores of voluntary blood donation knowledge of juniors and above were higher than those of lower grades (P<0.05). The rate of undergraduates participating voluntary blood donation in Beijing was 30.98% (333/1 075). A total of 67.26% (723/1 075) of students had donation intention, 9.49% (102/1 075) didn’t and 23.25% (250/1 075) were not sure. No statistically significant differences in blood donation intention were observed among undergraduates by genders and grades (P>0.05). The rate of medical students’ intention to donate blood was higher than that of other subjects (P<0.05). 【Conclusion】 The rate of voluntary blood donation among undergraduates in Beijing was above the middle level compared with other regions in China, but the practice of voluntary blood donation is far away from the intention. Therefore, it’s necessary to improve the level of knowledge, attitude and practice of undergraduates, especially non-medical college students, so as to improve the rate of voluntary blood donation among the undergraduates in Beijing.
5.Jinyinqingre Oral Liquid alleviates LPS-induced acute lung injury by inhibiting the NF-κB/NLRP3/GSDMD pathway.
Shuhui WANG ; Pan LEI ; Ying FENG ; Mingzhu JIANG ; Zegan LIU ; Ting SHEN ; Shinan MA ; Libo WANG ; Xingrong GUO ; Shiming DU
Chinese Journal of Natural Medicines (English Ed.) 2023;21(6):423-435
Acute lung injury (ALI) is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers, resulting in high incidence and mortality rates. Currently, there is a lack of safe and effective drugs for the treatment of ALI. In a previous clinical study, we observed that Jinyinqingre oral liquid (JYQR), a Traditional Chinese Medicine formulation prepared by the Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical settings. However, the potential role of JYQR in ALI/acute respiratory distress syndrome (ARDS) and its anti-inflammatory mechanism remains unexplored. Thus, the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide (LPS)-induced ALI and an in vitro RAW264.7 cell model. JYQR yielded substantial improvements in LPS-induced histological alterations in lung tissues. Additionally, JYQR administration led to a noteworthy reduction in total protein levels within the BALF, a decrease in MPAP, and attenuation of pleural thickness. These findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced ALI. Mechanistic investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins, namely NLRP3 and GSDMD, as well as proinflammatory cytokine levels in mice and RAW2647 cells. Consequently, JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway. JYQR exerts a protective effect against LPS-induced ALI in mice, and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway.
Humans
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NF-kappa B/metabolism*
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Lipopolysaccharides/metabolism*
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NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
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Acute Lung Injury/metabolism*
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Lung
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Phosphate-Binding Proteins/therapeutic use*
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Pore Forming Cytotoxic Proteins/therapeutic use*