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.The mechanism of knockdown of E2F1 inhibiting the proliferation and migration of human tongue squamous cell carcinoma cells
Acta Universitatis Medicinalis Anhui 2024;59(12):2127-2134
Objective:
To investigate the effects of knockdown of E2F transcription factor 1(E2F1) in human tongue squamous cell carcinoma cells on proliferation, migration, and invasion of tongue squamous cell carcinoma cells, and to explore its possible mechanisms.
Methods:
The expression ofE2F1in human tongue squamous cell carcinoma was detected by RT-PCR, and the background expression ofE2F1gene in HOEC, SCC-9, CAL-27, TSCCa and SCC-25 cells was detected by RT-PCR, and the cell lines with significantly high expression of E2F1 were screened for subsequent experiments. CCK-8, EdU, colony formation, cell scratch, Transwell, apoptosis and cell cycle experiments were used to detect the effects of knockdown ofE2F1on proliferation, migration, invasion and apoptosis of human tongue squamous cell carcinoma cells after knockdown ofE2F1gene in tongue squamous cell carcinoma candidate cells. Western blot was used to detect the expression of epithelial mesenchymal transition markers E-cadherin, N-cadherin and snail family transcription inhibitor 1(Snail) protein and WNT signaling pathway markers WNT family members 3A(WNT3A), β-catenin and cyclin D1(CCND1).
Results:
RT-PCR results showed that the expression ofE2F1in cancer tissues was significantly higher than that in adjacent tissues(P<0.001). At the same time, compared with HOEC cells, the expression ofE2F1in SCC-9, CAL-27, TSCCa and SCC-25 cells significantly increased(P<0.05), and the high expression in SCC-25 cells was the most obvious. SCC-25 would be used as an experimental cell line in subsequent experiments. After knocking downE2F1in SCC-25 cells, the viability of CCK-8 cells was significantly inhibited(P<0.001). The number of EdU positive cells decreased significantly(P<0.001). The number of cell clones was significantly reduced(P<0.001). The proportion of total apoptosis significantly increased(P<0.001). The proportion of cells in G1phase increased(P<0.01). The proportion of cells in G2phase decreased(P<0.01). The cell migration and invasion ability were significantly inhibited(P<0.001). Western blot showed that the expression of WNT signaling pathway proteins WNT3A, β-catenin and CCND1 decreased(P<0.001), while the expression of EMT-related proteins N-cadherin and Snail decreased(P<0.001), while the expression of E-cadherin increased(P<0.001).
Conclusion
Knockdown ofE2F1inhibits the proliferation, migration, invasion and EMT process of human tongue squamous cell carcinoma SCC-25 cells, and promotes apoptosis. This anti-tumor effect may be achieved by blocking the activation of WNT signaling pathway.
4.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.
5.The progress on post-exposure prophylaxis of tetanus immunological preparation in adults
Juan DU ; Zhongsong ZHANG ; Xinyao LIAN ; Xuezeng WANG ; Mingzhu XIE ; Tianshuo ZHAO ; Qingbin LU ; Jiang WU
Chinese Journal of Preventive Medicine 2022;56(7):1004-1010
The tetanus has been eliminated in the pregnancy women and newborns in China. However, there is a gap for adult tetanus immunization, and the risk of tetanus infection cannot be ignored. In order to clearly understand the effect of the tetanus to human beings and the current use of tetanus immunological preparation for adult post-exposure prophylaxis, the incidence of the tetanus, the use status of tetanus immunological preparation and recommendations for post-exposure prophylaxis at home and abroad were reviewed and summarized, which may provide academic evidence for post-exposure prophylaxis procedures and use of tetanus immunological preparation.
6.The progress on post-exposure prophylaxis of tetanus immunological preparation in adults
Juan DU ; Zhongsong ZHANG ; Xinyao LIAN ; Xuezeng WANG ; Mingzhu XIE ; Tianshuo ZHAO ; Qingbin LU ; Jiang WU
Chinese Journal of Preventive Medicine 2022;56(7):1004-1010
The tetanus has been eliminated in the pregnancy women and newborns in China. However, there is a gap for adult tetanus immunization, and the risk of tetanus infection cannot be ignored. In order to clearly understand the effect of the tetanus to human beings and the current use of tetanus immunological preparation for adult post-exposure prophylaxis, the incidence of the tetanus, the use status of tetanus immunological preparation and recommendations for post-exposure prophylaxis at home and abroad were reviewed and summarized, which may provide academic evidence for post-exposure prophylaxis procedures and use of tetanus immunological preparation.
7.Identification of Age-associated Proteins and Functional Alterations in Human Retinal Pigment Epithelium
Jin XIUXIU ; Liu JINGYANG ; Wang WEIPING ; Li JIANGFENG ; Liu GUANGMING ; Qiu RUIQI ; Yang MINGZHU ; Liu MENG ; Yang LIN ; Du XIAOFENG ; Lei BO
Genomics, Proteomics & Bioinformatics 2022;20(4):633-647
Retinal pigment epithelium(RPE)has essential functions,such as nourishing and sup-porting the neural retina,and is of vital importance in the pathogenesis of age-related retinal degen-eration.However,the exact molecular changes of RPE during aging remain poorly understood.Here,we isolated human primary RPE(hRPE)cells from 18 eye donors distributed over a wide age range(10-67 years old).A quantitative proteomic analysis was performed to analyze changes in their intracellular and secreted proteins.Age-group related subtypes and age-associated proteins were revealed and potential age-associated mechanisms were validated in ARPE-19 and hRPE cells.The results of proteomic data analysis and verifications suggest that RNF123-and RNF149-related protein ubiquitination plays an important role in protecting hRPE cells from oxidative damage dur-ing aging.In older hRPE cells,apoptotic signaling-related pathways were up-regulated,and endo-plasmic reticulum organization was down-regulated both in the intracellular and secreted proteomes.Our work paints a detailed molecular picture of hRPE cells during the aging process and provides new insights into the molecular characteristics of RPE during aging and under other related clinical retinal conditions.
8.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.
9.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*