1.Effect of Guipitang on ERK1/2 and p38 MAPK in Rats with Myocardial Ischemia
Jiangli WU ; Yutao JIA ; Cheng DAI ; Xiaoying WANG ; Ruijia LI ; Jiahuan SUN ; Weiwei ZHOU ; Aiying LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(2):1-8
ObjectiveTo explore the therapeutic effect and mechanism of Guipitang on rats with myocardial ischemia. MethodFifty SD rats were divided into five groups: a control group, a model group, low and high-dose Guipitang (7.52, 15.04 g·kg-1) groups, and a trimetazidine group (0.002 g·kg-1). By intragastric administration of vitamin D3 and feeding rats with high-fat forage and injecting isoproterenol, the rat model of myocardial ischemia was established. After drug treatment of 15 d, an electrocardiogram (ECG) was performed to analyze the degree of myocardial injury. A fully automatic biochemical analyzer was used to detect the changes in the serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C). Hematoxylin-eosin (HE) staining and Masson staining were used to observe myocardial histopathological changes. TdT-mediated dUTP nick end labeling (TUNEL) staining was used to detect cardiomyocyte apoptosis. Western blot was adopted to detect the protein levels of extracellular signal-regulated kinase 1/2 (ERK1/2), phospho-ERK1/2 (p-ERK1/2), p38 mitogen-activated protein kinase (p38 MAPK), phospho-p38 MAPK (p-p38 MAPK), B-cell lymphoma-2 (Bcl-2)-associated X (Bax), Bcl-2, and cleaved cysteine aspartate proteolytic enzyme (cleaved Caspase-3). ResultCompared with the control group, the ECG S-T segment decreased in the model group. The serum levels of TC, TG, and LDL-C were increased significantly (P<0.05). The arrangement of myocardial tissue was disordered, and the proportion of cardiomyocyte apoptosis increased. The protein levels of cleaved Caspase-3, Bax, and p-p38 MAPK in the heart were increased, and the Bcl-2 expression was decreased (P<0.05). Compared with the model group, the S-T segment downward shift was restored in the low and high-dose Guipitang groups and trimetazidine group, and the levels of TC, TG, and LDL-C were decreased. The protein expression of cleaved Caspase-3 and Bax in the heart dropped, and p-p38 MAPK and p-ERK1/2 protein expressions increased significantly (P<0.05). The degree of myocardial injury was alleviated, and the proportion of cardiomyocyte apoptosis decreased. Bcl-2 protein expression was increased significantly in the low-dose Guipitang group (P<0.05). ERK1/2 and p38 MAPK proteins had no significant difference among different groups. ConclusionGuipitang could alleviate myocardial injury and inhibit cardiomyocyte apoptosis in rats by activating the expression of ERK1/2 and p38 MAPK.
2.Aerobic glycolysis in colon cancer is repressed by naringin via the HIF1Α pathway.
Guangtao PAN ; Ping ZHANG ; Aiying CHEN ; Yu DENG ; Zhen ZHANG ; Han LU ; Aoxun ZHU ; Cong ZHOU ; Yanran WU ; Sen LI
Journal of Zhejiang University. Science. B 2023;24(3):221-231
Metabolic reprogramming is a common phenomenon in cancer, with aerobic glycolysis being one of its important characteristics. Hypoxia-inducible factor-1α (HIF1Α) is thought to play an important role in aerobic glycolysis. Meanwhile, naringin is a natural flavanone glycoside derived from grapefruits and many other citrus fruits. In this work, we identified glycolytic genes related to HIF1Α by analyzing the colon cancer database. The analysis of extracellular acidification rate and cell function verified the regulatory effects of HIF1Α overexpression on glycolysis, and the proliferation and migration of colon cancer cells. Moreover, naringin was used as an inhibitor of colon cancer cells to illustrate its effect on HIF1Α function. The results showed that the HIF1Α and enolase 2 (ENO2) levels in colon cancer tissues were highly correlated, and their high expression indicated a poor prognosis for colon cancer patients. Mechanistically, HIF1Α directly binds to the DNA promoter region and upregulates the transcription of ENO2; ectopic expression of ENO2 increased aerobic glycolysis in colon cancer cells. Most importantly, we found that the appropriate concentration of naringin inhibited the transcriptional activity of HIF1Α, which in turn decreased aerobic glycolysis in colon cancer cells. Generally, naringin reduces glycolysis in colon cancer cells by reducing the transcriptional activity of HIF1Α and the proliferation and invasion of colon cancer cells. This study helps to elucidate the relationship between colon cancer progression and glucose metabolism, and demonstrates the efficacy of naringin in the treatment of colon cancer.
Glycolysis
;
Colonic Neoplasms/metabolism*
;
Humans
;
Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
;
Phosphopyruvate Hydratase/metabolism*
;
Flavanones/pharmacology*
;
Cell Line, Tumor
;
Databases, Genetic
;
Cell Proliferation/drug effects*
;
Transfection
;
Warburg Effect, Oncologic
3.Correlation of arterial blood lactic acid level in patients with septic shock and mortality 28 days after entering the intensive care unit
Cuicui ZHANG ; Fang NIU ; Lin WU ; Chunling ZHANG ; Cuiping HAO ; Aiying MA ; Qinghe HU ; Chang GAO
Journal of Chinese Physician 2021;23(8):1164-1168
Objective:To investigate the relationship between the arterial blood lactic acid level after entering the intensive care unit (ICU) and the 28-day mortality of patients with septic shock.Methods:The clinical data of 303 patients with septic shock hospitalized in the department of critical medicine of the Affiliated Hospital of Jining Medical College from April 2015 to June 2019 were analyzed retrospectively. According to the blood lactate (Lac) level, the patients were divided into <4 mmol/L group ( n=203), 4-10 mmol/L group ( n=69) and >10 mmol/L group ( n=31). The baseline characteristics of the patients were analyzed. Multiple logistic regression analysis was used to analyze the independent influencing factors of the 28-day mortality of patients with septic shock. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of the Lac level after entering the ICU for 28-day mortality, and Kaplan-Meier survival curve was performed according to the best cut-off value. Results:A total of 303 patients with septic shock were included, with 179 died in 28 days, and the total mortality was 59.08%. There were 203, 69, 31 patients in Lac<4 mmol/L, 4-10 mmol/L and >10 mmol/L group, respectively. There were significant differences in Acute Physiology and Chronic Health Evalution Ⅱ (APACHE Ⅱ), Sequential Organ Failure Assessment (SOFA), oxygenation index (PaO 2/FiO 2), abdominal infection, the proportion of vasoactive drugs use among the three groups ( P<0.05). Multiple logistic regression analysis showed that the independent influencing factor of the 28-day mortality of septic shock were age, SOFA, use of mechanical ventilation, lactic acid (Lac). ROC curve analysis showed that the area under the ROC curve (AUC) for predicting 28-day mortality of patients with septic shock was 0.604 5 (95% CI: 0.540 8-0.668 2). When the optimal cut-off value was 3.55 mmol/L, the sensitivity was 0.508 4, the specificity was 0.733 9, the positive likelihood ratio was 1.910 3 and the negative likelihood ratio was 0.669 9. According to the best cut-off value of entrance Lac, patients were divided into high Lac group (≥3.55 mmol/L) and low Lac group (<3.55 mmol/L), and their 28-day mortality rates were 73.39%(91/124) and 49.16%(88/179). Kaplan-Meier survival curve showed that the 28-day cumulative survival rate of the high Lac group was significantly lower than that of the low Lac group ( P<0.001). Multiple logistic regression analysis showed that after adjusting for confounding factors, the 28 d mortality increased to 1.22 times for each increase of 1 mmol/L of Lac [odds ratio ( OR)=1.22, 95% confidence interval (95% CI) was 1.08-1.37, P=0.001 4]. The 28 d mortality in high Lac group was 3.53 times higher than that in low Lac group ( OR=3.53, 95% CI was 1.36-7.09, P=0.000 4). Conclusions:In patients with ICU septic shock, the arterial blood Lac level after admission was associated with 28-day mortality. Patients with septic shock whose arterial blood Lac level exceeded 3.55 mmol/L within 1 hour of entering the room had a significantly increased risk of death.
4.Comprehensive application of multiple methods in determination of half-sibling relationship
Hongyan WU ; Lin ZHANG ; Kejie WANG ; Aiying FAN
Chinese Journal of Forensic Medicine 2018;33(1):55-57,61
Objective To identify the half-sibling relationship by comprehensive using three different methods. Methods STR genotype was performed on A, A's mother, B and B's mother by using PowerPlex21 kit, AGCU Expressmarker 21+1 kit, Microreader 23sp-B kit and AGCU X-19 STR kit respectively. Based on the results of STR genotype and X-STR, we determined half-sibling relationship by ITO, discriminant function analysis and IBS. Results HIS was between 1.36×102and 2.09×105in ITO which indicated that A and B had the same father. The IBS and discriminant function analysis also had the same conclusion. Conclusion Comprehensive using multiple methods can obtain reliable result to identify the half-sibling relationship from the same father.
5.Analysis of mutation of 20 autosomal short tandem repeat loci in Henan Han population
Lin ZHANG ; Kejie WANG ; Hongyan WU ; Aiying FAN ; Xupeng SUN ; Zhendong ZHU
Chinese Journal of Forensic Medicine 2017;32(1):33-35
Objective To investigate the mutation phenomenon of 20 autosomal STR loci in Henan Han population. Methods A total of 3011 parentage confirmed cases were collected to screen mutation events, ascertain the source of mutation, calculate mutation rate, analyze mutation rules and compare with the mutation condition of populations in different regions. Results 76 mutation events were observed in 19 STR loci, the average and accumulative mutation rate reached to 0.08% and 1.6629%, respectively. The ration of paternal versus maternal mutation was 8:1. Mutation rates of Penta E and D12S391 loci in Henan Han population were lower than the Han population of northern China(P<0.05); the mutation rate of CSF1PO locus were lower than Guangdong population and Yunan Han population(P<0.05); the mutation rates of D6S1043 and D12S391 loci were lower than Guangdong population(P<0.05). Conclusion STR mutation events were common in paternity testing. Region differences among mutation rate were significant.
6.Clinical study on berberine, amoxicillin, lansoprazole, bismuth quadruple therapy for Helicobacter pylori eradication in 283 patients
Lijuan LIANG ; Aiying NIE ; Chao LEI ; Qiong WU ; Zhen NI ; Yongquan SHI
Chinese Journal of Digestion 2017;37(3):167-171
Objective To assess the efficacy and safety of berberine, amoxicillin, lansoprazole, bismuth quadruple therapy for Helicobacter pylori (H.pylori)eradication.Methods From December 2015 to April 2016,566 patients with initial treatment of H.pylori infection were prospectively enrolled.Patients were divided into observation group (berberine, amoxicillin, lansoprazole, bismuth) and control group (clarithromycin, amoxicillin, lansoprazole, bismuth), 283 cases in each group, and the treatment courses in two groups were both 14 days.Four weeks after completion of the treatment, the eradication rate of H.pylori and adverse effect rate of the two groups were compared.Student t test and Chi square test were performed for comparison between the two groups.Results There was no statistically significant difference in the baseline demographic data including gender,age, body mass index (BMI), symptom score between patients of the two groups (all P>0.05).Four weeks after completion of the treatment, the eradication rates of observation group and control group were 87.5%(244/279) and 87.1%(242/278) according to per-protocol analysis, and which were 86.2%(244/283) and 85.5 %(242/283) according to intention-to-treat analysis.There was no statistically significant difference between the two groups (x2=0.021,0.058;both P>0.05).The adverse effect rates of the two groups were 12.5%(35/279) and 16.5%(46/278), and there was no statistically significant difference (x2=1.795,P=0.180).Conclusions Both the new quadruple regimen containing berberine, amoxicillin and bismuth, and the standard quadruple regimen containing clarithromycin, amoxicillin and bismuth both can effectively eradicate H.pylori infection.The new regimen might be recommended as first-line eradication regimen in Xi′an district or area with high clarithromycin resistance.
7.A holistic strategy for quality and safety control of traditional Chinese medicines by the"iVarious"standard system
Chen ANZHEN ; Sun LEI ; Yuan HANG ; Wu AIYING ; Lu JINGGUANG ; Ma SHUANGCHENG
Journal of Pharmaceutical Analysis 2017;7(5):271-279
An effective quality control system is the key to ensuring the quality, safety and efficacy of traditional Chinese medicines (TCMs). However, the current quality standard research lacks top-level design and systematic design, mostly based on specific technologies or evaluation methods. To resolve the challenges and questions of quality control of TCMs, a brand-new quality standard system, named "iVarious", was proposed. The system comprises eight elements in a modular format. Meaning of every element was specifically illustrated via corresponding research instances. Furthermore, frankincense study was taken as an example for demonstrating standards and research process, based on the "iVarious" system. This system highlighted a holistic strategy for effectiveness, security, integrity and systematization of quality and safety control standards of TCMs. The establishment of "iVarious" integrates multi-disciplinary technologies and progressive methods, basis elements and key points of standard construction. The system provides a novel idea and technological demonstration for regulation establishment of TCMs quality standards.
8.A holistic strategy for quality and safety control of traditional Chinese medicines by the"iVarious"standard system
Chen ANZHEN ; Sun LEI ; Yuan HANG ; Wu AIYING ; Lu JINGGUANG ; Ma SHUANGCHENG
Journal of Pharmaceutical Analysis 2017;7(5):271-279
An effective quality control system is the key to ensuring the quality, safety and efficacy of traditional Chinese medicines (TCMs). However, the current quality standard research lacks top-level design and systematic design, mostly based on specific technologies or evaluation methods. To resolve the challenges and questions of quality control of TCMs, a brand-new quality standard system, named "iVarious", was proposed. The system comprises eight elements in a modular format. Meaning of every element was specifically illustrated via corresponding research instances. Furthermore, frankincense study was taken as an example for demonstrating standards and research process, based on the "iVarious" system. This system highlighted a holistic strategy for effectiveness, security, integrity and systematization of quality and safety control standards of TCMs. The establishment of "iVarious" integrates multi-disciplinary technologies and progressive methods, basis elements and key points of standard construction. The system provides a novel idea and technological demonstration for regulation establishment of TCMs quality standards.
9.Relationship between morphological changes of autophagy and apoptosis in PC12 cells induced by oxygen-glucose deprivation and reoxygenation
Xiaofei JIN ; Ying ZHANG ; Aiying LI ; Mishan WU ; Xiaohong ZHOU ; Yanmeng ZHAO ; Weijuan GAO
Chinese Journal of Pathophysiology 2016;32(12):2157-2162
[ ABSTRACT] AIM:To investigate the relationship between morphological changes of autophagy and apoptosis in the PC12 cells induced by oxygen-glucose deprivation and reoxygenation .METHODS:The PC12 cells were randomly di-vided into normal control group , oxygen-glucose deprivation and reoxygenation group , autophagy inhibitor group and auto-phagy activator group .The cells in oxygen-glucose deprivation and reoxygenation group , autophagy inhibitor group and au-tophagy activator group were exposed to reoxygenation (12 h) after 3 h of oxygen-glucose deprivation, and autophagy inhib-itor 3-methyladenine and autophagy activator rapamycin were added into the cells at the same time .Using transmission elec-tron microscope and monodansylcadaverine fluorescence staining , the morphological changes of autophagosome were ob-served.The apoptosis of the PC12 cells were analyzed by flow cytometry with Annexin V-FITC/PI staining and TUNEL method.RESULTS: Compared with normal control group , the numbers of autophagosomes and the apoptotic rates in-creased in oxygen-glucose deprivation and reoxygenation group (P<0.05).Compared with oxygen-glucose deprivation and reoxygenation group , the numbers of autophagosomes decreased obviously ( P<0.05 ) and the apoptotic rates increased markedly in autophagy inhibitor group (P<0.05).The numbers of autophagosomes increased obviously (P<0.05), the apoptotic rates decreased markedly ( P<0.05 ) , the autophagosomes became bigger in size , and autolysosomes was also found in autophagy activator group .CONCLUSION: Oxygen-glucose deprivation and reoxygenation induce autophagy in PC12 cells, and autophagy inhibits cell apoptosis to play a protective role .
10.Clinical significance of soluble CD30/CD30L and CD40/CD40L system imbalance in ovarian serous tumors
Hongfen NI ; Juanfang SONG ; Yuehong WU ; Junmei ZHU ; Aiying CHENG
Chinese Journal of Endocrine Surgery 2016;10(3):225-227
Objective To investigate clinical significance of soluble CD30/CD30L and CD40/CD40L system imbalance in ovarian serous tumors.Methods 40 patients of serous cystadenoma and 30 patients of serous cystadenocarcinoma were selected,and 40 age-and weight-matched healthy women were also recruited as the control group.Peripheral venous blood (3 ml) of the healthy control and patients with ovarian serous tumors before surgery and 7 days after surgery were collected.After separation of serum,ELISA was used to detect levels of sCD30,sCD30L,sCD40 and sCD40L.Results Compared to the control group,levels of sCD30,sCD30L,sCD40 and sCD40L in both serous cystadenoma and serous cystadenocarcinoma groups were significantly in creased (P<0.05).And in those serous cystadenocarcinoma group,levels of such soluble proteins were much higher than in serous cystadenoma group (P<0.05).7 days after surgery,levels of such soluble proteins were significantly decreased in both serous cystadenoma and serous cystadenocarcinoma groups (P<0.05).Conclusion Detection of serum sCD30/sCD30L and sCD40/sCD40L is possible to have a certain guiding significance to early diagnosis of ovarian tumors and the prognosis of patients.

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