1.Effects of Baicalin on the Expressions of JAK1 and STAT3 in Mice with Chronic Atrophic Gastritis
Li-Ying DUAN ; Ming-Yang ZHU ; Yong YU ; Han HAN ; Ye DING
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(1):200-206
Objective To investigate the repair mechanism of baicalin on gastric mucosa of chronic atrophic gastritis mice based on the network pharmacology and animal experiments.Methods(1)Applied network pharmacology to predict and analyze the potential key targets of baicalin in the treatment of chronic atrophic gastritis.(2)Animal experiment:40 C57BL/6N mice were randomly divided into normal group,model group,Vitacoenzyme group and baicalin group,10 mice in each group.Except for the normal group,the other three groups of mice were treated with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)by gavage combined with hunger and satiety disorder method to construct a chronic atrophic gastritis model.At the end of drug administration,the histopathological changes of gastric mucosa were observed by hematoxylin-eosin(HE)staining,the changes of gastrin(GAS)and prostaglandin E2(PGE2)levels in serum were detected by enzyme-linked immunosorbent assay(ELISA),and the mRNA and protein expression levels of Janus tyrosine kinase 1(JAK1),signal transducer and activator of transcription 3(STAT3)in the gastric mucosa were detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)and protein immunoblotting(Western Blot)methods,respectively.Results The results of network pharmacology showed that baicalin could spontaneously bind to the core targets JAK1 and STAT3.The results of animal experiments showed that compared with the normal group,the gastric mucosa of mice in the model group suffered from atrophy,disordered gland arrangement,the presence of a large number of lymphocytes,a significant increase in apoptotic index of the gastric mucosa(P<0.05),a significant decrease in the levels of GAS and PGE2 in serum(P<0.05),and a significant increase in the levels of mRNA and protein expressions of JAK1 and STAT3 in the gastric mucosa(P<0.05);compared with the model group,the pathological changes of gastric mucosa in the Vitacoenzyme group and baicalin group were alleviated,the glands were arranged relatively neatly,the structure was more intact,the apoptosis index of gastric mucosal cells was significantly decreased(P<0.05),the levels of GAS and PGE2 in serum were significantly increased(P<0.05),and the mRNA and protein expression levels of JAK1 and STAT3 in gastric mucosa were significantly decreased(P<0.05).There was no significant difference in the above-mentioned indexes between the baicalin group and the Vitacoenzyme group(P>0.05).Conclusion Baicalin can effectively repair gastric mucosal lesions in mice with chronic atrophic gastritis,and its mechanism may be related to the down-regulation of mRNA and protein expressions of JAK1 and STAT3.
2.miR-375 Attenuates The Migration and Invasion of Osteosarcoma Cells by Targeting MMP13
Zhong LIU ; Lei HE ; Jian XIAO ; Qing-Mei ZHU ; Jun XIAO ; Yong-Ming YANG ; Yong-Jian LUO ; Zhong-Cheng MO ; Yi-Qun ZHANG ; Ming LI
Progress in Biochemistry and Biophysics 2024;51(5):1203-1214
ObjectiveTo explore whether miR-375 regulates the malignant characteristics of osteosarcoma (OS) by influencing the expression of MMP13. MethodsPlasmid DNAs and miRNAs were transfected into OS cells and HEK293 cells using Lipofectamine 3000 reagent. Real-time quantitative polymerase chain reaction was performed to measure the expression of miR-375 and MMP13 in OS patients and OS cells. Western blot was performed to analyze the MMP13 protein in the patients with OS and OS cells. The targeting relationship between miR-375 and MMP13 was analyzed by luciferase assay. Migration and invasion were analysed by heal wound and transwell assays, respectively. ResultsmiR-375 expression in OS tissues was lower than that in normal tissues. The expression of MMP13 was upregulated in OS tissues. MMP13 expression was negatively correlated withmiR-375 expression in patients with OS. Migration and invasion were significantly inhibited in OS cells with the miR-375 mimic compared with OS cells with the miRNA control. MMP13 partially reversed the inhibition of migration and invasion induced by miR-375 in the OS cells. ConclusionmiR-375 attenuates migration and invasion by downregulating the expression of MMP13 in OS cells.
3.Effects of emodin modulation of the HIF-1α/VEGF pathway on vascular endothelial cells damage in diabetic macroangiopathy rats
Qiu-Xiao ZHU ; Hui-Yao HAO ; Zi-Bo LIU ; Ming GAO ; Fang ZHANG ; Jing ZHOU ; Zhi-Hua HAO ; Li-Hui ZHANG ; Yong-Mei HAO
The Chinese Journal of Clinical Pharmacology 2024;40(6):859-863
Objective To investigate the impact of emodin(EM)on vascular endothelial cell injury in rats with diabetes macroangiopathy by regulating hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods SD rats were divided into blank group and modeling group,the rats in the modeling group were fed with high fat and high sugar combined with N-nitro-L-arginine methyl ester to build the diabetes macroangiopathy model,and the blank group was fed with ordinary diet.The vascular endothelial cells successfully isolated from the thoracic aorta of rats in blank group and modeling group were named control group and model group,respectively.The vascular endothelial cells in the modeling group were divided into model group,dimethyloxallyl glycine(DMOG)group(10 μmol·L-1DMOG),combined group(80 mg·L-1EM+10 μmol·L-1 DMOG)and experimental-L,-M,-H groups(20,40,80 mg·L-1 EM).The apoptosis of rat vascular endothelial cells was detected by flow cytometry;Western blot was applied to detect the expression of HIF-1αand VEGF proteins in rat vascular endothelial cells.Results The apoptosis rates of vascular endothelial cells in experimental-M,-H groups,DMOG group,combined group,model group and control group were(10.18±0.36)%,(6.28±0.20)%,(24.96±1.18)%,(12.36±0.49)%,(18.76±0.68)%and(4.59±0.26)%;HIF-1α protein levels were 0.96±0.07,0.78±0.06,2.03±0.12,1.05±0.13,1.58±0.12 and 0.69±0.05;VEGF protein levels were 0.59±0.05,0.23±0.02,0.98±0.06,0.63±0.04,0.86±0.07 and 0.11±0.01.The above indexes in the model group were compared with the control,DMOG,experimental-M and experimental-H groups,and the above indexes in the combined group were compared with the experimental-H group,and the differences were statistically significant(all P<0.05).Conclusion EM may inhibit HIF-1α/VEGF pathway to improve vascular endothelial cell injury in rats with diabetes macroangiopathy.
4.Pathological mechanism of hypoxia-inducible factor-1α in tumours and the current status of research on Chinese medicine intervention
Yu LIU ; Li-Ying ZHANG ; Guo-Xiong HAO ; Ya-Feng QI ; Qian XU ; Ye-Yuan LIU ; Chao YUAN ; Peng ZHU ; Yong-Qi LIU ; Zhi-Ming ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(11):1670-1674
Traditional Chinese medicine can regulate the hypoxia-inducible factor-1α(HIF-1α)signalling pathway and slow down tumour progression mainly by inhibiting tumour angiogenesis,glycolysis,epithelial mesenchymal transition and other pathological processes.This paper,starting from HIF-1α and related factors,reviews its pathological mechanism in tumours and the research of traditional Chinese medicine interventions with the aim of providing theoretical references for the treatment of tumours with traditional Chinese medicine.
5.Negative association between composite dietary antioxidant index and excess heart age
ZHANG Wanyao ; HUANG Dongdong ; LU Ming ; REN Yong ; ZHU Tongjian ; LI Bin
China Tropical Medicine 2024;24(2):150-
Objective To investigate the relationship between the composite dietary antioxidant index (CDAI) and excess heart age (EHA), offering theoretical insights into the nutritional prevention of cardiovascular disease (CVD). Methods Data for this cross-sectional analysis was derived from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2020, which included 16 442 participants aged 30 to 74 years without a history of CVD. The heart age was estimated using the Framingham risk score function, and EHA was subsequently calculated. The CDAI was formulated based on intake levels of vitamins A, C, E, zinc, selenium, and carotenoids to represent the overall level of antioxidants. The association between CDAI and EHA was evaluated using multivariate linear regression, multivariate logistic regression, and restricted cubic splines (RCS). Results Multiple regression analysis indicated that CDAI was negatively correlated with both EHA (β=-0.07, 95%CI: -0.14 to -0.01) and high CVD risk (defined as EHA≥10 years) (OR=0.98, 95%CI: 0.96 to 1.00), with RCS analysis suggesting that this relationship is a nonlinear and inverse L-shaped. In the female subgroup, significant negative, nonlinear associations were observed between CDAI and both EHA (β=-0.10, 95%CI: -0.12 to 0.00) and high CVD risk (OR=0.97, 95%CI: 0.94 to 0.99). Conversely, in males, these correlations did not reach statistical significance. Conclusions Our findings suggest that individuals with higher CDAI compliance had a lower risk of CVD, and this negative correlation was gender specific. This discovery offers new theoretical guidance for the nutritional prevention of CVD, underlining the necessity for more comprehensive clinical and foundational research to further explore this association.
6.Establishment and evaluation methods of a novel animal model of liver depression transforming into fire syndrome-related depression
Dan SU ; Jian LI ; Gen-hua ZHU ; Ming YANG ; Liang-liang LIAO ; Zhi-fu AI ; Hui-zhen LI ; Ya-li LIU ; Yong-gui SONG
Acta Pharmaceutica Sinica 2024;59(6):1680-1690
Through a compound induction method, combined with neurobehavioral, macroscopic characterization and objective pathological evaluation indicators, a murine depression model of liver depression transforming into fire syndrome was constructed and confirmed. The model was constructed using a combination of sleep deprivation, light exposure, and alternate-day food deprivation. Evaluation was conducted at three levels: face validity, constructs validity, and predictive validity. The establishment of the liver depression transforming into fire syndrome depression model was further validated through the counterproof of traditional Chinese medicine formulas. In terms of face validity, compared to the control group, mice in the model group exhibited typical depressive symptoms in neurobehavioral assessments; the general observation of the model group mice reveals disheveled and lackluster fur, along with delayed and easily agitated responses. Additionally, there is a substantial increase in water consumption. In the sleep phase detection of mouse, the model group showed a significant increase in the proportion of time spent in the wake phase during sleep, accompanied by a significant decrease in the proportions of time spent in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep phases. There are significant differences in physiological indicators such as average blood flow velocity, blood flow rate, tongue, urine, and claw color (r values) in the internal carotid artery. Structural validity demonstrated that levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and
7.Effects of template and pore-forming agent method on the structure and drug delivery of porous maltodextrin
Zhe LI ; Xiao-sui LUO ; Wei-feng ZHU ; Qiong LI ; Yong-mei GUAN ; Zheng-ji JIN ; Li-hua CHEN ; Liang-shan MING
Acta Pharmaceutica Sinica 2024;59(8):2381-2395
This study using maltodextrin as raw material, 1%-5% polyvinylpyrrolidone K30 as template agent, 1%-5% ammonium bicarbonate as pore-forming agent, curcumin and ibuprofen as model drugs. Porous maltodextrin was prepared by template and pore-forming agent methods, respectively. The structure and drug delivery behavior of porous maltodextrin prepared by different technologies were comprehensively characterized. The results showed that the porous maltodextrin prepared by pore-forming agent method had larger specific surface area (6.449 4 m2·g-1) and pore size (32.804 2 nm), which was significantly better than that by template agent method (3.670 2 m2·g-1, 15.278 5 nm). The adsorption kinetics between porous maltodextrin prepared by pore-forming agent method and curcumin were suitable for quasi-first order adsorption kinetic model, and that between porous maltodextrin and ibuprofen were suitable for quasi-second order adsorption kinetic model. While the adsorption kinetics between porous maltodextrin prepared by template agent method and two model drugs were both suitable for the quasi-first order adsorption kinetic model. In addition, the dissolution behavior analysis showed that the porous maltodextrin prepared by the two technologies can significantly improve the dissolution behavior of insoluble drugs, and the drug release was both carried out by diffusion mechanism, which suitable for the Peppas kinetic release model, but the porous maltodextrin prepared by template agent method had a faster release rate. The change of nozzle diameter had no significant effect on the adsorption process and drug release behavior of porous maltodextrin. In conclusion, the porous maltodextrins prepared by two different technologies were both beneficial to the delivery of insoluble drugs, and the template agent method was the best for delivery of insoluble drugs. This study can provide theoretical basis for the preparation of porous particles, promote the application of porous particles in insoluble drugs, and improve the bioavailability of insoluble drugs.
8.Research advances in endoplasmic reticulum autophagy and its roles in associated diseases
Sen TONG ; Ning DONG ; Xiao-Mei ZHU ; Yong-Ming YAO
Medical Journal of Chinese People's Liberation Army 2024;49(9):1062-1072
Endoplasmic reticulum is an important organelle in eukaryotic cells,which is responsible for the folding,processing and transportation of secretory proteins.A variety of stimuli inside and outside cells can lead to the accumulation of misfolded or unfolded proteins in the endoplasmic reticulum,resulting in abnormal structure and function of the endoplasmic reticulum,which is called endoplasmic reticulum stress(ERS).Endoplasmic reticulum autophagy is an important endogenous mechanism to alleviate ERS.It is often considered as a cell protective procedure,which participates in many important physiological processes,such as metabolism,immune response,inflammatory response and cell proliferation.Endoplasmic reticulum autophagy is an important endogenous protective mechanism to alleviate endoplasmic reticulum stress and restore the endoplasmic reticulum homeostasis,through eliminating redundant and disabled endoplasmic reticulum membrane and macromolecular protein complexes,which is critical to cell function and fate.This paper reviews the types of endoplasmic reticulum autophagy,related specific receptors,main regulatory mechanisms,and its role and significance in the related diseases.
9.Predictive value of effective hepatic blood flow in postopera-tive liver insufficiency in patients with hepatocellular carci-noma
Sen CHEN ; Yan-Guo LIU ; Yong-Ming ZHANG ; Song-Zhu YANG
Chinese Journal of Current Advances in General Surgery 2024;27(5):373-376
Objective:To investigate the value of effective hepatic blood flow in predicting the occurrence of liver insufficiency after operation of hepatocellular carcinoma(HCC).Methods:The 15-minute clearance of Indocyanine Green(ICGR15)and EHBFwere measured in 123 patients with hepatocellular carcinoma(HCC)after hepatectomy.To compare the difference of ICGR15 and EHBF in different groups of liver function recovery and the incidence of postoperative liver function insufficiency in different groups of ICG R15 and EHBF.The diagnostic value of ICG R15 and EHBF was compared by receiver operating characteristic(ROC)curve.Results:Of the 123 patients,41(33.3%)developed liver insufficiency after operation.The average values of ICG R15 and EHBF in patients with good liver function were(8.95±7.18)%and(1.01±0.37)min,respectively,while those in patients with liver insufficiency were(15.88±11.55)%and(0.75±0.28)min,respec-tively.The difference was statistically significant(P<0.05).The incidence of postoperative liver in-sufficiency was 13.0%in EHBF≥1.0 L/min group and 45.5%in<1.0 L/min group,the difference was statistically significant(P<0.05).The area under the ICG R15 ROC curve was 0.710(95%CI:0.616-0.804),the critical value was 7.6,the sensitivity was 78.0%,and the specificity was 59.8%.The area under the EHBF ROC curve was 0.718(95%CI:0.624-0.813),the critical value was 0.35,the sensitivity was 73.2%,and the specificity was 70.7%.Conclusion:EHBF can effec-tively predict the occurrence of liver insufficiency after hepatocellular carcinoma operation,and may have the same testing efficacy as ICGR15.
10.Associations of reproductive health indicators with lung function and COPD among female community residents aged 40 years and above in Songjiang District,Shanghai
Xin YIN ; Yi-Ling WU ; Shan-Shan HOU ; Jing LI ; Wei LUO ; Min-Jun YU ; Jin-Xin ZANG ; Wei WANG ; Xu-Yan SU ; Qi ZHAO ; Yin-Feng ZHU ; Gen-Ming ZHAO ; Yong-Gen JIANG ; Qing-Wu JIANG ; Na WANG
Fudan University Journal of Medical Sciences 2024;51(6):882-889
Objective To investigate the associations of reproductive health indicators with lung function and chronic obstructive pulmonary disease(COPD)among women aged 40 years and above.Methods From Jul to Sep,2021,female subjects aged 40 years and above were randomly selected from the Shanghai Suburban Adult Cohort and Biobank for COPD screening.A questionnaire was used to obtain information on demographic characteristics and reproductive health indicators.Linear regression was used to analyze the effects of reproductive health indicators on forced vital capacity(FVC)and forced expiratory volume in the first second(FEV1).Logistic regression was also used to analyze the effects of reproductive health factors on FVC as a percentage of the predicted value(FVC%Pred)and FEV1%Pred as well as on COPD.Results A total of 1876 women aged 40 years and above were enrolled with mean age of(62.1±8.2)years old,among them,78.1%were menopausal,and 40.9%had been pregnant≥3 times.Multivariate analysis showed that FVC and FEV1 decreased in postmenopausal women,but menopause was not associated with a decrease in their percentage of predicted values.Pregnancies≥3 times was a risk factor for COPD(for 3 times,OR=4.92,95%CI:1.48-19.95,P<0.05;for≥4 times,OR=9.06,95%CI:2.32-41.57,P<0.01),while pregnancies of 2 times did not increase the risk of COPD.Conclusion In women aged 40 years and above,menopause is associated with poorer FVC and FEV1,and excessive pregnancy(≥3 times)is a risk factor for COPD.

Result Analysis
Print
Save
E-mail