1.The regulation of ovarian reserve function by Zuogui pills combined with cetrorelix
Qing-yu LI ; Jing-jing GAO ; Yan-jin FU ; Meng-sha LONG ; Yi-yao ZHANG ; Zu-yu MENG ; Shao-zi LIN ; Jia-jia QIN
Acta Pharmaceutica Sinica 2022;57(7):2108-2114
The purpose of this study was to investigate how Zuogui pills from the Kidney-tonifying and Nourishing Yin formula, in combination with the gonadotrophin-releasing hormone antagonist cetrorelix, affected the ovarian local oxidative stress response in decreasing ovarian reserve (DOR) mice. All animal experiments were carried out in accordance with the guidelines and standards established by Jinan University's Experimental Animal Management Committee. Cyclophosphamide (CTX)-treated DOR mice were given Zuogui pills, cetrorelix, or a combination of the two drugs intragastrically. After treatment, there were changes in the estrous cycle, serum sex hormone levels, oxidative stress-related indexes, growth biochemical factor levels, and SIRT1/P53/P21 expression. In comparison to the model group, the Zuogui pills and the cetrorelix+Zuogui pills group had significantly prolonged estrous periods and shortened interestrous periods, and the cetrorelix+Zuogui pills group had a significantly shortened cycle length. Follicle-stimulating hormone (FSH) decreased and estradiol (E2) increased in all treatment groups compared to the model group, oxidative stress indexes nitric oxide synthase (NOS), nitric oxide (NO), and reactive oxygen species (ROS) decreased, growth biochemical factors brain derived neurotrophic factor (BDNF) and growth differentiation factor 9 (GDF-9) concentrations increased significantly, and leukemia inhibitory factor (LIF) showed no significant change. SIRT1/P53/P21 immunohistochemical results revealed that, when compared to the model group, the expression of SIRT1 increased while the expression of P53 and P21 proteins decreased in all treatment groups, with the cetrorelix+Zuogui pills group having the largest decrease, with significant differences in all indicators. We conclude that cetrorelix combined with Zuogui pills for kidney nourishing and Yin recipe improved the oxidative stress response in the follicle by regulating the SIRT1/P53/P21 pathway, reducing peroxide product production, protecting ovarian function, and regulating ovarian hormone secretion, and its efficacy is superior to that of cetrorelix or Zuogui pills alone.
2.Study on Attitudes towards Deprescribing among Elderly Patients with Chronic Diseases in Several Communities of Chongqing
Sha ZHANG ; Long MENG ; Jiadan YANG ; Ling LUO ; Feng QIU
China Pharmacy 2018;29(10):1408-1411
OBJECTIVE:To provide reference for promoting smoothly implementation of deprescribing. METHODS:A total of 335 elderly patients with chronic disease were randomly selected from 4 communities and 9 village clinic of a Chongqing community health service center. Questionnaire survey was conducted about general information of respondents,disease and drug use condition and attitude to deprescribing by using Australian Patients'Attitudes Towards Deprescribing questionnaire as reference. The results of questionnaire survey were analyzed statistically. The cognitive function was assessed by Hastgawa Dementia Scale. The degree of weakness was evaluated by Chinese edition of Edmonton Frail Scale. The quality of life was evaluated by Chinese edition of European Five Dimensional Health (EQ-5D) Scale. RESULTS:Totally 311 valid questionnaires were obtained,with effective recovery rate of 92.8%. Overall,311 participants were recruited,with a median age of 70 years,5 types of median disease (hypertension was most common) and 5 types of median medication (mainly calcium channel blocker and non-insulin hypoglycemic agent);54.7%(170 cases)participants took multiple drugs. The attitudes towards deprescribing were that 39.5% of respondents believed that they took too many drugs;73.9% had a desire to reduce their drugs;83.6% reported that they would be willing to reduce drugs if their doctor said it was possible. The patients taking multiple drugs preferred to use less drugs (P=0.001) and reduce current drugs (P=0.001),and were more willing to reduce drug cost by reducing drug use;they were also more worried about drug side effects than those without taking multiple drugs (P=0.005). CONCLUSIONS:The phenomenon of elderly chronic diseases patients with multiple diseases and multiple drug use are popular in community. It is necessary to simpilfy prescription. Most elderly patients would like to reduce their medications if doctors say it is possible;the patients with multiple drug use are more willing to simplify prescription than those without multiple drug use.
3.Phosphodiesterase 5 Inhibitors Attenuate Unilateral Ureteral Obstruction-Induced Renal Fibrosis
Qing-xian ZHAI ; Meng LI ; Luo-sha LONG ; Bai-en LIANG ; Wei-dong WANG
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(6):931-942
ObjectiveTo investigate whether phosphodiesterase (PDE) 5 inhibitors sildenafil (SIL) or LW1646 prevented renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO). MethodsMale C57BL/6 mice were randomly divided into four groups (n =6), namely the Sham group, 7UUO group, 7UUO+SIL group and 7UUO+LW1646 group. Sildenafil (SIL) or LW1646, or vehicle was administered 1 hour before surgery, and the mice were continuously treated once daily (i. g., 50 mg/kg) for 7 days. The obstructed kidneys were harvested on day 7. Hematoxylin-eosin (HE) and Masson’s staining was used to examine renal histology. Immunoblotting and RT-qPCR were used to detect the expression levels of protein and mRNA for fibrosis, apoptosis, endoplasmic reticulum (ER) stress, autophagy, and pro-fibrotic factors. Human proximal tubule epithelial cells (HK-2) were treated with TGF-β1 for 48 hours or tunicamycin for 24 hours, respectively, to evaluate whether cyclic guanosine monophosphate (cGMP) or PDE5 inhibitors prevents ER stress and pro-fibrotic responses. ResultsAt the 7th days after UUO, the body weight of the mice showed a significant decrease (P< 0.000 1) compared with that in the sham group. The obstructed kidneys showed a significant tubular dilation and interstitial inflammation. The levels of protein and mRNA expression in apoptosis, ER stress, autophagy-related protein and pro-fibrotic factors were also markedly increased in UUO mice (P <0.05). In contrast, SIL or LW1646 treatment was associated with attenuated tubular dilation, infiltration of inflammatory cells and collagen content in the obstructed kidney of the mice. The protein and mRNA expression levels of renal TGF-β1 were markedly decreased, and the protein expression levels of apoptosis, endoplasmic reticulum stress, and autophagy markers were also significantly downregulated by PDE5 inhibitors. In HK-2 cells, TGF-β1 induced increased expression levels of fibronectin and BiP, which was at least partially reversed by cGMP, a product of PDE inhibition. Additionally, PDE5 inhibitors were found to modulate aberrant levels of autophagy and apoptosis. ConclusionIn conclusion, PDE5 inhibitors, in particular, LW1646, can alleviate the progression of fibrosis by improving ER stress, apoptosis and autophagy as well as downregulating protein and mRNA expression of TGF-β1.
4.Activation of TGR5 Attenuates Renal Fibrosis after Renal Ischemia Reperfusion Injury
Meng LI ; Luo-sha LONG ; Bai-en LIANG ; Long XU ; Xiao-duo ZHAO ; Wei-dong WANG ; Chun-ling LI
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(4):617-624
ObjectiveTo investigate the role of bile acid receptor TGR5 activation in renal fibrosis induced by unilateral ischemia reperfusion injury and contralateral nephrectomy (uIRIx) model. MethodsIn vivo: C57BL/6J mice were randomly divided into Sham group, uIRIx group and uIRIx+ lithcholic acid (LCA) group with 6 mice in each group. Kidney fibrosis was induced by uIRIx model, kidney function was evaluated by blood and urine biochemical indexes, and the degree of kidney injury was evaluated by HE staining. Masson staining and immunohistochemistry were used to evaluate the degree of renal fibrosis, and Western Blotting was used to detect the expression of related index proteins of renal cortical fibrosis. Sham group and uIRIx group were set in TGR5+/+ mice and TGR5-/- mice respectively, with 6 mice in each group. The degree of renal fibrosis in each group was detected by Western Blotting. In vitro: TGF-β1 was administered to induce pro-fibrosis response in human renal tubular epithelial cell line (HK2 cells), LCA was used for drug intervention, cytoskeleton was labeled with phalloidin-FITC staining and the expression of fibrosis related indicator protein in HK2 cells was detected by Western Blotting. ResultsIn vivo: Compared with the Sham group, plasma creatinine level (P=0.007) and urinary albumin/creatinine ratio (P=0.041) in uIRIx group were significantly increased, renal cortical protein TGR5 expression (P=0.002) was decreased, Fibronectin expression (P=0.020) and COL1A1 expression (P<0.001) were increased. At the same time, the kidney structure was damaged and collagen deposition was aggravated. LCA intervention effectively improved the kidney function and alleviated the degree of kidney injury and fibrosis. TGR5 gene knockout increased uIRIx-induced Fibronectin expression (P<0.001) and COL1A1 expression (P=0.001) compared with TGR5+/+ mice. In vitro: TGF-β1 induced morphological changes of HK2 cells, cytoskeletal depolymerization and recombination, and promoted the up-regulation of fibrosis index protein. LCA effectively inhibited the morphological changes and skeletal depolymerization induced by TGF-β1, and down-regulated the expression of fibrosis related indicator proteins. ConclusionsLCA alleviated renal fibrosis induced by uIRIx model, and knockout of TGR5 gene aggravated uIRIx induced renal fibrosis; In HK2 cells, LCA alleviated fibrogenic reaction induced by TGF-β1. This indicates that activation of TGR5 alleviates renal fibrosis induced by uIRIx.
5.BAX Deletion Accelerates Progression of BCR-ABL-Induced B-ALL in Mice.
Liang SHI ; Yuan-Yuan LONG ; Meng-QiSHA SHA ; Xi LUO ; Pei HUANG ; Yan CHEN
Journal of Experimental Hematology 2020;28(1):29-33
OBJECTIVE:
To explore whether BAX plays a role in the development of Philadelphia chromosome-positive leukemia and related mechanisms.
METHODS:
Target-gene knockout mice were used as bone marrow cell donors. Retrovirus over-expressing BCR-ABL were packaged. BCR-ABL-induced B-ALL mouse model was established through donor's B cells transfected by the retrovirus and the B cells over-expressing BCR-ABL were given to the receptor mice by tail vein injection. Western blot was used to detect the protein express and flow cytometry was used to analyze the B cell subpopulations in BAX and WT mouse bone marrows. Kaplan-Meier analysis was used to estimate the survival of diseased mice.
RESULTS:
BAX deletion caused faster development of BCR-ABL-induced leukemia in vitro and in vivo. BCR-ABL increased BCL-2 expression and enhanced BCL-2/BAX heterodimer formation.
CONCLUSION
The BAX deletion can accelerate the disease progression of BCR-ABL induced B-ALL.
6.Progress on the neuroprotective effects of ginsenoside Rg1
Jun-peng LONG ; Yang SUN ; Sha-sha LIU ; Jiao YAO ; Song-wei YANG ; Yan-tao YANG ; Gang PEI ; Lei MENG ; Qi-di AI ; Nai-hong CHEN
Acta Pharmaceutica Sinica 2023;58(1):21-26
Ginsenoside Rg1 is one of the most important saponins in ginseng. It has a wide range of pharmacological activities. It is considered to be a powerful neuroprotective agent. It has neuroprotective effects such as anti-neuroinflammation, anti-oxidative stress, anti-neuronal apoptosis, and enhancing memory. Rg1 shows a good application prospect in the prevention and treatment of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, stroke, and mental diseases such as depression. This paper reviews the research on the neuroprotective mechanism of Rg1 at home and abroad in recent years, in order to provide new research ideas for the clinical treatment of nervous system diseases.