1.Mechanism of Polyphyllin Ⅱ in Induction of Ferroptosis in Hepatocellular Carcinoma HepG2 Cells
Huizhong ZHANG ; Jian NI ; Hulinyue PENG ; Yibo ZHANG ; Xiaohan XU ; Shiman LI ; Yidan RUAN ; Yongqiang ZHANG ; Pingzhi ZHANG ; Aina YAO ; Ying WANG ; Xiaoxu DONG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):105-112
ObjectiveTo investigate the induction of ferroptosis by polyphyllin Ⅱ (PPⅡ) in hepatocellular carcinoma HepG2 cells and its underlying mechanism. MethodThe effect of PPⅡ (0, 1.5, 3.0, 4.5, 6.0, 9.0, 18.0 mg·L-1) on the in vitro proliferation of HepG2 cells was assessed using the methyl thiazolyl tetrazolium (MTT) assay. Colony formation ability of HepG2 cells was evaluated through a colony formation assay. Cell migration ability was assessed via a scratch assay. Lactate dehydrogenase (LDH) content in HepG2 cells was measured using a kit. Reactive oxygen species (ROS) levels in HepG2 cells were observed using a fluorescence inverted microscope. Malondialdehyde (MDA), glutathione (GSH), and free Fe2+ content in HepG2 cells were detected using respective kits. The mitochondrial ultrastructure in HepG2 cells was observed by transmission electron microscopy. The expression of ferroptosis-related proteins p53, solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), long-chain acyl-CoA synthetase 4 (ACSL4), and transferrin receptor 1 (TFR1) in HepG2 cells was detected using Western blot. ResultCompared with the control group, the PPⅡ treatment groups showed significantly decreased survival rate of HepG2 cells in a dose-dependent manner (P<0.01), significantly reduced number of cell colonies (P<0.01), significantly shortened scratch healing distance, inverse correlation of the migration distance with drug concentration (P<0.01), significantly increased LDH leakage in cells (P<0.01), significantly enhanced relative fluorescence intensity of intracellular ROS, and significantly increased accumulation of lipid peroxide MDA (P<0.01), decreased intracellular GSH content with increasing drug concentration (P<0.01), and significantly enhanced fluorescence intensity of FeRhoNox-1 in cells (P<0.01). Moreover, cells exhibited vacuolation, and mitochondria showed significant shrinkage with reduced or even disappeared cristae. Compared with the results in the control group, the expression of p53, ACSL4, and TFR1 proteins significantly increased, while the expression of SLC7A11 and GPX4 proteins significantly decreased in the PPⅡ treatment groups (P<0.05). ConclusionIn summary, PPⅡ induces ferroptosis in HepG2 cells by regulating the p53/SLC7A11/GPX4 signaling axis, promoting ACSL4 expression and Fe3+ uptake, leading to an imbalance in the antioxidant system.
2.Clinical effects of hyperbaric oxygen combined with citalopram on sleep disorders in patients with depression
Huijun DUAN ; Pingzhi WANG ; Aiping LI ; Xiaoqing CHEN
Chinese journal of nautical medicine and hyperbaric medicine 2020;27(1):46-49
Objective:To investigate the clinical effect and action mechanism of hyperbaric oxygen (HBO) combined with citalopram on sleep disorders.Methods:One hundred and forty patients with depression suffering from sleep disorder, admitted to Shanxi Bethune Hospital from March 2016 to June 2019, were enrolled and randomly divided into the observation group and the control group according to random number table method with 70 cases in each group. The control group was treated with citalopram, while the observation group was treated with HBO combined with citalopram. After 4 weeks treatment, the clinical effect, depression score, sleep disorder, serum interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cortisol levels of the two groups were observed.Results:After 4 weeks of treatment, the total effective rate of the observation group (94.29%) was significantly higher than that of the control group (77.14%), with statistically significant difference ( P<0.05). After treatment, the scores of sleep quality, sleep time, and depressive state of the two groups decreased significantly than those before treatment, and the decrease in the observation group was more significant after treatment, with statistically significant differences ( P<0.05 or P<0.01). The levels of IL-1, IL-6, TNF-α and cortisol in the two groups decreased significantly after treatment, and the decrease of the observation group was more significant, with statistically significant differences ( P<0.05 or P<0.01). Conclusion:HBO combined with citalopram could reduce the levels of serum IL-1, IL-6, TNF-α, and cortisol in patients with depression suffering from sleep disorders, and significantly improve depression and sleep disorders, indicating it can achieve satisfactory clinic effect.
3.Clinical effects of hyperbaric oxygen combined with citalopram on sleep disorders in patients with depression
Huijun DUAN ; Pingzhi WANG ; Aiping LI ; Xiaoqing CHEN
Chinese journal of nautical medicine and hyperbaric medicine 2020;27(1):46-49
Objective:To investigate the clinical effect and action mechanism of hyperbaric oxygen (HBO) combined with citalopram on sleep disorders.Methods:One hundred and forty patients with depression suffering from sleep disorder, admitted to Shanxi Bethune Hospital from March 2016 to June 2019, were enrolled and randomly divided into the observation group and the control group according to random number table method with 70 cases in each group. The control group was treated with citalopram, while the observation group was treated with HBO combined with citalopram. After 4 weeks treatment, the clinical effect, depression score, sleep disorder, serum interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cortisol levels of the two groups were observed.Results:After 4 weeks of treatment, the total effective rate of the observation group (94.29%) was significantly higher than that of the control group (77.14%), with statistically significant difference ( P<0.05). After treatment, the scores of sleep quality, sleep time, and depressive state of the two groups decreased significantly than those before treatment, and the decrease in the observation group was more significant after treatment, with statistically significant differences ( P<0.05 or P<0.01). The levels of IL-1, IL-6, TNF-α and cortisol in the two groups decreased significantly after treatment, and the decrease of the observation group was more significant, with statistically significant differences ( P<0.05 or P<0.01). Conclusion:HBO combined with citalopram could reduce the levels of serum IL-1, IL-6, TNF-α, and cortisol in patients with depression suffering from sleep disorders, and significantly improve depression and sleep disorders, indicating it can achieve satisfactory clinic effect.
4.Clinical effect of hyperbaric oxygen combined with transcranial electrical stimulation and memantine hydrochloride on cognitive impairment in the patients with craniocerebral injury
Yinlian LIU ; Shasha FAN ; Jing HUANG ; Pingzhi WANG ; Yajie YIN ; Liying XUE ; Ruijun CHEN ; Zhenping LIANG ; Jianwei DENG ; Ying LIANG
Chinese journal of nautical medicine and hyperbaric medicine 2019;26(4):320-323
Objective To investigate the clinical efficacy of hyperbaric oxygen (HBO) combined with transcranial electrical stimulation (tDCS) and memantine tablets on cognitive impairment in the patients with moderate to severe craniocerebral injury.Methods Forty-nine patients with moderate or severe cognitive impairment induced by trauma brain injury (TBI) who were admitted into the Rehabilitation Department and Neurosurgery Department of Shanxi University Hospital from May 2017 to May 2018 were enrolled for the study.The patients were divided into the HBO group (or group A,n =16),the HBO + tDCS group (or group B,n =16) and the HBO + tDCS + memantine group (or group C,n =17) in accordance with different treatment methods.The total scores of Montreal Cognitive Assessment Scale (MoCA) and the scores of each item before and 4 weeks after treatment,the Simple Mental State Examination Scale (MMSE) and Barthel Index (BI) were analyzed to determine improvement of cognitive impairment in the TBI patients.Results After 3 courses of treatment,MoCA comprehensive scores and sub-item scores were all significantly higher than those before treatment,with statistical significance (P < 0.01).In sub-items,the comprehensive scores of VS-EF,ATT,LANG,D-MEM and MoCA in group B were significantly higher than those in group A after treatment,also with statistical significance (P < 0.05).Following treatment,the scores of VS-EF,ATT,LANG and D-MEM in group C were all significantly higher than those in group B after treatment,also with statistical significance (P <0.05).The comprehensive scores of MMSE and ADL in group B and C after treatment were all significantly higher than those in group A,and statistical significance could be seen when comparisons were made between them (P < 0.01).The comprehensive scores of MMSE (21.23 ± 6.53) and ADL(64.38 ±12.80) in group C were all obviously higher than those in group B(17.61 ±6.35,5.39 ± 10.22),also with statistical significance (P < 0.05).Conclusion Comprehensive treatment with HBO + tDCS + memantine could achieve obvious better therapeutic effects on cognitive impairment of the patients with severe TBI.For this reason,it is worth further clinical application.
5.Clinical effect of hyperbaric oxygen combined with transcranial electrical stimulation and memantine hydrochloride on cognitive impairment in the patients with craniocerebral injury
Yinlian LIU ; Shasha FAN ; Jing HUANG ; Pingzhi WANG ; Yajie YIN ; Liying XUE ; Ruijun CHEN ; Zhenping LIANG ; Jianwei DENG ; Ying LIANG
Chinese journal of nautical medicine and hyperbaric medicine 2019;26(4):320-323
Objective To investigate the clinical efficacy of hyperbaric oxygen (HBO) combined with transcranial electrical stimulation (tDCS) and memantine tablets on cognitive impairment in the patients with moderate to severe craniocerebral injury.Methods Forty-nine patients with moderate or severe cognitive impairment induced by trauma brain injury (TBI) who were admitted into the Rehabilitation Department and Neurosurgery Department of Shanxi University Hospital from May 2017 to May 2018 were enrolled for the study.The patients were divided into the HBO group (or group A,n =16),the HBO + tDCS group (or group B,n =16) and the HBO + tDCS + memantine group (or group C,n =17) in accordance with different treatment methods.The total scores of Montreal Cognitive Assessment Scale (MoCA) and the scores of each item before and 4 weeks after treatment,the Simple Mental State Examination Scale (MMSE) and Barthel Index (BI) were analyzed to determine improvement of cognitive impairment in the TBI patients.Results After 3 courses of treatment,MoCA comprehensive scores and sub-item scores were all significantly higher than those before treatment,with statistical significance (P < 0.01).In sub-items,the comprehensive scores of VS-EF,ATT,LANG,D-MEM and MoCA in group B were significantly higher than those in group A after treatment,also with statistical significance (P < 0.05).Following treatment,the scores of VS-EF,ATT,LANG and D-MEM in group C were all significantly higher than those in group B after treatment,also with statistical significance (P <0.05).The comprehensive scores of MMSE and ADL in group B and C after treatment were all significantly higher than those in group A,and statistical significance could be seen when comparisons were made between them (P < 0.01).The comprehensive scores of MMSE (21.23 ± 6.53) and ADL(64.38 ±12.80) in group C were all obviously higher than those in group B(17.61 ±6.35,5.39 ± 10.22),also with statistical significance (P < 0.05).Conclusion Comprehensive treatment with HBO + tDCS + memantine could achieve obvious better therapeutic effects on cognitive impairment of the patients with severe TBI.For this reason,it is worth further clinical application.
6.Cost-minimization Analysis of Liraglutide and Insulin Glargine in the Treatment of Type 2 Diabetes Mellitus
Guangyi MENG ; Dongxiao WANG ; Jialian PANG ; Pingzhi PENG ; Jinquan MO ; Haolin YAN ; Hui LIANG ; Ping ZHANG
China Pharmacy 2016;27(17):2309-2311,2312
OBJECTIVE:To evaluate the clinical efficacy of liraglutide and insulin glargine in the treatment of type 2 diabetes mellitus (T2DM) and conduct pharmacoeconomic analysis, and to provide economical and reasonable T2DM treatment plan. METHODS:80 T2DM patients were randomized into liraglutide group and insulin glargine group,with 40 cases in each group. Both groups were given Metformin hydrochloride sustained-release tablet orally 0.5-2.0 g/d,and diabetes mellitus diet and sport training guide after oral antidiabetic drug withdrawal of previous treatment plan. Liraglutide group was given Liraglutide injection hypodermically,0.6-1.2 mg,qd;insulin glargine group was given insulin glargine hypodermically at 22 o’clock,initial dose of 0.2 IU/(kg·d),adjusted according to the levels of PG,FBG,nocturnal blood glucose level till FBG≤7 mmo1/L and 2 h PG ≤10 mmol/L in both group. Treatment course of 2 groups lasted for 12 weeks. The changes of FBG,2 h PG,HbA1c and BMI were ob-served in 2 groups before and after treatment. 2 therapy plans were evaluated and compared by cost-minimization analysis. RE-SULTS:After treatment,the levels of FBG,2 h PG and HbA1c decreased significantly in 2 groups,compared to before treatment, with statistical significance (P<0.05),but there was no statistical significant difference between 2 groups (P>0.05). After treat-ment,BMI of liraglutide group decreased significantly compared with before treatment and insulin glargine group,with statistical significance (P<0.05). There was no statistical significant difference in BMI of insulin glargine group before and after treatment (P>0.05). Cost-minimization analysis showed that the cost of insulin glargine group in reducing FBG,2 h PG and HbA1c were less than liraglutide group,but were more than liraglutide group in reducing BMI. Sensitivity analysis demonstrated the stability and reliability of cost-minimization analysis. CONCLUSIONS:Lira-glutide and insulin glargine have the same clinical efficacy,but insulin glargine need lower cost in blood glucose control,and liraglutide is better therapy plan for body weight control.
7.Bone marrow mesenchymal stem cells for repair of spinal cord injury:how to promote axonal regeneration?
Huili LI ; Chengfen DU ; Hongmei ZHENG ; Pingzhi HOU ; Yun WANG ; Zijun XIANG ; Guili LV ; Meng LI ; Haiqin YU ; Shanshan CHEN
Chinese Journal of Tissue Engineering Research 2014;(41):6703-6707
BACKGROUND:Stem cells have been shown to not only replace damaged cells, but also secrete trophic factors, bringing a bright future for the treatment of clinical spinal cord injury.
OBJECTIVE:To review the latest advances of bone marrow mesenchymal stem cells in animal and clinical research.
METHODS:A computer-based search of Kjmed and Wanfang databases was done for relevant articles published from April 2004 to April 2014 using the keywords of“stem cells, spinal cord injuries, embryonic stem cells, neural stem cells, mesenchymal stem cells”in English and Chinese, respectively.
RESULTS AND CONCLUSION:Total y 2 745 articles were initial y retrieved, and only 50 articles were included in result analysis. Bone marrow mesenchymal stem cells have become one of the most promising sources of stem cells in the treatment of spinal cord injury. Although the bone marrow mesenchymal stem cellin the treatment of spinal cord injury is stil in its infancy, it has certain effects on the repair of spinal cord injury. The mechanism of action of bone
marrow mesenchymal stem cells in the treatment of spinal cord injury is possibly related to the substitution effect, neurotrophic effects, suppression of the immune response and promoting axonal regeneration.

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