1.Honokiol alleviated neurodegeneration by reducing oxidative stress and improving mitochondrial function in mutant SOD1 cellular and mouse models of amyotrophic lateral sclerosis.
Yujun ZHOU ; Jingshu TANG ; Jiaqi LAN ; Yong ZHANG ; Hongyue WANG ; Qiuyu CHEN ; Yuying KANG ; Yang SUN ; Xinhong FENG ; Lei WU ; Hongtao JIN ; Shizhong CHEN ; Ying PENG
Acta Pharmaceutica Sinica B 2023;13(2):577-597
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons (MNs) with large unmet medical needs. Multiple pathological mechanisms are considered to contribute to the progression of ALS, including neuronal oxidative stress and mitochondrial dysfunction. Honokiol (HNK) has been reported to exert therapeutic effects in several neurologic disease models including ischemia stroke, Alzheimer's disease and Parkinson's disease. Here we found that honokiol also exhibited protective effects in ALS disease models both in vitro and in vivo. Honokiol improved the viability of NSC-34 motor neuron-like cells that expressed the mutant G93A SOD1 proteins (SOD1-G93A cells for short). Mechanistical studies revealed that honokiol alleviated cellular oxidative stress by enhancing glutathione (GSH) synthesis and activating the nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) pathway. Also, honokiol improved both mitochondrial function and morphology via fine-tuning mitochondrial dynamics in SOD1-G93A cells. Importantly, honokiol extended the lifespan of the SOD1-G93A transgenic mice and improved the motor function. The improvement of antioxidant capacity and mitochondrial function was further confirmed in the spinal cord and gastrocnemius muscle in mice. Overall, honokiol showed promising preclinical potential as a multiple target drug for ALS treatment.
2.Portable head and neck magnetic resonance imaging device in neurosurgery
Hongwei ZHU ; Houminji CHEN ; Long ZENG ; Qingshan XIAO ; Tao XIE ; Yanwu GUO ; Wangming ZHANG ; Qinghua WANG ; Chuanzhi DUAN ; Shizhong ZHANG ; Yiquan KE ; Hongbo GUO
Chinese Journal of Neuromedicine 2023;22(1):58-63
Objective:To explore the clinical application of portable head and neck magnetic resonance imaging (MRI) device in neurosurgery.Methods:A total of 213 patients with brain diseases who were scanned by portable head and neck MRI device in Center of Neurosurgery, Zhujiang Hospital, Southern Medical University from June to September 2022 were selected. The portable head and neck MRI images and 3.0T conventional MRI images of 10 randomly selected patients were compared; the differences in signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of different sequences were analyzed. Thirty-one patients accepted tracheal intubation/tracheotomy, or ventilator-assisted breathing were selected as special patient group, and another 30 patients were as general patient group; the differences in comprehensive diagnostic scores of portable head and neck MRI images were compared. Noise intensity differences in different sequences between 3.0T conventional MRI and portable head and neck MRI were statistically compared. Twenty hospitalized volunteers with normal hearing in our center from July to August 2022 were selected, conventional 3.0T MRI and portable head and neck MRI were performed successively, and the noise intensity of different sequences in them was evaluated by using a 5-point system.Results:Compared with those in 3.0T conventional MRI images, the SNR and CNR of T1WI, T2WI, and Liquid attenuated reverse recovery sequence (FLAIR) sequences in portable head and neck MRI images were significantly lower ( P<0.05). No significant difference was noted in the comprehensive diagnostic scores of portable head and neck MRI images between special patients and general patients ( P>0.05). Compared with that in the 3.0T conventional MRI, the noise intensity of different sequences in portable head and neck MRI was significantly reduced ( P<0.05). These volunteers had significantly reduced noise intensity scores of different sequences in portable head and neck MRI compared with that in conventional 3.0T MRI ( P<0.05). Conclusion:Portable head and neck MRI device is easy to use, enjoying high safety, imaging quality and suitability, which meets the clinical needs for neurosurgery patients.
3.Inhibition of ASCT2 induces hepatic stellate cell senescence with modified proinflammatory secretome through an IL-1α/NF-κB feedback pathway to inhibit liver fibrosis.
Feixia WANG ; Zhanghao LI ; Li CHEN ; Ting YANG ; Baoyu LIANG ; Zili ZHANG ; Jiangjuan SHAO ; Xuefen XU ; Guoping YIN ; Shijun WANG ; Hai DING ; Feng ZHANG ; Shizhong ZHENG
Acta Pharmaceutica Sinica B 2022;12(9):3618-3638
Senescence of activated hepatic stellate cells (aHSCs) is a stable growth arrest that is implicated in liver fibrosis regression. Senescent cells often accompanied by a multi-faceted senescence-associated secretory phenotype (SASP). But little is known about how alanine-serine-cysteine transporter type-2 (ASCT2), a high affinity glutamine transporter, affects HSC senescence and SASP during liver fibrosis. Here, we identified ASCT2 is mainly elevated in aHSCs and positively correlated with liver fibrosis in human and mouse fibrotic livers. We first discovered ASCT2 inhibition induced HSCs to senescence in vitro and in vivo. The proinflammatory SASP were restricted by ASCT2 inhibition at senescence initiation to prevent paracrine migration. Mechanically, ASCT2 was a direct target of glutaminolysis-dependent proinflammatory SASP, interfering IL-1α/NF-κB feedback loop via interacting with precursor IL-1α at Lys82. From a translational perspective, atractylenolide III is identified as ASCT2 inhibitor through directly bound to Asn230 of ASCT2. The presence of -OH group in atractylenolide III is suggested to be favorable for the inhibition of ASCT2. Importantly, atractylenolide III could be utilized to treat liver fibrosis mice. Taken together, ASCT2 controlled HSC senescence while modifying the proinflammatory SASP. Targeting ASCT2 by atractylenolide III could be a therapeutic candidate for liver fibrosis.
4.Study on Protective Effects of Scoparone on Acute Liver Injury Induced by CCl 4 in Mice
China Pharmacy 2021;32(2):231-235
OBJECTIVE:To study the protec tive effects of scoparone on acute liver injury induced by CCl 4 in mice and its potential molecular mechanism. METHODS :Fifty male Kunming mice were randomly divided into normal control group ,model group,silymarin group (positive control ,120 mg/kg),scoparone high-dose and low-dose groups (60,30 mg/kg),with 10 mice in each group. Administration groups were given relevant medicine intragastrically. Normal control group and model group were given constant volume of 0.5% sodium carboxymethyl cellulose solution ,once a day ,for 7 days. Two hours after last medication , except normal control group was intraperitoneally injected constant volume of olive oil ,other groups were intraperitoneally injected 0.1% CCl4 olive oil solution (10 mL/kg)at one time to establish the acute liver injury model. The pathological changes of liver tissues in mice were observed by HE staining ;the activity of AST ,ALT,SOD and CAT and the contents of IL- 1β,IL-6,TNF-α and MDA in serum were measured by ELISA ;the phosphorylation of nuclear factor κB(NF-κB)pathway related proteins (NF-κB p65,IκBα)in liver tissue were detected by Western blotting assay. RESULTS :Compared with normal control group ,serum activities of AST and ALT ,the contents of MDA ,IL-1β,IL-6 and TNF-α were significantly increased in model group,the activities of SOD and CAT were decreased significantly (P<0.05);obvious pathological changes were observed in liver tissues ; phosphorylation levels of NF-κB p65 and IκBα protein in liver tissues were significantly increased(P<0.05). Compared with model group ,the activities or contens of related factors in serum of mice were significantly reversed in silymarin group and scoparone high-dose and low-dose groups (P<0.05);the pathological changes of liver tissues were significantly reduced ;the phosphorylation levels of NF-κB p65 and IκBα protein in liver tissues were significantly reduced(P<0.05). CONCLUSIONS : Scoparone has a protective effect on CCl 4-induced acute liver injury in mice ,which is related to reducing oxidative stress levels and blocking the activation of NF-κB pathway,thereby inhibiting inflammatory response.
5.Mechanism of attention deficit hyperactivity disorder accompanied with obesity in children
Yiting JI ; Shizhong CAI ; Zhiying JIANG ; Xiaoyan SHI ; Cailong CHEN ; Ying WU ; Yan CHEN
Chinese Journal of Applied Clinical Pediatrics 2021;36(14):1118-1120
Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder among children and adolescents, and it is commonly accompanied with other developmental and psychological disorders.The prevalence of obesity in children continues to rise, and it is also a major social public concern that threatens human health.As a somatic comorbidity with ADHD, obesity is characterized by a high incidence.In this paper, the focus would be placed on the underlying mechanisms of ADHD accompanied with obesity from the aspects of genetics, perinatal period, environmental and neurobiological factors, which could provide a theoretical basis and intervention strategies for the early identification, rational treatment and long-term comprehensive management, as well as prevention and treatment effects of ADHD and its comorbidities.
6.Analysis of serum vitamin B levels and its correlation with social function in children with attention deficit hyperactivity disorder
Xiaoyun LU ; Yan CHEN ; Shizhong CAI ; Ling SHEN ; Zhiying JIANG ; Xuqin CHEN
Chinese Journal of Applied Clinical Pediatrics 2021;36(4):283-286
Objective:To analyze the associations between attention deficit hyperactivity disorder (ADHD) and serum vitamin B levels in children.Methods:A total of 103 ADHD children who were diagnosed in the Department of Child and Adolescent Healthcare of Children′s Hospital of Soochow University from September 2018 to April 2019 were selected as the ADHD group, and 89 children of the same age who underwent routine physical examinations served as the healthy control group.The serum levels of vitamin B, including vitamin B 1, vitamin B 2, vitamin B 6, vitamin B 9, and vitamin B 12, were measured by the methods of electrochemistry.Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) was applied to analyze the correlation between social function scores and vitamin B levels in ADHD children. Results:The levels of vitamin B 9[(12.55±2.22) nmol/L vs.(13.26±2.54) nmol/L] and vitamin B 12 [(278.54±32.00) ng/L vs.(288.90±31.32) ng/L] in ADHD children were significantly lower than those in healthy children( t=-2.064, -2.261, all P<0.05). No significant difference was observed in serum levels of vitamin B 1, vitamin B 2 and vitamin B 6 between the 2 groups (all P>0.05). Correlation analysis displayed that only vitamin B 12 level was significantly and negatively correlated with social function in the learning/school dimension ( r=-0.208, P=0.035), and no significant correlation was found between other vitamin B levels and social function (all P>0.05). Conclusions:The serum levels of vitamin B 9 and B 12 in ADHD children were obviously lower than those in healthy children of the same age.Serum vitamin B 12 deficiency had an influence on the social function of the learning/school in ADHD children.Attention to the monitoring and timely supplementation of vitamin B in childhood, especially vitamin B 9 and B 12, may be of positive significance in the prevention of the occurrence and development of ADHD to some extent.
7.Treatment of symptomatic severe carotid artery stenosis by angioplasty:clinical trial
Xiao CHEN ; Jing SU ; Shizhong ZHANG
Journal of Apoplexy and Nervous Diseases 2021;38(1):9-13
Objective To investigate the feasibility and efficacy of carotid endarterectomy and carotid artery stenting in the treatment of symptomatic severe carotid stenosis. Methods Retrospectively analyzed 203 patients with symptomatic severe carotid artery stenosis who received CEA or CAS treatment in Taishan Affiliated Hospital of Shandong First Medical University hospital from January 2016 to December 2018,The postoperative complications,and 1 year follow-up outcomes were recorded. Results A total of 203 patients with symptomatic severe carotid stenosis were included,and they were divided into the CAS group (n=132) and the CEA group (n=71). There were no statistically significant differences in age,gender,risk factors,blood pressure,etc. (P>0.05). In the analysis of perioperative complications,there were 3 cases of neck hematoma in CEA group (P=0.017). The proportion of stroke within 30 days in the CAS group was significantly higher than that in the CEA group (P=0.034). Results Of 1-year follow-up showed that the restenosis rate of CAS group was significantly higher than that of CEA group (P=0.047). There was no significant difference between the two groups in terms of myocardial infarction,death and stroke. Conclusion Both CAS group and CEA group can safely and effectively treat symptomatic severe carotid artery stenosis. In terms of perioperative complications,neck swelling in the CEA group was significantly higher than CAS group,and the proportion of stroke within 30 days and restenosis within 1-year flow up in the CAS group was significantly higher than that in the CEA group.
8. Research overview of the knee osteoarthritis from the theory of tendon
Dewan DENG ; Bin WANG ; Zhen ZHOU ; Shaoqing CHEN ; Shizhong WANG
International Journal of Traditional Chinese Medicine 2019;41(11):1274-1276
Knee osteoarthritis is characterized by degeneration of the articular cartilage and bone hyperplasia, expressed as pain, stiffness, swelling and limited activity in clinical practices. It belongs to the category of "tendon syndrome" in traditional Chinese medicine. The article aims to summarize the researches of "tendon syndrome" , and help to deepen the understanding of knee osteoarthritis underlying the treatment of "tendon syndrome" .
9. Analysis of the vascular risk factors for the elderly with mild cognitive impairment in community
Pei SUN ; Changjiang LUO ; Qingqing GENG ; Qian ZHANG ; Shuangshuang CHEN ; Wendi WANG ; Xiang WANG ; Yifeng DU ; Chuanqiang QU
Chinese Journal of Behavioral Medicine and Brain Science 2019;28(10):865-869
Objective:
To explore the effects of vascular risk factors on cognitive function among the elderly in community.
Methods:
A cross-sectional study was conducted in 1 269 elderly people (aged 65 and over) who were randomly selected from three communities.Through face-to-face interview, cognitive function was assessed by mini-mental state examination(MMSE), and blood samples were collected for laboratory examination.Logistic regression analysis was used to analyze the vascular risk factors affecting cognitive function.
Results:
Age ((73.1±6.6), (71.3±4.9),
10.Asiatic acid enhances the chemosensitivity of U87MG glioma cells to paclitaxel through inhibiting the expression of drug resistance related proteins
ZHANG Lei ; CHEN Lei ; CHEN Jie ; YANG Jingjing
Chinese Journal of Cancer Biotherapy 2018;25(4):340-345
[Abstract] Objective: To explore the inhibitive effect of asiatic acid (AA) on paclitaxel (PTX)-resistant glioma cells and its possible mechanism. Methods: The effects of AA on the proliferation and apoptosis of glioblastoma U87MG cells were detected by CCK-8 assay, Real-time quantitative polymerase chain reaction (qPCR) and Western blotting. The drug-resistant glioma cell line PR-U87MG was established by culturing the cells in concentration-increasing PTX. With U87MG cells as control, the PTX-resistance of PR-U87MG cells was confirmed using CCK-8 assay, and the mRNA and protein levels of MDR1 and LRP were measured with qPCR and western blotting. PR-U87MG cells were treated with AA, PTX or AA+PTX, and then the cell viability and apoptosis of each group were measured with CCK-8 assay, qPCR and Western blotting. Results: PTX-resistant PR-U87MG cell line was successfully established. AA inhibited the viability of U87MG and PR-U87MG cells in a dose-dependent manner (P<0.01) and significantly promoted their apoptosis (P<0.01). Compared with the group treated with AA or PTX alone, the group treated with the combination of AA and PTX had significantly decreased protein levels of PARP1 (P<0.01), drug-resistant related proteins (Pgp-1 and LRP [lung resistance protein], all P< 0.01), and markedly increased caspase 3 (P<0.01). Conclusion: AA could effectively enhance the sensitivity of U87MG cells to PTX, and the mechanism may be related to the suppressed expression of drug efflux-associated proteins Pgp-1 and LRP.


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