1.Mechanism of Different Dosage Forms of Kaixinsan in Improving Mitochondrial Function for Prevention and Treatment of Cognitive Disorder Based on AMPK/PGC-1α/SIRT3 Pathway
Shuyue KANG ; Yanzi YU ; Jiaqun SUN ; Wenxuan CHEN ; Yaqin YANG ; Qi WANG ; Weirong LI ; Limei YAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):15-24
ObjectiveTo explore the effects of different dosage forms of Kaixinsan (KXS) on the morphology and function of mitochondria in rat models of Alzheimer's disease (AD) and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group, model group, treatment groups receiving KXS decoction, powders, and granules (3.08 g·kg-1), as well as donepezil group (0.51×10-3 g·kg-1), with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin (STZ). After 30 days of administration, behavioral assessments were conducted, and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay (ELISA). Changes in mitochondrial membrane potential were measured via JC-1 staining, and superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and silent information regulator 3 (SIRT3) was detected by real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), and Western blot was used to examine the protein expression levels of optic atrophy protein1 (OPA1), mitochondrial fission protein 1 (FIS1), AMPK, p-AMPK, PGC-1α, and SIRT3. ResultsCompared with the sham group, rats in the model group had significantly lower recognition index, spontaneous alternation rate, escape latency, number of platform crossings, time spent in the target quadrant, and percentage of distance traveled in the target quadrant distance (P<0.05, P<0.01). Significant mitochondrial damage was observed in the hippocampal tissue, with a marked decrease in mitochondrial respiratory chain complex content (P<0.01) and reduced mitochondrial membrane potential (P<0.05). Additionally, the SOD activity was reduced, while ROS levels were elevated (P<0.01). The mRNA expression of PGC-1α and SIRT3 was significantly downregulated (P<0.01), along with decreased protein expression levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, whereas FIS1 protein expression was significantly upregulated (P<0.05, P<0.01). Compared with the model group, rats in KXS-treated groups (various dosage forms) showed significant improvement in behavioral indexes (P<0.05, P<0.01), reduced hippocampal mitochondrial damage, and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased (P<0.05, P<0.01), and mitochondrial membrane potentials were elevated (P<0.05). SOD activity was elevated, and ROS levels were significantly reduced (P<0.05, P<0.01). Furthermore, the mRNA expression of PGC-1α and SIRT3 was upregulated, with increased protein levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, while FIS1 protein expression levels were significantly reduced (P<0.05, P<0.01). Across the KXS-treated groups, the granule group showed a higher spontaneous alternation rate than the decoction and powder groups (P<0.05). ConclusionKXS decoction, powders, and granules can improve the learning and memory ability of rats, with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway, improvement of the mitochondrial function, and subsequent amelioration of the brain energy metabolism disorders.
2.Mechanism of Different Dosage Forms of Kaixinsan in Improving Mitochondrial Function for Prevention and Treatment of Cognitive Disorder Based on AMPK/PGC-1α/SIRT3 Pathway
Shuyue KANG ; Yanzi YU ; Jiaqun SUN ; Wenxuan CHEN ; Yaqin YANG ; Qi WANG ; Weirong LI ; Limei YAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):15-24
ObjectiveTo explore the effects of different dosage forms of Kaixinsan (KXS) on the morphology and function of mitochondria in rat models of Alzheimer's disease (AD) and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group, model group, treatment groups receiving KXS decoction, powders, and granules (3.08 g·kg-1), as well as donepezil group (0.51×10-3 g·kg-1), with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin (STZ). After 30 days of administration, behavioral assessments were conducted, and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay (ELISA). Changes in mitochondrial membrane potential were measured via JC-1 staining, and superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and silent information regulator 3 (SIRT3) was detected by real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), and Western blot was used to examine the protein expression levels of optic atrophy protein1 (OPA1), mitochondrial fission protein 1 (FIS1), AMPK, p-AMPK, PGC-1α, and SIRT3. ResultsCompared with the sham group, rats in the model group had significantly lower recognition index, spontaneous alternation rate, escape latency, number of platform crossings, time spent in the target quadrant, and percentage of distance traveled in the target quadrant distance (P<0.05, P<0.01). Significant mitochondrial damage was observed in the hippocampal tissue, with a marked decrease in mitochondrial respiratory chain complex content (P<0.01) and reduced mitochondrial membrane potential (P<0.05). Additionally, the SOD activity was reduced, while ROS levels were elevated (P<0.01). The mRNA expression of PGC-1α and SIRT3 was significantly downregulated (P<0.01), along with decreased protein expression levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, whereas FIS1 protein expression was significantly upregulated (P<0.05, P<0.01). Compared with the model group, rats in KXS-treated groups (various dosage forms) showed significant improvement in behavioral indexes (P<0.05, P<0.01), reduced hippocampal mitochondrial damage, and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased (P<0.05, P<0.01), and mitochondrial membrane potentials were elevated (P<0.05). SOD activity was elevated, and ROS levels were significantly reduced (P<0.05, P<0.01). Furthermore, the mRNA expression of PGC-1α and SIRT3 was upregulated, with increased protein levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, while FIS1 protein expression levels were significantly reduced (P<0.05, P<0.01). Across the KXS-treated groups, the granule group showed a higher spontaneous alternation rate than the decoction and powder groups (P<0.05). ConclusionKXS decoction, powders, and granules can improve the learning and memory ability of rats, with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway, improvement of the mitochondrial function, and subsequent amelioration of the brain energy metabolism disorders.
3.The current state of sunscreen development and analysis of its scientific application and safety
Shaomin ZHONG ; Yuchen TANG ; Wenxuan ZHANG ; Yan WU ; Hang LI
Chinese Journal of Preventive Medicine 2024;58(11):1771-1776
Regular and adequate use of broad-spectrum sunscreen has been proven to offer significant protection against acute Ultraviolet-induced photodamage, photoaging, immunosuppression, and the development of skin tumors. However, concerns regarding the safety and standardized use of sunscreens persist, including potential allergenicity and irritability of certain organic sunscreens, the impact of systemic absorption on the endocrine system, the effect on vitamin D synthesis and absorption, and environmental implications. Special caution is advised when using small molecule organic sunscreens and nanoparticle inorganic sunscreens, especially for infants, pregnant women, and areas with damaged skin.
4.A cortical thickness study of insomnia disorder patients based on MRI
Wei CHEN ; Hui WANG ; Ziyi LIU ; Yu SHANG ; Haining LI ; Wenxuan HAN ; Qiange ZHU ; Ming ZHANG
Journal of Practical Radiology 2024;40(11):1766-1769
Objective To investigate the changes of cortical thickness in patients with insomnia disorder(ID).Methods High-resolution MRI data were collected from 32 ID patients(ID group)and 30 healthy controls(HC)(HC group).The cortical thickness of both groups were analyzed using statistical parametric mapping 12(SPM12)software,while considering age,gender,and educational level as covariates.The cortical thickness in brain regions showed statistically significant differences was extracted for Pearson's correla-tion analyses with sleep and mood-related scales.Results Compared with the HC group,the ID group exhibited significantly decreased cortical thickness in brain regions such as the left insula,fusiform gyrus,orbitofrontal lobe,superior temporal gyrus,middle temporal gyrus,lateral occipital lobe and right caudal anterior cingulate gyrus[P<0.05,family-wise error(FWE)correction].Furthermore,reduced cortical thickness of the cingulate gyrus was negatively correlated with the Pittsburgh sleep quality index(PSQI)score(r=-0.437,P=0.012).Conclusion The cortical thickness of several brain regions associated with sleep and mood are significantly reduced in patients with ID,providing potential neuroimaging evidence for understanding the pathophysiological mechanism of ID.
5.Research advances on the regulation of microglia polarization by autophagy in ischemic stroke
Fangming WANG ; Wenxuan SHANG ; Jingwen ZHANG ; Yingxiao JI ; Litao LI
The Journal of Practical Medicine 2024;40(9):1324-1330
Ischemic stroke is feature by high incidence,high disability and high mortality.Inflammation plays an important role in the occurrence and development of ischemic stroke.Activated microglia exhibit two different phenotypes of proinflammatory(M1)and anti-inflammatory(M2),and regulating the transformation of microglia from M1 to M2 is the key to clinical benefit.Recent studies have shown that autophagy plays a key role in regulating phenotypic transformation of microglia.How to exert the regulatory role of autophagy and promote the transformation of microglia into M2 type has become a hotspot of clinical research in reducing secondary brain injury after stroke.This paper reviews the research progress of autophagy regulation of microglia polarization in ischemic stroke,aim-ing to provide a reference for further clinical and basic research in this field.
6.Exploration on the effects of Zhiganqing Prescription on insulin resistance and gluconeogenesis in NAFLD mice based on the PI3K/Akt/FoxO1 signaling pathway
Mingyu SHEN ; Jingya WANG ; Wenxuan XU ; Shuo WANG ; Leilei MA ; Jiahao HU ; Chao LI ; Xiaojin LA ; Ji'an LI
International Journal of Traditional Chinese Medicine 2024;46(10):1295-1302
Objective:To observe the protective effects of Zhiganqing Prescription on the liver of C57BL/6J non-alcoholic fatty liver disease (NAFLD) mice induced by high fat diet and its effects on PI3K/Akt/FoxO1 signaling pathway, insulin resistance (IR) and gluconogenesis.Methods:A total of 48 8-week-old male C57BL/6J mice were divided into control group ( n=8) and modeling group ( n=40) according to random number table method. The control group was fed with ordinary diet, and the model group was fed with high-fat diet. The NAFLD model was established after 8 weeks of feeding. The modeling group was divided into model group, Pioglitazone group, Zhiganqing Prescription low-, medium-, and high-dosage group ( n=8 in each group) according to random number table method, and drug intervention lasted for 8 weeks. The body mass of mice was measured regularly during administration. Fasting blood glucose (FBG) levels were measured at 0 and 8 weeks of administration, and oral glucose tolerance tests (OGTT) were conducted. After the experiment, serum levels of GPT, GOT, TC, TG, LDL-C, HDL-C, FINS and C-P were detected and HOMA-IR was calculated. The pathological morphology of liver was observed by HE and PAS staining. The expression levels of PI3K and p-Akt were detected by IHC staining. The protein expression levels of PI3K, Akt, p-Akt, FoxO1, p-FoxO1, G6PC and PCK1 were detected by Western blot. Results:Compared with model group, the body weight of mice in each administration group decreased at 4, 6 and 8 weeks ( P<0.05 or P<0.01). At the 8th week of administration, the levels of FBG and OGTT AUC in each administration group decreased ( P<0.05 or P<0.01), the levels of GPT, TC, TG and LDL-C decreased ( P<0.01), and the GOT levels in Zhiganqing Prescription medium- and high-dosage groups decreased ( P<0.01). The HDL-C level in Zhiganqing Prescription medium-dosage group decreased ( P<0.05 or P<0.01), and the HOMA-IR level in Zhiganqing Prescription low- and medium-dosage groups decreased ( P<0.05 or P<0.01). The levels of FINS and C-P in each administration group increased ( P<0.05 or P<0.01), and the expressions of PI3K protein and p-Akt/Akt, p-FoxO1 /FoxO1 protein in liver tissues increased ( P<0.05 or P<0.01). The protein expressions of G6PC and PCK1 decreased ( P<0.05 or P<0.01). Conclusion:Zhiganqing Prescription can effectively control the body mass, blood glucose, liver function and blood lipids of NAFLD mice, improve IR and gluconeogenesis, the mechanism of which may be related to the activation of PI3K/Akt/FoxO1 signaling pathway.
7.The current state of sunscreen development and analysis of its scientific application and safety
Shaomin ZHONG ; Yuchen TANG ; Wenxuan ZHANG ; Yan WU ; Hang LI
Chinese Journal of Preventive Medicine 2024;58(11):1771-1776
Regular and adequate use of broad-spectrum sunscreen has been proven to offer significant protection against acute Ultraviolet-induced photodamage, photoaging, immunosuppression, and the development of skin tumors. However, concerns regarding the safety and standardized use of sunscreens persist, including potential allergenicity and irritability of certain organic sunscreens, the impact of systemic absorption on the endocrine system, the effect on vitamin D synthesis and absorption, and environmental implications. Special caution is advised when using small molecule organic sunscreens and nanoparticle inorganic sunscreens, especially for infants, pregnant women, and areas with damaged skin.
8.Exploring the Mechanism of Action of Danshen Baoxin Cha on Depressed Mice with Coronary Heart Disease Based on Network Pharmacology and NLRP3 Inflammatory Pathway
Di ZHAO ; Yi HUANG ; Wenxuan CHEN ; Guoyang ZHENG ; Kairong ZHENG ; Limei YAO ; Huafeng PAN ; Weirong LI
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(10):1552-1561
Objective To explore the mechanism of action of Danshen Baoxin Cha(DBC) on depressed mice with coronary heart disease (CHD) based on network pharmacology and NLRP3 inflammatory pathway. Methods (1) TCMSP and BATMAN-TICAM databases were used to screen the DBC active ingredients and targets. The targets of CHD with depression were screened using the OMIM and Genecards databases. The targets of DBC active ingredients and related targets of CHD with depression were imported into Venny 2.1 online platform to obtain the intersection targets,which was the potential target of DBC in the treatment of CHD with depression. Protein-protein interaction (PPI) analysis was performed on the intersection targets using the STRING platform to screen the key targets. A "drug-active ingredients-disease-targets" network was created to select the main active ingredients and core targets of DBC for the treatment of CHD with depression. Thereafter,the primary targets were examined by GO function and KEGG pathway enrichment using the Metascape database.(2)Kunming mice were split into six groups of eight mice each at random:the control group,the model group,the positive control group (metoprolol tartrate 5.14 mg·kg-1+sertraline hydrochloride 10.3 mg·kg-1),and the DBC high-,middle-,and low-dose groups (30.8,15.4 and 7.7 g·kg-1·d-1). Chronic unpredictable mild stimulation (CUMS)and subcutaneous injection of isoprenaline hydrochloride (ISO) were used to induce a mice model of CHD with depression. Mice were treated orally with the corresponding drug once a day for 18 consecutive days. Behavioral experiments involving forced swimming test,tail suspension test,and open-field test were applied to detect depression levels of mice. Histopathological alterations in hippocampus tissues were noted using HE and Nissl staining. qPCR was used to determine the mRNA expression levels of IL-6,TNF-α,NLRP3,IL-1β,IL-10,and Caspase-1 in hippocampus tissues. Results(1) Sixty-five active components in Salvia and seven active components in green tea were screened out. A total of 1042 potential targets and 2116 CHD complicated with depression-related targets were obtained. The intersection of the targets of active components and disease-related targets was performed by Venny 2.1.0 platform to obtain 299 potential targets (common targets) of DBC in the treatment of CHD with depression. The core targets including IL-1β,AKT1,TNF-α,IL-6,VEGFA,CASP3 and IL-10 were screened through PPI network analysis of potential targets. Key active ingredients including vitamin B,luteolin,salvianolic acid,tanshinone ⅡA and catechin,as well as key targets,such as PTGS2、IL-1β、IL-6、TNF-α and IL-10,were obtained by network analysis of "drugs-active ingredients-disease-targets". The potential targets were correlated with biological processes such as inflammation response,regulation of tumour necrosis factor (TNF),glucocorticoid regulation,regulation of nuclear factor kappa B(NF-κB) transcription factor,as well as major pathways including PI3K-Akt signaling pathway,TNF signaling pathway,apoptosis signaling pathway,and NF-κB signaling pathway.(2) Compared with the control group,mice in the model group showed a significant decrease in the total and center distance of the open field (P<0.01) and a significant increase in the time of forced swimming and immobility time of tail suspension test (P<0.01). The mRNA expression of IL-6,TNF-α,NLRP3,IL-1β,and Caspase-1 was significantly up-regulated(P<0.01) in the hippocampus tissues,but IL-10 mRNA expression was down-regulated (P<0.05). Compared with the model group,the total and center distance in DBC high-,middle-,and low-dose groups were significantly up-regulated(P<0.05,P<0.01),and the time of forced swimming and immobility time of tail suspension test were significantly down-regulated (P<0.01). The mRNA expression of IL-6,TNF-α,NLRP3,IL-1β and Caspase-1 of the DBC high-,middle-,and low-dose groups were significantly down-regulated(P<0.01),IL-10 mRNA expression in mice hippocampus tissue of DBC high-and middle-dose groups was up-regulated (P<0.01). Conclusion The intervention effect of DBC on depressed mice with CHD may be achieved by active ingredients including luteolin,tanshinone,salvianolic acid and catechin acting on the key targets,such as IL-6,TNF-α,IL-1β and IL-10,to regulate the NLRP3 inflammatory signaling pathway.
9.Mediating role of health education competency in the relationship between supportive communication and general self-efficacy among medical undergraduates
Hui YIN ; Wenxuan LI ; Ying ZHANG ; Yuchun TAO ; Zehui LI ; Wei LIU ; Zuoming ZHANG ; Limin WANG ; Depin CAO
Chinese Journal of Medical Education Research 2024;23(3):347-352
Objective:To explore the factors influencing the supportive communication ability of medical undergraduates, and to propose strategies to improve supportive communication.Methods:By cluster sampling, we selected 388 medical undergraduates of grades 2017 and 2018 from Harbin Medical University for a questionnaire survey on supportive communication, general self-efficacy, and health education abilities. SPSS 22.0 was used for descriptive statistical analysis. AMOS 22.0 was used to construct a structural equation model to verify the relationship between the three variables. Mediating effects were also tested.Results:The students showed good supportive communication ability, with a total score of (74.28±10.84) points. The general self-efficacy score was (27.81±5.58) points, and the total score of health education ability was (25.50±4.76) points. General self-efficacy had direct positive effects on supportive communication and health education abilities ( β=0.75, 0.31, both P<0.001). Health education ability had a direct positive effect on supportive communication ability ( β=0.14, P<0.001). Health education ability played a significant mediating role in the influence of general self-efficacy on supportive communication ability (standardized mediating effect value=0.042, P<0.01), with the mediating effect accounting for 5.1%. Conclusions:The health education competency of medical undergraduates can mediate the effect of general self-efficacy on supportive communication ability. By strengthening medical humanities education to increase general self-efficacy and also emphasizing the cultivation of health education competency, the supportive communication ability of students can be improved.
10.Immune reconstitution and influencing factors in HIV infected men who have sex with men with access to antiviral therapy in Guangxi Zhuang Autonomous Region from 2005 to 2021
Ni CHEN ; He JIANG ; Huanhuan CHEN ; Qiuying ZHU ; Xiuling WU ; Jianjun LI ; Nengxiu LIANG ; Qin MENG ; Xuanhua LIU ; Jinghua HUANG ; Wenxuan HOU ; Zhaoquan WANG ; Guanghua LAN
Chinese Journal of Epidemiology 2024;45(4):529-535
Objective:To analyze immune reconstitution and influencing factors in HIV infected men who have sex with men (MSM) with access to antiviral therapy (ART) in Guangxi Zhuang Autonomous Region (Guangxi) during 2005-2021.Methods:The data were collected from Chinese Disease Prevention and Control Information System. The study subjects were HIV infected MSM with access to the initial ART for ≥24 weeks in Guangxi from 2005 to 2021 and HIV RNA lower than the detection limit within 24 months. The proportion of infected MSM who had immune reconstitution after ART was calculated. Cox proportional hazard regression model was used to analyze the influencing factors of immune reconstitution. Software SPSS 24.0 was used for statistical analysis.Results:A total of 3 200 HIV infected MSM were enrolled, in whom 15.56 % (498/3 200) had no immune reconstitution, 14.78% (473/3 200) had moderate immune reconstitution, and the rate of complete immune reconstitution was 69.66% (2 229/3 200). The M ( Q1, Q3) of ART time for immune reconstitution was 12 (5, 27) months. Multivariate Cox proportional risk regression model analysis results showed that compared with those with initial ART at age ≥30 years, WHO clinical stage Ⅲ/Ⅳ illness, baseline BMI <18.50 kg/m 2 and baseline CD4 +T lymphocyte (CD4) counts <200 cells/μl, HIV infected MSM with initial ART at age <30 years, WHO clinical stageⅠ/Ⅱ illness, baseline BMI≥24.00 kg/m 2 and baseline CD4 counts ≥200 cells/μl were more likely to have complete immune reconstitution. Conclusions:In the HIV infected MSM in Guangxi, failures to achieve moderate and complete immune reconstitution were observed. Surveillance and ART regimen should be improved for key populations, such as those with older age and low baseline CD4 counts.

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