1.Mechanism of Aerobic Exercise in Delaying Brain Aging in Aging Mice by Regulating Tryptophan Metabolism
De-Man ZHANG ; Chang-Ling WEI ; Yuan-Ting ZHANG ; Yu JIN ; Xiao-Han HUANG ; Min-Yan ZHENG ; Xue LI
Progress in Biochemistry and Biophysics 2025;52(6):1362-1372
ObjectiveTo explore the molecular mechanism of aerobic exercise to improve hippocampal neuronal degeneration by regulating tryptophan metabolic pathway. Methods60 SPF-grade C57BL/6J male mice were divided into a young group (2 months old, n=30) and a senile group (12 months old, n=30), and each group was further divided into a control group (C/A group, n=15) and an exercise group (CE/AE group, n=15). An aerobic exercise program was used for 8 weeks. Learning memory ability was assessed by Y-maze, and anxiety-depression-like behavior was detected by absent field experiment. Hippocampal Trp levels were measured by GC-MS. Nissl staining was used to observe the number and morphology of hippocampal neurons, and electron microscopy was used to detect synaptic ultrastructure. ELISA was used to detect the levels of hippocampal Trp,5-HT, Kyn, KATs, KYNA, KMO, and QUIN; Western blot was used to analyze the activities of TPH2, IDO1, and TDO enzymes. ResultsGroup A mice showed significant decrease in learning and memory ability (P<0.05) and increase in anxiety and depressive behaviors (P<0.05); all of AE group showed significant improvement (P<0.05). Hippocampal Trp levels decreased in group A (P<0.05) and increased in AE group (P<0.05). Nidus vesicles were reduced and synaptic structures were degraded in group A (P<0.05), and both were significantly improved in group AE (P<0.05). The levels of Trp, 5-HT, KATs, and KYNA were decreased (P<0.05) and the levels of Kyn, KMO, and QUIN were increased (P<0.05) in group A. The activity of TPH2 was decreased (P<0.05), and the activities of IDO1 and TDO were increased (P<0.05). The AE group showed the opposite trend. ConclusionThe aging process significantly reduces the learning memory ability and increases the anxiety-depression-like behavior of mice, and leads to the reduction of the number of nidus vesicles and degenerative changes of synaptic structure in the hippocampus, whereas aerobic exercise not only effectively enhances the spatial learning memory ability and alleviates the anxiety-depression-like behavior of aging mice, but also improves the morphology and structure of neurons in hippocampal area, which may be achieved by the mechanism of regulating the tryptophan metabolic pathway.
2.Ablation of macrophage transcriptional factor FoxO1 protects against ischemia-reperfusion injury-induced acute kidney injury.
Yao HE ; Xue YANG ; Chenyu ZHANG ; Min DENG ; Bin TU ; Qian LIU ; Jiaying CAI ; Ying ZHANG ; Li SU ; Zhiwen YANG ; Hongfeng XU ; Zhongyuan ZHENG ; Qun MA ; Xi WANG ; Xuejun LI ; Linlin LI ; Long ZHANG ; Yongzhuo HUANG ; Lu TIE
Acta Pharmaceutica Sinica B 2025;15(6):3107-3124
Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.
3.Correlation of CD200-CD200R axis and diseases and its research progress
Han XU ; Yu-xin BI ; Gui-xia LI ; Jian LI ; Liu-li WANG ; Rui-jia HAO ; Xue-min ZHENG ; Rui-jing HUANG ; Jin HAN ; Fei LI ; Gen-bei WANG
Acta Pharmaceutica Sinica 2024;59(4):822-830
CD200 and its receptor CD200R constitute an endogenous inhibitory signal. The binding of CD200 and CD200R can regulate the immune response to pathogenic stimuli, which has received much attention in recent years. It has been found that CD200-CD200R is involved in the regulation of many kinds of pathological inflammation, including autoimmune diseases, cardiac cerebrovascular disease, infection and tumor. This paper reviews the protein structure, distribution, expression, biological function of CD200-CD200R and the correlation with diseases, and analyses the current status and development ideas of CD200-CD200R as drug targets. It aims to provide theoretical support for new drug research and development based on this target.
4.Chemical diversity of azaphilones from the marine-derived fungus Talaromyces sp. HK1-18
Jia-cheng XUE ; Zhong-hui LI ; Bao-cong HAO ; Yao-yao ZHENG ; Xia-hao ZHU ; Zhi-xin CHEN ; Min CHEN
Acta Pharmaceutica Sinica 2024;59(5):1478-1483
GNPS-based mass spectrum-molecular networks is an effective strategy for rapidly identifying known natural products and discovering novel structures. The chemical diversity of azaphilones from the fermentation extracts of
5.Effects of Zhuangyao Shuanglu Tongnao Formula on neuronal apoptosis of rats with ischemia-reperfusion induced injury
Yang ZHAI ; Xue-Ni MO ; Hong-Li TENG ; Yue-Qiang HU ; Guang-Shan ZHENG ; Wei MA ; Peng YANG ; Xiao-Ping MEI ; Min ZOU ; Kai-Hua WANG
Chinese Traditional Patent Medicine 2024;46(3):795-802
AIM To investigate the effects of Zhuangyao Shuanglu Tongnao Formula on neuronal apoptosis in rats with cerebral ischemia-reperfusion injury based on the study of oxidative stress and inflammatory response.METHODS The rats were randomly divided into the sham operation group,the model group,the edaravone group(3.0 mg/kg),the low,medium and high dose groups(9.0,18.0,36.0 g/kg)of Zhuangyao Shuanglu Tongnao Formula,with 18 rats in each group.The middle cerebral artery occlusion/reperfusion was conducted by thread embolism method to simulate cerebral ischemia reperfusion injury in rats followed by 6 days corresponding drugs administration.Subsequently,the rats had their neurological function deficit scored by Zeal Longa scoring method;their sizes of cerebral infarction areas measured by TTC staining;their pathological damage and apoptosis of neurons in hippocampal CA1 area of ischemic penumbra of the brain tissue detected by HE staining and TUNEL staining;their SOD activity and levels of GSH,MDA,IL-6,IL-1β,TNF-α in brain tissue detected by kits;and their protein expressions of Bax,Bcl-2,caspase-3,cleaved-capase-3,TLR4,NF-κB p65,Nrf2,HO-1 in rat brain tissue determined by Western blot.RESULTS Compared with the model group,the groups intervened with edaravone,medium and high dose of Zhuangyao Shuanglu Tongnao Formula displayed improvements in the scores of nerve function defects,the rate of cerebral infarction,the rate of neuronal apoptosis,the levels of IL-6,IL-1β,TNF-α and MDA in the ischemic penumbra of brain tissues,the protein expressions of Bax and TLR4,the ratio of cleaved-capase-3/caspase-3 and p-NF-κB p65/NF-κB p65(P<0.05),the levels of GSH,the activity of SOD and the protein expressions of Bcl-2,Nrf2 and HO-1(P<0.05).CONCLUSION Being an inhibitor of oxidative stress and inflammatory response,Zhuangyao Shuanglu Tongnao Formula can alleviate brain injury in rats with cerebral ischemia reperfusion injury through the inhibition of neuronal apoptosis and improvement of neural function mediated by the inhibition of TLR4/NF-κB signal pathway and activation of Nrf2/HO-1 signal pathway.
6.Effect of Therapeutic Communication on Anxiety and Hope Level of Cervical Cancer Surgery Patients
Caixia ZHENG ; Xue LI ; Shuiying DONG ; Min XIE ; Xuesong CAO ; Pan LEI
Chinese Medical Ethics 2024;35(4):396-400
The aim is to evaluate the effect of therapeutic communication on cervical cancer patients’ preoperative anxiety and hope level. The convenience sampling method was used to select the inpatients who will receive radical surgery for cervical cancer in the department of obstetrics and gynecology of the Second Affiliated Hospital of Xi’an Jiaotong University from November 2016 to November 2019 as the research object. 50 patients were grouped by the random number table method: 25 patients were in the intervention group, and 25 patients were in the control group. Patients in the intervention group were given therapeutic communication on the basis of routine nursing, and patients in the control group were given routine nursing. Both groups were investigated with the Self-Rating Anxiety Scale (SAS) and Herth Hope Index (HHI) on the first day of admission and the day before surgery. Before the intervention, there was no statistically significant difference between the two groups (P>0.05) . After the intervention, the anxiety level of the intervention group was lower than that of the control group (P<0.05), and the hope level was higher than that of the control group (P<0.05). It can be seen that therapeutic communication can alleviate preoperative anxiety of cervical cancer patients, improve their hope level, promote patient recovery, and ease tense medical relationship.
7.Study on the Mechanism of Guanyuan Mingmen Sequential Acupuncture Activating FSHR/cAMP/PKA Pathway to Promote Granulosa Cell Proliferation in POI Model Rats
Jiang-Hong XU ; Yue-Lai CHEN ; Ping YIN ; Xue-Dan ZHAO ; Hui-Min ZHENG ; Jun-Wei HU ; Lu-Min LIU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(4):965-972
Objective To observe the therapeutic effects and mechanisms of Guanyuan Mingmen Sequential Acupuncture on rats with premature ovarian insufficiency(POI)model.Methods Female SD rats were divided into the blank group,the model group,the protein kinase A(PKA)inhibitor(H89)+acupuncture group,and the acupuncture group,with 12 rats in each group.Except for the blank group,the POI model was prepared by gavage with Tripterygium Glycosides Tablets in the other three groups of rats.After the model was successfully established,the blank group and the model group were bundled once a day;in the acupuncture group,Guanyuan(RN4)point was taken during the intermotility period,and in the pre-motility period,Mingmen(DU4)point was taken;in the H89+acupuncture group,the intervention was performed in accordance with the acupuncture protocol of the acupuncture group,and H89 was injected intraperitoneally for 30 minutes prior to each acupuncture session.Continuous intervention was performed for 20 days.Samples were taken from each group of rats in the first estrus period and in proestrus period after intervention.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of follicle stimulating hormone(FSH)and estradiol(E2)during the estrous phase,Western Blot was used to measure the protein expressions of follicle stimulating hormone receptor(FSHR)and aromatase P450(P450arom)during the estrous phase,and the activity of granulocytes during the estrous phase and the proestrus phase were measured using the cell-counting kit 8(CCK-8)method.The immunohistochemistry method was used to detect the protein expression of pre-motility proliferating cell nuclear antigen(PCNA).Results(1)Compared with the blank group,the serum FSH level of the model group and H89+acupuncture group was significantly increased(P<0.01),and the E2 level was significantly decreased(P<0.001);there was no difference between the FSH level of the H89+acupuncture group and that of the model group(P>0.05),and the E2 level of the H89+acupuncture group was lower than that of the model group(P<0.05);the FSH level of the acupuncture group was lower than that of the model group and that of the H89+acupuncture group(P<0.05),had no difference with the blank group(P>0.05),E2 level was significantly higher than the model group and H89+ acupuncture group(P<0.01),still being lower than the blank group(P<0.05).(2)The protein expressions of FSHR and P450arom in the model group and H89 + acupuncture group was lower than those in the blank group;the protein expression of FSHR in the H89 + acupuncture group was not different from that in the model group(P>0.05),while the protein expression level of P450arom was lower than that in the model group(P<0.05);the protein expression levels of FSHR and P450arom in the acupuncture group were higher than those in the model group and H89 + acupuncture group,but still lower than those in the blank group(P<0.05).(3)Both GCs activity and average optical density value of PCNA in the model group and H89+acupuncture group were lower than the blank group(P<0.05);both GCs activity and average optical density value of PCNA in the H89+acupuncture group were lower than the model group(P<0.05);the activity of GCs and average optical density value of PCNA of the acupuncture group were significantly higher than that of the model group and H89+acupuncture group(P<0.05 or P<0.01).Conclusion Guanyuan Mingmen Sequential Acupuncture can regulate sex hormone levels,increase GCs activity and promote GCs cell proliferation by up-regulating protein expressions of follicle stimulating hormone receptor(FSHR)/cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)pathway FSHR,P450arom,thus improving POI.
8.TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children
Xi MING ; Liqun WU ; Ziwei WANG ; Bo WANG ; Jialin ZHENG ; Jingwei HUO ; Mei HAN ; Xiaochun FENG ; Baoqing ZHANG ; Xia ZHAO ; Mengqing WANG ; Zheng XUE ; Ke CHANG ; Youpeng WANG ; Yanhong QIN ; Bin YUAN ; Hua CHEN ; Lining WANG ; Xianqing REN ; Hua XU ; Liping SUN ; Zhenqi WU ; Yun ZHAO ; Xinmin LI ; Min LI ; Jian CHEN ; Junhong WANG ; Yonghong JIANG ; Yongbin YAN ; Hengmiao GAO ; Hongmin FU ; Yongkun HUANG ; Jinghui YANG ; Zhu CHEN ; Lei XIONG
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(7):722-732
Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.
9.The Effect of Blood Lipid Profiles on Chronic Kidney Disease in a Prospective Cohort:Based on a Regression Discontinuity Design
Lyu KANG ; Liu SHAODONG ; Liu YANLI ; You JINLONG ; Wang XUE ; Jiang MIN ; Yin CHUN ; Zhang DESHENG ; Bai YANA ; Wang MINZHEN ; Zheng SHAN
Biomedical and Environmental Sciences 2024;37(10):1158-1172
Objective Previous studies on the association between lipid profiles and chronic kidney disease(CKD)have yielded inconsistent results and no defined thresholds for blood lipids. Methods A prospective cohort study including 32,351 subjects who completed baseline and follow-up surveys over 5 years was conducted.Restricted cubic splines and Cox models were used to examine the association between the lipid profiles and CKD.A regression discontinuity design was used to determine the cutoff value of lipid profiles that was significantly associated with increased the risk of CKD. Results Over a median follow-up time of 2.2(0.5,4.2)years,648(2.00%)subjects developed CKD.The lipid profiles that were significantly and linearly related to CKD included total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),TC/HDL-C,and TG/HDL-C,whereas low-density lipoprotein cholesterol(LDL-C)and LDL-C/HDL-C were nonlinearly correlated with CKD.TC,TG,TC/HDL-C,and TG/HDL-C showed an upward jump at the cutoff value,increasing the risk of CKD by 0.90%,1.50%,2.30%,and 1.60%,respectively,whereas HDL-C showed a downward jump at the cutoff value,reducing this risk by 1.0%.Female and participants with dyslipidemia had a higher risk of CKD,while the cutoff values for the different characteristics of the population were different. Conclusion There was a significant association between lipid profiles and CKD in a prospective cohort from Northwest China,while TG,TC/HDL-C,and TG/HDL-C showed a stronger risk association.The specific cutoff values of lipid profiles may provide a clinical reference for screening or diagnosing CKD risk.
10.A cross-sectional survey on the types of antiviral treatment plans for patients with chronic hepatitis B
Xiulan XUE ; Qianguo MAO ; Qingfa RUAN ; Feng MIN ; Wenqi HUANG ; Xiaoting ZHENG ; Huiqing LIANG
Chinese Journal of Hepatology 2024;32(1):29-34
Objective:To understand the current antiviral treatment status and various clinical types of treatment plans in Xiamen City so as to explore ways to improve and optimize the diagnosis and treatment standards for chronic hepatitis B.Methods:A cross-sectional survey method was used to study the antiviral treatment status and treatment plans for chronic hepatitis B patients who visited and were diagnosed in the Department of Infectious Diseases and Hepatology of all tertiary hospitals in Xiamen City at 0:00~23:59 on May 25, 2022.Results:A total of 665 cases were surveyed in this study, with an antiviral treatment rate of 81.2%(540/665). The antiviral treatment rate of patients who accorded with the current guidelines for antiviral treatment indications was 85.8%(507/591). The antiviral treatment rate for 362 outpatients was 72.9%(264/362). Among them, the antiviral treatment rates were 80.1%, 89.3%, and 25.0%(226/282, 25/28, 13/52), respectively, for patients diagnosed with chronic hepatitis B, hepatitis B cirrhosis, and hepatitis B surface antigen-carrying status. The treatment plan for all outpatient patients was mainly oral nucleos(t)ide analogues, accounting for 59.1%(214/362). The antiviral treatment rate for 303 inpatients was 91.1%(276/303). The various clinical types of antiviral therapy rates among all patients were 70%~95%. The antiviral treatment plan for inpatients was mainly based on pegylated interferon alpha treatment, accounting for 72.6%(220/303).Conclusion:Antiviral treatment for chronic hepatitis B in Xiamen City can still be strengthened to meet the current demand for expanding antiviral treatment indications. Antiviral treatment rates and various types of treatment plans differ between outpatients and inpatients; thus, further awareness and acceptance of the goal of improving antiviral therapy, especially in outpatients, and the possibility for a clinical cure based on pegylated interferon alpha treatment are needed to maximize the benefit to more patients.

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