1.Screening of Antidepressant Active Components from Curcumae Rhizoma and Its Mechanism in Regulating Nrf2/GPX4/GSH Pathway
Yonggui SONG ; Delin DUAN ; Meixizi LAI ; Yali LIU ; Zhifu AI ; Genhua ZHU ; Huanhua XU ; Qin ZHENG ; Ming YANG ; Dan SU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):211-221
ObjectiveTo screen and evaluate the antidepressant compounds of Curcumae Rhizoma, and explore its mechanism of regulating the nuclear factor erythroid 2-related factor 2(Nrf2)/glutathione(GSH) peroxidase 4(GPX4)/GSH pathway from an antioxidant perspective. MethodsThe antioxidant activities in vitro of 11 characteristic components from Curcumae Rhizoma, including curcumol, curgerenone, curdione, curzerene, curcumenol, curcumenone, dehydrocurdione, isocurcumenol, furanodienone, furanodiene and zederone, were detected using 1,1-diphenyl-2-picrylhydrazyl(DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt(ABTS) radical scavenging assays. The depression in Drosophila melanogaster was induced by chronic unpredictable mild stress(CUMS), and W1118 wild-type male D. melanogaster were randomly divided into blank group, model group, curcumol group, curgerenone group, curdione group, curzerene group, curcumenol group,curcumenone group, dehydrocurdione group, isocurcumenol group, furanodienone group, furanodiene group, zederone group and fluoxetine group(10 μmol·L-1). The treatment groups received a dose of 0.1 g·L-1 of 11 characteristic components from Curcumae Rhizoma, while the blank and model groups were administered equivalent volumes of solvent. The sucrose preference test, climbing test and forced swimming test were used to evaluate the behavioral indicators of depression in D. melanogaster. Liquid chromatography-mass spectrometry(LC-MS) was used to detect the levels of 5-hydroxytryptamine(5-HT) and dopamine(DA) in the brain of D. melanogaster, and the entropy weight method was used to comprehensively evaluate neurobehavioral and neurotransmitter indicators, resulting in the identification of the antidepressant active components of Curcumae Rhizoma. In addition, a mouse depression model was established by CUMS, and C57BL/6J mice were randomly divided into blank group, model group, low and high dose groups of curzerene(0.5, 1 mg·kg-1), and fluoxetine group(10 mg·kg-1) to confirm the antidepressant effect of the optimal active ingredient by behavioral analysis. Flow cytometry was used to detect the content of reactive oxygen species(ROS) in the hippocampus of mice from each group. Enzyme-linked immunosorbent assay was used to detect the contents of adenosine triphosphate(ATP), superoxide dismutase(SOD), catalase(CAT) and GSH. Transmission electron microscope(TEM) was used to observe the effect of curzerene on the ultrastructure of mitochondria in hippocampal tissue. Western blot was performed to determine the level of Nrf2 protein, and Nrf2 inhibitor(ML385) was used to verify the relationship between the antidepressant effect of curzerene and regulation of Nrf2. Real time fluorescence quantitative polymerase chain reaction(Real-time PCR) was employed to detect the effect of curzerene on the mRNA expression level of GPX. ResultsIn vitro antioxidant experiments showed that curzerene and curgerenone exhibited the most significant ability to scavenge free radicals, and comprehensive evaluation results of entropy weight method indicated that curzerene stood out as the most promising active component. Compared with the blank group, the model group exhibited a significant decrease in sucrose preference coefficient and the number of times entering the open field center(P<0.01), as well as a significant increase in immobility time in the forced swimming and tail suspension tests(P<0.01), and the ROS content in hippocampus significantly elevated(P<0.01), while the ATP content significantly reduced(P<0.01). In the hippocampal neurons of the model group, mitochondrial cristae were disordered, with vacuolation of the inner membrane and severe damage. Nrf2 protein expression level in the model group was significantly decreased(P<0.05), and the antioxidant enzymes SOD, CAT and GSH contents were also significantly reduced(P<0.05, P<0.01), and the gene expression levels of GPX1, GPX4 and GPX7 were significantly decreased(P<0.01). Compared with the model group, the high-dose group of curzerene showed a significant increase in the sucrose preference coefficient and the number of times entering the open field center(P<0.05), as well as a significant decrease in immobility time in the forced swimming and tail suspension tests(P<0.05, P<0.01). The ROS content in the hippocampus of the high-dose group of curzerene was significantly reduced(P<0.01), while the ATP content was significantly increased(P<0.05). The neuronal mitochondrial damage in the hippocampus of the high-dose group of curzerene was alleviated, and the expression level of Nrf2 protein was significantly increased(P<0.05). The Nrf2 inhibitor ML385 reversed the improvement of curzerene on depressive behaviors in CUMS mice. The GSH content in the hippocampal neurons of the high-dose group of curzerene was significantly increased(P<0.01), while there were no significant differences in SOD and CAT contents. The expression level of GPX4 gene in the hippocampal neurons of the high-dose group of curzerene was significantly increased(P<0.05), while there were no significant differences in other GPX genes. ConclusionCurzerene is the best component with antidepressant activity in Curcumae Rhizoma. It may improve mitochondrial dysfunction to exert its antidepressant effect by regulating Nrf2 and its downstream GPX4/GSH pathway rather than CAT or SOD pathways.
2.The difference of regional homogeneity of resting-state brain activity between overweight and normal weight male patients with type 2 diabetes mellitus
Han XU ; Min WANG ; Yali DING ; Min ZHANG ; Tian HUANG ; Xue CHAI ; Jun HU ; Kaitang ZHU
Journal of Practical Radiology 2024;40(2):181-185
Objective To explore the differences of regional homogeneity(ReHo)between overweight and normal weight male patients with type 2 diabetes mellitus(T2DM)during rest and their correlations with clinical features.Methods Twenty-five untreated male overweight T2DM(OW-T2DM)patients,25 untreated male normal weight T2DM(NW-T2DM)patients and 25 healthy controls(HC)were enrolled.The brain structure and resting-state functional magnetic resonance imaging(rs-fMRI)data were collected from all subjects.The brain structure and rs-fMRI data were preprocessed,and ReHo values of all brain regions were calculated for all subjects.ReHo values were compared among three groups and between groups respectively via the methods of one-way analysis of variance and two-sample t-test.To address the problem of multiple comparisons,the method of AlphaSim was performed(the threshold was set at P<0.005,the number of voxel clusters was>12).In addition,Pearson correlation analysis was performed to explore the relationships between ReHo values of the abnormal brain regions and clinical features in patients.Results(1)The brain regions showed differences of ReHo values among three groups were mainly distributed in the right hemisphere,including the superior parietal gyrus,superior marginal gyrus and superior occipital gyrus;(2)Compared with HC,NW-T2DM patients showed significantly decreased ReHo values in the right medial superior frontal gyrus,right middle cingulate gyrus and left anterior cingulate gyrus;(3)Compared with HC,OW-T2DM patients showed significantly decreased ReHo values in the bilateral postcentral gyrus and bilateral middle cingulate gyrus;(4)Compared with NW-T2DM patients,OW-T2DM patients showed significantly decreased ReHo values in the right superior parietal gyrus,right superior occipital gyrus and left cuneus;(5)ReHo values of the right medial superior frontal gyrus and right superior parietal gyrus were negatively correlated with hemoglobinA1c(HbA1c)level and body mass index(BMI),respectively,in all patients.Conclusion The occurrence of T2DM in male patients may lead to the declined activity of brain regions located in the default mode network(DMN),while overweight may further lead to decreased brain activity within the attention and visual recognition network in male T2DM patients.
3.Construction and validation of Alignment Diagram model for risk of parenteral nutrition-associated cholestasis in extremely/ultra-low birth weight infants
Shuyan CHEN ; Jinglin XU ; Yali CAI ; Yunting HU ; Qingling ZHU ; Zhiyong LIU ; He WANG ; Jingyang ZHENG ; Dongmei CHEN
Chinese Pediatric Emergency Medicine 2024;31(2):114-119
Objective:To explore the high-risk factors for parenteral nutrition associated cholestasis(PNAC)in extremely/ultra-low birth weight infants,and establish a risk Alignment Diagram prediction model.Methods:We retrospectivly analyzed the clinical data of hospitalized extremely/ultra-low birth weight infants admitted to Neonatology Department at Quanzhou Children's Hospital from January 2019 to December 2020,using multivariate Logistic regression analysis to screen for independent risk factors for the occurrence of PNAC.An Alignment Diagram model prediction model for PNAC was constructed by using R software,and the performance of the model was evaluated through receiver operating characteristic curves.Results:A total of 203 extremely/ultra-low birth weight infants were included,with a median gestational age of 29.14(28.00,30.86)weeks and a median birth weight of 1 170(1 000,1 300)g.Among them,26(12.81%)cases developed PNAC.Multivariate Logistic regression analysis showed that the duration of parenteral nutrition( OR=1.015 ,95% CI 1.003-1.034),the cumulative amount of glucose( OR=1.014 ,95% CI 1.001-1.028),small for gestational age( OR=3.455 ,95% CI 1.127-10.589),and neonatal sepsis( OR=3.142 ,95% CI 1.039-9.503)were independent risk factors for PNAC( P<0.05);The four independent risk factors mentioned above were introduced into R software to construct an Alignment Diagram model,the area under the receiver operating characteristic curve was 0.835(95% CI 0.842-0.731),and the results of the Hosmer Limeshow goodness of fit test show that:χ 2=5.34,degree of freedom=8, P=0.72.A calibration curve indicated good consistency between the predicted probability of the model and the actual occurrence rate,with good accuracy. Conclusion:The Alignment Diagram model constructed based on four independent risk factors of the duration of parenteral nutrition,glucose accumulation,small for gestational age infants,and neonatal sepsis exhibits high predictive ability,and is expected to provide an intuitive and convenient visualization tool for preventing or reducing the occurrence of PNAC in extremely/ultra-low birth weight infants
4.Tianma Goutengyin and Its Single Herb in Treatment of Parkinson's Disease: A Review
Renyan ZHU ; Yali WANG ; Yingmei ZHANG ; Renrui CHANG ; Shaocong LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):239-248
Parkinson's disease (PD) is a kind of chronic progressive neurodegenerative disease that has a high prevalence rate in recent years, especially in the elderly. PD belongs to the category of "tremor disease" and "tremor" in traditional Chinese medicine, and Tianma Goutengyin is a classic prescription contained in the Synopsis of The New Significance of Patterns and Treatment in Miscellaneous Diseases(《中医内科杂病证治新义》). This article explored the theory of Tianma Goutengyin in the treatment of PD, and based on network pharmacological research, the article summarized relevant research on Tianma Goutengyin and its single herb in the treatment of PD. Moreover, it discussed the clinical applications and mechanisms of Tianma Goutengyin and its single herb in the treatment of PD. It is found that the mechanisms of Tianma Goutengyin in treating PD may be related to resisting oxidative stress, inhibiting inflammatory response, regulating neurotransmitters, and protecting dopamine (DA) neurons. Besides, the main components of the single herb in Tianma Goutengyin for treating PD are gastrodin, rhynchophylline, geniposide, gardenial alcohol, eucommitol glycoside, motherwort alkaloid, baicalin, pachyman, and achyranthes bidentata sterol. They can improve the related symptoms of PD patients by inhibiting inflammatory response, resisting oxidative stress, affecting calcium ion concentration, restoring mitochondrial function, and and protecting DA neurons. This article summarized the research progress of Tianma Goutengyin and its single herb in treating PD, so as to provide a reference for the prescription and medication of Tianma Goutengyin in the treatment of PD and subsequent research on the mechanisms of Tianma Goutengyin and its single herb in the treatment of PD and give play to the advantages of traditional Chinese medicine in the treatment of PD.
5.Experience in eliminating the mother-to-child transmission of hepatitis B virus in China
Yali LUO ; Wei WANG ; Yuchen PAN ; Jing JIANG ; Hanlong ZHENG ; Xueli WU ; Hui CHEN ; Shiben ZHU ; Jinlin HOU
Journal of Clinical Hepatology 2024;40(11):2145-2151
Reducing the mother-to-child transmission of hepatitis B virus(HBV)is crucial for achieving HBV elimination.Launched in July 2015 at the Great Hall of the People in Beijing,China,the"Zero Hepatitis B Mother-to-Child Transmission Project"(Shield Project)is a public welfare initiative integrating scientific prevention and applied research and aims to perform standardized management of pregnant women with hepatitis B using the mobile application of"Shield Project",in order to further reduce or eliminate the mother-to-child transmission of HBV.At present,the Shield Project has expanded nationwide,offering detailed implementation strategies,successful practices,and reliable data to support the global effort to eliminate the mother-to-child transmission of HBV.This article introduces the implementation strategies and outcomes of the Shield Project in four representative cases,in order to provide strong evidence for further understanding and preventing the mother-to-child transmission of HBV.
6.Establishment of a risk prediction model for catheter-associated urinary tract infection in elderly critically ill patients
Rui ZHU ; Yali TIAN ; Min HUANG ; Minjuan CHU
Journal of Clinical Medicine in Practice 2024;28(24):143-148
Objective To analyze the risk factors for catheter-associated urinary tract infection (CAUTI) in elderly critically ill patients and construct a related risk prediction model. Methods Clinical materials of 8 905 patients with catheterization in the geriatric ICU ward of Jiangsu Provincial People's Hospital from January 2014 to June 2024 were retrospectively collected. The patients were divided into infection group (
7.Changes of the morphology and apparent diffusion coefficient value for myometrium and junctional zone in endometrial fibrosis
Ke MA ; Hui ZHU ; Nan ZHOU ; Huanhuan WANG ; Peipei JIANG ; Qing HU ; Yongjing FENG ; Yali HU ; Zhengyang ZHOU
Journal of Practical Radiology 2024;40(8):1312-1315
Objective To explore the changes of the thickness of myometrium(MT),apparent diffusion coefficient value of myometrium(ADCM),thickness of junctional zone(JZT)and apparent diffusion coefficient value of junctional zone(ADCJz)in patients with endometrial fibrosis.Methods A total of 59 patients with endometrial fibrosis and 34 healthy women(volunteer)of childbearing age were prospectively included.The JZT,ADCJz,MT and ADCM were measured.Independent samples t-test was used to compare the differences in JZT,ADCJZ,MT,and ADCM between the two groups.A combined prediction model was established using binary logistic regression analysis(combining mean JZT,mean ADCJZ,and mean MT).The efficiency of each parameter's mean value and the combined prediction model in diagnosing endometrial fibrosis was evaluated using the receiver operating characteristic(ROC)curve.Results JZT(anterior wall,posterior wall,fundus and mean;P=0.007,0.035,0.001 and<0.001,respectively),ADCJZ(anterior wall,posterior wall,fundus and mean;all P<0.001)and MT(anterior wall,posterior wall and mean;P=0.003,<0.001 and 0.003,respectively)were significantly larger in patients with endometrial fibrosis compared to volunteer.Mean ADCJZ[area under the curve(AUC)=0.872]and the combined prediction model(AUC=0.953)had high value for diagnosing endometrial fibrosis.Conclusion MRI can be used for noninvasively assessing the changes of myometrium and JZ in patients with endometrial fibrosis.
8.Application of"hospital-family integration"transitional care joint case management model in patients with diabetes mellitus
Yali XIONG ; Lihong ZHU ; Qi HUANG
Journal of Shenyang Medical College 2024;26(5):454-458
Objective:To explore the application effect of"hospital-family integration"transitional care joint case management model in patients with diabetes mellitus.Methods:A total of 80 patients with diabetes mellitus admitted to our hospital from Jan 2023 to Apr 2024 were divided into the control group and the observation group according to random number table method,with 40 patients in each group.The control group was given routine nursing,and the observation group was given"hospital-family integration"transitional care joint case management model based on routine nursing.Blood glucose level,self-care ability and quality of life were compared between the two groups.Results:The levels of fasting blood glucose,2 h postprandial blood glucose and glycosylated hemoglobin in the observation group were lower than those in the control group(P<0.05).The scores of Self-care Behavior Scale(SDSCA-6)and Health Survey Summary Form(SF-36)in the observation group were higher than those in the control group(P<0.05).Conclusion:"Hospital-family integration"transitional care joint case management model is helpful to improve blood glucose management,self-care ability and quality of life in patients with diabetes mellitus.
9.Research Progress of Regulating Mechanism and Traditional Chinese Medicine Intervention of Iron Lipid Metabolic Disorder Based on Ferroptosis
Shuwen WANG ; Xufeng BAI ; Qingyu CAO ; Yali LIU ; Huiming HU ; Yanchen ZHU
Herald of Medicine 2024;43(11):1816-1821
Ferroptosis is a form of iron-dependent cell death caused by a disorder of iron lipid metabolism.Its mechanism mainly includes lipid metabolism and iron metabolism,which are complicated and strictly regulated by various metabolic and signaling pathways.Current studies have shown that ferroptosis is associated with cancer,atherosclerosis,and neurological diseases.Traditional Chinese medicine(TCM)is characterized by various active ingredients,relatively high safety,and lower treatment costs,which possess unique advantages in clinical applications.It has been widely used in the treatment of various diseases.Taking the regulation of ferroptosis by traditional Chinese medicine as the entry point may be a new direction for the future prevention and treatment of various diseases.In this review,we discussed the mechanism of iron lipid metabolic disorders based on ferroptosis and the research progress of traditional Chinese medicine intervention to provide reference and treatment strategies for the prevention and treatment of related diseases.
10.Effects of Huatan Quyu Decoction on cognitive function of vascular dementia rats by regulating Wnt/β-catenin signal pathway
Mengyuan LIU ; Yongjun FANG ; Yali HU ; Pengfang WEI ; Sen QIAO ; Yuqian TIAN ; Xinya ZHAO ; Hui LIU ; Jingyuan KONG ; Xiaona ZHU
International Journal of Traditional Chinese Medicine 2024;46(10):1310-1315
Objective:To observe the effects of Huatan Quyu Decoction on the protein expressions of β-catenin and GSK-3 β and the expression of anticardiolipin antibody and β-amyloid protein related to cognitive function in rats with vascular dementia based on Wnt/β-catenin signal pathway.Methods:A total of 96 male SD rats were divided into blank group, model group, Donepezil hydrochloride group and Huatan Quyu Decoction low-, midium-, high-dosage group according to random number table method, with 16 rats in each group. Except for the blank group, the rat model of vascular dementia was prepared by modified 2-VO method. Huatan Quyu Decoction low-, medium- and high-dosage groups were administrated with Huatan Quyu Decoction 6.1, 12.1 and 24.2 g/kg, respectively; the Western medicine group was administrated with Donepezil hydrochloride 0.5 mg/kg; the blank group and the model group were administrated with the same amount of normal saline for 28 consecutive days. On the 1st, 7th, 14th and 28th day after administration, the learning and memory ability of rats was evaluated by Morris water maze test, the levels of ACA and Aβ in serum were measured by enzyme linked immunosorbent assay (ELISA), and the expressions of β-catenin and GSK-3β proteins related to Wnt/β-catenin signal pathway in hippocampus were measured by Western blot.Results:Compared with model group, the escape latency was shortened in the Huatan Quyu Decoction high-dosage group and Donepezil group on 7 and 14 days of administration ( P<0.05), and the times of crossing the platform increased in Huatan Quyu Decoction high-dosage group on 1 and 28 days of administration ( P<0.05). Compared with model group, the serum ACA level in Donepezil group, Huatan Quyu Decoction medium- and high-dosage groups decreased at day 1, 7, 14 and 28 after administration ( P<0.05). The serum Aβ level in Donepezil group, Huatan Quyu Decoction medium- and high-dosage groups decreased at 7, 14 and 28 days after administration ( P<0.05); On the 14th and 28th days after administration, the levels of ACA and Aβ in TCM low-dosage group decreased ( P<0.05). Compared with model group, the expression of β-catenin protein in hippocampus of Donepezil group and Huatan Quyu Decoction medium- and high-dosage groups increased ( P<0.05), while the expression of GSK-3β in hippocampus of Donepezil group and Huatan Quyu Decoction low-, medium- and high-dosage groups decreased ( P<0.01). Conclusion:Huatan Quyu Decoction can activate the Wnt/β-catenin signaling pathway, up-regulate the expression of β-catenin protein in hippocampal tissue of rats, inhibit the expression of GSK-3β, reduce the levels of ACA and Aβ in serum of rats, and improve the cognitive function of rats with vascular dementia.


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