1.Research on The Role of Dopamine in Regulating Sleep and Wakefulness Through Exercise
Li-Juan HOU ; Ya-Xuan GENG ; Ke LI ; Zhao-Yang HUANG ; Lan-Qun MAO
Progress in Biochemistry and Biophysics 2025;52(1):88-98
Sleep is an instinctive behavior alternating awakening state, sleep entails many active processes occurring at the cellular, circuit and organismal levels. The function of sleep is to restore cellular energy, enhance immunity, promote growth and development, consolidate learning and memory to ensure normal life activities. However, with the increasing of social pressure involved in work and life, the incidence of sleep disorders (SD) is increasing year by year. In the short term, sleep disorders lead to impaired memory and attention; in the longer term, it produces neurological dysfunction or even death. There are many ways to directly or indirectly contribute to sleep disorder and keep the hormones, including pharmacological alternative treatments, light therapy and stimulus control therapy. Exercise is also an effective and healthy therapeutic strategy for improving sleep. The intensities, time periods, and different types of exercise have different health benefits for sleep, which can be found through indicators such as sleep quality, sleep efficiency and total sleep time. So it is more and more important to analyze the mechanism and find effective regulation targets during sleep disorder through exercise. Dopamine (DA) is an important neurotransmitter in the nervous system, which not only participates in action initiation, movement regulation and emotion regulation, but also plays a key role in the steady-state remodeling of sleep-awakening state transition. Appreciable evidence shows that sleep disorder on humans and rodents evokes anomalies in the dopaminergic signaling, which are also implicated in the development of psychiatric illnesses such as schizophrenia or substance abuse. Experiments have shown that DA in different neural pathways plays different regulatory roles in sleep behavior, we found that increasing evidence from rodent studies revealed a role for ventral tegmental area DA neurons in regulating sleep-wake patterns. DA signal transduction and neurotransmitter release patterns have complex interactions with behavioral regulation. In addition, experiments have shown that exercise causes changes in DA homeostasis in the brain, which may regulate sleep through different mechanisms, including cAMP response element binding protein signal transduction, changes in the circadian rhythm of biological clock genes, and interactions with endogenous substances such as adenosine, which affect neuronal structure and play a neuroprotective role. This review aims to introduce the regulatory effects of exercise on sleep disorder, especially the regulatory mechanism of DA in this process. The analysis of intracerebral DA signals also requires support from neurophysiological and chemical techniques. Our laboratory has established and developed an in vivo brain neurochemical analysis platform, which provides support for future research on the regulation of sleep-wake cycles by movement. We hope it can provide theoretical reference for the formulation of exercise prescription for clinical sleep disorder and give some advice to the combined intervention of drugs and exercise.
2.Targeting B7-H3 inhibited growth,migration,and angiogenesis of human umbilical vein endothelial cells
Yu LIU ; Nan-Nan WANG ; Ke NIU ; Hui-Juan LING ; Ya-Yu ZHU ; Wei HU ; Li-Wen CHEN
Chinese Pharmacological Bulletin 2024;40(7):1311-1316
Aim To explore the effect of targeted inhi-bition of co-signaling molecule B7-H3 on the growth,migration,and angiogenesis ability of human umbilical vein endothelial cells(HUVECs).Methods Small interference RNA was used to knock down HUVECs B7-H3 molecules.CCK-8 test was used to detect cell proliferation at 24 h,48 h and 72 h.Transwell test was then used to detect 24 h cell migration,and three-dimensional cell culture was used to observe cell angio-genesis.Results Compared with the negative control group(siRNA-Control),siRNA-720,siRNA-1707 and siRNA-1690 had different inhibitory effects on the expression of B7-H3.B7-H3 inhibition of siRNA-1690 was significantly higher than that of siRNA-720 and siRNA-1707,and siRNA-1690 sequence was chosen for follow-up experiment.The results of CCK-8 cell vi-ability assay showed that the proliferation ability of HU-VECs decreased by 24%,22%(P>0.05,compared with 24 h)and 15%(P<0.05,compared with 48 h)respectively at 24 h,48 h and 72 h after B7-H3 knockout.The migration ability of B7-H3 for 24 h was significantly lower than that of siRNA-Control group(P<0.01).The results of three-dimensional cell cul-ture showed that the angiogenic ability of HUVECs de-creased significantly after si-B7-H3 knockdown of B7-H3 gene(P<0.01).Conclusion Targeting B7-H3 inhibits the growth,migration,and angiogenesis of hu-man umbilical vein endothelial cells.
3.Effects of berberine on expression of FXR and SHP in kidney of mice with diabetic nephropathy
Li-Juan DENG ; Jie-Yao HUANG ; Yan-Jun HU ; Wei CUI ; Wei FANG ; Ya-Ping XIAO
Chinese Pharmacological Bulletin 2024;40(12):2269-2276
Aim To explore the ameliorative effects of berberine(BBR)on diabetic nephropathy(DN)in mice and investigate its potential mechanisms through transcriptomic analysis.Methods 8-week-old db/db mice were randomly assigned into four groups:model group(DN group),BBR 50 mg·kg-1 group(BBR-L group),BBR 100 mg·kg-1 group(BBR-H group),and empagliflozin 10 mg·kg-1 group(EMPA group).Age-matched db/m mice were used as the control group(NC group),with eight mice in each group.Each group received intragastric administration once daily for eight weeks.After the treatment,serum,u-rine,and kidney samples were collected to evaluate re-nal function indicators and observe renal pathological changes.Differentially expressed genes(DEGs)in kidney tissue were identified through transcriptomic a-nalysis,followed by KEGG and GO enrichment analy-sis.Potential targets were further validated using mo-lecular docking,molecular dynamics simulations,West-ern blot,and immunohistochemistry.Results Both BBR and EMPA significantly reduced fasting blood glu-cose levels in DN mice,improved renal function,and alleviated renal injury and fibrosis.Compared to the NC group,855 DEGs were identified in the DN group,while 194 DEGs were identified in the BBR-H group compared to the DN group.KEGG enrichment analysis indicated that the mechanisms underlying BBR's effects on DN were primarily related to type 1 diabetes and bile secretion pathways.Molecular docking results demonstrated a strong binding affinity between BBR and FXR and a moderate binding affinity with SHP.Molecular dynamics simulations corroborated the doc-king results.FXR and SHP protein expression signifi-cantly decreased in the DN group compared to the NC group.At the same time,BBR treatment significantly increased the expression of these proteins compared to the DN group.Conclusion BBR may mitigate DN-in-duced renal injury by modulating bile acid and lipid homeostasis through the FXR-SHP pathway.
4.Research and Practice on Improving Ideological and Political Teaching of Genetics Course in Colleges and Universities
Yan-Wei WANG ; Ya-Juan REN ; Zhen-Xia LI ; Peng-Fei AI
Chinese Journal of Biochemistry and Molecular Biology 2024;40(9):1317-1328
It is necessary to pay close attention to the integration of ideological and political elements and the organic combination of professional curriculum content in the implementation of science and engineer-ing courses.The genetics course is highly specialized,and the course ideological and political develop-ment has its own unique methods.This paper first discusses the characteristics of contemporary college students,and points out the necessity of ideological and political ideas in contemporary college teaching.Based on the characteristics of genetics course,this paper explores the improvement strategies of ideolog-ical and political teaching from four aspects:teaching team building,teaching design optimization,ideo-logical and political elements mining,and organic integration of ideological and political materials into the course content.Taking the actual teaching situation of the author's teaching team as an example to con-duct subsequent teaching evaluation and reflection,the results show that more than 80%of the students believe that the implementation of the genetics course has improved their learning interest and comprehen-sive ability,and promoted the study of professional courses,and the total score of students has increased by about 5.5%on average.In this way,it can provide inspiration for the construction of other related courses,so that the curriculum ideology and politics can escort the improvement of students'ability and the optimization of their character.
5.Development of a Prognostic Model for Overall Survival Adult Patients with Core Binding Factor Acute Myeloid Leukaemia
Lu-Yao SHI ; Ling-Ling LI ; Tao LI ; Ya-Fei LI ; Yan-Fang LIU ; Zhong-Xing JIANG ; Shu-Juan WANG ; Chong WANG
Journal of Experimental Hematology 2024;32(3):693-701
Objective:To analyze the factors affecting overall survival(OS)of adult patients with core-binding factor acute myeloid leukemia(CBF-AML)and establish a prediction model.Methods:A total of 216 newly diagnosed patients with CBF-AML in the First Affiliated Hospital of Zhengzhou University from May 2015 to July 2021 were retrospectively analyzed.The 216 CBF-AML patients were divided into the training and the validation cohort at 7:3 ratio.The Cox regression model was used to analyze the clinical factors affecting OS.Stepwise regression was used to establish the optimal model and the nomogram.Receiver operating characteristic(ROC)curve,calibration curve and decision curve analysis(DCA)were used to evaluate the model performance.Results:Age(≥ 55 years old),peripheral blood blast(≥80%),fusion gene(AML1-ETO),KIT mutations were identified as independent adverse factors for OS.The area under the ROC curve at 3-year was 0.772 and 0.722 in the training cohort and validation cohort,respectively.The predicted value of the calibration curve is in good agreement with the measured value.DCA shows that this model performs better than a single factor.Conclusion:This prediction model is simple and feasible,and can effectively predict the OS of CBF-AML,and provide a basis for treatment decision.
6.Comparison of Blood Oxygen Saturation Detection Methods in Patients with Hyperleukocytic Acute Leukemia
Hui-Xia GUO ; Shu-Ya CAO ; Yi-Juan CHEN ; Qian LI ; Yue WU ; Yu-Xi SHANG ; Li-Ru WANG
Journal of Experimental Hematology 2024;32(4):1026-1031
Objective:To investigate which indicator is more advantageous when using arterial oxygen saturation(SaO2)and fingertip pulse oxygen saturation(SpO2)for blood oxygen detection in patients with hyperleukocytic acute leukemia(HAL).Methods:In this prospective research,the difference between SaO2 and SpO2 of 18 HAL patients(observation group)and 14 patients(control group),as well as the relationship between the difference and white blood cell(WBC)counts were analyzed.Results:SaO2 was lower than SpO2 in the observation group(P<0.05),and SpO2-SaO2 difference was positively correlated with WBC counts(r=0.47).However,there was no statistical difference between SaO2 and SpO2 in the control group.SaO2 and PO2 showed a downward trend with the prolongation of detection time after arterial blood was collected in the observation group,but there was no statistical difference.There was no downward trend of SaO2 and PO2 in the control group.Conclusion:HAL patients have a phenomenon where SaO2 is lower than SpO2,that is pseudohypoxemia,and this phenomenon may be caused by excessive consumption of oxygen by the leukemia cells in vitro.SpO2 can be monitored bedside in real time and is non-invasive,it is a better way to detect the blood oxygen status of HAL patients.
7.The implementation status and policy analysis of the"Dual-channel"management for drugs in national medical insurance negotiations
Bo PENG ; Xiao-Tong JIANG ; Xiao-Juan ZHANG ; Yuan YE ; Xiao-Lin CAO ; Yang LIU ; Ya-Zi LI
Chinese Journal of Health Policy 2024;17(5):9-16
Objective:This study analyzed the provincial policy on the"dual channel"management of drugs,provided suggestions for improving the"dual channel"management models.Methods:From May 10,2021 to April 10,2024,the official websites of the Healthcare Security Administration and the Health Commission of various provinces were searched for policy documents related to the"dual channel"management,and the text data were statistically analyzed.Results:The"dual-channel"management policies of various provinces coexisted with commonalities and differences.Conclusions:It is recommended to refine the access standards of the drug catalog,standardize the setting of the entry threshold of pharmaceutical institutions,scientifically determine the level of medical insurance treatment,and formulate differentiated drug identification and management methods,so as to further weaken the policy restrictive factors.
8.The crosstalk of Wnt/β-catenin signaling and p53 in acute kidney injury and chronic kidney disease
Wen-Hua MING ; Lin WEN ; Wen-Juan HU ; Rong-Fang QIAO ; Yang ZHOU ; Bo-Wei SU ; Ya-Nan BAO ; Ping GAO ; Zhi-Lin LUAN
Kidney Research and Clinical Practice 2024;43(6):724-738
Wnt/β-catenin is a signaling pathway associated with embryonic development, organ formation, cancer, and fibrosis. Its activation can repair kidney damage during acute kidney injury (AKI) and accelerate the occurrence of renal fibrosis after chronic kidney disease (CKD). Interestingly, p53 has also been found as a key modulator in AKI and CKD in recent years. Meantime, some studies have found crosstalk between Wnt/β-catenin signaling pathways and p53, but more evidence is required on whether they have synergistic effects in renal disease progression. This article reviews the role and therapeutic targets of Wnt/β-catenin and p53 in AKI and CKD and proposes for the first time that Wnt/β-catenin and p53 have a synergistic effect in the treatment of renal injury.
9.Impact of bladder-neck angle on urination:An application study based on fluid-structure interaction
Xu-Dong JIA ; Xiao-Wan GUO ; Wan-Ze ZHANG ; Li-Juan LU ; Ya-Xuan WANG ; Kai-Long LIU ; Dong-Bin WANG ; Yue-Peng LIU ; Jin-Chun QI
National Journal of Andrology 2024;30(9):789-797
Objective:To assess the deformation of the bladder-neck opening and the impact of the bladder-neck angle(BNA)on urination in male patients by fluid-structure interaction(FSI)analysis.Methods:We established geometric models of the blad-der,prostate and urethra were established,incorporating both normal and enlarged BNAs,and assessed the effects of BNA alteration on urinary flow by FSI simulation of the flow rate and pressure of the urine within the bladder,bladder neck and urethra,and that of pros-tate displacement as well.We retrospectively analyzed the clinical data on 145 male patients from the Second Hospital of Hebei Medical University between June 2020 and June 2023,39 with acute urine retention(the AUR group)and 106 without(the non-AUR group),and evaluate the impact of BNA on urination based on the urinary flow rate and prostate volume.Results:Comparative simulation a-nalysis showed significant differences in the total urethral pressure and flow rate between the normal and enlarged BNA models(P<0.05).The maximum prostate displacement was found at the bladder neck,with moderate displacement and unchanged urethral diame-ter in the normal BNA model,but significant displacement and a reduced urethral opening diameter in the enlarged BNA model.FSI analysis confirmed an evident impact of enlarged BNA on urination,more significant in the AUR than in the non-AUR patients(P<0.05).The BNAs in the patients with the maximum urinary flow rate(Qmax)of<10,10-15 or>15 ml/s were 83.7°±2.5°,67.5°±1.8° and 65.1°±4.8° respectively,with statistically significant difference between the former one and the latter two groups(P<0.05).The BNAs in the patients with normal prostate volume or BPH of grade Ⅰ,Ⅱ,Ⅲ or Ⅳ were 65.0°±3.7°,67.2°±3.1°,71.5°±2.0°,82.8°±3.5° and 105.8°±6.0°,respectively(P<0.05),with statistically significant difference between BPH grades Ⅲ and Ⅳ(P<0.05)as well as between these two and the other three groups(P<0.05),but not among the normal prostate volume,BPH grade Ⅰ and BPH grade Ⅱ groups(P>0.05).Spearman correlation analysis indicated that BNA was strongly correlated with total prostate volume(TPV),transition zone volume(TZV),intravesical prostatic protrusion(IPP),prostatic urethral angle(PUA),IPSS,and Qmax(P<0.05).Conclusion:Changes in BNA affect urination and are closely associated with the se-verity of prostate hyperplasia.The BNA may be an important anatomical factor for assessing the severity of lower urinary tract symptoms in BPH patients.
10.Mechanism of lipopolysaccharide inhibiting scrotal wound healing under hypoxic conditions
Ya XU ; Xiao-Bin CONG ; Huai-Yuan ZHENG ; Juan LIU
National Journal of Andrology 2024;30(10):903-909
Objective:To investigate the effect of lipopolysaccharide(LPS)on the crawling ability of fibroblasts derived from the scrotal skin under hypoxic conditions,its impact on vascular regeneration during wound healing,and the potential mechanism un-derlying chronic non-healing scrotal wound caused by gram-negative bacterial infection.Methods:We extracted peripheral blood buffy coats from healthy donors after venous blood centrifugation,divided them into four groups(normoxia,normoxia+LPS,hypoxia,and hypoxia+LPS)for pretreatment,and isolated the corresponding cultured supernatant.Then we measured the levels of VEGF-A,FGF and IL-8 secreted using enzyme-linked immunosorbent assay(ELISA),determined the cytotoxicity of different pretreated superna-tants by lactate dehydrogenase(LDH)release assay,and detected the cell migration ability and vascular formation in human-umbical vein endothelial cells(HUVEC).Results:Under hypoxic conditions,the expression of HIF-1 α was significantly lower in the fibro-blasts from the chronic scrotal wound than in the normal fibroblasts(0.09±0.00 vs 0.48±0.01,P<0.05),the viability of the cells showed no statistically significant difference from that under normoxic conditions(P>0.05),and the proliferation and migration abilities of the cells were markedly improved([83.09±2.56]%vs[17.84±1.12]%,P<0.05).The viability of the scrotal fibroblasts was significantly lower in the normoxia+LPS than in the hypoxia+LPS group([20.15±1.19]%vs[32.54±1.57]%,P<0.05).The cells treated with LPS,compared with those in the non-LPS groups,exhibited remarkably decreased endo-thelial cell tubes formed(5.20±0.15 va 55.30±1.15,P<0.05),down-regulated expression of VEGF(OD value:0.59±0.07 vs 1.25±0.11,P<0.05)and up-regulated expression of IL-8(OD value:2.42±0.07 vs 0.87±0.11,P<0.05).Conclusion:The supernatant derived from the peripheral blood buffy coats treated with LPS has a stronger cytotoxicity and weaker an-giogenesis than that untreated under hypoxic or normoxic conditions,which may be one of the critical factors for difficult healing of scrotal wound.

Result Analysis
Print
Save
E-mail