1.Huazhuo Jiedu Prescription Treats Ulcerative Colitis by Inhibiting Excessive Mitophagy via PINK1/Parkin Signaling Pathway
Haofeng ZHANG ; Jinye ZHOU ; Ziwei LIU ; Yican WANG ; Yirui CHENG ; Zheng ZHI ; Qian YANG ; Bolin LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):182-189
ObjectiveTo investigate the mechanism of Huazhuo Jiedu prescription in treating ulcerative colitis (UC) by regulating mitophagy. MethodsThe genes related to mitophagy and UC were retrieved from GeneCards, and then the common genes of mitophagy and UC were analyzed by metascape to identify the genes related to mitophagy in UC. Animal experiments were carried out to decipher the mechanism by which Huazhuo Jiedu prescription treated UC by regulating mitophagy. Sixty C57BL/6 male mice were randomized into normal, model, high-, medium-, and low-dose (50, 25, 12.5 g·kg-1, respectively) Huazhuo Jiedu prescription, and mesalazine (0.52 g·kg-1·d-1) groups, with 10 mice in each group. After successful modeling by the dextran sulfate sodium-free drinking method, the colonic mucosal damage was observed by hematoxylin-eosin staining, and the ultracellular structure of colon mucosa was observed by transmission electron microscopy. The expression levels of mitophagy-related proteins PTEN-induced putative kinase 1 (PINK1) and Parkin protein were determined by Western blot. The expression of prohibitin 2 (PHB2), ubiquitin-specific protease 15 (USP15), ubiquitin-specific protease 30 (USP30) in the colon tissue was detected by immunofluorescence (IF). ResultsAll the drug intervention groups showed ameliorated pathological manifestations of the colonic mucosa and improved mitochondrial structures in UC mice. Compared with the normal group, the model group demonstrated up-regulated protein levels of PINK1 and Parkin (P<0.05), enhanced average fluorescence intensity of PHB2 (P<0.05), and weakened average fluorescence intensity of USP15 and USP30 (P<0.05). Compared with the model group, the mesalazine group and the high- and medium-dose Huazhuo Jiedu prescription groups showcased down-regulated protein levels of PINK1 and Parkin (P<0.05), decreased average fluorescence intensity of PHB2 (P<0.05), and enhanced average fluorescence intensity of USP15 and USP30 (P<0.05). The low-dose Huazhuo Jiedu prescription group showed down-regulated protein levels of PINK1 and Parkin (P<0.05), weakened average fluorescence intensity of PHB2 (P<0.05), and enhanced average fluorescence intensity of USP15 and USP30 (P<0.05). ConclusionHuazhuo Jiedu prescription can attenuate the intestinal mucosal injury and improve the mitochondrial cell ultrastructure in UC mice by regulating the expression of PINK1-Parkin pathway and inhibiting excessive mitophagy.
2.Huazhuo Jiedu Prescription Treats Ulcerative Colitis by Inhibiting Excessive Mitophagy via PINK1/Parkin Signaling Pathway
Haofeng ZHANG ; Jinye ZHOU ; Ziwei LIU ; Yican WANG ; Yirui CHENG ; Zheng ZHI ; Qian YANG ; Bolin LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):182-189
ObjectiveTo investigate the mechanism of Huazhuo Jiedu prescription in treating ulcerative colitis (UC) by regulating mitophagy. MethodsThe genes related to mitophagy and UC were retrieved from GeneCards, and then the common genes of mitophagy and UC were analyzed by metascape to identify the genes related to mitophagy in UC. Animal experiments were carried out to decipher the mechanism by which Huazhuo Jiedu prescription treated UC by regulating mitophagy. Sixty C57BL/6 male mice were randomized into normal, model, high-, medium-, and low-dose (50, 25, 12.5 g·kg-1, respectively) Huazhuo Jiedu prescription, and mesalazine (0.52 g·kg-1·d-1) groups, with 10 mice in each group. After successful modeling by the dextran sulfate sodium-free drinking method, the colonic mucosal damage was observed by hematoxylin-eosin staining, and the ultracellular structure of colon mucosa was observed by transmission electron microscopy. The expression levels of mitophagy-related proteins PTEN-induced putative kinase 1 (PINK1) and Parkin protein were determined by Western blot. The expression of prohibitin 2 (PHB2), ubiquitin-specific protease 15 (USP15), ubiquitin-specific protease 30 (USP30) in the colon tissue was detected by immunofluorescence (IF). ResultsAll the drug intervention groups showed ameliorated pathological manifestations of the colonic mucosa and improved mitochondrial structures in UC mice. Compared with the normal group, the model group demonstrated up-regulated protein levels of PINK1 and Parkin (P<0.05), enhanced average fluorescence intensity of PHB2 (P<0.05), and weakened average fluorescence intensity of USP15 and USP30 (P<0.05). Compared with the model group, the mesalazine group and the high- and medium-dose Huazhuo Jiedu prescription groups showcased down-regulated protein levels of PINK1 and Parkin (P<0.05), decreased average fluorescence intensity of PHB2 (P<0.05), and enhanced average fluorescence intensity of USP15 and USP30 (P<0.05). The low-dose Huazhuo Jiedu prescription group showed down-regulated protein levels of PINK1 and Parkin (P<0.05), weakened average fluorescence intensity of PHB2 (P<0.05), and enhanced average fluorescence intensity of USP15 and USP30 (P<0.05). ConclusionHuazhuo Jiedu prescription can attenuate the intestinal mucosal injury and improve the mitochondrial cell ultrastructure in UC mice by regulating the expression of PINK1-Parkin pathway and inhibiting excessive mitophagy.
3.From Physiology to Pathology of Astrocytes: Highlighting Their Potential as Therapeutic Targets for CNS Injury.
Yimin YUAN ; Hong LIU ; Ziwei DAI ; Cheng HE ; Shangyao QIN ; Zhida SU
Neuroscience Bulletin 2025;41(1):131-154
In the mammalian central nervous system (CNS), astrocytes are the ubiquitous glial cells that have complex morphological and molecular characteristics. These fascinating cells play essential neurosupportive and homeostatic roles in the healthy CNS and undergo morphological, molecular, and functional changes to adopt so-called 'reactive' states in response to CNS injury or disease. In recent years, interest in astrocyte research has increased dramatically and some new biological features and roles of astrocytes in physiological and pathological conditions have been discovered thanks to technological advances. Here, we will review and discuss the well-established and emerging astroglial biology and functions, with emphasis on their potential as therapeutic targets for CNS injury, including traumatic and ischemic injury. This review article will highlight the importance of astrocytes in the neuropathological process and repair of CNS injury.
Astrocytes/drug effects*
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Humans
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Animals
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Central Nervous System/pathology*
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Central Nervous System Diseases/physiopathology*
4.A research of omics-based biological aging clocks and their applications
Ziwei ZHU ; Shanshan CHENG ; Xiang CHENG ; Weihong CHEN ; Chaolong WANG
Chinese Journal of Epidemiology 2024;45(9):1291-1301
Aging, a process of functional decline with the increase of chronological age, is a major risk factor for chronic diseases. Aging shows significant individual differences, which is influenced by both genetic and environmental factors. Accurate measurement of physiological age helps identify individuals with accelerated aging and those at high risk for chronic diseases and mortality, which would promote individual health management and precision medicine for healthy aging. In this paper, we summarize the omics-based aging clocks and discuss their current and future applications.
5.2-APB inhibits H2O2-induced chondrocyte apoptosis through PKCα/HIF-1α signaling pathway
Ziwei OUYANG ; Lei DONG ; Yan WANG ; Yuanzhi CHENG ; Rendi ZHU ; Renpeng ZHOU ; Yingjie ZHAO ; Wei HU
Acta Universitatis Medicinalis Anhui 2024;59(7):1150-1156
Objective To explore the effect of 2-aminoethoxy-diphenyl borate(2-APB)on H2O2-induced chondro-cyte apoptosis and its mechanism.Methods The experiment was divided into control group,H2O2 group,2-APB group and H2O2+2-APB group.CCK-8 method was used to detect the cell viability of each group;The effect of 2-APB on the morphological changes of chondrocytes induced by H2O2 was observed under microscopy;TUNEL meth-od and flow cytometry were used to detect chondrocyte apoptosis;Flow cytometry was used to detect Lipid reactive oxygen species(ROS);Western blot was used to detect the protein expressions of Cleaved-PARP,p-PKCα and HIF-1α in H2O2-induced cells by 2-APB;Immunofluorescence was used to detect the fluorescent expression of HIF-1α in cells induced by H2O2 by PKCα inhibitor BIM-1.Results 2-APB inhibited H2O2-induced apoptosis in chon-drocytes,and the inhibitory effect was the most significant when the concentration of 2-APB was 100 pmol/L(F=235.80,P<0.01);22-APB could inhibit the positive rate of H2O2-induced apoptosis of chondrocytes(F=114.80,P<0.01)and the level of ROS(F=52.99,P<0.01).and inhibited the expression of Cleaved-PARP(F=10.10,P<0.05),p-PKCα(F=24.56,P<0.05)and HIF-1α proteins(F=6.85,P<0.05).The PKCα in-hibitor BIM-Ⅰ could inhibit the increase in HIF-1α fluorescence intensity caused by H2O2.Conclusion 2-APB can inhibit chondrocytes apoptosis induced by H2O2 through the PKCα/HIF-1α pathway and thus protect chondro-cytes.
6.A study on the consistency of myocardial extracellular volume quantification in the systole and diastole phases using dual-layer detector spectral CT
Zixuan LIU ; Yu ZHANG ; Yanjun LI ; Yong CHENG ; Tao SHUAI ; Ziwei WANG ; Zhenlin LI
Chinese Journal of Radiology 2024;58(2):165-171
Objective:To investigate the consistency of myocardial extracellular volume between systole and diastole using dual-layer detector spectral CT.Methods:This was a cross-sectional study. Thirty-five patients who underwent cardiac spectral CT examination in West China Hospital of Sichuan University from April 2022 to December 2022 were retrospectively collected. Hematocrit was collected within 3 days before the CT scan. The delayed phases holographic spectral images in systole (45%) and diastole (75%) were obtained using dual-layer spectral CT. CT data were processed using a spectral post-processing workstation, and the extracellular volume (ECV) based on iodine density images, referred as CT-ECV, in systolic and diastolic phases were calculated, respectively. According to the American Heart Association′s 16-segment model of left ventricular, the standard short-axis images were constructed, and the myocardium was standardized into 16 segments at the basal, mid-cavity, and apical levels of the left ventricle. Two radiologists performed a subjective evaluation in the image quality of the CT-ECV images of the whole heart and the three sections in systole and diastole using a "five-point" scale. The ECV of the 16 segments and the whole heart in systole and diastole was calculated. The consistency of subjective evaluations between systole and diastole was assessed using Kappa statistics. Wilcoxon signed-rank tests were used to compare the differences in scores between systole and diastole. Paired sample t-test was used to compare the differences in CT-ECV scores between systole and diastole. The intraclass correlation coefficient was used to test the intra-and inter-observer consistency of CT-ECV measurements between two radiologists. P<0.05 was statistically significant. Results:There was good agreement between the two radiologists on subjective scores of CT-ECV image quality between systole and diastole ( Kappa>0.80), and there was no statistical difference in image quality among the basal, mid-cavity, and apical levels of the left ventricle and whole heart between systole and diastole ( P>0.05). The systolic and diastolic CT-ECV for the entire heart obtained through the delay phase were (33.29±3.46)% and (33.50±3.39)%, respectively, with no statistically significant difference ( t=-0.78, P=0.442). CT-ECV in systole and diastole were (34.15±3.94)% and (35.30±3.99)% for segment 8, (34.03±3.76)% and (35.46±3.74)% for segment 9, and (33.98±3.32)% and (35.05±3.98)% for segment 14, respectively. The mean values of the systolic CT-ECV of segments 8, 9 and 14 were significantly lower than those of diastolic CT-ECV ( t=-2.65, -3.26, -2.42, P=0.012, 0.003, 0.022, respectively). The ICCs for CT-ECV measurements of 16 segments by the two radiologists were greater than 0.90 in both systolic and diastolic, indicating good agreement. Conclusions:There is no significant difference in whole heart CT-ECV values between systolic and diastolic myocardial ECV based on dual-layer spectral CT. However, minor differences (less than 2%) are found between systolic and diastolic myocardial CT-ECV for some segments. Myocardial CT-ECV measurement should be performed on the same segment during the same phase to obtain stable and accurate ECV values.
7.Comparison analysis of the results of hysterosalpingography with different iodized oil-based contrast medium in primary infertility patients
Yin WANG ; Ziwei DU ; Wenjian XU ; Cheng LI ; Maoquan LI
Journal of Practical Radiology 2024;40(9):1514-1517
Objective To compare and analyze the results of hysterosalpingography(HSG)in primary infertility patients who received ultra-liquefied ethiodized poppyseed oil-based contrast medium or iodized oil-based contrast medium.Methods A total of 212 patients with primary infertility who received HSG examination were enrolled,of which 96 patients were in the ultra-liquefied ethiodized pop-pyseed oil-based contrast medium group,while 116 patients were in the iodized oil-based contrast medium group.The visual analogue scale(VAS)score of pain during HSG,adverse reactions(allergic reaction of contrast medium,contrast medium reflux,etc.),24 h-peri-toneal distribution and natural pregnancy rate within 1 year after HSG were analyzed between the two groups.Results The VAS score[(1.62±0.92)points]and the incidence of contrast medium reflux(5.2%)in the ultra-liquefied ethiodized poppyseed oil-based con-trast medium group were lower than those in the iodized oil-based contrast medium group[(3.2±1.42)points and 13.8%],respectively and the differences between the two groups were statistically significant(P<0.05).In the 24 h-peritoneal distribution,the diagnosis rate of mild pelvic adhesion in the ultra-liquefied ethiodized poppyseed oil-based contrast medium group(26%)was lower than that in the iodized oil-based contrast medium group(39.7%),and the difference was statistically significant(P=0.041).The natural pregnancy rate of the two groups within 1 year was significantly improved,but there was no significant difference between the two groups(P>0.05).Conclusion Ultra-liquefied ethiodized poppyseed oil-based contrast medium has less pain,lower incidence adverse reactions and better peritoneal distribution,and improve the natural pregnancy rate in primary infertility patients undergoing HSG.It is a high priority contrast medium for HSG.
8.Role of selenoprotein M knockdown in the melatonin antagonism of nickel-induced apoptosis and endoplasmic reticulum stress in mouse heart.
Xintong ZHANG ; Xiaoxue GAI ; Lihua XU ; Wenxue MA ; Qiaohan LIU ; Bendong SHI ; Cheng FANG ; Jingzeng CAI ; Ziwei ZHANG
Journal of Zhejiang University. Science. B 2023;24(5):406-417
The aim of this study was to investigate the role of selenoprotein M (SelM) in endoplasmic reticulum stress and apoptosis in nickel-exposed mouse hearts and to explore the detoxifying effects of melatonin. At 21 d after intraperitoneal injection of nickel chloride (NiCl2) and/or melatonin into male wild-type (WT) and SelM knockout (KO) C57BL/6J mice, NiCl2 was found to induce changes in the microstructure and ultrastructure of the hearts of both WT and SelM KO mice, which were caused by oxidative stress, endoplasmic reticulum stress, and apoptosis, as evidenced by decreases in malondialdehyde (MDA) content and total antioxidant capacity (T-AOC) activity. Changes in the messenger RNA (mRNA) and protein expression of genes related to endoplasmic reticulum stress (activating transcription factor 4 (ATF4), inositol-requiring protein 1 (IRE1), c-Jun N-terminal kinase (JNK), and C/EBP homologous protein (CHOP)) and apoptosis (B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase-3, Caspase-9, and Caspase-12) were also observed. Notably, the observed damage was worse in SelM KO mice. Furthermore, melatonin alleviated the heart injury caused by NiCl2 in WT mice but could not exert a good protective effect in the heart of SelM KO mice. Overall, the findings suggested that the antioxidant capacity of SelM, as well as its modulation of endoplasmic reticulum stress and apoptosis, plays important roles in nickel-induced heart injury.
Animals
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Male
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Mice
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Antioxidants/pharmacology*
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Apoptosis
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Endoplasmic Reticulum Stress
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Melatonin/pharmacology*
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Mice, Inbred C57BL
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Nickel/adverse effects*
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Selenoproteins/genetics*
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Heart/drug effects*
9.Medical-electrical cross-case teaching and its teaching practice under the background of medical-industrial integration
Li CHENG ; Ziwei TANG ; Xuetong ZHAO ; Lijun YANG ; Liang YU
Chinese Journal of Medical Education Research 2023;22(5):650-653
This paper introduces the teaching method of medical-electrical cross-integration and the teaching practice experience in the past three years by taking the integration of medicine and electrical engineering as an example. Starting from the analysis of the characteristics of learning situation, the teaching introduction process, the case discussion and analysis, and the after-class tracking and improvement, this paper analyzes the characteristics of the medical-electrical cross-teaching and proposes the corresponding teaching methods and supporting cases. Preliminary exploration attempts show that this teaching method can improve students' comprehensive ability, especially multidisciplinary thinking ability, and has a certain positive effect.
10.Mechanism of Zhishi Xiebai Guizhitang in Alleviating Myocardial Injury in Rats with Myocardial Infarction Based on TNF/NF-κB Signaling Pathway
Ziwei LIN ; Liujun WU ; Huihui WU ; Xiaofang XIE ; Cheng PENG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(18):8-16
ObjectiveTo investigate the effect of Zhishi Xiebai Guizhitang (ZXGT) on isoproterenol (ISO)-induced myocardial infarction (MI) in rats through the tumor necrosis factor/nuclear factor-κB (TNF/NF-κB) signaling pathway. MethodForty-eight SD rats were randomly divided into control group (blank), model group, perindopril group (4 mg·kg-1), ZXGT group (24.4 g·kg-1), ZXGT +inhibitor group (ZXGT, 24.4 g·kg-1, TNF-α receptor inhibitor R7050, 5 mg·kg-1), and an inhibitor group (R7050, 5 mg·kg-1), with eight rats in each group. The rats in each group were orally administered with their respective drugs for 7 days. Additionally, in the ZXGT + inhibitor group and the inhibitor group, R7050 was injected intraperitoneally at a dose of 5 mg·kg-1 on the 6th and 7th days. Except for the control group, all other groups were given intraperitoneal injections of ISO for 2 consecutive days to induce MI in rats. On the 7th day of the experiment, the rats were anesthetized 30 min after ISO injection, and their electrocardiograms (ECGs) were recorded to observe ST-segment elevation. Small animal echocardiography was used to measure global longitudinal strain (GLS) and cardiac synchrony. Blood samples were collected from the abdominal aorta to measure the levels of serum cardiac troponin T (cTnT), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). Histopathological changes in myocardial tissue were observed using hematoxylin-eosin (HE) staining. Immunohistochemistry (IHC) was used to detect the expression of TNF-α, NF-κB p65, and p-NF-κB p65 proteins in myocardial tissue. Western blot was performed to measure the expression of tumor necrosis factor receptor 1 (TNFR1), tumor necrosis factor receptor-associated factor 2 (TRAF2), transforming growth factor-beta-activated kinase 1 (TAK1), NF-κB inhibitory protein alpha (IκBα), phosphorylated (p)-IκBα, NF-κB p65, and p-NF-κB p65 proteins in myocardial tissue. ResultCompared with the control group, the model group showed significant ST segment elevation on the ECG (P<0.01), increased GLS, and reduced cardiac synchrony on echocardiography (P<0.01). Histopathological examination revealed extensive myocardial necrosis. Furthermore, the serum levels of cTnT, CK-MB, LDH, TNF-α, and IL-1β were significantly increased (P<0.01), and the expression levels of TNF-α, TNFR1, TRAF2, TAK1, p-IκBα, and p-NF-κB p65 proteins in myocardial tissue were significantly elevated (P<0.01), while the expression level of IκBα was significantly decreased (P<0.01). Compared with the model group, the perindopril group, the ZXGT group, the ZXGT + inhibitor group, and the inhibitor group rats showed a significant reduction in ST-segment elevation on the ECG (P<0.05, P<0.01), improvement in GLS and cardiac synchrony (P<0.05, P<0.01), a decrease in the area of myocardial necrosis, and reduced serum levels of cTnT, CK-MB, LDH, TNF-α, and IL-1β (P<0.01). Additionally, the ZXGT group, the ZXGT + inhibitor group, and the inhibitor group downregulated the increased TNF-α, TNFR1, TRAF2, TAK1, p-IκBα, and p-NF-κB p65 protein expression levels and upregulated IκBα expression levels in the myocardial tissue (P<0.05, P<0.01). No significant differences were observed between the ZXGT group and the ZXGT + inhibitor group or the inhibitor group. ConclusionZXGT can protect against ISO-induced myocardial injury in rats and improve cardiac function, and its mechanism of action may be related to the regulation of the TNF/NF-κB signaling pathway.


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