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.Effect of Xianglian Huazhuo Prescription on Hedgehog Signaling Pathway in Rats with Chronic Atrophic Gastritis
Jinye ZHOU ; Haofeng ZHANG ; Ziwei LIU ; Yican WANG ; Yanru CAI ; Yuxi GUO ; Jie WANG ; Zheng ZHI ; Qian YANG ; Bolin LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):41-47
ObjectiveTo explore the therapeutic effect and mechanism of Xianglian Huazhuo prescription on chronic atrophic gastritis (CAG) in rats based on the Hedgehog signaling pathway. MethodsThe CAG rat model was established by sodium salicylate, N-methyl-N′-nitro-N-nitroguanidine (MNNG), and irregular feeding. The successfully modeled rats were randomly divided into a model group (180 mg·L-1), a moradan group (1.4 g·kg-1), and Xianglian Huazhuo Prescription groups with high, medium, and low doses (36, 9, 18 g·kg-1), followed by drug intervention. Hematoxylin-eosin (HE) staining was used to observe morphological changes in the gastric mucosa. Transmission electron microscopy was used to observe the ultrastructure of gastric mucosa cells. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of Sonic Hedgehog (Shh), Patched 1 (Ptch1), and Glioma-associated oncogene homolog 1 (Gli1). Western blot was used to detect the protein expression levels of Shh, Ptch1, and Gli1 in the gastric mucosa. Immunohistochemistry was used to observe the protein expression of the epithelial marker E-cadherin. ResultsCompared with the normal group, the CAG model group showed a reduction in gastric mucosal intrinsic glands and infiltration of inflammatory cells. The ultrastructure of gastric mucosal cells showed nuclear pyknosis, fewer mitochondria, and abnormal mitochondrial structure. The mRNA and protein expression of Shh, Ptch1, and Gli1 in the gastric mucosa were significantly decreased (P<0.05), and E-cadherin protein expression was decreased. Compared with the model group, the intervention groups showed varying degrees of improvement in histopathological morphology and cellular ultrastructure. The mRNA and protein expression of Shh, Ptch1, Gli1, and E-cadherin increased to varying degrees. Xianglian Huazhuo Prescription upregulated the expression of key Hedgehog pathway factors and E-cadherin at both the mRNA and protein levels (P<0.05). ConclusionXianglian Huazhuo prescription has a therapeutic effect on CAG in rats, and its mechanism may be related to activation of the Hedgehog signaling pathway and inhibition of epithelial-mesenchymal transition (EMT).
4.Effectiveness of autologous platelet-rich plasma for blood conservation and its prognostic impact in patients with type A aortic dissection
Qian ZHENG ; Shoumei CHEN ; Ming XIE ; Shenshen ZHI ; Kun LIU ; Ting JIANG
Chinese Journal of Blood Transfusion 2025;38(8):1035-1042
Objective: To investigate the effects of autologous platelet-rich plasma (aPRP) collected using a continuous blood cell separator on blood conservation and prognosis in patients with type A aortic dissection. Methods: The clinical data of patients who underwent emergency aortic replacement for acute type A aortic dissection at our hospital from January 2020 to December 2023 were respectively analyzed. Patients were divided into two groups based on whether they received aPRP collection before surgery for subsequent reinfusion: the aPRP group (n=32) and the control group (n=35). The volume of aPRP collected and the platelet concentration in the aPRP were recorded. The volumes of allogeneic blood and blood products transfused, and the associated costs during hospitalization were compared between two groups. Intraoperative blood loss, perioperative laboratory parameter changes, 24-hour postoperative drainage volume, duration of ICU stay and mechanical ventilation, length of hospital stay, and mortality rate of the two groups were also compared. Results: The platelet concentration in aPRP was (491.5±85.4)×10
/L, accounting for (24.1±9.6)% of the patient's total platelet count. The volume of aPRP collected accounted for (23.0±6.3)% of the patient's total plasma volume. Compared with the control group, the aPRP group demonstrated significantly reduced transfusion volumes of allogeneic red blood cells, plasma, and platelets (P<0.05), along with significantly lower blood-related costs during hospitalization (P<0.05). Postoperative coagulation parameters (APTT, PT, INR, and TEG) were significantly improved (P<0.05), and platelet counts were markedly increased (P<0.05) in aPRP group as compared with the control group. No statistically significant differences were observed in postoperative use of prothrombin complex concentrate and fibrinogen between the two groups. Similarly, there were no significant differences in postoperative 24-hour drainage volume, 24-hour extubation rate, ICU length of stay, duration of mechanical ventilation, or total hospital length of stay. The incidence of complications and mortality did not differ significantly between the two groups. Conclusion: The administration of aPRP significantly reduces the requirement for perioperative allogeneic blood transfusion in patients undergoing surgery for type A aortic dissection. Furthermore, it enhances coagulation function and reduces associated transfusion costs, thereby establishing itself as an effective and safe strategy for blood conservation.
5. Advances on cardiovascular effects of GLP-lRAs
Zhi-Qiang KE ; Chao LIU ; Zhi-Qiang KE ; Qian-Qian MA ; Zheng-Ding SU ; Dan LI ; Xin-Yuan ZHAO
Chinese Pharmacological Bulletin 2024;40(3):426-430
Glucagon-like peptide-1 ( GLP-1 ) is secreted by gut enteroendocrine cells. GLP-1 receptor agonists ( GLP-1 RAs) control glucose-related augmentation of insulin and suppress glu-cagon secretion. GLP-lRAs also inhibit gastric emptying, food intake and limit weight gain. In the past decade, significant progresses have been made in the investigation on the effects of GLP-1 RAs on cardiovascular system. The potential advantages of oral small-molecule GLP-1 RAs could improve the application of this class of drugs. This review highlights the multiple cardiovascular profiles of GLP-1 RAs in the treatment of cardiovascular diseases to provide new insights into cardiovascular benefits of GLP-1 RAs.
6.Research progress of anti-gout small molecules targeting the NLRP3 inflammasome
Zhen-qian WANG ; Zhi-jiao ZHANG ; Xin-yong LIU ; Peng ZHAN
Acta Pharmaceutica Sinica 2024;59(3):543-553
Currently, clinically used drugs for the treatment of gout inflammation, such as colchicine, nonsteroidal anti-inflammatory drugs, and glucocorticoids, can only relieve the pain of joint inflammation and have severe hepatorenal toxicity and multiple organ adverse reactions. The NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is a key complex that induces the onset of gout inflammation and has become a crucial target in the development of anti-gout drugs. This article reviews the research progress of anti-gout small molecules targeting the NLRP3 inflammasome and their bioactivity evaluation methods in the past five years, in order to provide information for the development of specific drugs for the treatment of gout inflammation.
7.Preparation modification strategies for clinical treatment drugs of Parkinson's disease
Meng-jiao HE ; Yi-fang XIAO ; Xiang-an-ni KONG ; Zhi-hao LIU ; Xiao-guang WANG ; Hao FENG ; Jia-sheng TU ; Qian CHEN ; Chun-meng SUN
Acta Pharmaceutica Sinica 2024;59(3):574-580
Parkinson's disease (PD) is a chronic neurodegenerative disease. At present, levodopa and other drugs are mainly used for dopamine supplementation therapy. However, the absorption of levodopa in the gastrointestinal tract is unstable and its half-life is short, and long-term use of levodopa will lead to the end-of-dose deterioration, dyskinesia, the "ON-OFF" phenomenon and other symptoms. Therefore, new preparations need to be developed to improve drug efficacy, reduce side effects or improve compliance of patients. Based on the above clinical needs, this review briefly introduced the preparation modification strategies for the treatment of PD through case analysis, in order to provide references for the research and development of related preparations.
8.Analysis of hypothermia factors for elderly patients with malnutrition during proximal femoral nail antirota-tion internal fixation under general anesthesia
Qian-Nan FAN ; Zhi-Yong YAN ; Hao WU ; Jing-Ying LIU ; Ying GENG ; Ti-Jun DAI
Journal of Regional Anatomy and Operative Surgery 2024;33(2):145-148
Objective To analyze the incidence and risk factors of hypothermia in elderly patients with malnutrition during proximal femoral nail antirotation(PFNA)internal fixation under general anesthesia.Methods A total of 139 elderly patients underwent PFNA internal fixation under general anesthesia were selected,and the nutritional status scores 1 day before surgery ranged from 0 to 11 points.Univariate and multivariate Logistic binary regression analysis was performed to analyze the related factors that may lead to intraoperative hypothermia.Results Among 139 elderly patients with preoperative nutritional scores of 0 to 11 points,79 cases(56.83%)developed intraoperative hypothermia.The results of univariate and multivariate Logistic binary regression analysis suggested that age≥75 years old,mini nutritional assessment short form(MNA-SF)nutritional score 0 to 7 points,BMI<18.5 kg/m2,duration of general anesthesia≥2 hours,intraoperative flushing fluid volume≥1 000 mL and intraoperative fluid volume≥1 000 mL were the risk factors for the occurrence of intraoperative hypothermia in elderly patients(OR>1,P<0.05).The use of warm blanket insulation was the protective factor against the occurrence of intraoperative hypothermia(OR<1,P<0.05).Conclusion The incidence of intraoperative hypothermia during PFNA internal fixation under general anesthesia in elderly patients with mainutrition before operation is high,and patients with poor nutritional status are more likely to develop intraoperative hypothermia.Patients with older age,poor nutritional status,lower BMI,longer duration of general anesthesia,and more intraoperative flushing fluid volume and intraoperative fluid volume are likely to lead to intraoperative hypothermia.The use of warm blanket can reduce the incidence of intraoperative hypothermia.
9.An in vitro evaluation of the hydromechanical properties on transcatheter edge-to-edge repair
Hao WANG ; Da ZHU ; Zhi-Qian LU ; Zhao-Ming HE ; Li LIU ; Xiang-Bin PAN
Chinese Journal of Interventional Cardiology 2024;32(2):89-95
Objective To establish a method for testing isolated mitral valve in vitro and quantitatively evaluate the effect of transcatheter edge-to-edge repair technology(TEER)on functional mitral regurgitation(FMR)(non-A2-P2 regurgitation).Methods In this study,an FMR(non-A2-P2 regurgitation)model was developed by dilating the annulus orifice and displacing the papillary muscle in isolated porcine mitral valve.The hydrodynamics characteristics of 6 valves were tested by a pulsatile flow testing system under different physiological and pathological conditions before and after TEER.Results The results show that the valve regurgitation improved from moderate-severe[regurgitant fraction(60.2±17.5)%]to mild-moderate[regurgitant fraction(34.7±12.0)%]by repair(P<0.001).The EOA[(3.8±1.6)cm2 vs.(2.2±0.5)cm2,P<0.001]and the forward cross valve pressure difference[(1.8±1.3)mmHg vs.(3.8± 1.8)mmHg,P<0.001],which characterize the forward flow performance of the valve,were compared before and after repair,and the differences were statistically significant.At the same time,the repair caused valve stenosis(the effective orifice area decreased by 40%and the positive differential pressure increased by 110%),but the valves was still within the normal physiological range,and no iatrogenic stenosis was caused.Conclusions It can be seen that TEER has an effect on FMR.This study provides validation and evaluation methods in vitro for expanding indications and improving TEER,and reference for developing standards of transcatheter valve repair testing in vitro.
10.Analysis of Correlation Between the Occurrence of Seasonal Allergic Rhinitis in Ren-Yin Stem-Branch Year of Chinese Lunar Calendar and Innate Circuit Qi Endowment of the Patients
Zhao-Qian WANG ; Xiang-Ting MA ; Chang GAO ; Ting-Ting CAI ; Zhi-Han CHEN ; Jing LIU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(5):1116-1122
Objective To analyze the innate circuit qi endowment of patients with seasonal allergic rhinitis(SAR)in Renyin year(Ren-Yin stem-branch year of Chinese lunar calendar).Methods A retrospective study was conducted in 8 918 SAR patients who were treated in the Department of Otorhinolaryngology of Xiyuan Hospital,China Academy of Chinese Medical Sciences in pollen seasons of the spring and autumn(i.e.,the period of March 5 to May 21,and the period of August 7 to September 23)in 2022(Renyin year).The characteristics of circuit qi at birth date of the SAR patient were analyzed.Results The occurrence of SAR in Renyin year was related to the suiyun(yearly circuit phase),sitian(the first half of the alterable yearly circuit qi),dominant qi,and circuit qi combination.The two-factor model analysis showed that the occurrence of SAR in Renyin year was closely related with suiyun-sitian and dominant qi-guest qi.High morbidity of SAR was shown in the patients born in the year of heavenly-stem Ren and earthly-branch Xu,and with the circuit qi features of five circuits being wood circuit,Suiyun being excessive wood circuit,sitian of yangming dryness-gold,zaiquan(the second half of the alterable yearly circuit qi)of shaoyin monarch-fire,dominant qi being yangming dryness-gold,and circuit qi combination being disharmony.The two-factor model analysis showed that the morbidity of SAR was increased in the year with the circuit qi features of suiyun-sitian being excessive wood circuit and taiyang cold-water,and the combination of dominant qi and guest qi being yangming dryness-gold and taiyang cold-water.Conclusion Among the innate circuit qi factors,suiyun,sitian,dominant qi,and circuit qi combination have an impact on the occurrence of SAR.The interaction between innate circuit qi and circuit qi at onset may be one of the important mechanisms leading to the occurrence of SAR.

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