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Asperuloside Promotes Apoptosis of Cervical Cancer Cells through Endoplasmic Reticulum Stress-Mitochondrial Pathway

Chinese Journal of Integrative medicine 2024年第1期30卷 34-41页

作者： QI Zhi-min WANG Xia LIU Xia ZHAO Juan Medical Examination center Hebei Province Hospital of Chinese MedicineShijiazhuang(050011)China Department of Gynaecology and Obstetrics Hebei Province Hospital of Chinese MedicineShijiazhuang(050011)China experimental center for Teaching Hebei Medical UniversityShijiazhuang(050017)China

Objective: To investigate the effects of asperuloside on cervical cancer based on endoplasmic reticulum(ER) stress and mitochondrial pathway. Methods: Different doses(12.5–800 μg/mL) of asperuloside were used to treat cervical cancer cell lines Hela and CaSki to calculate the half maximal inhibitory concentration(IC_(50)) of asperuloside. The cell proliferation was analyzed by clone formation assay. Cell apoptosis, intracellular reactive oxygen species(ROS) and mitochondrial membrane potential were determined by flow cytometry. The protein expressions of cleaved-caspase-3, Bcl-2, Bax, Cyt-c, cleaved-caspase-4 and glucose-regulated protein 78(GRP78) were analyzed by Western blot. And the inhibitor of ER stress, 4-phenyl butyric acid(4-PBA) was used to treat cervical cancer cells to further verify the role of ER stress in the apoptosis of cervical cancer cells induced by asperuloside. Results: Asperuloside of 325, 650, and 1300 μg/mL significantly inhibited the proliferation and promoted apoptosis of Hela and CaSki cells(P<0.01). All doses of asperuloside significantly increased intracellular ROS levels, reduced mitochondrial membrane potential, significantly reduced Bcl-2 protein expression level, and increased Bax, Cyt-c, GRP78 and cleaved-caspase-4 expressions(P<0.01). In addition, 10 mmol/L 4-PBA treatment significantly promoted cell proliferation and reduced apoptosis(P<0.05), and 650 μg/mL asperuloside could reverse 4-PBA-induced increased cell proliferation, decreased apoptosis and cleaved-caspase-3,-4 and GRP78 protein expressions(P<0.05). Conclusion: Our study revealed the role of asperuloside in cervical cancer, suggesting that asperuloside promotes apoptosis of cervical cancer cells through ER stress-mitochondrial pathway.

关键词： asperuloside Chinese medicine cervical cancer endoplasmic reticulum stress mitochondrial damage apoptosis

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Nanobodies against African swine fever virus p72 and CD2v proteins as reagents for developing two cELISAs to detect viral antibodies

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Virologica Sinica 2024年第3期39卷 478-489页

作者： Jiahong Zhu Qingyuan Liu Liuya Li Runyu Zhang Yueting Chang Jiakai Zhao Siyu Liu Xinyu Zhao Xu Chen Yani Sun Qin Zhao Department of Preventive Veterinary medicine College of Veterinary MedicineNorthwest A&F UniversityYangling Observing and Experimental Station of National Data Center of Animal HealthMinistry of AgricultureYangling712100China

African swine fever virus(ASFV)poses a significant threat to the global swine ***,there are no effective vaccines or treatments available to combat ASFV infection in *** primary means of controlling the spread of the disease is through rapid detection and subsequent elimination of infected ***,a lower virulent ASFV isolate with a deleted EP402R gene(CD2v-deleted)has been reported in China,which further complicates the control of ASFV infection in pig ***,an EP402R-deleted ASFV variant has been developed as a potential live attenuated vaccine candidate ***,it is crucial to develop detection methods that can distinguish wild-type and EP402R-deleted ASFV *** this study,two recombinant ASFV-p72 and-CD2v proteins were expressed using a prokaryotic system and used to immunize Bactrian ***,eight nanobodies against ASFV-p72 and ten nanobodies against ASFV-CD2v were *** the production of these nanobodies with horse radish peroxidase(HRP)fusion proteins,the ASFV-p72-Nb2-HRP and ASFV-CD2v-Nb22-HRP fusions were selected for the development of two competitive ELISAs(cELISAs)to detect anti-ASFV *** two cELISAs exhibited high sensitivity,good specificity,repeatability,and *** coincidence rate between the two cELISAs and commercial ELISA kits was 98.6%and 97.6%,***,the two cELISA for detecting antibodies against ASFV demonstrated ease of operation,a low cost,and a simple production *** two cELISAs could determine whether pigs were infected with wild-type or CD2v-deleted ASFV,and could play an important role in monitoring ASFV infections in pig farms.

关键词： African swine fever virus(ASFV) ASFV-p72 ASFV-CD2v Nanobody-HRP Competitive ELISA

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Protective mechanism of Coprinus comatus polysaccharide on acute alcoholic liver injury in mice,the metabolomics and gut microbiota investigation

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Food Science and Human Wellness 2024年第1期13卷 401-413页

作者： Jinyan Yu Jianguang Sun Min Sun Weidong Li Dongmei Qi Yongqing Zhang Chunchao Han School of Pharmacy Shandong University of Traditional Chinese MedicineJinan 250355China Hepatology Department of Affiliated Hospital of Shandong University of Traditional Chinese medicine Jinan 250355China experimental center Shandong University of Traditional Chinese MedicineJinan 250355China

Coprinus comatus polysaccharide(CCP)has significant hepatoprotective *** explore hepatoprotective mechanism of CCP,the study analyzed preventive effect of CCP on acute alcoholic liver injury in mice by histopathological examination and biochemical ***,hepatoprotective mechanism was also analyzed in conjunction with metabolomics and proliferation of gut *** results showed that CCP significantly decreased alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)levels in serum of alcoholic liver disease(ALD)*** examination showed that CCP can significantly improve liver *** results showed that there were significant differences in the level of metabolites in liver tissue of control group,ALD group and CCP group,including taurine,xanthosine,fumaric acid and arachidonic acid,among *** pathways analysis showed that hepatoprotective effect of CCP was related to energy metabolism,biosynthesis of unsaturated fatty acids,amino acids metabolism and lipid ***,CCP inhibited an increase in the number of Clostridium perfringens,Enterobacteriaceae and Enterococcus,and a decrease in the number of Lactobacillus and Bifidobacterium in the gut of ALD *** these findings suggested that CCP treatment reversed the phenotype of ethanol-induced liver injury and the associated metabolites pathways.

关键词： Coprinus comatus Polysaccharide Alcoholic liver disease Metabolomics Gut microbiota

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Effect on serum metabolomics of rats with premature ovarian insufficiency by Zhibian(BL54) through Shuidao(ST28) acupuncture

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Journal of Traditional Chinese medicine 2024年第4期44卷 722-733页

作者： YAN Jing FENG Huimin QIU Fang WANG Haijun YIN Luyun JIN Xiaofei ZHAO Jiyu WANG Hongyang YAN Xiaoqin Second Clinical College of Shanxi University of Traditional Chinese medicine Jinzhong 030619China Research center of experimental Acupuncture Science Tianjin University of Traditional Chinese MedicineTianjin 301617China Department of Cervical and Lumbar Vertebral Diseases Jinzhong Hospital Affiliated to Shanxi University of Traditional Chinese MedicineJinzhong 030600China

OBJECTIVE:To analyze the serum metabolic targets of the"Zhibian(BL54)through Shuidao(ST28)"acupuncture technique in cyclophosphamide(CTX)-induced premature ovarian insufficiency(POI)model rats and to elucidate the potential molecular mechanism of acupuncture in improving ***:We used an intraperitoneal injection of CTX to establish the POI rat model(POI group)and compared serum hormone levels and ovarian histopathological changes to evaluate the effect of the Zhibian(BL54)through Shuidao(ST28)technique(ZS+POI group)on ovarian ***,nontargeted metabolomics was performed using rat serum by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS).RESULTS:After acupuncture intervention,the serum hormone levels and ovarian pathological morphology of POI rats were effectively ***,UPLC-Q-TOF/MS results showed that the ZS+POI group showed a significant reversal of the levels of 6 differential *** them,the levels of four serum metabolic markers,divanillyltetrahydrofuran ferulate,trans-ferulic acid,tryptamine,and neuraminic acid,increased *** analysis of biological effects showed that all metabolites were involved in the regulation of reproductive hormone levels and antioxidant and antiapoptotic ***:The"Zhibian(BL54)through Shuidao(ST28)"acupuncture method may improve the ovarian function of POI rats by regulating serum metabolite markers to exert antioxidant and antiapoptotic effects,which provides a theoretical basis for the clinical application of acupuncture in the treatment of POI.

关键词： acupuncture premature ovarian insufficiency metabolomics ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry Zhibian(BL54)through Shuidao(ST28)

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Heterobimetallic[NiCo]integration in a hydrogenase mimic for boosting light-driven hydrogen evolution in CaTiO_(3)

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Nano Research 2024年第8期17卷 6888-6894页

作者： Kang Li Juanji Hong Ningning Song Zhanjun Guo Minmin Liang experimental center of Advanced Materials School of Materials Science&EngineeringBeijing Institute of TechnologyBeijing 10081China

Light-drive hydrogen production using titanium-based perovskite is one sustainable way to reduce current reliance on fossil fuels,but its wide applications are still limited by high electron−hole recombination and sluggish surface ***,the developments for low-cost and highly efficient co-catalysts remain *** by natural[NiFe]-hydrogenase active center structure,a hydrogenase-mimic,NiCo_(2)S_(4) nanozyme was synthesized,and subsequently decorated onto the CaTiO_(3) to catalyze the hydrogen evolution reaction(HER).Among the following test,CaTiO_(3)with a 15%loading of NiCo_(2)S_(4) nanozyme exhibited the highest HER rate of 307.76μmol·g^(–1)·h^(–1),which is 60 times higher than that of the CaTiO_(3) *** results reveal that NiCo_(2)S_(4) not only significantly increased the charge separation efficiency of the photogenerated carriers,but also substantively lowered the HER activation *** studies show that NiCo_(2)S_(4) readily splits H_(2)O by forming the Ni(OH)-Co intermediate and only Ni in the bimetallic center alters the oxidation state during the HER process in a manner analogous to the[NiFe]-*** contrast to the often-expensive synthetic catalysts that rely on rare elements such as ruthenium and platinum,this study shows a promising way to develop the nature-inspired cocatalysts to enhance the photocatalysts’HER performance.

关键词： hydrogen evolution reaction hydrogenase-mimic nanozyme photocatalyst water-splitting

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A combined nanotherapeutic approach targeting farnesoid X receptor,ferroptosis,and fibrosis for nonalcoholic steatohepatitis treatment

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2228-2246页

作者： Jiangtao Fu Pingping Zhang Zhiguo Sun Guodong Lu Qi Cao Yiting Chen Wenbin Wu Jiabao Zhang Chunlin Zhuang Chunquan Sheng Jiajun Xu Ying Lu Pei Wang The center for Basic Research and Innovation of medicine and Pharmacy(MOE) School of PharmacyNaval Medical UniversityShanghai 200433China National Demonstration center for experimental Pharmaceutical Education Naval Medical University/Second Military Medical UniversityShanghai 200433China Department of Diving and Hyperbaric medicine Naval Special Medical CenterNaval Medical UniversityShanghai 200433China

Obeticholic acid(OCA),a farnesoid X receptor(FXR)agonist with favorable effects on fatty and glucose metabolism,has been considered the leading candidate drug for nonalcoholic steatohepatitis(NASH)***,its limited effectiveness in resolving liver fibrosis and lipotoxicity-induced cell death remains a major ***,a newly recognized form of cell death characterized by uncontrolled lipid peroxidation,is involved in the progression of *** oxide(NO)is a versatile biological molecule that can degrade extracellular *** this study,we developed a PEGylated thiolated hollow mesoporous silica nanoparticles(MSN)loaded with OCA,as well as a ferroptosis inhibitor liproxsatin-1 and a NO donor S-nitrosothiol(ONL@MSN).Biochemical analyses,histology,multiplexed flow cytometry,bulk-tissue RNA sequencing,and fecal 16S ribosomal RNA sequencing were utilized to evaluate the effects of the combined nanoparticle(ONL@MSN)in a mouse NASH *** with the OCA-loaded nanoparticles(O@MSN),ONL@MSN not only protected against hepatic steatosis but also greatly ameliorated fibrosis and ***@MSN also displayed enhanced therapeutic actions on the maintenance of intrahepatic macrophages/monocytes homeostasis,inhibition of immune response/lipid peroxidation,and correction of microbiota *** findings present a promising synergistic nanotherapeutic strategy for the treatment of NASH by simultaneously targeting FXR,ferroptosis,and fibrosis.

关键词： Nonalcoholic steatohepatitis Nanotherapy Farnesoid X receptor Ferroptosis Fibrosis Obeticholic acid S-Nitrosothiol Liproxstatin-1

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Adenosine triphosphate mediates the pain tolerance effect of manual acupuncture at Zusanli(ST36) in mice

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Journal of Traditional Chinese medicine 2024年第4期44卷 660-669页

作者： LI Zhongzheng ZHAO Yadan Ma Weigang Zhang Yonglong XU Zhifang XI Qiang LI Yanqi QIN Siru ZHANG Zichen WANG Songtao ZHAO Xue LIU Yangyang GUO Yi GUO Yongming Research center of experimental Acupuncture Science Tianjin University of Traditional Chinese MedicineTianjin 301617China National Clinical Research center for Chinese medicine Acupuncture and Moxibustion Tianjin 301617China Department of Acupuncture and Moxibustion Qingdao Hiser Hospital Affiliated of Qingdao University(Qingdao Traditional Chinese Medicine Hospital)Qingdao 266033China School of Traditional Chinese medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China School of Acupuncture and Moxibustion and Tuina Tianjin University of Traditional Chinese MedicineTianjin 301617China

OBJECTIVE:To investigate the mechanisms behind the effects of acupuncture in Traditional Chinese medicine,we delved into the adenosine triphosphate/peripheral purinergic P2X receptor 3(ATP/P2X3)receptor signaling system as an indicator of the body's energy state,commonly referred to as"Qi".METHODS:The tail-flick test was utilized to explore the impact of acupuncture on pain tolerance threshold(PTT)in mice,while also assessing adenosine(ADO)levels and adenylate energy charge(EC)at Zusanli(ST36).The study further investigated the dose-dependent effects of acupuncture on PTT and ADO levels at Zusanli(ST36).To shed light on the underlying mechanisms of acupuncture's effects,the study examined the impact of ATP,a P2X3 receptor antagonist,and adenosine disodium on PTT following acupuncture ***:Acupuncture at Zusanli(ST36)led to significant improvements in PTT in mice,with the most effective interventions being twirling for 2 min and needle retention for 28 *** interventions also resulted in significant increases in ATP *** effects of acupuncture were further augmented by administration of different doses of ATP at Zusanli(ST36),and pretreatment with a P2X3 receptor antagonist decreased *** EC peaked at 30 min after intraperitoneal injection of ATP,and pretreatment with various doses of *** 30 min prior to acupuncture increased PTT in a dose-dependent ***,pretreatment with an *** intramuscular injection of adenosine disodium enhanced the effects of ***:This research provides compelling evidence that ATP is involved in the regulation of PTT through acupuncture,revealing new avenues for achieving enhanced clinical outcomes.

关键词： acupuncture point ST36(Zusanli) adenosine triphosphate receptors,purinergic P2X3 energy state

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Neutrophils are shaped by the tumor microenvironment:novel possibilities for targeting neutrophils in cancer

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1788-1790页

作者： Carlos Silvestre-Roig Lydia Kalafati Triantafyllos Chavakis Institute of experimental Pathology(ExPat) Center for Molecular Biology of Inflammation(ZMBE)University of MünsterMünsterGermany Institute for Clinical Chemistry and Laboratory medicine University Hospital and Faculty of MedicineTechnische Universität DresdenDresdenGermany

In a recent paper published in Science,Ng et *** seminal insights into the process through which neutrophils are reprogrammed by the tumor environment,leading to a convergent transition from different neutrophil states towards a unique end-stage differentiated pro-tumor phenotype.1 These findings have major translational implications as they provide potential neutrophil-related targets for tumor immunotherapy.

关键词： al. neutrophils tumor

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Establishment of acquired tracheoesophageal fistula using a modified magnetic compression technique in rabbits and its postmodeling evaluation

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World Journal of Gastrointestinal Surgery 2024年第5期16卷 1385-1394页

作者： Han Meng Fu-Yao Nan Na Kou Qin-Yan Hong Ming-Sheng Lv Ju-Bo Li Bao-Jie Zhang Hang Zou Lei Li Hong-Wu Wang Respiratory Disease center Dongzhimen HospitalBeijing University of Chinese MedicineBeijing 100029China The First Clinical Medical College Beijing University of Chinese MedicineBeijing 100700China Department of Animal experimental center National Center for CardiovascularFuwai HospitalBeijing 100037China

BACKGROUND Previous studies have validated the efficacy of both magnetic compression and surgical techniques in creating rabbit tracheoesophageal fistula(TEF)*** compression achieves a 100%success rate but requires more time,while surgery,though less frequently successful,offers rapid model establishment and technical maturity in larger animal *** To determine the optimal approach for rabbit disease modeling and refine the *** TEF models were created in 12 rabbits using both the modified magnetic compression technique and *** of the time to model establishment,success rate,food and water intake,weight changes,activity levels,bronchoscopy findings,white blood cell counts,and biopsies were *** response to the failures encountered during modified magnetic compression modeling,we increased the sample size to 15 rabbit models and assessed the repeatability and stability of the models,comparing them with the original magnetic compression *** The modified magnetic compression technique achieved a 66.7%success rate,whereas the success rate of the surgery technique was 33.3%.Surviving surgical rabbits might not meet subsequent experimental requirements due to TEF-related *** the modified magnetic compression group,one rabbit died,possibly due to magnet corrosion,and another died from tracheal magnet *** events occurred during the second round of modified magnetic compression modeling,with one rabbit possibly succumbing to aggravated lung *** operation time of the first round of modified magnetic compression was 3.2±0.6 min,which was significantly reduced to 2.1±0.4 min in the second round,compared to both the first round and that of the original *** The modified magnetic compression technique exhibits lower stress responses,a simple procedure,a high success rate,and lower modeling costs,making it a more appropriate choice for constructing TEF models in

关键词： Tracheoesophageal fistula Modified magnetic compression technique Post-modeling evaluation Pneumonia Malnutrition

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Hypomethylation of glycine dehydrogenase promoter in peripheral blood mononuclear cells is a new diagnostic marker of hepatitis B virus-associated hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 35-42页

作者： Li-Li Miao Jing-Wen Wang Hui-Hui Liu Shuai Gao Yu-Chen Fan Kai Wang Department of Hepatology Qilu Hospital of Shandong UniversityJinan 250012China experimental center Shandong University of Traditional Chinese MedicineJinan 250355China Institute of Hepatology Shandong UniversityJinan 250012China

Background: Glycine dehydrogenase(GLDC) plays an important role in the initiation and proliferation of several human cancers. In this study, we aimed to detect the methylation status of GLDC promoter and its diagnostic value for hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC). Methods: We enrolled 197 patients, 111 with HBV-HCC, 51 with chronic hepatitis B(CHB), and 35 healthy controls(HCs). The methylation status of GLDC promoter in peripheral mononuclear cells(PBMCs) was identified by methylation specific polymerase chain reaction(MSP). The mRNA expression was examined using real-time quantitative polymerase chain reaction(q PCR). Results: The methylation frequency of the GLDC promoter was significantly lower in HBV-HCC patients(27.0%) compared to that in CHB patients(68.6%) and HCs(74.3%)( P < 0.001). The methylated group had lower alanine aminotransferase level( P = 0.035) and lower rates of tumor node metastasis(TNM) Ⅲ/Ⅳ( P = 0.043) and T3/T4( P = 0.026). TNM stage was identified to be an independent factor for GLDC promoter methylation. GLDC mRNA levels in CHB patients and HCs were significantly lower than those in HBV-HCC patients( P = 0.022 and P < 0.001, respectively). GLDC mRNA levels were significantly higher in HBV-HCC patients with unmethylated GLDC promoters than those with methylated GLDC promoters( P = 0.003). The diagnostic accuracy of alpha-fetoprotein(AFP) combined with GLDC promoter methylation for HBV-HCC was improved compared with that of AFP alone(AUC: 0.782 vs. 0.630, P < 0.001). In addition, GLDC promoter methylation was an independent predictor for overall survival of HBV-HCC patients( P = 0.038). Conclusions: The methylation frequency of GLDC promoter was lower in PBMCs from HBV-HCC patients than that from patients with CHB and HCs. The combination of AFP and GLDC promoter hypomethylation significantly improved the diagnostic accuracy of HBV-HCC.

关键词： Hepatocellular carcinoma Glycine dehydrogenase DNA methylation Peripheral blood mononuclear cells

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