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Apolipoprotein E4 interferes with lipid metabolism to exacerbate depression-like behaviors in 5xFAD mice

Animal Models and experimental medicine 2024年第3期7卷 347-361页

作者： Yanju Gong Mingfeng Li Min Liu Xinghan Wu Yanhong Li Chuan Qin Ling Zhang iNHC Key Laboratory of Human Disease comparative medicine Beijing Engineering Research Center for Experimental Animal Models of Human Critical DiseasesInternational Center for Technology and lnnovation of Animal ModelComparative Medicine CenterInstitute of Laboratory Animal SciencesChinese Academy of Medical Sciences(CAMS)and Peking Union Medical College(PuMC)BeijingChina Changping National Laboratory(CPNL) BeijingChina

Background:Apolipoprotein E4(ApoE4)allele is the strongest genetic risk factor for late-onset Alzheimer's disease,and it can aggravate depressive symptoms in non-AD ***,the impact of ApoE4 on AD-associated depression-l ike behaviors and its underlying pathogenic mechanisms remain ***:This study developed a 5xFAD mouse model overexpressing human ApoE4(E4FAD).Behavioral assessments and synaptic function tests were conducted to explore the effects of ApoE4 on cognition and depression in 5xFAD *** in peripheral and central lipid metabolism,as well as the levels of serotonin(5-HT)andγ-aminobutyric acid(GABA)neurotransmitters in the prefrontal cortex,were *** addition,the protein levels of 24-dehydrocholesterol reductase/glycogen synthase kinase-3 beta/mammalian target of rapamycin(DHCR24/GSK3β/m TOR)and postsynaptic density protein 95/calmodulin-dependent protein kinase II/brain-derived neurotrophic factor(PSD95/CaMK-II/BDNF)were measured to investigate the molecular mechanism underlying the effects of ApoE4 on AD ***:Compared with 5xFAD mice,E4FAD mice exhibited more severe depressionlike behaviors and cognitive *** mice also exhibited increased amyloid-beta deposition in the hippocampus,increased astrocyte numbers,and decreased expression of depression-related neurotransmitters 5-HT and GABA in the prefrontal ***,lipid metabolism disorders were observed in E4FAD,manifesting as elevated low-density lipoprotein cholesterol and reduced high-density lipoprotein cholesterol in peripheral blood,decreased cholesterol level in the prefrontal cortex,and reduced expression of key enzymes and proteins related to cholesterol synthesis and *** expression of proteins related to the DHCR24/GSK3β/m TOR and PSD95/CaMK-II/BDNF pathways was also ***:This study found that ApoE4 overexpression exacerbates depressionlike behaviors in 5xFAD mice and confirmed that ApoE4 reduces co

关键词： 5xFAD mice Alzheimer's disease ApoE4 allele depression like

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

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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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Ultrasound-driven self-decomposition porphyrins as metal-free CO precursors for gas and sonodynamic synergistic therapy

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Science China Chemistry 2024年第5期67卷 1624-1635页

作者： Shuxin Liu Jinjuan Ma Xiang Xu Aiguo Wang Nan Zheng School of Chemical Engineering Dalian University of TechnologyDalian 116024China Department of comparative medicine Laboratory Animal center Dalian Medical UniversityDalian 116000China Cancer Hospital of Dalian University of Technology Shenyang 116000China

Carbon monoxide(CO) is an endogenous therapeutic gas with an anti-tumor effect. The precise delivery and controlled release of CO in tumor tissues play crucial roles in anti-cancer treatment. However, efficient in situ generation of CO from metal-free COreleasing molecules(CORMs) remains a formidable challenge. Herein, we develop ultrasound(US)-driven self-decomposition porphyrin as organic and metal-free US-CORMs, which can spatiotemporally control the CO release(347 mmol CO/mol porphyrin) efficiently under physiologically harmless US conditions(1.0 MHz, 1.5 W/cm^(2), 50% duty cycle, 50 min). Moreover,porphyrin as a sonosensitizer can also generate reactive oxygen species(ROS) under US treatment to achieve sonodynamic therapy(SDT). Advanced functions of such porphyrin-based CORMs in CO gas-sonodynamic synergistic treatment have been demonstrated by evaluating the in vitro and in vivo anti-tumor effects.

关键词： porphyrin sonodynamic therapy metal-free CO precursors ultrasound-driven gas therapy

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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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Role of doxycycline in the treatment of dengue infection: An open-label, randomized, controlled, pilot trial

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Asian Pacific Journal of Tropical medicine 2024年第4期17卷 160-165页

作者： Banothu Vinod Kumar Kajal Kamboj Ashok Kumar Pannu Ashok Kumar Yadav Mandip Bhatia Atul Saroch Department of Internal medicine PGIMER ChandigarhIndia Department of experimental medicine&Biotechnology PGIMER ChandigarhIndia

Objective:To measure the effect of doxycycline on inflammatory marker[IL-6,TNF-α,ferritin and C reactive protein(CRP)]levels in patients with dengue ***:A single-centre,open-label,parallel-group randomized controlled trial was done in PGIMER Chandigarh from June 2021 to October *** were randomized using a simple randomization process into two groups:the doxycycline treatment group(n=35)and the control group(n=34).Patients in the treatment group were given oral doxycycline 100 mg twice daily for five days along with standard treatment,whereas patients in the control group received only standard *** objective was to measure the effect of doxycycline on inflammatory markers in dengue ***:On comparative analysis at day 5,there was a statistically significant reduction in the median values of ferritin and CRP in cases compared to the control group(ferritin:P=0.006 and CRP:P=0.006).No significant reduction was noted in the levels of IL-6 and TNF-α.Conclusions:Doxycycline treatment led to a reduction of inflammatory markers in dengue infection.

关键词： Dengue Cytokine Doxycycline Serum ferritin C reactive protein

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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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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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