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Construction and evaluation of an alcohol vapor chamber system

The Journal of Biomedical research 2023年第2期37卷 115-124页

作者： Wan Jiang Jiajia Chen Olivia Ewi Vidjro Yingying Zhang Gengni Guo Ziyi Li Yize Qi Rouli Dai Tengfei Ma School of Pharmacy Nanjing Medical UniversityNanjingJiangsu 211166China translational medicine research center for drug dependence and withdrawal Nanjing Medical UniversityJiangsu 211166China National Institute of drug Clinical Trial The Fourth Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210031China

An increasing number of studies demonstrated that alcohol vapor chamber is an effective way to model physical signs of alcohol use disorders. Although researchers are developing different vapor chambers to study chronic alcohol exposure model worldwide, few studies build and modify their own vapor chambers in ***, we designed and established an alcohol vapor chamber system for small animals. We described a paradigm showing how to control and monitor alcohol concentration in whole system. The vapor chamber system with several advantages including accommodating up to ten standard mouse cages. Furthermore, the system was tested by evaluating the blood alcohol concentration and neuron injury in mice. Importantly, the alcohol withdrawal after vapor exposure caused motor coordination impairment, anxiolytic-and depression-like behavior. Finally, the Nmethyl-D-aspartate receptor(NMDAR)-mediated glutamatergic transmissions in the medial prefrontal cortex was changed after alcohol vapor exposure-induced behaviors. The frequency and amplitude of spontaneous excitatory postsynaptic currents between control and alcohol groups were not different, suggesting that alcohol exposureinduced behaviors are associated with the change in NMDAR response. Taken together, the new alcohol vapor chamber system was constructed, which would help to research the relationship between the stable alcohol exposure and withdrawal behaviors and to study chronic alcohol exposure-induced disorders in China.

关键词： alcohol use disorders alcohol vapor model anxiety depression NMDA receptor

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withdrawal of anti-tumour necrosis factor α therapy in inflammatory bowel disease

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World Journal of Gastroenterology 2015年第16期21卷 4773-4778页

作者： Konstantinos Papamichael Severine Vermeire Department of Clinical and Experimental medicine Translational Research Center for Gastrointestinal Disorders

Anti-tumour necrosis factor α(anti-TNFα) therapy is an established treatment in inflammatory bowel ***, this treatment is associated with high costs and the possibility of severe adverse events representing a true challenge for patients, clinicians and health care ***, a crucial question is raised namely if therapy can be stopped once remission is achieved and if so, how and in ***, in a real-life clinical setting, discontinuation may also be considered for other reasons such as the patient's preference, pregnancy, social reasons as moving to countries or continents with less access, or different local policy or *** contrast to initiation of anti-TNFα therapy guidelines regarding stopping of this treatment are *** a result, the decision of discontinuation is still a challenging aspect in the use of anti-TNFα *** this is typically based on an estimated, case-by-case, benefit-risk *** editorial is intended to provide an overview of recent data on this topic and shed light on the proposed drug withdrawal strategies.

关键词： Inflammatory bowel disease Anti-tumournecrosis factor α therapy withdrawal Remission Infliximab

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The Other Face of the Nucleus Accumbens:Aversion

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Neuroscience Bulletin 2016年第6期32卷 569-571页

作者： Ying Han Lin Lu Institute of Mental Health National Clinical Research Center for Mental DisordersKey Laboratory of Mental Healthand Peking University Sixth HospitalPeking University National Institute on drug dependence and Beijing Key Laboratory of drug dependence Peking University Peking-Tsinghua center for Life Sciences and PKU-IDG/McGovern Institute for Brain research Peking University

The nucleus accumbens （NAc） is thought to integrate information that is conveyed by （1） dopaminergic inputs from the midbrain and （2） glutamatergic inputs from limbic and cortical regions, including the amygdala, prefrontal cortex （PFC）, hippocampus, and thalamus [1], and signal to the basal ganglia motor system to guide appropriate behaviors. Addictive drug use is proposed to hijack this system, enhancing the brain＇s reactivity to drug cues and triggering drug-seeking and relapse after prolonged with- drawal [2, 3]. Both positive reinforcement （rewarding effects of drugs） and negative reinforcement （aversive emotional state associated with withdrawal） have been considered to play critical roles in the etiology and main- tenance of drug addiction, and NAc neurons are capable of processing both reward and aversion [4, 5]. Optogenetic activation of inputs from the PFC, ventral hippocampus （vHipp）, and basolateral amygdala （BLA） to the NAc drives positive reinforcement and facilitates reward- seeking behavior [6, 7], but a recent paper in Nature [8] has identified another face of the NAc. The pathway from the paraventricular nucleus of the thalamus （PVT） to the NAc is key to the aversive emotional state of drug withdrawal.

关键词： PVT MSNs

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Unique Pharmacology,Brain Dysfunction,and Therapeutic Advancements for Fentanyl Misuse and Abuse

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Neuroscience Bulletin 2022年第11期38卷 1365-1382页

作者： Ying Han Lu Cao Kai Yuan Jie Shi Wei Yan Lin Lu National Institute on drug dependence and Beijing Key Laboratory of drug dependence Peking UniversityBeijing 100191China Peking University Sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)Beijing 100191China Peking-Tsinghua center for Life Sciences and PKU-IDG/McGovern Institute for Brain research Peking UniversityBeijing 100871China

Fentanyl is a fully synthetic opioid with analgesic and anesthetic *** has become a primary driver of the deadliest opioid crisis in the United States and elsewhere,consequently imposing devastating social,economic,and health burdens ***,the neural mechanisms that underlie the behavioral effects of fentanyl and its analogs are largely unknown,and approaches to prevent fentanyl abuse and fentanyl-related overdose deaths are *** review presents the abuse potential and unique pharmacology of fentanyl and elucidates its potential mechanisms of action,including neural circuit dysfunction and *** discuss recent progress in the development of pharmacological interventions,anti-fentanyl vaccines,anti-fentanyl/heroin conjugate vaccines,and monoclonal antibodies to attenuate fentanyl-seeking and prevent fentanyl-induced respiratory ***,translational studies and clinical trials are still *** the present opioid crisis,the development of effective pharmacological and immunological strategies to prevent fentanyl abuse and overdose are urgently needed.

关键词： Fentanyl abuse Neural mechanisms Pharmacological interventions Fentanyl vaccines

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Discovery of N-benzyl hydroxypyridone carboxamides as a novel and potent antiviral chemotype against human cytomegalovirus (HCMV)

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Acta Pharmaceutica Sinica B 2022年第4期12卷 1671-1684页

作者： Sameera Senaweera Tiffany C.Edwards Jayakanth Kankanala Yan Wang Rajkumar Lalji Sahani Jiashu Xie Robert J.Geraghty Zhengqiang Wang center for drug Design College of PharmacyUniversity of MinnesotaMinneapolisMN 55455USA translational medicine R&D center Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

Current drugs for treating human cytomegalovirus(HCMV)infections are limited by resistance and treatment-associated *** developing mechanistically novel HCMV antivirals,we discovered an N-benzyl hydroxypyridone carboxamide antiviral hit(8a)inhibiting HCMV in submicromolar *** describe herein the structure–activity relationship(SAR)for 8a,and the characterization of potent analogs for cytotoxicity/cytostatic property,the preliminary mechanism of action,and the absorption,distribution,metabolism and excretion(ADME)*** SAR revealed a few pharmacophore features conferring optimal antiviral profile,including the 5-OH,the N-1 benzyl,at least one–CH_(2)−in the linker,and a di-halogen substituted phenyl ring in the amide *** the end,we identified numerous analogs with sub-micromolar antiviral potency and good selectivity *** preliminary mechanism of action characterization used a pUL89-C biochemical endonuclease assay,a virus entry assay,a time-of-addition assay,and a compound withdrawal *** profiling measuring aqueous solubility,plasma and liver microsomal stability,and parallel artificial membrane permeability assay(PAMPA)permeability demonstrated largely favorable drug-like ***,these studies validate the N-benzyl hydroxypyridone carboxamide as a viable chemotype for potent and mechanistically distinct antivirals against HCMV.

关键词： Human cytomegalovirus N-Benzyl hydroxypyridone carboxamides Structureeactivity relationship Mechanism of action

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Piceatannol enhances Beclin-1 activity to suppress tumor progression and its combination therapy strategy with everolimus in gastric cancer

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Science China(Life Sciences) 2023年第2期66卷 298-312页

作者： Longtao Huangfu Xiaoyang Wang Shanshan Tian Junbing Chen Xueying Wang Biao Fan Qian Yao Gangjian Wang Cong Chen Jing Han Xiaofang Xing Jiafu Ji Key Laboratory of Carcinogenesis and translational research(Ministry of Education) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital&InstituteBeijing 100142China Department of Pharmacy Peking University Cancer Hospital&InstituteBeijing 100142China National Institute on drug dependence Peking UniversityBeijing 100191China Gastrointestinal Cancer center Peking University Cancer Hospital&InstituteBeijing 100142China Department of Pathology Peking University Cancer Hospital&InstituteBeijing 100142China

The effects and regulation of Beclin-1-an autophagy-related protein-have not been fully defined, however, a negative correlation has been reported between Beclin-1 expression and carcinogenesis. Meanwhile, no compound has been shown to directly inhibit its activity. Here, we evaluate piceatannol, a naturally occurring polyphenolic compound, as a potential targeting agonist of Beclin-1, to assess its efficacy as an antitumor agent against gastric cancer. More specifically, we determine the effects of piceatannol treatment on cell viability using a monitoring system and colony forming assay. Piceatannol was found to efficiently inhibit the proliferation of several human gastric cancer cell lines. Autophagic flux is increased by piceatannol treatment, and correlates with inhibition of cell proliferation and colony formation. Additionally, microscale thermophoresis and surface plasmon resonance results show a direct interaction between piceatannol and Beclin-1, which reduces the phosphorylation activity of Beclin-1 at the Ser-295 site. Notably, piceatannol impairs the binding of Beclin-1 to Bcl-2 and enhances the recruitment of binding of UV radiation resistance-associated gene protein, which further triggers Beclin-1-dependent autophagy signaling. An increase in autophagic activity via treatment with the mTOR inhibitor, everolimus, effectively sensitizes piceatannol-induced antitumor effects. Xenograft models confirmed that piceatannol inhibits tumor development and elicits a potent synergistic effect with everolimus in vivo. Taken together, the findings of this study strongly support the application of combinatorial piceatannol and everolimus therapy in future clinical trials for gastric cancer patients.

关键词： piceatannol Beclin-1 autophagy everolimus gastric cancer drug synergy

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Causal relationships between chronotype and risk of multiple cancers by using longitudinal data and Mendelian randomization analysis

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Science China(Life Sciences) 2023年第10期66卷 2433-2436页

作者： Shanshan Tian Longtao Huangfu Sizhi Ai Junwei Zheng Le Shi Wei Yan Ximei Zhu Qianwen Wang Jiahui Deng Yanping Bao Suhua Chang Lin Lu Peking University Sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)Beijing 100191China Key Laboratory of Carcinogenesis and translational research(Ministry of Education) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital&InstituteBeijing 100142China Department of Cardiology Heart CenterThe First Affiliated Hospital of Xinxiang Medical UniversityXinxiang 453100China National Institute on drug dependence and Beijing Key Laboratory of drug dependence Peking UniversityBeijing 100191China Chinese Academy of Medical Sciences research Unit(No.2018RU006) Peking UniversityBeijing 100191China Peking-Tsinghua center for Life Sciences PKU-IDG/McGovern Institute for Brain ResearchBeijing 100871China

Dear Editor,Cancer is the second leading cause of death worldwide,and the cancer situation is becoming more complicated(Zhou et al.,2022).The International Agency for research on Cancer(IARC)Monographs Working Group c... 详细信息

关键词： Cancer death

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Clinical Study on Combined Acupuncture and Psychological Desensitization Therapy for Anxiety due to Heroin Addiction

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Journal of Acupuncture and Tuina Science 2010年第2期8卷 116-118页

作者：宋小鸽胡玲蔡荣林梅益斌李晓婷 research Institute of Acupuncture and Meridian Anhui College of Traditional Chinese Medicien Hefei 230038 P. R. China Anhui Provincial drug-withdrawal Rehabilitation center Hefei 230001 P. R. China

Objective： To observe the clinical efficacy of combined acupuncture and psychological desensitization therapy for anxiety in those with heroin addiction. Methods： All 90 cases were randomly allocated into a treatment group （45 cases） and a control group （45 cases）. Cases in the treatment group received 30 min of combined acupuncture and psychological desensitization therapy for each treatment, twice a week and 8 weeks in total, whereas cases in the control group received no treatment. After that, the anxiety score and state were observed. In addition, the mental state prior to and after cue-elicited heroin craving was evaluated. Results： The total and standard scores of anxiety in the treatment group were significantly reduced compared to the control group （P〈0.05）, coupled with a significant reduction of heroin craving （P〈0.01）. Conclusion： Combined acupuncture and psychological desensitization can alleviate anxiety and inhibit the short-term heroin craving.

关键词： Heroin dependence Substance withdrawal Syndrome Anxiety Acupuncture- moxibustion Therapy Desensitization, Psychologic

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Association of ABCB1 Gene Polymorphisms with Efficacy and Adverse Reaction to Risperidone or Paliperidone in Han Chinese Schizophrenic Patients

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Neuroscience Bulletin 2016年第6期32卷 547-549页

作者： Weifeng Mi Feihu Liu Yongqiao Liu Bo Du Weidong Xiao Lingzhi Li Lan Huang Tianlan Lu Jia He Le Shi Weihua Yue Hongyan Zhang Peking University Sixth Hospital Peking University Instituteof Mental Health Key Laboratory of Mental Health Ministry of Health (Peking University) National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital) Beijing 100191 China The Mental Health center of Xi'an Xi'an 710061 China The Sixth People's Hospital of Hebei Province Baoding 07100 China The People's Hospital of Hubei Province Wuhan 430060China National Institute on drug dependence and Beijing KeyLaboratory of drug dependence Peking UniversityBeijing 100191 China Department of Pharmacology School of Basic Medical Sciences Peking University Health Science CenterBeijing 100191 China

Dear editor, P-glycoprotein （P-gp, also known as ATP-binding cassette transport sub-family B member 1, ABCB1） is a potent ATP-dependent efflux pump for a wide variety of drugs. Although studies of its substrates are abundant [ 1, 2], and ABCB1 is a well-conserved gene, there is increasing evi- dence that its polymorphisms affect substrate specificity [3]. A previous study reported that the synonymous single nucleotide polymorphism （SNP） C3435T （rs1045642） affects the timing of co-translational folding and insertionof P-gp into the membrane,

关键词： PANSS Association of ABCB1 Gene Polymorphisms with Efficacy and Adverse Reaction to Risperidone or Paliperidone in Han Chinese Schizophrenic Patients

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Recent advances in the development of in vitro liver models for hepatotoxicity testing

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Bio-Design and Manufacturing 2021年第4期4卷 717-734页

作者： Siming Lu Jingwei Zhang Sha Lin Danfeng Zheng Yan Shen Jiale Qin Yangyang Li Shuqi Wang Department of Laboratory medicine The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalNational Clinical Research Center for Infectious DiseasesZhejiang University School of MedicineHangzhou 310003China Institute of translational medicine Zhejiang UniversityHangzhou 310029China Key Laboratory of Women’s Reproductive Health of Zhejiang Province Women’s HospitalZhejiang University School of MedicineHangzhou 310006China Key Laboratory of Tissue Engineering and Regenerative medicine of Zhejiang Province Zhejiang University School of MedicineHangzhou 310027China

Liver injury is a common cause of drug approval withdrawal during drug development,pre-clinical research,and clinical *** not properly treated,patients with severe liver injury can suffer from acute liver failure or even ***,utilization of the convenient in vitro hepatotoxicity assessment model for early detection of drug-induced hepatotoxicity is vital for drug development and safe personalized ***(e.g.,hydrogels,nanofibers,decellularized liver matrix)and bioengineering technologies(e.g.,microarrays,micropatterns,3D printing,and microfluidics)have been applied for in vitro hepatotoxicity assessment *** review summarizes the structure and functions of the liver as well as the components of in vitro hepatotoxicity assessment *** addition,it highlights the latest advances in developing hepatotoxicity models with the ultimate goal of further clinical translation.

关键词： Liver injury drug toxicity In vitro model 3D culture

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