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A novel dual serotonin transporter and M-channel inhibitor D01 for antidepression and cognitive improvement

Acta Pharmaceutica Sinica B 2024年第3期14卷 1457-1466页

作者： Yaqin Wei Xiangqing Xu Qiang Guo Song Zhao Yinli Qiu Dongli Wang Wenwen Yu Yani Liu KeWei Wang School of Pharmacy Xuzhou Medical UniversityXuzhou 221004China Institute of Pharmaceutical Research Jiangsu Nhwa Pharmaceutical Co.Ltd.&Jiangsu Key Laboratory of Central Nervous System Drug Research and DevelopmentXuzhou 221116China Department of Pharmacology School of PharmacyQingdao University Medical CollegeQingdao 266073China Institute of Innovative Drug Qingdao UniversityQingdao 266021China center for Brain Science and Brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay AreaGuangzhou 510515China

Cognitive dysfunction is a core symptom common in psychiatric disorders including depression that is primarily managed by antidepressants lacking efficacy in improving *** this study,we report a novel dual serotonin transporter and voltage-gated potassium Kv7/KCNQ/M-channel inhibitor D01(a 2-methyl-3-aryloxy-3-heteroarylpropylamines derivative)that exhibits both anti-depression effects and improvements in cognition.D01 inhibits serotonin transporters(K_(i)=30.1±6.9 nmol/L)and M channels(IC_(50)=10.1±2.4μmol/L).D01 also reduces the immobility duration in the mouse FST and TST assays in a dose-dependent manner without a stimulatory effect on *** administrations of D01(20 and 40 mg/kg)can significantly shorten the immobility time in a mouse model of chronic restraint stress(CRS)-induced depression-like ***,D01 dose-dependently improves the cognitive deficit induced by CRS in Morris water maze test and increases the exploration time with novel objects in normal or scopolamine-induced cognitive deficits in mice,but not ***,D01 reverses the long-term potentiation(LTP)inhibition induced by *** together,our findings demonstrate that D01,a dual-target serotonin reuptake and M channel inhibitor,is highly effective in the treatment-resistant depression and cognitive deficits,thus holding potential for development as therapy of depression with cognitive deficits.

关键词： SERT 5-HT Kv7/KCNQ/M current D01 Depression Cognition

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Potentiation of PIEZO2 mechanically-activated currents in sensory neurons mediates vincristine-induced mechanical hypersensitivity

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Acta Pharmaceutica Sinica B 2023年第8期13卷 3365-3381页

作者： Mingli Duan Yurui Jia Lifang Huo Yiting Gao Jia Wang Wei Zhang Zhanfeng Jia Department of Pharmacology Hebei Medical UniversityShijiazhuang 050017China center of Innovative Drug Research and Evaluation Institute of Medical Science and HealthHebei Medical UniversityShijiazhuang 050017China The Key Laboratory of Neural and Vascular Biology Ministry of EducationShijiazhuang 050017China The Key Laboratory of New Drug Pharmacology and Toxicology Shijiazhuang 050017China The Hebei Collaboration Innovation center for Mechanism Diagnosis and Treatment of Neurological and Psychiatric DiseaseShijiazhuang 050017China Department of Pharmacology Institute of Chinese Integrative MedicineHebei Medical UniversityShijiazhuang 050017China

Vincristine,a widely used chemotherapeutic agent for treating different cancer,often induces severe peripheral neuropathic pain.A common symptom of vincristine-induced peripheral neuropathic pain is mechanical allodynia and ***,mechanisms underlying vincristine-induced mechanical allodynia and hyperalgesia are not well *** the present study,we show with behavioral assessment in rats that vincristine induces mechanical allodynia and hyperalgesia in a PIEZO2 channel-dependent manner since gene knockdown or pharmacological inhibition of PIEZO2 channels alleviates vincristine-induced mechanical *** results show that vincristine potentiates PIEZO2 rapidly adapting(RA)mechanically-activated(MA)currents in rat dorsal root ganglion(DRG)*** have found that vincristine-induced potentiation of PIEZO2 MA currents is due to the enhancement of static plasma membrane tension(SPMT)of these cells following vincristine *** SPMT of DRG neurons by cytochalasin D(CD),a disruptor of the actin filament,abolishes vincristine-induced potentiation of PIEZO2 MA currents,and suppresses vincristine-induced mechanical hypersensitivity in ***,enhancing SPMT and subsequently potentiating PIEZO2 MA currents in primary afferent neurons may be an underlying mechanism responsible for vincristineinduced mechanical allodynia and hyperalgesia in *** to inhibit PIEZO2 channels may be an effective analgesic method to attenuate vincristine-induced mechanical hypersensitivity.

关键词： Vincristine Peripheral neuropathic pain Mechanical hypersensitivity Dorsal root ganglion neurons PIEZO2mechanically-activated currents

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A kidney-brain neural circuit drives progressive kidney damage and heart failure

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Signal Transduction and Targeted Therapy 2023年第6期8卷 3087-3097页

作者： Wei Cao Zhichen Yang Xiaoting Liu Siqiang Ren Huanjuan Su Bihui Yang Youhua Liu Christopher S.Wilcox Fan Fan Hou Division of Nephrology Nanfang HospitalSouthern Medical UniversityState Key Laboratory of Organ Failure ResearchNational Clinical Research Center of Kidney DiseaseGuangdong Provincial Institute of NephrologyGuangzhouPR China Guangdong-Hong Kong-Macao Greater Bay Area center for Brain Science and Brain-Inspired Intelligence Key Laboratory of Mental Health of the Ministry of EducationGuangdong Province Key Laboratory of Psychiatric DisordersSouthern Medical UniversityGuangzhouGuangdongChina Division of Nephrology and Hypertension Georgetown University Medical CentralWashingtonDCUSA

Chronic kidney disease(CKD)and heart failure(HF)are highly prevalent,aggravate each other,and account for substantial ***,the mechanisms underlying cardiorenal interaction and the role of kidney afferent nerves and their precise central pathway remain ***,we combined virus tracing techniques with optogenetic techniques to map a polysynaptic central pathway linking kidney afferent nerves to subfornical organ(SFO)and thereby to paraventricular nucleus(PVN)and rostral ventrolateral medulla that modulates sympathetic *** kidney-brain neural circuit was overactivated in mouse models of CKD or HF and subsequently enhanced the sympathetic discharge to both the kidney and the heart in each *** of the pathway by kidney deafferentation,selective deletion of angiotensin II type 1a receptor(AT1a)in SFO,or optogenetic silence of the kidney-SFO or SFO-PVN projection decreased the sympathetic discharge and lessened structural damage and dysfunction of both kidney and heart in models of CKD and ***,kidney afferent nerves activate a kidney-brain neural circuit in CKD and HF that drives the sympathetic nervous system to accelerate disease progression in both *** results demonstrate the crucial role of kidney afferent nerves and their central connections in engaging cardiorenal interactions under both physiological and disease *** suggests novel therapies for CKD or HF targeting this kidney-brain neural circuit.

关键词： kidney damage organs

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Role of early life exposure and environment on neurodegeneration: implications on brain disorders

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Translational Neurodegeneration 2014年第1期3卷 53-66页

作者： Shweta Modgil Debomoy K Lahiri Vijay L Sharma Akshay Anand Department of Neurology Neuroscience Research LabPost Graduate Institute of Medical Education and Research#3036Research Block-B160012 ChandigarhIndia Department of Zoology Panjab UniversityChandigarhIndia Department of Psychiatry Institute of Psychiatric ResearchIndiana University Medical Center IndianapolisIndianapolisUSA

Neurodegenerative diseases such as Alzheimer’s disease(AD),Parkinson’s disease(PD),Amyotrophic lateral sclerosis(ALS)and retinal degeneration have been studied extensively and varying molecular mechanisms have been proposed for onset of such *** genetic analysis of these diseases has also been described,yet the mechanisms governing the extent of vulnerability to such diseases remains *** studies have,therefore,focused on the role of environmental exposure in progression of such diseases especially in the context of prenatal and postnatal life,explaining how molecular mechanisms mediate epigenetic changes leading to degenerative *** review summarizes both the animal and human studies describing various environmental stimuli to which an individual or an animal is exposed during in-utero and postnatal period and mechanisms that promote *** SNPs mediating gene environment interaction are also ***,preventive and therapeutic strategies are suggested for effective intervention.

关键词： Aging Metals Epigenetics LEARn Methylation Pesticides

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Classification of musical hallucinations and the characters along with neural-molecular mechanisms of musical hallucinations associated with psychiatric disorders

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World Journal of Psychiatry 2024年第9期14卷 1386-1396页

作者： Xin Lian Wei Song Tian-Mei Si Naomi Zheng Lian Department of Radiology and Biomedical Imaging Shanxi Bethune HospitalShanxi Academy of Medical SciencesTaiyuan 030032Shanxi ProvinceChina Department of Psychiatry and Behavioral Neurosciences McMaster UniversityHamilton L8S 4L8ONCanada Department of Psychopharmacology Peking University Sixth HospitalBeijing 100191China Department of Psychiatry Hartford HealthCareSt Vincent’s Medical CenterWestportCT 06088United States

BACKGROUND Musical hallucinations(MH)involve the false perception of music in the absence of external stimuli which links with different *** pathomechanisms of MH encompass various *** etiological classification of MH is of particular importance and offers valuable insights to understand MH,and further to develop the effective treatment of *** the recent decades,more MH cases have been reported,revealing newly identified medical and psychiatric causes of *** imaging studies reveal that MH activates a wide array of brain *** up-to-date analysis on MH,especially on MH comorbid psychiatric conditions is *** To propose a new classification of MH;to study the age and gender differences of MH in mental disorders;and neuropathology of *** Literatures searches were conducted using keywords such as“music hallucination,”“music hallucination and mental illness,”“music hallucination and gender difference,”and“music hallucination and psychiatric disease”in the databases of PubMed,Google Scholar,and Web of *** cases were collected and categorized based on their *** t-test and ANOVA were employed(Ppsychiatric *** We carried out a more comprehensive review of MH *** the first time according to our knowledge,we demonstrated the psychiatric conditions linked and/or associated with MH from statistical,biological and molecular point of view.

关键词： Pathomechanism Etiological factors Classification Gender difference Neuropathway Psychotic musical hallucination and non-psychotic musical hallucination Neuropathway Biological and molecular mechanism

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Applications of tetrahedral DNA nanostructures in wound repair and tissue regeneration

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Burns & Trauma 2022年第1期10卷 685-698页

作者： Yikai Dou Weitong Cui Xiao Yang Yunfeng Lin Xiaohong Ma Xiaoxiao Cai State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu610041China psychiatric Laboratory and Mental Health center West China Hospital of Sichuan UniversityChengduSichuan610064China psychiatric Laboratory and Mental Health center the State Key Laboratory of BiotherapyWest China Hospital of Sichuan UniversityChengdu610041China

Tetrahedral DNA nanostructures(TDNs)are molecules with a pyramidal structure formed by folding four single strands of DNA based on the principle of base *** DNA has polyanionic properties,the special spatial structure of TDNs allows them to penetrate the cell membrane without the aid of transfection agents in a caveolin-dependent manner and enables them to participate in the regulation of cellular processes without obvious toxic side *** of their stable spatial structure,TDNs resist the limitations imposed by nuclease activity and innate immune responses to *** addition,TDNs have good editability and biocompatibility,giving them great advantages for biomedical *** studies have found that TDNs have a variety of biological properties,including promoting cell migration,proliferation and differentiation,as well as having anti-inflammatory,antioxidant,anti-infective and immune regulation ***,we confirmed that TDNs can promote the regeneration and repair of skin,blood vessels,muscles and bone *** on these findings,we believe that TDNs have broad prospects for application in wound repair and *** article reviews recent progress in TDN research and its applications.

关键词： Tetrahedral DNA nanostructures Wound treatment Injury repair Injury regeneration Tissue regeneration

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Analytical study of care quality and moral distress in clinical situations and patient care

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Frontiers of Nursing 2019年第4期6卷 327-334页

作者： Masoumeh Hasanlo Arezo Azarm Parvaneh Asadi Kourosh Amini Hossein Ebrahimi Mohammad Asghari Jafarabadi Department of Surgical Technology Zanjan University of Medical SciencesZanjanIran Education and Treatment center of Beheshti Zanjan University of Medical SciencesZanjanIran Kermanshah University of Medical Sciences KermanshahIran Zanjan Social Determinations of Health Research center Zanjan University of Medical SciencesZanjanIran Department of psychiatric Nursing Faculty of Nursing and MidwiferyTabriz University of Medical SciencesTabrizIran Health Services Management Research center Faculty of Public HealthTabriz University of Medical SciencesTabrizIran

Objective: Nursing profession conventionally meets a high standard of ethical behavior and action. One of the ethical challenges in nursing profession is moral distress. Nurses frequently expose to this phenomenon which leads to different consequences such as being bored by delivering patient care that decline care quality and make it challenging to achieve health purposes. This study was conducted to investigate the association between the aspects of moral distress and care ***: In this descriptive–analytical study, 545 nurses of intensive and cardiac care units and dialysis and psychiatric wards were recruited by census sampling. Three questionnaires, Sociodemographics, Moral Distress Scale, and Quality Patient Care Scale, were distributed among the participants and collected within 9 months. Data analysis was conducted by descriptive statistics, analysis of variance, and the least significant difference in SPSS ***: Investigating moral distress domains(ignoring patient, decision-making power, and professional competence) and care quality domains(psychosocial, physical, and communicational) demonstrated that in being exposed to moral distress, ignoring patient had no effect on psychosocial domain(P=0.056), but decision-making and professional competence of moral distress had positive effect on psychosocial, physical(bodily), and communication domains of care ***: Because moral distress domains are effective on patient care quality, it is recommended to enhance the knowledge of nurses, especially beginners, about moral distress, increase their strength alongside standardizing nursing services in decisionmaking domains, improve the professional competence, and pay attention to patients.

关键词： quality of healthcare moral distress clinical situations nurse patients

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Prevalence of ENT Diseases in the Mental Deficient Patients

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International Journal of Otolaryngology and Head & Neck Surgery 2021年第3期10卷 229-237页

作者： Ndadi Tchiengang Kadielle Junie Adama Koundoul Kizonde Kalungwe Yannick Diom Siga Evelyne ENT and CCF Department Peace Hospital Ziguinchor Senegal Emile Badiane psychiatric center Ziguinchor Senegal ENT and CCF Department Dakar-Senegal “Principal” Hospital Dakar Senegal

Introduction: Patients with mental deficiency have increased health needs. They develop certain ailments more than the rest of the general population. ENT pathology includes all the ailments concerning the nose, throat and ear and is a frequent reason for consultation in our health facilities. The aim of this study was to report the prevalence of ENT diseases in mental deficient. Material and Methods: This was a prospective, longitudinal study on a population of patients received in ENT consultation, during the days of October 15, 2019 and February 18, 2020 on the occasion of health campaigns organized by the Senegal Special Olympics Association. All admitted patients were mental deficient. Results: Out of a total of 334 patients received in general consultation (all specialties combined), 61 patients underwent an ENT consultation, i.e. a prevalence of 18.26%. There were more men (N = 39) than women (N = 32). The average age of the patients was 20 years. A past history of chronic otitis media was reported in 9.83% of patients (N = 6). Functional signs were dominated by hypoacusis (N = 16). Seventy point forty-nine patients (N = 43) had otologic conditions. Thirty-four patients had trisomy 21 (64.15%). Conclusion: The prevalence of ENT diseases among the mental deficient is considerable. This study is the first of its type in Senegal which superimposes the ENT on mental deficiency.

关键词： ENT Mental Deficiency Ziguinchor

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Current problems in the research and development of more effective antidepressants

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上海精神医学 2016年第3期28卷 160-165页

作者： Tianmei SI Xin YU Peking University Institute of Mental Health (the Sixth Hospital) Beijing China National Clinical Medical Research center for psychiatric Disorders and National Key Laboratory for Mental Health Beijing China

概述:受2015十月在北京举行的第一届中国抗抑郁药研究与发展峰会上的讨论的启发,我们撰写了这篇述评。该峰会由中国医师协会精神科医师分会精神药理学和药物治疗工作委员会(Chinese Psychiatrist Psychopharmacology Commission,CPPC)发... 详细信息

概述:受2015十月在北京举行的第一届中国抗抑郁药研究与发展峰会上的讨论的启发,我们撰写了这篇述评。该峰会由中国医师协会精神科医师分会精神药理学和药物治疗工作委员会(Chinese Psychiatrist Psychopharmacology Commission,CPPC)发起,参与人员包括一流的精神科临床医生、神经科学研究者和国内外大型制药企业研发人员,会议重点讨论了那些限制了更有效的抗抑郁药物发展的主要问题。在没有明确的抑郁症生物标志物的情况下,临床医生必须在临床现象的基础上做出治疗决策;缺乏明确的生物靶点导致目前可用的抗抑郁药需要很长一段时间才有效,完全缓解率低,并且复发率高。中国神经科学家对抑郁症的基础研究是国际公认的,但他们提出的。作为治疗抑郁症潜在的候选化学成分大部分在临床试验时失败了。这种试剂的高失败率和大部分可用药物的不令人满意的结果迅速增加了新药进入市场的成本,所以制药公司更喜欢"调整"目前的药物而不是冒资金风险来支持新的抗抑郁药的发展。因此,发展新的、更有效的抑郁症治疗成为一个僵局。鉴于抑郁症对中国和其他国家的经济发展的巨大影响,在临床医生、研究人员和制药行业的共同努力下积极争取政府和社区的支持来克服这种僵局是必不可少的。

关键词：抗抑郁药物临床医生开发治疗方案基础研究抑郁症制药行业临床试验

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Biological correlates of psychological states among young children:a cross-sectional examination of roles of aspartate transaminase/alanine aminotransferase,insulin,and cytokines

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Chinese Science Bulletin 2014年第35期59卷 5102-5112页

作者： Kuo-Hsuan Chung Chien-Ming Hu Ying-Ru Chen Hung-Yi Chiou Yi-Hua Chen Department of Psychiatry and psychiatric Research center Taipei Medical University Hospital Department of Psychiatry College of MedicineTaipei Medical University Emergency Department Taipei Medical University Hospital Department of General Medicine School of MedicineCollege of MedicineTaipei Medical University Department of Psychiatry Shuang Ho HospitalTaipei Medical University School of Public Health College of Public Health and NutritionTaipei Medical University

Compared to data on adolescents and adults,limited research has been conducted on biological correlates among young children with possible psychological difficulties,especially in Asian *** focusing on various peripheral biochemical indicators,we investigated potential biological correlates of psychological states in a community sample of Taiwan Residents school children aged6–10 *** total,307 students(159 obese children and148 normal-weight children) were selected from first- and fourth-grade school children in eight elementary schools in the Taipei metropolitan area in *** children underwent a comprehensive health examination,including a physical examination,blood sample analysis,andquestionnaire administration in a *** in anthropometric and serum biochemical readings were compared between children with average and worse levels on each of the five psychological *** found that interleukin(IL)-1β [b = 1.29,95 % confidence interval(CI) 0.50–2.09],IL-10(b = 1.61,95 % CI \0.01–3.24),fasting blood glucose(b = 0.08,95 % CI 0.01–0.15),homocysteine(b = 0.63,95 % CI 0.09–1.18),and aspartate transaminase(AST)(b = 0.15,95 % CI \0.01–0.31)were significantly positively associated with *** addition,IL-1β,insulin,AST,and alanine aminotransaminase(ALT) were significantly positively associated with *** and disruptive behaviors were also related to specific biological *** biological correlates,including AST/ALT,cardiovascular diseaserelated variables,and specific cytokines,were linked to particular psychological states among young children in this Asian *** might provide a route for better understanding the biological aspects of children's mental health and might contribute to research on diagnostic or predictive biomarkers for psychiatric diseases in young children.

关键词：心理状态谷丙转氨酶细胞因子健康检查天冬氨酸转氨酶生物相胰岛素幼儿

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