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Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

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Neural Regeneration Research 2025年第1期20卷 265-276页

作者： Yao Yuan Lingqi Yu Xudong Zhuang Dongjing Wen Jin He Jingmei Hong Jiayu Xie Shengan Ling Xiaoyue Du Wenfeng Chen Xinrui Wang Institute of Life Sciences College of Biological Science and EngineeringFuzhou UniversityFuzhouFujian ProvinceChina NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate(Fujian Maternity and Child Health Hospital) FuzhouFujian ProvinceChina Medical Research Center Fujian Maternity and Child Health HospitalCollege of Clinical Medicine for Obstetrics&Gynecology and PediatricsFujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology and Institute of Neurology of The First Affiliated Hospital Institute of Neuroscienceand Fujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian ProvinceChina

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory *** develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause *** located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)*** addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive *** these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut *** found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in *** heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal *** Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

关键词： ATP1A1 Atpα bang-sensitive paralysis Charcot-Marie-Tooth disease type 2 CRISPR/Cas9 homology-directed repair Na^(+)/K^(+)-ATPase point mutation seizures sodium pump

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Relationship between sleep quality and blood pressure level in nurses performing shift work

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Frontiers of Nursing 2024年第1期11卷 77-84页

作者： Antonina Tsipkalo Kateryna Kozak Mariya Marushchak Department of Functional and Laboratory Diagnostics I.Horbachevsky Ternopil National Medical UniversityTernopil 46001Ukraine Department of pediatrics No.2 I.Horbachevsky Ternopil National Medical UniversityTernopil 46001Ukraine

Objective:The aim of the study was to evaluate the quality of sleep in nurses performing shift work in therapeutic and surgical depar tments and to establish possible relationships between level of blood pressure(BP)and quality of ***:A total of 20 nurses of the therapeutic depar tments and 20 nurses of the surgical depar tments were enrolled in the *** quality was assessed using the Pittsburgh Sleep Quality Index(PSQI).BP was measured according to the standard protocol using the Korotkoff method;a sphygmomanometer was used for this twice with an interval of 2 min between 10:00 *** 10:30 *** average value for the 2 indicators was *** diagnosis of essential ar terial hyper tension(AH)was established according to the recommendations of the European Association of Cardiology and the European Association of Hypertension(2018).Results:The overall assessment of the sleep quality of the nurses involved in shift work indicates poor sleep quality;this was true in respondents of both the surgical and therapeutic ***,it was observed that the quality of sleep was significantly lower in nurses of the therapeutic ***,poor sleep quality was associated with AH,which was diagnosed in 65%of the nurses of the therapeutic departments and 45%of the nurses of the surgical departments,that is,in almost all of the ***,in the nurses of the therapeutic departments,the level of systolic BP exceeded that of the nurses of the surgical ***:Poor sleep quality is a significant risk factor for AH development and is relevant to nurses performing shift *** clinical studies should be conducted to better understand the mechanisms underlying such adverse cardiometabolic outcomes associated with sleep disorders in the health-sector shift workers.

关键词： blood pressure nurses shift work sleep quality Pittsburgh Sleep Quality Index

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Yin and Yang of mesenchymal stem cells and aplastic anemia

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World Journal of Stem Cells 2017年第12期9卷 219-226页

作者： Larisa Broglie David Margolis Jeffrey A Medin Department of pediatrics Medical College of Wisconsin departments of pediatrics and Biochemistry Medical College of Wisconsin

Acquired aplastic anemia(AA) is a bone marrow failure syndrome characterized by peripheral cytopenias and bone marrow hypoplasia. It is ultimately fatal without treatment, most commonly from infection or hemorrhage. Current treatments focus on suppressing immune-mediated destruction of bone marrow stem cells or replacing hematopoietic stem cells(HSCs) by transplantation. Our incomplete understanding of the pathogenesis of AA has limited development of targeted treatment options. Mesenchymal stem cells(MSCs) play a vital role in HSC proliferation; they also modulate immune responses and maintain an environment supportive of hematopoiesis. Some of the observed clinical manifestations of AA can be explained by mesenchymal dysfunction. MSC infusions have been shown to be safe and may offer new approaches for the treatment of this disorder. Indeed, infusions of MSCs may help suppress auto-reactive, T-cell mediated HSC destruction and help restore an environment that supports hematopoiesis. Small pilot studies using MSCs as monotherapy or as adjuncts to HSC transplantation have been attempted as treatments for AA. Here we review the current understanding of the pathogenesis of AA and the function of MSCs, and suggest that MSCs should be a target for further research and clinical trials in this disorder.

关键词： Hematopoiesis Targeted therapies Stem cells Hematopoietic stem cell transplantation Aplastic anemia Mesenchymal stem cells

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Dopaminergic system does not play a major role in the precipitated cannabinoid withdrawal syndrome

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中国药理学报 1999年第12期20卷 1121-1124页

作者： M Clara SANUDO-PENA Michelle FORCE TSOU Kang Gabrielle McLEMORE Langdon ROBERTS J Michael WALKER Schrier Research Laboratory Departments of Psychology and NeuroscienceBrownUniversityProvidence RI 02912USA

AIM:To determine the dopaminergic system involvement in precipitated cannabinoid withdrawal ***:The dopamine D_(1)receptor antagonist SCH23390 or the dopamine D_(2)receptor antagonist sulphide was administered to rats chronically treated with either△^(9)-tetrahydrocannabinol(THC)or *** were then injected with either SR141716A or vehicle and behavior was observed for 1 ***:Administration of the cannabinoid receptor antagonist SR141716A to animals chronically treated with THC as described by Tsou et al(1995)produced a profound withdrawal *** with dopamine antagonists did not attenuate cannabinoid precipitated withdrawal syndrome in THC tolerant animals while the agonists increased the ***:It is unlikely that the dopaminergic system plays a major role in mediating the behavioral aspects of the cannabinoid withdrawal syndrome.

关键词： cannabinoids tetrahydrocannabinol SR141716A substance withdrawal syndrome dopamine D_(1)receptors dopamine D_(2)receptors dopamine antagonists pruritus pain

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Investigating the role of Ca^(2+)/calmodulin-dependent protein kinaseⅡin the survival of retinal ganglion cells

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Neural Regeneration Research 2022年第5期17卷 1001-1002页

作者： Xinzheng Guo Bo Chen departments of Ophthalmology and neuroscience Icahn School of Medicine at Mount SinaiNew YorkNYUSA

Retinal ganglion cells(RGCs)are the sole output neurons of the retina that project long axons and transmit visual information to the *** degeneration of RGCs leads to irreversible vision loss in a variety of pathologi... 详细信息

关键词： degeneration glaucoma irreversible

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Nitric oxide:a newly discovered function on wound healing

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Acta Pharmacologica Sinica 2005年第3期26卷 259-264页

作者： Alex F CHEN departments of Pharmacology and Neurology and the neuroscience Program Michigan State University East Lansing MI 48824-1317 USA

Wound healing impairment represents a particularly challenging clinical problemto which no efficacious treatment regimens currently *** factors ensuringappropriate intercellular communication during wound repair are not *** protein-type mediators are well-established players in thisprocess,emerging evidence from both animal and human studies indicates thatnitric oxide (NO) plays a key role in wound *** beneficial effects of NO onwound repair may be attributed to its functional influences on angiogenesis,inflammation,cell proliferation,matrix deposition,and *** find-ings from in vitro and in vivo studies of NO on wound repair are summarized inthis *** unveiled novel mechanisms support the use of NO-containingagents and/or NO synthase gene therapy as new therapeutic regimens for im-paired wound healing.

关键词： angiogenesis inflammation nitric oxide proliferation wound healing

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Prevalence and risk factors of asymptomatic hepatitis C virus infection in Egyptian children

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World Journal of Gastroenterology 2007年第12期13卷 1828-1832页

作者： MS El-Raziky M El-Hawary G Esmat AM Abouzied N El-Koofy N Mohsen S Mansour A Shaheen M Abdel Hamid H El-Karaksy departments of pediatrics Cairo University Cairo Egypt departments of Tropical Medicine Cairo University Cairo Egypt Tropical Medicine Research Institute Cairo Egypt

AIM: To identify the prevalence, risk factors and manifestations of asymptomatic hepatitis C virus (HCV) infection in Egyptian children. METHODS: Children at the age of 1-9 years were screened for HCV antibodies and alanine aminotransferase (ALT) levels. Every child with elevated ALT and/or detectable HCV antibodies was tested for HCV RNA by RT-PCR and compared with two negative controls for risk factors and signs and symptoms of liver ***: We screened 1042 children, six of them had elevated ALT, negative HCV antibody and positive RNA, likely representing acute hepatitis C cases. Fifteen children were HCV seropositive, 5 of them were HCV RNA positive. Asymptomatic HCV infection was present in 2.02% (positive results for either HCV antibodies or HCV-RNA or both). Symptoms such as diarrhea, abdominal pain, history of fatigue and school absence because of illness and risk factors such as dental care were significantly more common among HCV positive cases than among controls. None of the HCV positive children was diagnosed as having signs of advanced liver disease upon clinical or ultrasonographic examination. CONCLUSION: Asymptomatic HCV infection is detectable in 2.02% Egyptian children.

关键词： Hepatitis C virus Child Egypt Prevalence Transfusion Risk factor

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Reprogram to pluripotency: a new logic and a chemical cocktail

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National Science Review 2014年第1期1卷 6-7页

作者： Hongjun Song Guo-li Ming Institute for Cell Engineering Departments of Neurology and Neuroscience Johns Hopkins University School of Medicine

Somatic cells rom animals and humans can be reprogrammed into pluripotent stem cells by pluripotency *** Deng and colleagues discovered that pluripotency can also be induced with exogenous lineage speciiers via balancing competing diferentiation *** a related study they achieved,for the irst time,restoration of pluripotency in adult somatic cells using a chemical cocktail alone.

关键词： GATA Reprogram to pluripotency a new logic and a chemical cocktail PSCs SOX

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Attitudes and Practices of Lumbar Puncture among Students, Interns, and Residents of the Pediatric Department of the Mohammed VI University Hospital Center of Oujda, Morocco

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Open Journal of pediatrics 2024年第3期14卷 598-608页

作者： Hasnae Elhaddadi Ayyad Ghanam Hind Zahiri Amal Hamami Aziza Elouali Abdeladim Babakhouya Maria Rkain Department of pediatrics University Hospital Center Mohammed VI Oujda Morocco Faculty of Medicine and Pharmacy Mohammed First University Oujda Morocco

Introduction: Even though lumbar puncture (LP) represents an important tool in the diagnosis of certain neurological diseases, this procedure is little practiced by our students. We aimed to evaluate the attitudes and practices of students, interns, and residents about LP, and to assess their feelings about how this procedure is taught. Materials and Methods: We conducted a cross-sectional study of 160 participants, using an anonymous questionnaire, to evaluate the attitudes and practices of students, interns and residents in the pediatrics department concerning lumbar puncture. Results: Half of the participants had never performed LP, usually because of the risk involved or lack of confidence, while 20% had performed it more than 4 times. None of the participants had learned to perform the procedure through simulation sessions, while (42%) had learned it under the supervision of a senior physician and had not been able to perform it successfully the first time. Most participants inform the patient about the procedure before performing it. Only 44% of participants acknowledged that LP can be performed under local anesthetic. The sitting position (60%) was by far the most commonly used. Most LPs were performed for diagnostic purposes. Most participants stated that the pediatric ward and the pediatric emergency department are among the departments that perform LP most frequently, and that they would be interested in taking part in simulated lumbar puncture sessions in children in the future. Conclusion: The results of our study show that LP is perceived by students as a risky procedure that is difficult to perform. Teachers should reconsider how this technical procedure is taught, by integrating simulation on mannequins into student training.

关键词： Lumbar Puncture Learning Healthcare Simulation Stress Clinical Competency

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Hypercholesterolemia,low density lipoprotein receptor and proprotein convertase subtilisin/kexin-type 9

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The Journal of Biomedical Research 2015年第5期29卷 356-361页

作者： Hong-mei Gu Da-wei Zhang departments of pediatrics and Biochemistry Group on the Molecular and Cell Biology of LipidsUniversity of Alberta

Atherosclerotic cardiovascular disease is the main cause of mortality and morbidity in the world. Plasma levels of low density lipoprotein cholesterol （LDL-C） are positively correlated with the risk of atherosclerosis. High plasma LDL concentrations in patients with hypercholesterolemia lead to build-up of LDL in the inner walls of the arteries, which becomes oxidized and promotes the formation of foam cells, consequently initiating atherosclerosis. Plasma LDL is mainly cleared through the LDL receptor （LDLR） pathway. Mutations in the LDLR cause familiar hyperch- olesterolemia and increase the risk of premature coronary heart disease. The expression of LDLR is regulated at the transcriptional level via the sterol regulatory element binding protein 2 （SREBP-2） and at the posttranslational levels mainly through proprotein convertase subtilisin/kexin-type 9 （PCSK9） and inducible degrader of the LDLR （IDOL）. In this review, we summarize the latest advances in the studies of PCSK9.

关键词： hypercholesterolemia low density lipoprotein receptor statin atherosclerosis proprotein convertasesubtilisin/kexin -type 9

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