检索结果-内蒙古大学图书馆

Anti-cancer mechanisms of action of therapeutic alternating electric fields(tumor treating fields[TTFields])

Journal of Molecular Cell Biology 2022年第8期14卷 1-16页

作者： Shadi Shams Chirag B.Patel Rowan University School of Osteopathic Medicine StratfordNJ 08028USA Department of Neuro-Oncology The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Neuroscience Graduate Program The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical SciencesHoustonTX 77030USA Cancer Biology Program The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical SciencesHoustonTX 77030USA

Despite improved survival outcomes across many cancer types,the prognosis remains grim for certain solid organ cancers including glioblastoma and pancreatic *** in these cancers,the control achieved by time-limited interventions such as traditional surgical resection,radiation therapy,and chemotherapy is short-lived.A new form of anti-cancer therapy called therapeutic alternating electric fields(AEFs)or tumor treating fields(TTFields)has been shown,either by itself or in combination with chemotherapy,to have anti-cancer effects that translate to improved survival outcomes in *** the pre-clinical and clinical data are promising,the mechanisms of TTFields are not fully *** investigations are underway to better understand how and why TTFields is able to selectively kill cancer cells and impede their *** purpose of this review is to summarize and discuss the reported mechanisms of action of TTFields from pre-clinical studies(both in vitro and in vivo).An improved understanding of how TTFields works will guide strategies focused on the timing and combination of TTFields with other therapies,to further improve survival outcomes in patients with solid organ cancers.

关键词： alternating electric fields(AEFs) cancer mechanism of action pre-clinical tumor treating fields(TTFields)

来源：评论

学校读者我要写书评

暂无评论

Ketamine,a trauma analgesic with sex-specific immunomodulatory function

引用

Neural Regeneration Research 2023年第6期18卷 1263-1264页

作者： Haley F.Spencer Rina Y.Berman Martin Boese Kwang H.Choi Program in Neuroscience Uniformed Services UniversityBethesdaMDUSA Center for the Study of Traumatic Stress Uniformed Services UniversityBethesdaMDUSA Daniel K.Inouye Graduate School of Nursing Uniformed Services UniversityBethesdaMDUSA Department of Psychiatry F.E.Hébert School of MedicineUniformed Services UniversityBethesdaMDUSA

Ketamine,a multimodal dissociative anesthetic,produces powerful analgesia at subanesthetic doses in traumatically injured *** ketamine does not induce respiratory depression or hemodynamic instability,the Committee on Tactical Combat Casualty Care for the US military recommends the use of subanesthetic doses of ketamine for acute pain management(Butler et al.,2014).Additionally,ketamine may have immunomodulatory effects after injury at subanesthetic doses,mediating the balance of pro-and anti-inflammatory processes(Loix et al.,2011;De Kock et al.,2013).

关键词： doses acute

来源：评论

学校读者我要写书评

暂无评论

Mending the broken in amyotrophic lateral sclerosis: DNA damage and repair in motor neuron degeneration

引用

Neural Regeneration Research 2021年第1期16卷 104-105页

作者： Byung Woo Kim Lee J.Martin Department of Pathology Division of Neuropathologythe Pathobiology Graduate Training ProgramJohns Hopkins University School of MedicineBaltimoreMDUSA Department of Neuroscience Johns Hopkins University School of MedicineBaltimoreMDUSA

Amyotrophic lateral sclerosis(ALS)is a fatal neurodegenerative disease that causes paralysis and respiratory failure(Petrov et al.,2017).The driving mechanisms are unknown,and there are no effective treatments(Petrov et al.,2017).Aging and a few gene mutations,a common one being missense mutations in superoxide dismutase-1(SOD1),are risk factors for ALS(Figure 1).The recent Food and Drug Administration approval of edaravone for the treatment of ALS putatively supports a role for oxidative and nitrative stresses in the disease processes(Figure 1A).DNA damage,abnormalities in DNA repair,and other nuclear abnormalities are implicated also in the pathogenesis of human ALS(Bradley and Krasin,1982;Kim et al.,2020).

关键词： al. damage degeneration

来源：评论

学校读者我要写书评

暂无评论

Traumatic brain injury induced by exposure to blast overpressure via ear canal

引用

Neural Regeneration Research 2022年第1期17卷 115-121页

作者： Yang Ou Brad AClifton Jinghui Li David Sandlin Na Li Li Wu Chunming Zhang Tianwen Chen Jun Huang Yue Yu Jerome Allison Fan Fan Richard JRoman James Shaffery Wu Zhou Yi Pang Hong Zhu Departmant of Otolaryngology and Head Neck Surgery Department of Neurobiology and Anatomical Sciences MD Program School of Medicine Graduate Program in Neuroscience Department of Pediatrics Department of Pharmacology and Toxicology Department of Psychiatry and Human Behavior University of Mississippi Medical CenterJacksonMSUSA Kunming Medical University KunmingYunnan ProvinceChina Department of Otolaryngology First Affiliated HospitalShanxi Medical UniversityTaiyuanShanxi ProvinceChina

Exposure to explosive shockwave often leads to blast-induced traumatic brain injury in military and civilian *** ears are most often damaged following exposure to *** there is an association between tympanic membrane perforation and TBI in blast exposure victims,little is known about how and to what extent blast energy is transmitted to the central nervous system via the external ear *** present study investigated whether exposure to blasts directed through the ear canal causes brain injury in LongEvans *** were exposed to a single blast(0–30 pounds per square inch(psi))through the ear canal,and brain injury was evaluated by histological and behavioral outcomes at multiple *** exposure not only caused tympanic membrane perforation but also produced substantial neuropathological changes in the brain,including increased expression of c-Fos,induction of a profound chronic neuroinflammatory response,and apoptosis of *** blast-induced injury was not limited only to the brainstem most proximal to the source of the blast,but also affected the forebrain including the hippocampus,amygdala and the habenula,which are all involved in cognitive ***,the animals exhibited long-term neurological deficits,including signs of anxiety in open field tests 2 months following blast exposure,and impaired learning and memory in an 8-arm maze 12 months following blast *** results suggest that the unprotected ear canal provides a locus for blast waves to cause *** study was approved by the Institutional Animal Care and Use Committee at the University of Mississippi Medical Center(Animal protocol#0932 E,approval date:September 30,2016 and 0932 F,approval date:September 27,2019).

关键词： anxiety blast ear ear protection learning memory microglia neuroinflammation neuron rat traumatic brain injury

来源：评论

学校读者我要写书评

暂无评论

Exploring genes that control microglial heterogeneity and transition

引用

Neural Regeneration Research 2021年第12期16卷 2397-2398页

作者： Tomomi Okajima Fuminori Tsuruta Graduate School of Life and Environmental Sciences University of TsukubaTsukubaIbarakiJapan Master’s and Doctoral Programs in Biology Faculty of Life and Environmental SciencesUniversity of TsukubaTsukubaIbarakiJapan Master’s and Doctoral Program in Neuroscience Graduate School of Comprehensive Human SciencesUniversity of TsukubaTsukubaIbarakiJapan PhD Program in Human Biology School of Integrative and Global MajorsUniversity of TsukubaTsukubaIbarakiJapan PhD Program in Humanics School of Integrative and Global MajorsUniversity of TsukubaTsukubaIbarakiJapan

Microglia,which comprise approximately 10%of total cells in the brain,are the resident immune cells in the central nervous system and contribute to maintaining the brain homeostasis through monitoring their microenvironment(Kettenmann et al.,2011).Recent studies have reported that microglia also regulate neural circuit formation after *** functional transition in microglia has been considered to correlate with their morphological changes over time.

关键词： al. homeostasis transition

来源：评论

学校读者我要写书评

暂无评论

PTPσ-mediated PI3P regulation modulates neurodegeneration in C9ORF72-ALS/FTD

引用

Neuron 2025年第8期113卷 1190-1205.e9页

作者： Zhang, Zhe Fu, Xiujuan Wright, Noelle Wang, Weiren Ye, Yingzhi Asbury, Julie Li, Yini Zhu, Chengzhang Wu, Rong Wang, Shaopeng Sun, Shuying Department of Physiology Johns Hopkins University School of Medicine Baltimore 21205 MD United States Brain Science Institute Johns Hopkins University School of Medicine Baltimore 21205 MD United States Cellular and Molecular Physiology Graduate Program Johns Hopkins University School of Medicine Baltimore 21205 MD United States Biotechology Master Program Johns Hopkins University Baltimore 21205 MD United States Notre Dame of Maryland University Baltimore 21210 MD United States Cellular and Molecular Medicine Graduate Program Johns Hopkins University School of Medicine Baltimore 21205 MD United States The Solomon H. Snyder Department of Neuroscience and Department of Pathology Johns Hopkins University School of Medicine Baltimore 21205 MD United States

The most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the repeat expansion in C9ORF72. Dipeptide repeat (DPR) proteins translated from both sense and antisense repeats, especially arginine-rich DPRs (R-DPRs), contribute to neurodegeneration. Through CRISPR interference (CRISPRi) screening in human-derived neurons, we identified receptor-type tyrosine-protein phosphatase S (PTPσ) as a strong modifier of poly-GR-mediated toxicity. We showed that reducing PTPσ promotes the survival of both poly-GR- and poly-PR-expressing neurons by elevating phosphatidylinositol 3-phosphate (PI3P), accompanied by restored early endosomes and lysosomes. Remarkably, PTPσ knockdown or inhibition substantially rescues the PI3P-endolysosomal defects and improves the survival of C9ORF72-ALS/FTD patient-derived neurons. Furthermore, the PTPσ inhibitor diminishes GR toxicity and rescues pathological and behavioral phenotypes in mice. Overall, these findings emphasize the critical role of PI3P-mediated endolysosomal deficits induced by R-DPRs in disease pathogenesis and reveal the therapeutic potential of targeting PTPσ in C9ORF72-ALS/FTD. © 2025 Elsevier Inc.

关键词： ALS C9ORF72 CRISPR screening endosome FTD lysosome PI3P poly-GR/PR PTPσ

来源：评论

学校读者我要写书评

暂无评论

Structural Basis for p19 Targeting by Anti–IL-23 Biologics: Correlations with Short- and Long-Term Efficacy in Psoriasis

引用

JID Innovations 2024年第2期4卷 100261-100261页

作者： Daniele, Stefano G. Eldirany, Sherif A. Damiani, Giovanni Ho, Minh Bunick, Christopher G. MD-PhD Program Yale School of Medicine New Haven CT United States Department of Dermatology University of Connecticut Health Center Farmington CT United States Italian Center of Precision Medicine and Chronic Inflammation Milan Italy Department of Biomedical Surgical and Dental Sciences University of Milan Milan Italy Graduate Program (PhD) in Pharmacological Sciences Department of Pharmaceutical and Pharmacological Sciences University of Padua Padua Italy Department of Dermatology Yale School of Medicine New Haven CT United States Program in Translational Biomedicine Yale School of Medicine New Haven CT United States

IL-23 is central to psoriasis pathogenesis. Biologics targeting IL-23 are important therapies against psoriasis. IL-23 inhibitors risankizumab, tildrakizumab, and guselkumab bind the IL-23 p19 subunit, whereas ustekinumab binds p40;however, the structural composition of the IL-23–binding epitopes and how these molecular properties relate to clinical efficacy are not known. Utilizing epitope data derived from hydrogen-deuterium exchange or crystallographic experiments, we mapped inhibitor epitope locations, hydrophobicity, and surface charge onto the IL-23 surface. Molecular properties of each inhibitor epitope, including solvent-accessible surface area, were correlated to binding affinity, kinetic values, and clinical efficacy scores for plaque psoriasis through linear regression analysis. Each IL-23 inhibitor binds an epitope with a unique size, composition, and location except for a 10-residue overlap region outside of the IL-23 receptor epitope. We observed strong correlations between epitope surface area and K_D and k_off but not k_on. Epitope surface area, K_D, and k_off were further associated with short-term (10–16 weeks) and long-term (44–60 weeks) clinical efficacy according to PASI-90 responses, with risankizumab demonstrating highest efficacy among IL-23 biologics. In contrast, k_on, epitope hydrophobicity, polarity, and charge content did not correlate with efficacy. These data exemplify how molecular principles of medications within a therapeutic class can explain their differential clinical responses. © 2024 The Authors

关键词： Guselkumab Inflammatory skin disease epitope Risankizumab Tildrakizumab Ustekinumab

来源：评论

学校读者我要写书评

暂无评论

Targeting multiple signaling pathways:the new approach to acute myeloid leukemia therapy

引用

Signal Transduction and Targeted Therapy 2021年第1期6卷 41-69页

作者： Jenna LCarter Katie Hege Jay Yang Hasini AKalpage Yongwei Su Holly Edwards Maik Hüttemann Jeffrey WTaub Yubin Ge Cancer Biology Graduate Program Wayne State University School of MedicineDetroitMIUSA MD/PhD Program Wayne State University School of MedicineDetroitMIUSA Department of Oncology Wayne State University School of MedicineDetroitMIUSA Molecular Therapeutics Program Barbara Ann Karmanos Cancer InstituteWayne State University School of MedicineDetroitMIUSA Center for Molecular Medicine and Genetics Wayne State University School of MedicineDetroitMIUSA National Engineering Laboratory for AIDS Vaccine Key Laboratory for Molecular Enzymology and EngineeringThe Ministry of EducationSchool of Life SciencesJilin UniversityChangchunChina Division of Pediatric Hematology/Oncology Children’s Hospital of MichiganDetroitMIUSA Department of Pediatrics Wayne State University School of MedicineDetroitMIUSA

Acute myeloid leukemia(AML)is the most common form of acute leukemia in adults and the second most common form of acute leukemia in *** this,very little improvement in survival rates has been achieved over the past few *** is partially due to the heterogeneity of AML and the need for more targeted therapeutics than the traditional cytotoxic chemotherapies that have been a mainstay in therapy for the past 50 *** the past 20 years,research has been diversifying the approach to treating AML by investigating molecular pathways uniquely relevant to AML cell proliferation and *** we review the development of novel therapeutics in targeting apoptosis,receptor tyrosine kinase(RTK)signaling,hedgehog(HH)pathway,mitochondrial function,DNA repair,and c-Myc *** has been an impressive effort into better understanding the diversity of AML cell characteristics and here we highlight important preclinical studies that have supported therapeutic development and continue to promote new ways to target AML *** addition,we describe clinical investigations that have led to FDA approval of new targeted AML therapies and ongoing clinical trials of novel therapies targeting AML survival *** also describe the complexity of targeting leukemia stem cells(LSCs)as an approach to addressing relapse and remission in AML and targetable pathways that are unique to LSC *** comprehensive review details what we currently understand about the signaling pathways that support AML cell survival and the exceptional ways in which we disrupt them.

关键词： myeloid approach approval

来源：评论

学校读者我要写书评

暂无评论

Deep and shallow data science for multi-scale optical neuroscience

arXiv

引用

arXiv 2024年

作者： Mishne, Gal Charles, Adam Halıcıoğlu Data Science Institute Department of Electrical and Computer Engineering the Neurosciences Graduate Program UC San Diego 9500 Gilman Drive La Jolla CA92093 United States Department of Biomedical Engineering Kavli Neuroscience Discovery Institute Center for Imaging Science Department of Neuroscience Mathematical Institute for Data Science Johns Hopkins University BaltimoreMD21287 United States

Optical imaging of the brain has expanded dramatically in the past two decades. New optics, indicators, and experimental paradigms are now enabling in-vivo imaging from the synaptic to the cortex-wide scales. To match the resulting flood of data across scales, computational methods are continuously being developed to meet the need of extracting biologically relevant information. In this pursuit, challenges arise in some domains (e.g., SNR and resolution limits in micron-scale data) that require specialized algorithms. These algorithms can, for example, make use of state-of-the-art machine learning to maximally learn the details of a given scale to optimize the processing pipeline. In contrast, other methods, however, such as graph signal processing, seek to abstract away from some of the details that are scale-specific to provide solutions to specific sub-problems common across scales of neuroimaging. Here we discuss limitations and tradeoffs in algorithmic design with the goal of identifying how data quality and variability can hamper algorithm use and dissemination. © 2024, CC BY.

关键词： Neuroimaging

来源：评论

学校读者我要写书评

暂无评论

Modulation of microglial phenotypes improves sepsis-induced hippocampus-dependent cognitive impairments and decreases brain inflammation in an animal model of sepsis (vol 134, pg 765, 2020)

引用

CLINICAL SCIENCE 2020年第13期134卷 1677-1677页

作者： Michels, Monique Abatti, Mariane Vieira, Andriele Avila, Pricila Goulart, Amanda Indalecio Borges, Heloisa Corneo, Emily Dominguini, Diogo Barichello, Tatiana Dal-Pizzol, Felipe Laboratory of Experimental Pathophysiology Graduate Program in Health Sciences University of Southern Santa Catarina Criciúma SC Brazil Laboratory of Experimental Microbiology Graduate Program in Health Sciences Health Sciences Unit University of Southern Santa Catarina (UNESC) Criciúma SC Brazil Translational Psychiatry Program Department of Psychiatry and Behavioral Sciences McGovern Medical School The University of Texas Health Science Center at Houston (UTHealth) Houston TX U.S.A. Neuroscience Graduate Program The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Houston TX U.S.A.

Background: In order to modulate microglial phenotypes in vivo, M1 microglia were depleted by administration of gadolinium chloride and the expression of M2 microglia was induced by IL-4 administration in an animal model of sepsis to better characterize the role of microglial phenotypes in sepsis-induced brain dysfunction. Methods: Wistar rats were submitted to sham or cecal ligation and perforation (CLP) and treated with IL-4 or GdCl3. Animals were submitted to behavioral tests 10 days after surgery. In a separated cohort of animals at 24 h, 3 and 10 days after surgery, hippocampus was removed and cytokine levels, M1/M2 markers and CKIP-1 levels were determined. Results: Modulation of microglia by IL-4 and GdCl3 was associated with an improvement in long-term cognitive impairment. When treated with IL-4 and GdCl3, the reduction of pro-inflammatory cytokines was apparent in almost all analyzed time points. Additionally, CD11b and iNOS were increased after CLP at all time points, and both IL-4 and GdCl3 treatments were able to reverse this. There was a significant decrease in CD11b gene expression in the CLP+GdCl3 group. IL-4 treatment was able to decrease iNOS expression after sepsis. Furthermore, there was an increase of CKIP-1 in the hippocampus of GdCl3 and IL-4 treated animals 10 days after CLP induction. Conclusions: GdCl3 and IL-4 are able to manipulate microglial phenotype in an animal models of sepsis, by increasing the polarization toward an M2 phenotype IL-4 and GdCl3 treatment was associated with decreased brain inflammation and functional recovery.

关键词： M1/M2 microglia neuroinflammation sepsis

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：