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Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies

Signal Transduction and Targeted Therapy 2024年第1期9卷 173-210页

作者： Md Entaz Bahar Hyun Joon Kim Deok Ryong Kim department of Biochemistry and Convergence Medical Sciences and Institute of Medical Science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea department of anatomy and Convergence Medical Sciences and Institute of Medical Science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea

Metastatic dissemination of solid tumors,a leading cause of cancer-related mortality,underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis,chemoresistance,and the mechanistic backgrounds of individuals whose cancers are prone to *** most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase(MAPK)pathway,encompassing the RAS–RAF–MAPK kinase(MEK)–extracellular signal-related kinase(ERK)*** kinase is a primary mediator of the MAPK pathway,responsible for the sequential activation of downstream targets,such as MEK and the transcription factor ERK,which control numerous cellular and physiological processes,including organism development,cell cycle control,cell proliferation and differentiation,cell survival,and *** in this signaling cascade are associated with diseases such as *** inhibitors(RAFi)combined with MEK blockers represent an FDAapproved therapeutic strategy for numerous RAF-mutant cancers,including melanoma,non-small cell lung carcinoma,and thyroid ***,the development of therapy resistance by cancer cells remains an important ***,an intracellular lysosome-dependent catabolic recycling process,plays a critical role in the development of RAFi resistance in ***,targeting RAF and autophagy could be novel treatment strategies for RAF-mutant *** this review,we delve deeper into the mechanistic insights surrounding RAF kinase signaling in tumorigenesis and ***,we explore and discuss the ongoing development of next-generation RAF inhibitors with enhanced therapeutic ***,this review sheds light on the functional interplay between RAF-targeted therapies and autophagy in cancer.

关键词： RAF insight mechanism

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The combined application of stem cells and three-dimensional bioprinting scaffolds for the repair of spinal cord injury

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Neural Regeneration Research 2024年第8期19卷 1751-1758页

作者： Dingyue Ju Chuanming Dong department of anatomy Medical College of Nantong UniversityNantongJiangsu ProvinceChina Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education Co-innovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina

Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous *** surgery,the poor regenerative capacity of nerve cells and the generation of new scars can make it very difficult for the impaired nervous system to restore its neural *** treatments can only alleviate secondary injuries but cannot fundamentally repair the spinal ***,there is a critical need to develop new treatments to promote functional repair after spinal cord *** recent years,there have been seve ral developments in the use of stem cell therapy for the treatment of spinal cord *** significant developments in the field of tissue engineering,three-dimensional bioprinting technology has become a hot research topic due to its ability to accurately print complex *** led to the loading of three-dimensional bioprinting scaffolds which provided precise cell *** three-dimensional bioprinting scaffolds co uld repair damaged neural circuits and had the potential to repair the damaged spinal *** this review,we discuss the mechanisms underlying simple stem cell therapy,the application of different types of stem cells for the treatment of spinal cord injury,and the different manufa cturing methods for three-dimensional bioprinting *** particular,we focus on the development of three-dimensional bioprinting scaffolds for the treatment of spinal cord injury.

关键词： biomaterials embryonic stem cells induced pluripotent stem cells mesenchymal stem cells nerve regeneration spinal cord injury stem cell therapy stem cells three-dimensional bioprinting

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Revealing the role of honokiol in human glioma cells by RNA-seq analysis

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BIOCELL 2024年第6期48卷 945-958页

作者： YUNBAO GUO XU LIU QI XU XIAOTONG ZHOU JIAWEI LIU YANYAN XU YAN LU HAIYAN LIU The department of Neurosurgery First Hospital of Jilin UniversityChangchun130021China The department of anatomy College of Basic Medical SciencesJilin UniversityChangchun130021China The Third College of Clinical Medicine Jilin UniversityChangchun130021China

Background:Glioma is a kind of tumor that easily deteriorates and originates from glial cells in nerve *** is a bisphenol compound that is an essential monomeric compound extracted from the roots and bark of Magnoliaceae *** also has anti-infection,antitumor,and immunomodulatory *** this study,we found that honokiol induces cell apoptosis in the human glioma cell lines U87-MG and ***,the mechanism through which honokiol regulates glioma cell apoptosis is still ***:We performed RNA-seq analysis of U251-MG cells treated with honokiol and control ***-protein interaction(PPI)network analysis was performed,and the 10 top hub unigenes were examined via real-time quantitative ***,MAPK signaling and ferroptosis were detected via western ***:332 differentially expressed genes(DEGs)were found,comprising 163 increased and 169 decreased *** of the DEGs revealed that various biological processes were enriched,including‘response to hypoxia’,‘cerebellum development cellular response to hypoxia,’‘iron ion binding,’‘oxygen transporter activity,’‘oxygen binding,’‘ferric iron binding,’and‘structural constituent of cytoskeleton.’Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis revealed that the DEGs were enriched in the following pathways:‘mitogen-activated protein kinases(MAPK)’,‘Hypoxia-inducible factor 1(HIF-1)’,‘ferroptosis,’‘Peroxisome proliferator-activated receptor(PPAR),’‘Phosphatidylinositol-4,5-bisphosphate 3-kinase(PI3K)-protein kinase B(Akt),’and‘phagosome.’Among these pathways,the MAPK signaling pathway and ferroptosis were veriﬁ***:This study revealed the potential mechanism by which honokiol induces apoptosis and provided a comprehensive analysis of DEGs in honokiol-treated U251-MG cells and the associated signaling *** data could lead to new ideas for future research and therapy for patients with glioma.

关键词： Human glioma Honokiol RNA-seq Apoptosis Ferroptosis MAPK

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Location and expression of neurotrophin-3 and its receptor in the brain of human embryos during early development

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Neural Regeneration Research 2008年第12期3卷 1277-1280页

作者： Jian Li Yongjie Mi Dajun Ma department of Human anatomy Histology and Embryology Chengdu Medical College Chengdu 610083 Sichuan Province China

BACKGROUND： Cell culture in vitro trials have demonstrated that neurotrophin-3 （NT-3） can enhance the survival of sensory neurons and sympathetic neurons, and can also support embryo-derived motor neurons. This effect is dependent on nerve growth factor on the surface of cells. Understanding the role of NT-3 and its receptor in the early development of human embryonic brains will help to investigate the correlation between early survival of nerve cells and the microenvironment of neural regeneration. OBJECTIVE： To observe the proliferation of cerebral neurons in the development of human embryonic brain, and to investigate the location, expression and distribution of NT-3 and its receptor TrkC during human brain development. DESIGN, TIME AND SETTING： An observation study on cells was performed in the department of ttuman anatomy, histology and embryology, Chengdu Medical College in September 2007. MATERIALS： Fifteen specimens of flesh human embryo, aged 6 weeks, were used in this study. METHODS： The proliferation of cerebral neurons was detected using proliferating cell nuclear antigen, and the immunocytochemistry ABC technique was applied to observe the location, expression and distribution of NT-3 and its receptor TrkC in the brain of the human embryo. MAIN OUTCOME MEASURES： Location, expression and distribution of NT-3 and its receptor in the brain of the human embryo. RESULTS： In the early period （aged 6 weeks） of human embryonic development, proliferating cell nuclear antigen-positive reactive substances were mainly observed in the nucleus of the forebrain ventricular zone and subventricular zone, and the intensity was stronger in the subventricular zone than the forebrain ventricle. NT-3 positive reactive substance was mainly distributed in the cytoblastema of the forebrain neuroepithelial layer and nerve cell process, while TrkC was mainly distributed in the cell membrane of the forebrain ventricular zone and subventricular zone. During embryonic development,

关键词： neurotrophin-3 TrkC human embryo brain development

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RPLP0/TBP are the most stable reference genes for human dental pulp stem cells under osteogenic differentiation

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World Journal of Stem Cells 2024年第6期16卷 656-669页

作者： Daniel B Ferreira Leticia M Gasparoni Cristiane F Bronzeri Katiucia B S Paiva Laboratory of Extracellular Matrix Biology and Cellular Interaction Department of AnatomyInstitute of Biomedical SciencesUniversity of São PauloSão Paulo 05508-000São PauloBrazil

BACKGROUND Validation of the reference gene(RG)stability during experimental analyses is essential for correct quantitative real-time polymerase chain reaction(RT-qPCR)data ***,in an unreliable way,several studies use genes involved in essential cellular functions[glyceraldehyde-3-phosphate dehydro-genase(GAPDH),18S rRNA,andβ-actin]without paying attention to whether they are suitable for such experimental conditions or the reason for choosing such ***,such studies use only one gene when Minimum Information for Publication of Quantitative Real-Time PCR Experiments guidelines recom-mend two or more *** impacts the credibility of these studies and causes dis-tortions in the gene expression *** tissue engineering,the accuracy of gene expression drives the best experimental or therapeutical *** cultivated DPSCs under two conditions:Undifferentiated and osteogenic dif-ferentiation,both for 35 *** evaluated the gene expression of 10 candidates for RGs[ribosomal protein,large,P0(RPLP0),TATA-binding protein(TBP),GAPDH,actin beta(ACTB),tubulin(TUB),aminolevulinic acid synthase 1(ALAS1),tyro-sine 3-monooxygenase/tryptophan 5-monooxygenase activation protein,zeta(YWHAZ),eukaryotic translational elongation factor 1 alpha(EF1a),succinate dehydrogenase complex,subunit A,flavoprotein(SDHA),and beta-2-micro-globulin(B2M)]every 7 d(1,7,14,21,28,and 35 d)by *** data were analysed by the four main algorithms,ΔCt method,geNorm,NormFinder,and BestKeeper and ranked by the RefFinder *** subdivided the samples into eight *** All of the data sets from clonogenic and osteogenic samples were analysed using the RefFinder *** final ranking showed RPLP0/TBP as the two most stable RGs and TUB/B2M as the two least stable *** theΔCt method or NormFinder analysis showed TBP/RPLP0 as the two most stable ***,geNorm analysis showed RPLP0/EF1αin the first *** algorithms’two least stab

关键词： Dental pulp stem cells Reference gene Housekeeping gene Endogenous gene Osteogenic differentiation RefFinder

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Morphometric Study of the Mastoid Process and its Role in Sex Differentiation:A Nigerian Computed Tomography Study

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Journal of Forensic Science and Medicine 2024年第1期10卷 1-10页

作者： Beryl Shitandi Ominde John NIgabari Joyce Ekeme Ikubor department of Human anatomy and Cell Biology Delta State UniversityAbrakaNigeria department of Mathematics Delta State UniversityAbrakaNigeria department of Radiology Delta State University Teaching HospitalOgharaNigeria

Background:The mastoid process can be utilized in forensic identification due to its resistance to alterations and population variations in its *** study investigated the role of mastoid parameters in the determination of sex in a Nigerian *** and Objectives:The aim of this study was to determine the gender differences in measurements of the mastoid ***,the study aimed at assessing the percentage accuracy of using the mastoid variables in sex *** and Methods:This cross-sectional study used computed tomographic images of the brain,stored in the radiology unit of a referral hospital in Delta State,*** was granted by the hospital’s Ethics *** measurements of the mastoid process were taken on images of 310 patients(170 males and 140 females)aged 20-80 *** were summarized using means and standard ***,side,and age group comparisons were assessed using the independent t-test,paired t-test,and analysis of variance,*** association between variables was probed using Pearson’s correlation *** discriminant function analysis was used to determine the accuracy of correct sex *** probability value was set at<***:All the measurements were larger in males than in females(P<0.05).All except the conventional height,oblique sagittal diameter,and mediolateral inclination angle showed significant differences between age groups(P<0.05).The true height and oblique coronal diameter showed a significant positive correlation with age(0

关键词： Forensic mastoid process measurements sex determination

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Pretreatment can alleviate programmed cell death in mesenchymal stem cells

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World Journal of Stem Cells 2024年第8期16卷 773-779页

作者： Xin-Xing Wan Xi-Min Hu Qi Zhang Kun Xiong department of Endocrinology Third Xiangya HospitalCentral South UniversityChangsha 410013Hunan ProvinceChina department of Dermatology Xiangya HospitalCentral South UniversityChangsha 410008Hunan ProvinceChina department of anatomy and Neurobiology Central South UniversityChangsha 410000Hunan ProvinceChina department of anatomy and Neurobiology School of Basic Medical ScienceCentral South UniversityChangsha 410013Hunan ProvinceChina

In this editorial,we delved into the article titled“Cellular preconditioning and mesenchymal stem cell ferroptosis.”This groundbreaking study underscores a pivotal discovery:Ferroptosis,a type of programmed cell death,drastically reduces the viability of donor mesenchymal stem cells(MSCs)after engraftment,thereby undermining the therapeutic value of cell-based ***,the article proposes that by manipulating ferroptosis mechanisms through preconditioning,we can potentially enhance the survival rate and functionality of MSCs,ultimately amplifying their therapeutic *** the crucial role ferroptosis plays in shaping the therapeutic outcomes of MSCs,we deem it im-perative to further investigate the intricate interplay between programmed cell death and the therapeutic effectiveness of MSCs.

关键词： Mesenchymal stem cells Programmed cell death Apoptosis Autophagy Ferroptosis

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The expression of Usp26 gene in mouse testis and brain

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Asian Journal of Andrology 2009年第4期11卷 748-749页

作者： Jie Zhang Hong Tian Yong-Wei Huo Dang-Xia Zhou Hai-Xu Wang Li-Rong Wang Qiu-Yang Zhang Shu-Dong Qiu department of anatomy Histology & Embryology Medical College of Xi'an Jiaotong University Xi'an 710061 China.

In this article, published on 1 July 2009, the following colored figures were wrongly published in black and white Asian Journal of Andrology would like to apologize to the authors and readers for the error and any c... 详细信息

关键词： ubiquitin-specific protease 26 (USP26) Usp26 gene deubiquitination enzymes protein degradation spermatogenesis mouse

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Contribution of Anti-p63 Antibodies in the Interpretation of Benign Label Prostatic Biopsies

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Open Journal of Pathology 2024年第2期14卷 31-44页

作者： Ibou Thiam Fabrice Senghor Frenette Codja Kor Ndiaye Mohamed Moustapha Cherif Dial Pathological anatomy department Aristide Le Dantec University Hospital Dakar Senegal Pathological anatomy department H&#244pital de la Paix Ziguinchor Senegal Pathological anatomy department Idrissa Pouye University Hospital Dakar Senegal

Introduction: Prostate cancer is the second most common cancer in men. The diagnosis is most often based on the prostate biopsies’ analysis and on histological criteria recognizable on standard coloring. In some cases, the use of immunohistochemistry is important. Objectives: This paper aims to specify the p63 phenotypic profile of lesions diagnosed benign, with minimal suspect foci, difficult to interpret, HGPIN (high grade intraepithelial neoplasia) and LGPIN (low-grade prostatic intraepithelial neoplasia) and evaluate the manual technique of p63 immunohistochemistry. Patients and Method: This was a retrospective, descriptive study of prostate biopsies recorded in the PAC service of the HALD from January 1st, 2018 to December 31st, 2018. It was completed by a manual immunohistochemical study of the blocks enrolled from November 19th to December 4th, 2020 in the PAC department of the HPD. The studied parameters were: registry number, age, clinical stage, prostate volume, PSA level, microscopic appearance and p63 immunohistochemical profile. Results: Our study included 60 prostate biopsies. The ages of our patients varied from 45 to 77 years, with an average of 64.2 years and a standard deviation of 6.2. The majority of patients were at clinical stage cT2b (33%) with a prostate volume varying between 33.15 and 169.4 cc. The minimum value of PSA in our series is 5 ng/ml, the maximum being 100 ng/ml with an average level of 24.1 ng/ml and a standard deviation of 21.2. Our series included 50 adenomyomatous hyperplasias, 7 adenomyomatous hyperplasias associated with chronic prostatitis, 2 HGPIN and 1 LGPIN. After re-reading we found 5 discordant cases, which corresponded to minimal suspect foci (kappa = 0.5098). The p63 marking was informative in 53 cases, i.e. 88%, and non-informative in 7 cases, i.e. 12%. Among the uninformative markings, 2 were due to lack of tissue adhesion to the slides. Among the informative markings, 11 were negative. p63 immunohistochemistry was

关键词： Prostate Cancer Diagnosis Anti-p6 Antibody

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Metabotropic glutamate receptors(mGluRs)in epileptogenesis:an update on abnormal mGluRs signaling and its therapeutic implications

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Neural Regeneration Research 2024年第2期19卷 360-368页

作者： Leyi Huang Wenjie Xiao Yan Wang Juan Li Jiaoe Gong Ewen Tu Lili Long Bo Xiao Xiaoxin Yan Lily Wan department of anatomy and Neurobiology Central South University Xiangya Medical SchoolChangshaHunan ProvinceChina department of Neurology Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina department of Neurology Hunan Children’s HospitalChangshaHunan ProvinceChina department of Neurology Brain Hospital of Hunan ProvinceChangshaHunan ProvinceChina

Epilepsy is a neurological disorder characterized by high morbidity,high recurrence,and drug *** signaling through the excitatory neurotransmitter glutamate is intricately associated with *** glutamate receptors(mGluRs)are G protein-coupled receptors activated by glutamate and are key regulators of neuronal and synaptic *** mGluR signaling has been associated with various neurological disorders,and numerous studies have shown a close relationship between mGluRs expression/activity and the development of *** this review,we first introduce the three groups of mGluRs and their associated signaling ***,we detail how these receptors influence epilepsy by describing the signaling cascades triggered by their activation and their neuroprotective or detrimental roles in *** addition,strategies for pharmacological manipulation of these receptors during the treatment of epilepsy in experimental studies is also *** hope that this review will provide a foundation for future studies on the development of mGluR-targeted antiepileptic drugs.

关键词： antiepileptic drugs epileptogenesis metabotropic glutamate receptors(mGluRs) signal pathways therapeutic potentials

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