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Introduction: The overdiagnosing of papillary thyroid carcinoma (PTC) in China necessitates the development of an evidence-based diagnosis and prognosis strategy in line with precision medicine. A landscape of PTC in Chinese cohorts is needed to provide comprehensiveness. Methods: 6 paired PTC samples were employed for whole-exome sequencing, RNA sequencing, and data-dependent acquisition mass spectrum analysis. Weighted gene co-expression network analysis and protein-protein interactions networks were used to screen for hub genes. Moreover, we verified the hub genes' diagnostic and prognostic potential using online databases. Logistic regression was employed to construct a diagnostic model, and we evaluated its efficacy and specificity based on TCGA-THCA and GEO datasets. Results: The basic multiomics landscape of PTC among local patients were drawn. The similarities and differences were compared between the Chinese cohort and TCGA-THCA cohorts, including the identification of PNPLA5 as a driver gene in addition to BRAF mutation. Besides, we found 572 differentially expressed genes and 79 differentially expressed proteins. Through integrative analysis, we identified 17 hub genes for prognosis and diagnosis of PTC. Four of these genes, ABR, AHNAK2, GPX1, and TPO, were used to construct a diagnostic model with high accuracy, explicitly targeting PTC (AUC=0.969/0.959 in training/test sets). Discussion: Multiomics analysis of the Chinese cohort demonstrated significant distinctions compared to TCGA-THCA cohorts, highlighting the unique genetic characteristics of Chinese individuals with PTC. The novel biomarkers, holding potential for diagnosis and prognosis of PTC, were identified. Furthermore, these biomarkers provide a valuable tool for precise medicine, especially for immunotherapeutic or nanomedicine based cancer therapy.
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For several neurodegenerative disorders, including Parkinson's Disease (PD) and Alzheimer's Disease (AD), microRNAs (miRNAs) have been known to play a crucial role. So, in this study miR-132 and its role in PD cell models was investigated. We wanted to investigate the survival or death pathway involved in PD. We observed the expression levels of miR-132 in MPP+ - treated SH-SY5Y cell line, which acted as a PD cell model, and found an increased expression of miR-132. Moreover, through the Dual-Luciferase® Reporter (DLR™) Assay, it was also revealed that miR-132 targets SIRT1 3'UTR, a histone deacetylase, and decreases its activity, which results in increased acetylation of p53, an apoptotic inducer. p53 acetylation leads to overexpression of other pro-apoptotic genes like Puma and Noxa, which eventually leads to cell death. Here, we show that the upregulation of miR-132 in SH-SY5Y cells can induce apoptosis through the SIRT1/p53 pathway.
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Morte Celular/fisiologia , Neurônios Dopaminérgicos/fisiologia , Genes p53/fisiologia , MicroRNAs/biossíntese , Transdução de Sinais/fisiologia , Sirtuína 1/fisiologia , Animais , Proteínas Reguladoras de Apoptose/biossíntese , Proteínas Reguladoras de Apoptose/genética , Linhagem Celular , Sobrevivência Celular/genética , Genes p53/genética , Humanos , Camundongos , Camundongos Transgênicos , MicroRNAs/genética , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/genética , Transdução de Sinais/genética , Sirtuína 1/genéticaRESUMO
The hippocampal CA3 contributes to spatial working memory (SWM), but which stage of SWM the CA3 neurons act on and whether the lateralization of CA3 function occurs in SWM is also unknown. Here, we reveal increased neural activity in both sample and choice phases of SWM. Left CA3 (LCA3) neurons show higher sensitivity in the choice phase during the correct versus error trials compared with right CA3 (RCA3) neurons. LCA3 initiates firing prior to RCA3 in the choice phase. Optogenetic suppression of pyramidal neurons in LCA3 disrupts SWM only in the choice phase. Furthermore, we discover that parvalbumin (PV) neurons, rather than cholinergic neurons in the medial septum (DB were cholinergic neurons), can project directly to unilateral CA3. Selective suppression of PV neurons in the MS projecting to LCA3 impairs SWM. The findings suggest that MSPV-LCA3 projection plays a crucial role in manipulating the lateralization of LCA3 in the retrieval of SWM.
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Região CA3 Hipocampal/fisiologia , Memória de Curto Prazo , Neurônios/fisiologia , Memória Espacial , Animais , Comportamento Animal , Mapeamento Encefálico/métodos , Neurônios Colinérgicos/fisiologia , Feminino , Masculino , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos C57BL , Parvalbuminas/fisiologiaRESUMO
Neurodegenerative diseases (NDs) are considered heterogeneous disorders characterized by progressive pathological changes in neuronal systems. Transcription factors are protein molecules that are important in regulating the expression of genes. Although the clinical manifestations of NDs vary, the pathological processes appear similar with regard to neuroinflammation, oxidative stress, and proteostasis, to which, as numerous studies have discovered, transcription factors are closely linked. In this review, we summarized and reviewed the roles of transcription factors in NDs, and then we elucidated their functions during pathological processes, and finally we discussed their therapeutic values in NDs.
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Encéfalo/metabolismo , Doenças Neurodegenerativas/genética , Neurônios/metabolismo , Fatores de Transcrição/genética , Animais , Regulação da Expressão Gênica , Humanos , Doenças Neurodegenerativas/metabolismo , Estresse Oxidativo , Proteostase , Fatores de Transcrição/metabolismoRESUMO
Stem cell research has recently become a hot research topic in biomedical research due to the foreseen unlimited potential of stem cells in tissue engineering and regenerative medicine. For many years, medicine has been facing intense challenges, such as an insufficient number of organ donations that is preventing clinicians to fulfill the increasing needs. To try and overcome this regrettable matter, research has been aiming at developing strategies to facilitate the in vitro culture and study of stem cells as a tool for tissue regeneration. Meanwhile, new developments in the microfluidics technology brought forward emerging cell culture applications that are currently allowing for a better chemical and physical control of cellular microenvironment. This review presents the latest developments in stem cell research that brought new therapies to the clinics and how the convergence of the microfluidics technology with stem cell research can have positive outcomes on the fields of regenerative medicine and high-throughput screening. These advances will bring new translational solutions for drug discovery and will upgrade in vitro cell culture to a new level of accuracy and performance. We hope this review will provide new insights into the understanding of new brain treatments from the perspective of stem cell technology especially regarding regenerative medicine and tissue engineering.
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Encéfalo/citologia , Técnicas de Cultura de Células/métodos , Células-Tronco/citologia , Animais , Descoberta de Drogas , Humanos , Técnicas Analíticas Microfluídicas , Medicina Regenerativa , Engenharia Tecidual , Pesquisa Translacional BiomédicaRESUMO
Research over the years has shown that causes of Alzheimer's disease are not well understood, but over the past years, the involvement of epigenetic mechanisms in the developing memory formation either under pathological or physiological conditions has become clear. The term epigenetics represents the heredity of changes in phenotype that are independent of altered DNA sequences. Different studies validated that cytosine methylation of genomic DNA decreases with age in different tissues of mammals, and therefore, the role of epigenetic factors in developing neurological disorders in aging has been under focus. In this review, we summarized and reviewed the involvement of different epigenetic mechanisms especially the DNA methylation in Alzheimer's disease (AD), late-onset Alzheimer's disease (LOAD), familial Alzheimer's disease (FAD), and autosomal dominant Alzheimer's disease (ADAD). Down to the minutest of details, we tried to discuss the methylation patterns like mitochondrial DNA methylation and ribosomal DNA (rDNA) methylation. Additionally, we mentioned some therapeutic approaches related to epigenetics, which could provide a potential cure for AD. Moreover, we reviewed some recent studies that validate DNA methylation as a potential biomarker and its role in AD. We hope that this review will provide new insights into the understanding of AD pathogenesis from the epigenetic perspective especially from the perspective of DNA methylation.