scholarly journals DNA Methylation, Histone Modifications, and Signal Transduction Pathways: A Close Relationship in Malignant Gliomas Pathophysiology

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Raúl Alelú-Paz ◽  
Nadia Ashour ◽  
Ana González-Corpas ◽  
Santiago Ropero
Keyword(s):  
Adult Population ◽  
Malignant Gliomas ◽  
Primary Brain Tumor ◽  
New Approach ◽  
Tremendous Progress ◽  
Close Relationship ◽  
Molecular Etiology ◽  
New Biomarkers ◽  
And Function

Gliomas are the most common type of primary brain tumor. Although tremendous progress has been achieved in the recent years in the diagnosis and treatment, its molecular etiology remains unknown. In this regard, epigenetics represents a new approach to study the mechanisms that control gene expression and function without changing the sequence of the genome. In the present paper we describe the main findings about the alterations of cell signaling pathways in the most aggressive glioma in the adult population, namely, glioblastoma, in which epigenetic mechanisms and the emerging role of cancer stem cell play a crucial function in the development of new biomarkers for its detection and prognosis and the corresponding development of new pharmacological strategies.

microRNA-422a Inhibits DCC Expression in a Manner Dependent on SNP rs12607853

2020 ◽  
Vol 160 (2) ◽  
pp. 63-71
Author(s):  
Yunxiao Li ◽  
Xugang Shi ◽  
Xintong Cai ◽  
Yongsheng Zhu ◽  
Yuanyuan Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Opioid Addiction ◽  
Heroin Addiction ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Protein Levels ◽  
Gene Assay ◽  
New Biomarkers ◽  
And Function

DCC netrin 1 receptor (DCC) affects the structure and function of the dopamine circuitry, which in turn affects the susceptibility to developing addiction. In a previous study, we found that single nucleotide polymorphism (SNP) rs12607853 in the 3′ untranslated region (3′-UTR) of DCC was significantly associated with heroin addiction. In the current study, we first used bioinformatics prediction to identify the DCC rs12607853 C allele as a potential hsa-miR-422a and hsa-miR-378c target site. We then used vector construction and dual-luciferase reporter assays to investigate the targeting relationship of DCC rs12607853 with hsa-miR-422a and hsa-miR-378c. The dual-luciferase reporter gene assay confirmed that the C allele of rs12607853 in combination with hsa-miR-422a led to repressed dual-luciferase gene expression. Moreover, gene expression assays disclosed that hsa-miR-422a inhibited DCC expression at both the mRNA and protein levels. We also found that morphine inhibited the expression of hsa-miR-422a but increased the expression of DCC mRNA, and this change in the expression of hsa-miR-422a could not be reversed by naloxone, which suggested that the role of DCC in opioid addiction might be regulated by hsa-miR-422a. In summary, this study improves our understanding of the role of hsa-miR-422a and identifies the genetic basis of rs12607853, which might contribute to the discovery of new biomarkers or therapeutic targets for opioid addiction.

scholarly journals Immunomodulation by Gut Microbiota: Role of Toll-Like Receptor Expressed by T Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Mariagrazia Valentini ◽  
Alessia Piermattei ◽  
Gabriele Di Sante ◽  
Giuseppe Migliara ◽  
Giovanni Delogu ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Gut Microbiota ◽  
Cell Types ◽  
Mutual Regulation ◽  
Close Relationship ◽  
Numerous Cell ◽  
Specific Receptors ◽  
And Function

A close relationship exists between gut microbiota and immune responses. An imbalance of this relationship can determine local and systemic immune diseases. In fact the immune system plays an essential role in maintaining the homeostasis with the microbiota that normally resides in the gut, while, at the same time, the gut microbiota influences the immune system, modulating number and function of effector and regulatory T cells. To achieve this aim, mutual regulation between immune system and microbiota is achieved through several mechanisms, including the engagement of toll-like receptors (TLRs), pathogen-specific receptors expressed on numerous cell types. TLRs are able to recognize ligands from commensal or pathogen microbiota to maintain the tolerance or trigger the immune response. In this review, we summarize the latest evidences about the role of TLRs expressed in adaptive T cells, to understand how the immune system promotes intestinal homeostasis, fights invasion by pathogens, and is modulated by the intestinal microbiota.

The Letter of Paul to the Galatians: a Deliberative Speech

1989 ◽  
Vol 35 (1) ◽  
pp. 1-26 ◽  
Author(s):  
Joop Smit
Keyword(s):  
New Approach ◽  
And Function ◽  
Literary Composition ◽  
Point Of Departure ◽  
Roman Rhetoric

This study's point of departure is the important article of H. D. Betz, ‘The literary composition and function of Paul's letter to the Galatians’, published in this journal in 1975. In that article the author suggests a new approach to the letter to the Galatians, by using the generative rules of Graeco-Roman rhetoric to analyse the structure of the letter. A rigorous examination leads him to the conclusion that the form of the various parts and the order in which they are arranged completely conform to the classical rules of rhetoric for a judicial speech (genus iudiciale). Paul is under accusation by opponents. The Galatians play the role of judges. The letter contains a speech in which Paul, following all the rules of the art, defends himself before the jury.

scholarly journals Peran Ninik Mamak Dalam Pencegahan dan Pengurangan Resiko Penyakit HIV/AIDS pada Remaja di Kota Solok 2019

2021 ◽  
Vol 16 (2) ◽  
pp. 89-98
Author(s):  
Abdul Gafar ◽  
Syahrum Syahrum
Keyword(s):  
Cultural Values ◽  
Qualitative Methodology ◽  
Study Approach ◽  
Close Relationship ◽  
And Function ◽  
Role And Function ◽  
Depth Interviews ◽  
Hiv Aids

To inhibit the increase and spread of HIV-AIDS, it is necessary to partnership between civil society, people with HIV-AIDS, government and the role of community leaders. In Minangkabau Ninik Mamak is obliged to educate nephews in the field of religion, customary values, culture in community life to be able to live harmoniously. Data from the Solok City Health Office with HIV-AIDS in 2019 amounted to 54 cases and 30 of them died. The purpose of this study is to find out how Ninik Mamak's role in the application of indigenous and cultural values to the prevention and reduction of the risk of HIV-AIDS disease in adolescents in solok city. This research uses qualitative methodology with a case study approach, data collected through in-depth interviews. The results of the study of most ninik mamak have not played a role in maximally applying and instilling the values of Indigenous and Cultural Minangkabau to the youth nephew about the prevention and reduction of the risk of HIV-AIDS disease. Ninik Mamak as an informal leader who has a close relationship with the nephew must provide motivation, direction, guidance, and teaching wisely and wisely to the nephew to do it in everyday life. Suggestions that Ninik Mamak increase its role and function to instill indigenous values and Minangkabau culture in the daily life of youth nephews as an awareness effort in the prevention and reduction of the risk of HIV-AIDS disease.

scholarly journals Glioma Stem Cells: Signaling, Microenvironment, and Therapy

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Brandon D. Liebelt ◽  
Takashi Shingu ◽  
Xin Zhou ◽  
Jiangong Ren ◽  
Seul A. Shin ◽  
...  
Keyword(s):  
De Novo ◽  
Current Knowledge ◽  
Primary Brain Tumor ◽  
Tumor Formation ◽  
Therapeutic Approaches ◽  
Microenvironmental Factors ◽  
Xenograft Models ◽  
And Function ◽  
Vascular Formation

Glioblastoma remains the most common and devastating primary brain tumor despite maximal therapy with surgery, chemotherapy, and radiation. The glioma stem cell (GSC) subpopulation has been identified in glioblastoma and likely plays a key role in resistance of these tumors to conventional therapies as well as recurrent disease. GSCs are capable of self-renewal and differentiation; glioblastoma-derived GSCs are capable ofde novotumor formation when implanted in xenograft models. Further, GSCs possess unique surface markers, modulate characteristic signaling pathways to promote tumorigenesis, and play key roles in glioma vascular formation. These features, in addition to microenvironmental factors, present possible targets for specifically directing therapy against the GSC population within glioblastoma. In this review, the authors summarize the current knowledge of GSC biology and function and the role of GSCs in new vascular formation within glioblastoma and discuss potential therapeutic approaches to target GSCs.

scholarly journals Muscle-tendon Crosstalk During Muscle Wasting

2021 ◽  
Author(s):  
Alec M. Avey ◽  
Keith Baar
Keyword(s):  
Mechanical Loading ◽  
Muscle Wasting ◽  
Fibroblast Growth Factors ◽  
Structure And Function ◽  
Fibroblast Growth ◽  
Tendon Development ◽  
Close Relationship ◽  
And Function

In organisms from flies to mammals, the initial formation of a functional tendon is completely dependent on chemical signals from muscle (myokines). However, how myokines affect the maturation, maintenance, and regeneration of tendons as a function of age is completely unstudied. Here we discuss the role of four myokines - fibroblast growth factors (FGF), myostatin, the secreted protein acidic and rich in cysteine (SPARC), and miR-29 - in tendon development and hypothesize a role for these factors in the progressive changes in tendon structure and function as a result of muscle wasting (disuse, aging and disease). Because of the close relationship between mechanical loading and muscle and tendon regulation, disentangling muscle-tendon crosstalk from simple mechanical loading is experimentally quite difficult. Therefore, we propose an experimental framework that hopefully will be useful in demonstrating muscle-tendon crosstalk in vivo. Though understudied, the promise of a better understanding of muscle-tendon crosstalk is the development of new interventions that will improve tendon development, regeneration, and function throughout the lifespan.

Effects of P-gpMAbNano-structured material nanoparticles on epilepsy and expression of SRY-related HMG Box 21 in epilepsy

2020 ◽  
Vol 10 (4) ◽  
pp. 585-593
Author(s):  
Qi Li ◽  
Jing Deng ◽  
Juan Yang ◽  
Tao Xu ◽  
Xinyuan Yu ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Temporal Cortex ◽  
New Approach ◽  
Hmg Box ◽  
Transcription Inhibitors ◽  
The Central Nervous System ◽  
And Function ◽  
Necrosis Factor

SRY-related HMG box (SOX)21, one of the most highly expressed transcription inhibitors in the central nervous system (CNS), is involved in neurogenesis-related transcription and proliferation, which are associated with certain neurological disorders. However, it is the role of SOX21 in the pathogenesis of epilepsy remains unclear. In this study, our aim was to examine the expression and function of SOX21 in patients with temporal lobe epilepsy (TLE), as well as pentylenetetrazol (PTZ)-kindled rats, and to identify the possible roles of SOX21 in epileptogenesis. We found that SOX21 localized in neurons is upregulated, especially in TLE patients. SOX21 is present in the hippocampus or adjacent temporal cortex in the PTZ-kindled epileptic rat model. In addition, the P-gpMAbNano-structured material (PNM) nanoparticles carrying anti-epileptic drugs (AEDs) were injected into the epileptic model rats using an intravenous injection. The expression of tumor necrosis factor peptide in the rats was detected to verify whether the drug-carrying nanoparticles could bypass macrophages and reach the target for treatment. We also found an interaction between SOX21 and SOX2 in PTZ-kindled rats. These results indicate that SOX21 is mainly located in neurons and may regulate the pathogenesis of epilepsy, possibly in association with SOX2. Moreover, PNM nanoparticles equipped with AEDs can reach the target through macrophages in vivo, providing a new approach for the clinical treatment of epilepsy.

scholarly journals Cardiac Filaminopathies: Illuminating the Divergent Role of Filamin C Mutations in Human Cardiomyopathy

2021 ◽  
Vol 10 (4) ◽  
pp. 577
Author(s):  
Matthias Eden ◽  
Norbert Frey
Keyword(s):  
High Risk ◽  
Genetic Alterations ◽  
Myofibrillar Myopathy ◽  
Gene Encoding ◽  
Sarcomeric Protein ◽  
The Past ◽  
Tremendous Progress ◽  
Molecular Etiology ◽  
Filamin C

Over the past decades, there has been tremendous progress in understanding genetic alterations that can result in different phenotypes of human cardiomyopathies. More than a thousand mutations in various genes have been identified, indicating that distinct genetic alterations, or combinations of genetic alterations, can cause either hypertrophic (HCM), dilated (DCM), restrictive (RCM), or arrhythmogenic cardiomyopathies (ARVC). Translation of these results from “bench to bedside” can potentially group affected patients according to their molecular etiology and identify subclinical individuals at high risk for developing cardiomyopathy or patients with overt phenotypes at high risk for cardiac deterioration or sudden cardiac death. These advances provide not only mechanistic insights into the earliest manifestations of cardiomyopathy, but such efforts also hold the promise that mutation-specific pathophysiology might result in novel “personalized” therapeutic possibilities. Recently, the FLNC gene encoding the sarcomeric protein filamin C has gained special interest since FLNC mutations were found in several distinct and possibly overlapping cardiomyopathy phenotypes. Specifically, mutations in FLNC were initially only linked to myofibrillar myopathy (MFM), but are now increasingly found in various forms of human cardiomyopathy. FLNC thereby represents another example for the complex genetic and phenotypic continuum of these diseases.

Perfusion-contraction mismatch with coronary microvascular obstruction: role of inflammation

2000 ◽  
Vol 279 (6) ◽  
pp. H2587-H2592 ◽  
Author(s):  
Hilmar Dörge ◽  
Till Neumann ◽  
Matthias Behrends ◽  
Andreas Skyschally ◽  
Rainer Schulz ◽  
...  
Keyword(s):  
Microvascular Obstruction ◽  
Regional Myocardial Blood Flow ◽  
Wall Thickening ◽  
Area At Risk ◽  
Close Relationship ◽  
Anesthetized Dogs ◽  
And Function ◽  
Relationship Of ◽  
The Relationship

A close relationship exists between regional myocardial blood flow (RMBF) and function during acute coronary inflow restriction (perfusion-contraction matching). However, the relationship of flow and function during coronary microvascular obstruction is unknown. In 12 anesthetized dogs, the left circumflex coronary artery was perfused from an extracorporeal circuit. After control measurements, 3,000 microspheres (42 μm diameter) per milliliter per minute inflow were injected to cause a microembolism (ME, n = 6). With unchanged systemic hemodynamics and RMBF, posterior systolic wall thickening (PWT) decreased from 19.8 ± 1.9% SD at control to 13.3 ± 4.0, 10.3 ± 3.8, and 6.9 ± 4.7% ( P < 0.05 vs. control) at 1, 4, and 8 h, respectively. For comparison, inflow was progressively reduced to match PWT to that of the ME group at 1, 4, and 8 h (stenosis, STE, n = 6). RMBF in the STE group was reduced in proportion to PWT. Infarct size was not different among groups (6.5 ± 4.5 vs. 3.4 ± 3.2%). However, the number of leukocytes infiltrating the area at risk was significantly greater in the ME group than in the STE group. Coronary microembolization results in perfusion-contraction mismatch and is associated with an inflammatory response.

Scanning electron microscopic study of collagen fibrillogenesis and extracellular compartmentalization in the chick embryo tendon

1986 ◽  
Vol 44 ◽  
pp. 208-209
Author(s):  
Grace C.H. Yang
Keyword(s):  
Chick Embryo ◽  
Extracellular Space ◽  
Fibroblast Cell ◽  
Collagen Fibrils ◽  
Electron Microscopic ◽  
Voltage Electron ◽  
Scanning Electron Microscopic Study ◽  
Microscopic Studies ◽  
And Function

The size and organization of collagen fibrils in the extracellular matrix is an important determinant of tissue structure and function. The synthesis and deposition of collagen involves multiple steps which begin within the cell and continue in the extracellular space. High-voltage electron microscopic studies of the chick embryo cornea and tendon suggested that the extracellular space is compartmentalized by the fibroblasts for the regulation of collagen fibril, bundle, and tissue specific macroaggregate formation. The purpose of this study is to gather direct evidence regarding the association of the fibroblast cell surface with newly formed collagen fibrils, and to define the role of the fibroblast in the control and the precise positioning of collagen fibrils, bundles, and macroaggregates during chick tendon development.

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