Browsing by Subject "Signaling pathways"

Now showing 1 - 7 of 7
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    Cancer stem cell as therapeutic target for melanoma treatment
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Alamodi, Abdulhadi A.; Eshaq, Abdulaziz M.; Hassan, Sofie Yasmin; Hmada, Youssef Al; El Jamal, Siraj M.; Fothan, Ahmed M.; Arain, Omair M.; Hassan, Sarah-Lilly; Haikel, Youssef; Megahed, Mosaad; Hassan, Mohamed
    Human malignant melanoma is a highly aggressive skin tumor that is characterized by its extraordinary heterogeneity, propensity for dissemination to distant organs and resistance to cytotoxic agents. Although chemo- and immune-based therapies have been evaluated in clinical trials, most of these therapeutics do not show significant benefit for patients with advanced disease. Treatment failure in melanoma patients is attributed mainly to the development of tumor heterogeneity resulting from the formation of genetically divergent subpopulations. These subpopulations are composed of cancer stem-like cells (CSCs) as a small fraction and non-cancer stem cells that form the majority of the tumor mass. In recent years, CSCs gained more attention and suggested as valuable experimental model system for tumor study. In melanoma, intratumoral heterogeneity, progression and drug resistance result from the unique characteristics of melanoma stem cells (MSCs). These MSCs are characterized by their distinct protein signature and tumor growth-driving pathways, whose activation is mediated by driver mutation-dependent signal. The molecular features of MSCs are either in a causal or consequential relationship to melanoma progression, drug resistance and relapse. Here, we review the current scientific evidence that supports CSC hypothesis and the validity of MSCs-dependent pathways and their key molecules as potential therapeutic target for melanoma treatment.
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    Farnesoid X receptor: a potential therapeutic target in multiple organs
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Zhang, Chao; Wang, Zixuan; Feng, Qingqing; Chen, Wei-Dong; Wang, Yan-Dong
    Farnesoid X receptor (FXR), a member of the nuclear receptor family, is a common receptor found in the intestine and liver, and helps to maintain systemic metabolic homeostasis through regulating bile acid, glucose, lipid metabolism, and energy homeostatsis. In addition, FXR regulates the functions of various organs, such as liver, intestine, kidney, breast, pancreas, cardiovascular system and brain. FXR also plays a key role in regulation of gut-microbiota through mediating the various signaling pathways. Accordingly, FXR has become an attractive therapeutic target in a variety of diseases. This review combines classical and recent research reports to introduce the basic information about FXR and its important roles in various organs of the body.
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    Microglia mediated neuroinflammation - signaling regulation and therapeutic considerations with special reference to some natural compounds
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Yao, Yue-yi; Ling, Eng-Ang; Lu, Di
    Neuroinflammation plays a central role in multiple neurodegenerative diseases and neurological disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), cerebral ischemic injury etc. In this connection, microglia, the key players in the central nervous system, mediate the inflammatory response process. In brain injuries, activated microglia can clear the cellular debris and invading pathogens and release neurotrophic factors; however, prolonged microglia activation may cause neuronal death through excessive release of inflammatory mediators. Therefore, it is of paramount importance to understand the underlying molecular mechanisms of microglia activation to design an effective therapeutic strategy to alleviate neuronal injury. Recent studies have shown that some natural compounds and herbal extracts possess anti- inflammatory properties that may suppress microglial activation and ameliorate neuroinflammation and hence are neuroprotective. In this review, we will update some of the common signaling pathways that regulate microglia activation. Among the various signaling pathways, the Notch-1, mitogen-activated protein kinases (MAPKs), and nuclear factor kappa-light-chain- enhancer of activated B cells (NF-κB) have been reported to exacerbate microglia mediated neuroinflammation that is implicated in different neuropathological diseases. The search for natural compounds or agents, specifically those derived from natural herbal extracts such as Gastrodin, scutellarin, Rg1 etc. has been the focus of many of our recent studies because they have been found to regulate microglia activation. The pharmacological effects of these agents and their potential mechanisms for regulating microglia activation are systematically reviewed here for a fuller understanding of their biochemical action and therapeutic potential for treatment of microglia mediated neuropathological diseases.
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    Molecular mechanisms and signaling pathways of reactive astrocytes responding to traumatic brain injury
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Li, Jiatong; Wang, Xiaoxuan; Qin, Song
    Traumatic brain injury (TBI) is one of the most common causes of death and disability worldwide. Astrocytes are the largest cell types in the central nervous system (CNS) with numerous functions both physiologically and pathologically. In response to TBI, astrocytes go through a series of alterations referred to as reactive astrogliosis. It is now generally recognized that reactive astrocytes play a dual role in TBI development and tissue repair. Many molecules and signaling pathways have been demonstrated to be involved in the activation of astrocytes, including vital life-supporting substances (such as ATP), regulating hormones (such as gonadal steroids), injury-induced cytokines and chemokines. In this review, we focus on the role of certain specific molecules and related signaling pathways in regulating the activation of astrocytes in TBI. We also discuss the dual role of reactive astrocytes after TBI, which will be critical in the discovery of more appropriate strategies for brain injury treatment.
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    Molecular mechanisms in dental follicle precursor cells during the osteogenic differentiation
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Morsczeck, Christian
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    The dexamethasone induced osteogenic differentiation of dental follicle cells
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Morsczeck, Christian; Reichert, Torsten E.
    Mesenchymal stem cells are excellent for in vitro studies about biological processes during the differentiation of osteogenic progenitor cells into mineralizing cells such as osteoblasts. Human dental follicle cells (DFCs) are dental mesenchymal stem cells and they can be isolated from third molar teeth. Because DFCs are the genuine progenitor cells of periodontal tissue cells, they have been used for the evaluation of molecular mechanisms during the differentiation of undifferentiated stem cells into alveolar osteoblasts and cementoblasts. To reveal molecular mechanisms of osteogenic differentiation, initial studies investigated the proteome and the transcriptome of DFCs after the induction of the osteogenic differentiation with the glucocorticoid dexamethasone. These studies showed for example that dexamethasone induces the transcription factor ZBTB16 (zinc finger and BTB domain containing protein 16) and that ZBTB16 is crucial for osteogenic differentiation of DFCs. This article is a survey of the molecular mechanisms in DFCs during osteogenic differentiation with dexamethasone.
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    Therapeutic effects of herbal compounds in cerebral ischemia with special reference to suppression of microglia activation implicated in neurodegeneration
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Jia, Wen Ji; Yuan, Yun; Wu, Chun Yun
    Cerebral ischemia affects many especially with the ageing population. The ensuing ischemic reactions include oxidative stress, inflammation, and excitotoxicity among others. In the search for effective therapeutic strategies for cerebral ischemia, activated microglia which are the key player in neuroinflammation are now recognized as a potential therapeutic target. Microglia possess both neurotoxic and neuroprotective roles. They are protective by continuously surveilling the microenvironment, phagocytosing dead cells, secreting trophic factors and sculpting the neuronal connections by removing axons and pruning excess synapses. On the other hand, hyperactivated microglia may impair cerebral oxidative metabolism, and produce excessive proinflammatory mediators that may exacerbate the brain damage. In view of this, suppression of microglial activation has been considered a therapeutic strategy to mitigate microglia-based neuroinflammation in cerebral ischemia. However, balancing the neuroprotective and neurotoxic roles of activated microglia remains a challenging issue. Many traditional Chinese herbal agents have been used in clinic for treatment of cerebral ischemia. Here, we provide an overview of five common Chinese herbs targeting specifically microglia-mediated neuroinflammation in cerebral ischemia. It is hoped that a common parallel may be drawn from their beneficial effects especially in the latter pathological conditions for their better and effective use in the future.