共查询到20条相似文献，搜索用时 15 毫秒
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Yagmur Esemen Mariam Awan Rabeeia Parwez Arsalan Baig Shahinur Rahman Ilaria Masala Sonia Franchini Dimitrios Giakoumettis 《International journal of molecular sciences》2022,23(5)
Glioblastoma (GBM) is the most common and malignant tumour of the central nervous system. Recent appreciation of the heterogeneity amongst these tumours not only changed the WHO classification approach, but also created the need for developing novel and personalised therapies. This systematic review aims to highlight recent advancements in understanding the molecular pathogenesis of the GBM and discuss related novel treatment targets. A systematic search of the literature in the PubMed library was performed following the PRISMA guidelines for molecular pathogenesis and therapeutic advances. Original and meta-analyses studies from the last ten years were reviewed using pre-determined search terms. The results included articles relevant to GBM development focusing on the aberrancy in cell signaling pathways and intracellular events. Theragnostic targets and vaccination to treat GBM were also explored. The molecular pathophysiology of GBM is complex. Our systematic review suggests targeting therapy at the stemness, p53 mediated pathways and immune modulation. Exciting novel immune therapy involving dendritic cell vaccines, B-cell vaccines and viral vectors may be the future of treating GBM. 相似文献
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Osteoporosis is a common skeletal disorder that occurs as a result of an imbalance between bone resorption and bone formation, with bone breakdown exceeding bone building. Bone resorption inhibitors, e.g., bisphosphonates, have been designed to treat osteoporosis. Teriparatide, an anabolic agent, stimulates bone formation and corrects the characteristic changes in the trabecular microarchitecture. However, these drugs are associated with significant side effects. It is therefore crucial that we continue to research the pathogenesis of osteoporosis and seek novel modes of therapy. This editorial summarizes and discusses the themes of the six articles published in our Special Issue “Osteoporosis: From Molecular Mechanisms to Therapies 3.0”, a continuation of our 2020 Special Issue \"Osteoporosis: From Molecular Mechanisms to Therapies\". These Special Issues detail important global scientific findings that contribute to our current understanding of osteoporosis. 相似文献
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Skin color is determined by the processes of melanin synthesis and distribution. Problems in various molecules or signaling pathways involved in melanin synthesis contribute to skin pigmentation defects. Several trials have been conducted on the production of pigmentation-regulating agents, and drug repositioning has emerged as a modern technique to identify new uses for existing drugs. Our research team has researched substances or drugs associated with pigmentation control and, as a result, nilotinib, sorafenib, and ICG-001 have been found to promote pigmentation, while 5-iodotubercidin inhibits pigmentation. Therefore, these substances or medications were suggested as potential therapeutics for pigmentation disorders by drug repositioning. 相似文献
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Oncogenic fusion genes have emerged as successful targets in several malignancies, such as chronic myeloid leukemia and lung cancer. Fusion of the fibroblast growth receptor 3 and the transforming acidic coiled coil containing protein—FGFR3-TACC3 fusion—is prevalent in 3–4% of human glioblastoma. The fusion protein leads to the constitutively activated kinase signaling of FGFR3 and thereby promotes cell proliferation and tumor progression. The subgroup of FGFR3-TACC3 fusion-positive glioblastomas presents with recurrent clinical and histomolecular characteristics, defining a distinctive subtype of IDH-wildtype glioblastoma. This review aims to provide an overview of the available literature on FGFR3-TACC3 fusions in glioblastoma and possible implications for actual clinical practice. 相似文献
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Female reproduction depends on the metabolic status, especially during the period of folliculogenesis. Even though it is believed that melatonin can improve oocyte competence, there is still limited knowledge of how it can modulate metabolic processes during folliculogenesis and which signaling pathways are involved in regulating gene expression. To investigate the effects of melatonin on metabolic signals during the antral stage of follicular development, human granulosa-like tumor cells (KGN) were treated with melatonin or forskolin, and gene expression was analyzed with RNA-seq technology. Following appropriate normalization and the application of a fold change cut-off of 1.5 (FC 1.5, p ≤ 0.05), 1009 and 922 genes were identified as differentially expressed in response to melatonin and forskolin, respectively. Analysis of major upstream regulators suggested that melatonin may activate PKB/mTOR signaling pathways to program the metabolism of KGN cells to support slower growth and differentiation and to prevent follicular atresia. Similarly, PKA activation through stimulation of cAMP synthesis with FSK seemed to exert the same effects as melatonin in reducing follicular growth and regulating differentiation. This study suggests that melatonin may act through PKA and PKB simultaneously in human granulosa cells to prevent follicular atresia and early luteinization at the antral stage. 相似文献
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Juneyoung Lee Attayeb Mohsen Anik Banerjee Louise D. McCullough Kenji Mizuguchi Motomu Shimaoka Hiroshi Kiyono Eun Jeong Park 《International journal of molecular sciences》2021,22(7)
The intestinal epithelium serves as a dynamic barrier to protect the host tissue from exposure to a myriad of inflammatory stimuli in the luminal environment. Intestinal epithelial cells (IECs) encompass differentiated and specialized cell types that are equipped with regulatory genes, which allow for sensing of the luminal environment. Potential inflammatory cues can instruct IECs to undergo a diverse set of phenotypic alterations. Aging is a primary risk factor for a variety of diseases; it is now well-documented that aging itself reduces the barrier function and turnover of the intestinal epithelium, resulting in pathogen translocation and immune priming with increased systemic inflammation. In this study, we aimed to provide an effective epigenetic and regulatory outlook that examines age-associated alterations in the intestines through the profiling of microRNAs (miRNAs) on isolated mouse IECs. Our microarray analysis revealed that with aging, there is dysregulation of distinct clusters of miRNAs that was present to a greater degree in small IECs (22 miRNAs) compared to large IECs (three miRNAs). Further, miRNA–mRNA interaction network and pathway analyses indicated that aging differentially regulates key pathways between small IECs (e.g., toll-like receptor-related cascades) and large IECs (e.g., cell cycle, Notch signaling and small ubiquitin-related modifier pathway). Taken together, current findings suggest novel gene regulation pathways by epithelial miRNAs in aging within the gastrointestinal tissues. 相似文献
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Nadia Senhaji Asmae Squalli Houssaini Salma Lamrabet Sara Louati Sanae Bennis 《International journal of molecular sciences》2022,23(13)
Glioblastoma is the most aggressive malignant tumor of the central nervous system with a low survival rate. The difficulty of obtaining this tumor material represents a major limitation, making the real-time monitoring of tumor progression difficult, especially in the events of recurrence or resistance to treatment. The identification of characteristic biomarkers is indispensable for an accurate diagnosis, the rigorous follow-up of patients, and the development of new personalized treatments. Liquid biopsy, as a minimally invasive procedure, holds promise in this regard. The purpose of this paper is to summarize the current literature regarding the identification of molecular and circulating glioblastoma biomarkers and the importance of their integration as a valuable tool to improve patient care. 相似文献
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Hyun Jung Hwang Nayeon Kim Allison B. Herman Myriam Gorospe Jae-Seon Lee 《International journal of molecular sciences》2022,23(17)
Aging causes a progressive decline in the structure and function of organs. With advancing age, an accumulation of senescent endothelial cells (ECs) contributes to the risk of developing vascular dysfunction and cardiovascular diseases, including hypertension, diabetes, atherosclerosis, and neurodegeneration. Senescent ECs undergo phenotypic changes that alter the pattern of expressed proteins, as well as their morphologies and functions, and have been linked to vascular impairments, such as aortic stiffness, enhanced inflammation, and dysregulated vascular tone. Numerous molecules and pathways, including sirtuins, Klotho, RAAS, IGFBP, NRF2, and mTOR, have been implicated in promoting EC senescence. This review summarizes the molecular players and signaling pathways driving EC senescence and identifies targets with possible therapeutic value in age-related vascular diseases. 相似文献
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Silvia Mara Baez Rodriguez Georgiana-Adeline Staicu Ani-Simona Sevastre Carina Baloi Vasile Ciubotaru Anica Dricu Ligia Gabriela Tataranu 《International journal of molecular sciences》2022,23(9)
Glioblastoma stem cells (GSCs) are cells with a self-renewal ability and capacity to initiate tumors upon serial transplantation that have been linked to tumor cell heterogeneity. Most standard treatments fail to completely eradicate GSCs, causing the recurrence of the disease. GSCs could represent one reason for the low efficacy of cancer therapy and for the short relapse time. Nonetheless, experimental data suggest that the presence of therapy-resistant GSCs could explain tumor recurrence. Therefore, to effectively target GSCs, a comprehensive understanding of their biology and the survival and developing mechanisms during treatment is mandatory. This review provides an overview of the molecular features, microenvironment, detection, and targeting strategies of GSCs, an essential information required for an efficient therapy. Despite the outstanding results in oncology, researchers are still developing novel strategies, of which one could be targeting the GSCs present in the hypoxic regions and invasive edge of the glioblastoma. 相似文献
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Yunxia Ma Desiree Charlotte Schrder Miljana Nenkov Maryam Noor Rizwan Mohamed Abubrig Jürgen Sonnemann Jos M. Murrieta-Coxca Diana M. Morales-Prieto Martin Westermann Nikolaus Gaßler Yuan Chen 《International journal of molecular sciences》2021,22(6)
Epithelial membrane proteins (EMP1-3) are involved in epithelial differentiation and carcinogenesis. Dysregulated expression of EMP2 was observed in various cancers, but its role in human lung cancer is not yet clarified. In this study, we analyzed the expression of EMP1-3 and investigated the biological function of EMP2 in non-small cell lung cancer (NSCLC). The results showed that lower expression of EMP1 was significantly correlated with tumor size in primary lung tumors (p = 0.004). Overexpression of EMP2 suppressed tumor cell growth, migration, and invasion, resulting in a G1 cell cycle arrest, with knockdown of EMP2 leading to enhanced cell migration, related to MAPK pathway alterations and disruption of cell cycle regulatory genes. Exosomes isolated from transfected cells were taken up by tumor cells, carrying EMP2-downregulated microRNAs (miRNAs) which participated in regulation of the tumor microenvironment. Our data suggest that decreased EMP1 expression is significantly related to increased tumor size in NSCLC. EMP2 suppresses NSCLC cell growth mainly by inhibiting the MAPK pathway. EMP2 might further affect the tumor microenvironment by regulating tumor microenvironment-associated miRNAs. 相似文献
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Jili Li Zhengyan Bi Linlin Wang Yinghao Xia Yuqi Xie Prof. Yanlan Liu 《Chembiochem : a European journal of chemical biology》2023,24(1):e202200364
Cellular senescence is a stable cell cycle arrest state that can be triggered by a wide range of intrinsic or extrinsic stresses. Increased burden of senescent cells in various tissues is thought to contribute to aging and age-related diseases. Thus, the detection and interventions of senescent cells are critical for longevity and treatment of disease. However, the highly heterogeneous feature of senescence makes it challenging for precise detection and selective clearance of senescent cells in different age-related diseases. To address this issue, considerable efforts have been devoted to developing senescence-targeting molecular theranostic strategies, based on the potential biomarkers of cellular senescence. Herein, we review recent advances in the field of anti-senescence research and highlight the specific visualization and elimination of senescent cells. Additionally, the challenges in this emerging field are outlined. 相似文献
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Neuropathological lesions in Alzheimer’s disease (AD) include amyloid plaques formed by the accumulation of amyloid peptides, neurofibrillary tangles made of hyperphosphorylated tau protein, synaptic and neuronal degenerations, and neuroinflammation. The cause of AD is unknown, but according to the amyloid hypothesis, amyloid oligomers could lead to the activation of kinases such as eukaryotic translation initiation factor 2-alpha kinase 2 (PKR), p38, and receptor-interacting serine/threonine-protein kinase 1 (RIPK1), which all belong to the same stress-activated pathway. Many toxic kinase activations have been described in AD patients and in experimental models. A p38 mitogen-activated protein kinase inhibitor was recently tested in clinical trials but with unsuccessful results. The complex PKR/P38/RIPK1 (PKR/dual specificity mitogen-activated protein kinase kinase 6 (MKK6)/P38/MAP kinase-activated protein kinase 2 (MK2)/RIPK1) is highly activated in AD brains and in the brains of AD transgenic animals. To delineate the implication of this pathway in AD, we carried out a search on PubMed including PKR/MKK6/p38/MK2/RIPK1, Alzheimer, and therapeutics. The involvement of this signaling pathway in the genesis of AD lesions, including Aβ accumulations and tau phosphorylation as well as cognitive decline, is demonstrated by the reports described in this review. A future combination strategy with kinase inhibitors should be envisaged to modulate the consequences for neurons and other brain cells linked to the abnormal activation of this pathway. 相似文献
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Anti-inflammatory therapies have been shown to be effective in the prevention of various cardiovascular diseases, tumors, and cancer complications. Thymoquinone (TQ), the main active constituent of Nigella sativa, has shown promising therapeutic properties in many in vivo and in vitro models. However, TQ has poor bioavailability and is hydrophobic, prohibiting clinical trials with TQ alone. Studies have explored the combination of TQ with biological nanomaterials to improve its bioavailability. The TQ nanoparticle formulation shows better bioavailability than free TQ, and these formulations are ready for clinical trials to determine their potential as therapeutic agents. In this paper, we review current knowledge about the interaction between TQ and the inflammatory response and summarize the research prospects in Korea and abroad. We discuss the different biological activities of TQ and various combination therapies of TQ and nanomaterials in clinical trials. 相似文献
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Ruth Naomi Hasnah Bahari Zhi Yi Ong Yong Yoke Keong Hashim Embong Retnagowri Rajandram Soo Huat Teoh Fezah Othman Rosnani Hasham Khoo Boon Yin Priyatharisni Kaniappan Muhammad Dain Yazid Zainul Amiruddin Zakaria 《International journal of molecular sciences》2022,23(11)
Andrographis paniculata is a local medicinal plant that is widely cultivated in Malaysia. It is comprised of numerous bioactive compounds that can be isolated using water, ethanol or methanol. Among these compounds, andrographolide has been found to be the major compound and it exhibits varieties of pharmacological activities, including anti-cancer properties, particularly in the lipid-dependent cancer pathway. Lipids act as crucial membrane-building elements, fuel for energy-demanding activities, signaling molecules, and regulators of several cellular functions. Studies have shown that alterations in lipid composition assist cancer cells in changing microenvironments. Thus, compounds that target the lipid pathway might serve as potential anti-cancer therapeutic agents. The purpose of this review is to provide an overview of the medicinal chemistry and pharmacology of A. paniculata and its active compounds in terms of anti-cancer activity, primary mechanism of action, and cellular targets, particularly in the lipid-dependent cancer pathway. 相似文献