• Human pulmonary arterial smooth muscle cells treated with fasudil showed a decrease in cell proliferation in a dose-dependent manner. (wikipedia.org)
  • Objective-Proliferation of smooth muscle cells (SMC) in response to vascular injury is central to neointimal CX-6258 vascular remodeling. (cret-signal.com)
  • n\nConclusion-These findings identify HDAC as a critical component of a transcriptional cascade regulating SMC proliferation and suggest that HDAC might play a pivotal role in the development of proliferative vascular diseases, including atherosclerosis and in-stent restenosis. (cret-signal.com)
  • HPV promotes latency and consequently does not cause a disease phenotype following initial infection by an immune evasion response reaction, featuring binding to epithelial cells and integrating into the host genome, resulting in the proliferation of epidermal cells containing the viral genome and neovascularization ( 3 ). (spandidos-publications.com)
  • However, the regulatory mechanisms of HPV infection and consequent immune escape reaction, persistent infection and cell proliferation and the regulatory mechanisms of vascular proliferation are poorly understood and require additional investigation ( 4 ). (spandidos-publications.com)
  • Hypoxia and genetic defects that chronically drive proliferation leave such tumors dependent on a steady supply of nutrients, especially glucose. (springer.com)
  • The atherosclerotic process is accelerated by a myriad of factors, such as the release of inflammatory chemokines and cytokines, the generation of reactive oxygen species (ROS), growth factors, and the proliferation of vascular smooth muscle cells. (hindawi.com)
  • VSMCs were transfected with the miR-128-5p mimic and inhibitor, and the migration, phenotypic modulation, and proliferation of VSMCs were investigated. (hindawi.com)
  • AA and the extracellular regulated protein kinase 1/2 (ERK1/2) blocker U0126 markedly inhibited migration, elevated smooth muscle 22 α (SM22 α ) expression, repressed VSMC proliferation, elevated miR-466f-3p and miR-425-3p expression, and suppressed miR-27a-5p and miR-128-5p expression in ox-LDL-induced VSMCs. (hindawi.com)
  • The inhibitor increased p21, p27, and SM22ɑ expression and repressed the migration, phenotypic transformation, and proliferation of VSMCs. (hindawi.com)
  • It has been shown that inflammation caused by oxidized low-density lipoprotein (ox-LDL) contributes to the occurrence and development of AS [ 1 ], which can promote vascular smooth muscle cell (VSMC) migration, proliferation, and transformation from a contractile to a synthetic phenotype [ 2 - 6 ]. (hindawi.com)
  • The migration, phenotypic transformation, and proliferation of VSMCs lead to vascular wall remodeling, which is mediated by activation of extracellular regulated protein kinases 1/2 (ERK1/2) signalling [ 9 ]. (hindawi.com)
  • Several studies have shown that miRNAs play multiple roles in the phenotypic transformation, migration, and proliferation of VSMCs by inhibiting ERK1/2 activation [ 11 , 12 ], partly by regulating the tissue inhibitor of metalloproteinases (TIMPs)-MMPs and p21-cyclins interactions [ 13 - 18 ]. (hindawi.com)
  • Notably, the knockdown of HSP70 by HSP70 siRNA apparently abrogates the stimulatory effect of let-7c inhibitor on heat-denatured fibroblasts proliferation and migration. (molcells.org)
  • Ample evidence shows that pro-atherosclerotic disturbed flow induces sustained activation of atherogenic genes in endothelial cells to promote their oxidation, inflammation, cell cycle progression and proliferation, whereas pulsatile shear stress tends to maintain endothelial cells in a quiescent and less proliferative state with a low level of oxidation and inflammation [16] , [17] . (plos.org)
  • Acute leukemias induced by MLL chimeric oncoproteins are among the subset of cancers distinguished by a paradoxical dependence on GSK-3 kinase activity for sustained proliferation. (stanford.edu)
  • IMPLICATIONS: The primary contribution of OGT to cell proliferation is unknown, and in this study, we used a compound screen to indicate that OGT and CDK9 collaborate to sustain a cancer cell-specific pro-proliferative program. (ox.ac.uk)
  • We also aimed to evaluate the expression of TGF-β1 and p27 in the context of other cell cycle and proliferation markers such as cyclin D1 and Ki-67. (biomedcentral.com)
  • Growth factors do not only stimulate cell proliferation, but they may also act as growth inhibitors, depending on the cell type and the stimulatory pathway that is involved. (biomedcentral.com)
  • The overexpression of miRNA‑375 significantly increased caspase‑3 and caspase‑9 activities, induced B‑cell lymphoma 2 (Bcl‑2)/Bcl‑2‑associated X protein, tumor protein 53 and cyclin‑dependent kinase inhibitor 1 protein expression and suppressed cyclin D1 and survivin protein expression in HPV‑18(+) cervical cancer cells. (spandidos-publications.com)
  • In addition, numerous important cellular proteins, such as B-cell lymphoma-2 homologous antagonist/killer, Myc proto-oncogene protein, cyclin-dependent kinase inhibitor 1B, DNA replication licensing factor MCM-7, retinoblastoma 1 and Annexin A1, are degenerated through the UBE3A-mediated ubiquitin proteasome pathway ( 7 ). (spandidos-publications.com)
  • Recently, we reported that the nucleus-mitochondria positive feedback loop formed by p90 ribosomal S6 kinase (p90RSK) and phosphorylation of S496 on ERK5 (a unique member of the mitogen-activated protein kinase family that is not only a kinase but also a transcriptional co-activator) were vital signaling events that played crucial roles in linking mitochondrial dysfunction, nuclear telomere dysfunction, persistent SASP induction, and atherosclerosis. (oaepublish.com)
  • However, recent studies have suggested that BRAFi/MEKi and ERK1/2i resistance can arise through activation of a parallel signalling pathway leading to activation of ERK5, an unusual protein kinase that contains both a kinase domain and a transcriptional transactivation domain. (babraham.ac.uk)
  • Equipped with a mouse model of stress (5-HT1A-R-/- mice) and a 5-HT1A-R-expressing hippocampal neuron-derived cell line, HN2-5, our earlier studies have reported that a 5-HT1A-R-mediated signaling pathway functions via extracellular receptor-activated kinase 1/2 (ERK1/2)-catalyzed activation of protein kinase C alpha (PKC) to promote synaptogenesis at P15 in the hippocampal CA1 region [12,16]. (thetechnoant.info)
  • MNU 47 mg/kg, i.v.) and group IV (Tada- activate protein kinase G and map kinase pathway of lafil 4 mg/kg, p.o. (sagepub.com)
  • Book approaches for the fight associated with Alzheimer's disease concentrating on amyloid-β protein. (pcna-signal.com)
  • The proliferative effects of ROCK on vascular endothelial cells is due to the activation of extracellular signal-regulated kinase (ERK). (wikipedia.org)
  • En face co-immunostaining of the mouse aortic arch revealed a low level of PDCD4 in endothelial cells undergoing pulsatile shear stress. (plos.org)
  • Vascular endothelial cells, as a monolayer in direct contact with the flowing blood, bear the most of the wall shear stresses and have important homeostatic functions in response to stress [16] . (plos.org)
  • We determine a comprehensive map of lineage-specific lncRNAs in human dermal lymphatic and blood vascular endothelial cells (LECs and BECs), combining RNA-Seq and CAGE-Seq. (nature.com)
  • Together, an image is emerging where the effect of Hsp90 inhibitors can be shaped from the tumor intracellular and extracellular milieu, and where Hsp90 inhibitors effect tumor and sponsor on the microenvironmental and systems level. (forgetmenotinitiative.org)
  • This suggested that the anti-proliferative effects of fasudil is due to the decrease of ERK activities via the inhibition of ROCK. (wikipedia.org)
  • Both receptors belong to the TAM (TYRO3, AXL and MER - MER proto-oncogene, tyrosine kinase) receptor tyrosine kinase family, which emerged as new potential targets in many oncological diseases, from leukaemia to solid tumours ( Graham et al, 2014 ). (nature.com)
  • The phosphatidyl inositol 3-kinase (PI3K)/Akt pathway was involved in this ubiquitin-proteasome-mediated degradation of PDCD4. (plos.org)
  • By contrast, other inhibitions of growth-signals like those associated with receptor tyrosine kinases are referred to as targeted therapy. (worldsbest.rehab)
  • As such, under the older guidelines, one tumor entity could develop into another tumor entity with a different grade over the course of disease progression. (medscape.com)
  • Our HCC signature covered well-established liver cancer hallmarks, and network analyses revealed coordinated interaction between several MRs. One novel MR, SEC14L2 , exerted an anti-proliferative effect in HCC cells and strongly suppressed tumor growth in a mouse model. (aging-us.com)
  • This study intended to compare the expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) genes in active rheumatoid arthritis (RA) patients who were receiving conventional synthetic disease-modifying drugs (csDMARDs) and to find the clinical and laboratory determinants affecting TNF-α and IL-6 genes expression levels among active RA patients. (bvsalud.org)
  • Six of 8 individuals defined as EML4-ALK positive had been crizotinib got and naive tumor shrinkage, and yet another affected person with crizotinib-refractory disease taken care of immediately ganetespib monotherapy. (forgetmenotinitiative.org)
  • Atherosclerosis is a chronic vascular inflammatory disease associated to oxidative stress and endothelial dysfunction. (hindawi.com)
  • Atherosclerosis (AS), the main pathological process of arterial lesions, is the cause of the majority of cardiovascular and cerebrovascular diseases. (hindawi.com)
  • For presence of aneurysms, atherosclerosis, a familial preponderance and polycystic kidney disease are the main risk factors. (biomedcentral.com)
  • Nevertheless, strong correlations have been found between heart disease, atherosclerosis, hypertension, fibrosis, and regeneration efficiency with senescent cell burden and its proinflammatory sequelae. (oaepublish.com)
  • Cardiovascular disease (CVD), including heart failure, hypertension, atherosclerosis, and cardiomyopathy, remains the leading cause of death worldwide and carries a severe socioeconomic burden. (oaepublish.com)
  • Furthermore, it promotes vascular remodeling, including calcification and fibrosis, which in turn precedes the development of hypertension and accelerates the progression of other vascular-related diseases such as atherosclerosis or heart failure [ 7 ] . (oaepublish.com)
  • Recent developments in the treatment of HCC proved insufficient to cure unresectable disease and to substantially prevent HCC progression. (aging-us.com)
  • This has led to the development of a range of ERK1/2 inhibitors (ERKi) that either inhibit kinase catalytic activity (catERKi) or additionally prevent the activating pT-E-pY dual phosphorylation of ERK1/2 by MEK1/2 (dual-mechanism or dmERKi). (babraham.ac.uk)
  • We show that OGT inhibition augments effects of CDK9 inhibitors on CTD phosphorylation and general transcription. (ox.ac.uk)
  • HDAC inhibition resulted in a transcriptional and posttranscriptional regulation of the cyclin-dependent kinase inhibitors p21(Cip1) and p27(Kip). (cret-signal.com)
  • Fasudil (INN) is a potent Rho-kinase inhibitor and vasodilator. (wikipedia.org)
  • Kaithwas, Gaurav 2019-10-24 00:00:00 Background: This study evaluates the anti-cancer effects of Tadalafil (potent PDE-5 inhibitor) in female albino wistar rats against n-methyl n-nitrosourea induced mammary gland carcinogenesis. (sagepub.com)
  • We recently developed a specific and potent inhibitor targeting this enzyme, and here, we report a synthetic lethality screen using this compound. (ox.ac.uk)
  • ERK1/2 inhibitors act as monovalent degraders inducing ubiquitylation and proteasome-dependent turnover of ERK2, but not ERK1. (babraham.ac.uk)
  • Innate or acquired resistance to small molecule BRAF or MEK1/2 inhibitors (BRAFi or MEKi) typically arises through mechanisms that sustain or reinstate ERK1/2 activation. (babraham.ac.uk)
  • This may be relevant to the suggestion of kinase-independent effects of ERK1/2 and the therapeutic use of ERKi. (babraham.ac.uk)
  • These resistance mechanisms frequently involve reinstatement of ERK1/2 signalling and BRAFi are now deployed in combination with one of three approved MEK1/2 inhibitors (MEKi) to provide more durable, but still transient, clinical responses. (babraham.ac.uk)
  • Agonist (100 nM 8-OH-DPAT) (D) treatment of freely dividing HN2-5 cells caused stimulation of PKC (Physique 1a) [25,26,27,28,29], which was blocked by the 5-HT1A-R antagonist WAY100635 (WAY) (10 M) but not by an inhibitor of the ERK1/2 kinase MEK (U0126) (U) (10 M) (Physique 1a). (thetechnoant.info)
  • ROCK induces vasoconstriction by phosphorylating the myosin-binding subunit of myosin light chain (MLC) phosphatase, thus decreasing MLC phosphatase activity and enhancing vascular smooth muscle contraction. (wikipedia.org)
  • Fasudil (HA-1077) is a selective RhoA/Rho kinase (ROCK) inhibitor. (wikipedia.org)
  • other specificity is tiny gene activity and distribution browser through the kinase of the R-RasGAP complex ileal to suitable or through the functionality of RhoA. (evakoch.com)
  • typically, reticulum of deaminase by kinase extends the download of primary transporters by docking the brain of RhoA. (evakoch.com)
  • Cardiovascular (CV) risk factors such as hypercholesterolemia, hyperglycaemia, obesity, hypertension, smoking, and aging promote vascular inflammation and endothelial activation [ 7 - 9 ]. (hindawi.com)
  • Over 500 products have been investigated for neuroprotective effects including those from the categories of free radical scavengers, anti-excitotoxic agents, apoptosis (programmed cell death) inhibitors, anti-inflammatory agents, neurotrophic factors, metal ion chelators, ion channel modulators, and gene therapy. (researchandmarkets.com)
  • Inhibition of O-GlcNAc Transferase Renders Prostate Cancer Cells Dependent on CDK9. (ox.ac.uk)
  • We report a novel synthetic lethal interaction between inhibitors of OGT and CDK9 that specifically kills prostate cancer cells, but not normal cells. (ox.ac.uk)
  • Regardless of this, the capacity of miR-92a to target various downstream effectors might be an advantage of miRNA-based therapeutic strategies and may overcome the limited therapeutic capacity of single growth factor or single gene therapies in ischemic diseases, since the highly organized process of vessel growth, maturation and functional maintenance is well known to require the fine-tuned regulation of a set of genes. (uni-frankfurt.de)
  • Endothelial nitric oxide synthase (eNOS) mediates the production of the vasodilator nitric oxide (NO). Pulmonary arterial cell cultures treated with fasudil showed a significant increase in eNOS mRNA levels in a dose dependent manner, and the half-life of eNOS mRNA increased 2-folds. (wikipedia.org)
  • cyclin D1 mRNA expression and cyclin D1 promoter activity. (cret-signal.com)
  • In addition to ROCK inhibition, fasudil has also been demonstrated to directly modulate the aggregation of α-synuclein, both in vitro and in cellular models of neurodegenerative disease. (wikipedia.org)
  • Finally, we provide evidence that these observations are applicable in vivo by demonstrating that HDAC inhibition decreased neointima formation and expression of cyclin D1 in a murine model of vascular injury. (cret-signal.com)
  • ERKi treatment of cells drives the poly-ubiquitylation and proteasome-dependent turnover of ERK2 and pharmacological or genetic inhibition of Cullin-RING E3 ligases prevents this. (babraham.ac.uk)
  • Our screen identified pan-cyclin-dependent kinase (CDK) inhibitor AT7519 as lethal in combination with OGT inhibition. (ox.ac.uk)
  • In this review, we will discuss the role of NAD + depletion in instigating SASP and its downstream signaling and regulatory mechanisms that lead to the premature onset of atherosclerotic cardiovascular diseases in cancer survivors. (oaepublish.com)
  • The TSEN placement Typically triggers 5' and 3' to the home', proliferating a downstream' vascular maturation on the 5' T and a 5' receptor nucleus on the 3' mitosis. (evakoch.com)
  • Pathomechanisms of diseases are described with steps at which neuroprotective therapies are directed. (researchandmarkets.com)
  • Breast cancer is the most common malignancy affecting women and there remains a need for effective adjuvant therapies for this disease, for which plant sterols may play a distinctive role. (mdpi.com)
  • Two generation myocardiocytes, ERCC5( XPG) and the extracellularspace of ERCC1 and ERCC4( XPF), have associated to the free favour subunit to appear the library planning that will migrate the caspase-dependent gamma from the small opening growth( Dunand-Sauthier et al. (evakoch.com)
  • The extract of Alisma orientale exerted a protective effect on nonalcoholic fatty liver disease and palmitate-induced cellular injury [ 21 , 22 ], suggesting that it could be a potential treatment for abnormal lipid metabolism syndrome. (hindawi.com)
  • Thus, MRs comprise typically a small number of TF-encoding genes (and their products) that control a disproportionate level of gene expression, giving rise to distinct molecular phenotypes associated with a particular disease. (aging-us.com)
  • Periodontitis is a complex inflammatory disease characterized by progressive destruction of the surrounding connective tissue and supporting alveolar bone of the teeth [ 1 ]. (biomedcentral.com)
  • A detailed history was reviewed for all patients in addition to a complete physical examination and assessment of the 28-joint disease activity score (DAS28). (bvsalud.org)
  • However, this activity is regulated in an androgen receptor (AR) dependent manner. (biomedcentral.com)
  • It has also been demonstrated that TGF-β induced cell cycle arrest can be partially attributed to the regulatory effects of TGF-β on both the expression and activity of cyclin-dependent kinase inhibitors [CDKI] such as p21 and p27. (biomedcentral.com)
  • Crizotinib and foretinib showed effective antitumour activity in LMS through TYRO3 and AXL deactivation indicating that clinical trials using TYRO3 and AXL inhibitors are warranted in advanced LMS. (nature.com)
  • ROCK is an enzyme that plays an important role in mediating vasoconstriction and vascular remodeling in the pathogenesis of pulmonary hypertension. (wikipedia.org)
  • As a result three different BRAF inhibitors (BRAFi) have now been approved for BRAFV600E/K- mutant melanoma and have transformed the treatment of this disease. (babraham.ac.uk)
  • Virk-Baker et al 2010) For example the combination of a natural VEGF inhibitor along with lower doses of a pharmacological agent may prove helpful in reducing the unwanted side effects of chemotherapy. (compassionateacupuncture.com)
  • Controlling these factors reduces the risk of acute vascular complications and death from CVD [ 1 , 7 ]. (hindawi.com)
  • This report describes the role of neuroprotection in acute disorders such as stroke and injuries of the nervous system as well as in chronic diseases such as neurodegenerative disorders because many of the underlying mechanisms of damage to neural tissues are similar in all these conditions and several products are used in more than one disorder. (researchandmarkets.com)
  • 3) We are defining the properties of cancer stem cells that initiate and sustain the unique disease features of acute leukemias through the use of various adoptive animal models. (stanford.edu)
  • The BVD EZR is usually caused by bovine viral diarrhea computer virus (BVDV) which belongs to Pestivirus genus within the family of Flaviviridae.1 The BVDV is capable of producing a broad range of clinical indicators, ranging from most often asymptomatic infection to severe acute disease with indicators from your enteric, reproductive or respiratory organs. (thetechnoant.info)
  • These similarities point towards the possibility that both diseases have common underlying pathogenic mechanisms, modulated by shared genetic susceptibility loci. (biomedcentral.com)
  • Currently, multiple LSD1 inhibitors are undergoing clinical trials and demonstrate considerable potential in the field of cancer treatment [ 12 ]. (biomedcentral.com)
  • Despite the strong link between aging and CVD, surprisingly few studies have directly investigated heart failure and vascular dysfunction in aged models and subjects. (oaepublish.com)
  • During development, the blood vascular system arises from endothelial cell progenitors that differentiate from mesodermal cells, mostly through the expression of the transcription factor (TF) ETV2. (nature.com)
  • Numerous studies have revealed the critical role of premature senescence induced by various cancer treatment modalities in the pathogenesis of aging-related diseases. (oaepublish.com)
  • However, lowering LDL levels is a common clinical practice to reduce oxidation and the risk of major events in patients with cardiovascular diseases (CVD). (hindawi.com)
  • Cardiovascular diseases (CVD) are the leading cause of mortality in the Western population [ 1 ]. (hindawi.com)
  • Woolsey Pharmaceuticals is developing BRAVYL (oral fasudil) for various neurodegenerative diseases. (wikipedia.org)
  • Aggregation of α-synuclein is a major hallmark of Parkinson's disease, and has also been observed in other neurodegenerative diseases. (wikipedia.org)
  • The incidence of target organ damage associated to CVD increases with age, and gender studies show global higher incidence in men for stroke and coronary artery disease (CAD) [ 10 ]. (hindawi.com)
  • Breast cancer is a heterogeneous disease associated with diverse biological behaviours and clinical outcome. (biomedcentral.com)
  • This study aimed to identify the role of AA in oxidized low-density lipoprotein (ox-LDL)-induced vascular smooth muscle cell (VSMC) behaviours and to explore the effects of microRNAs (miRNAs). (hindawi.com)
  • miR-128-5p targets the tissue inhibitor of metalloproteinases (TIMPs), silent information regulator 2 (SIRT2), peroxisome proliferator-activated receptor (PPAR), and p21 genes, which are linked to the behaviours of VSMCs. (hindawi.com)
  • In this review, we focus on early stages of the disease and we address both biomarkers and therapeutic approaches currently available and under research. (hindawi.com)
  • Therefore, identification and functional characterization of MRs is critical to understand associated disease processes and design effective therapeutic options [ 5 ]. (aging-us.com)
  • This information should help in the development of appropriate study models and improve therapeutic approaches to prevent disease recurrence. (biomedcentral.com)
  • After adjusting for the other major risk factors for CVD, one study found the odds of vascular diseases increased with every decade of life, demonstrating a strong increase in peripheral arterial disease (PAD), carotid artery stenosis, and abdominal aortic aneurysm (AAA) with advanced age [ 4 ] . (oaepublish.com)
  • The relevance of this miR-92a target is evidenced by severe vascular defects in the absence of Integrin a5. (uni-frankfurt.de)
  • 400 IU/ml was associated with more severe disease. (spandidos-publications.com)
  • Throughout Oct '08, the FDA approved quetiapine XR monotherapy for the treatment severe depressive installments of bpd and also serious manic as well as put together assaults within the disease I disorder based on a couple of placebo-control tests. (pcna-signal.com)
  • Our findings demonstrate that acquisition of MEK inhibitor resistance often occurs through gene amplification and can be suppressed by impeding cell cycle entry in drug. (babraham.ac.uk)
  • A better understanding on the role of Jak/STAT pathways in osteoclast differentiation will not only strengthen our knowledge on osteoclast biology but also provide invaluable insights into the development of anti-resorptive strategies for treating bone-lytic diseases. (koreascience.kr)
  • As for AgP, it has been known for a long time that CHD is strongly influenced by genetic factors [ 6 ], but it was not until recently that genetic risk loci contributing to the development of the disease were identified. (biomedcentral.com)
  • Tadalafil is a known phosphodiesterase-5 Distinct metastasis and resistance development by self- (PDE-5) inhibitor, which have anti-cancer effects in vari- renewing nascent cancer cells in response with the ous types of cancer [2]. (sagepub.com)
  • The cumulative cardiovascular disease (CVD) incidence of those who survived more than 10 years and reached age over 18 years was 45.5% relative to 15.7% of the age- and sex-matched controls. (oaepublish.com)
  • In addition, the incidence of metabolic diseases such as diabetes also increases significantly with age and contributes greatly to CVD morbidities and mortalities [ 8 ] . (oaepublish.com)
  • Activation of the VEGFA/VEGFR2 signaling and expression of blood vascular endothelial cell (BEC) markers, such as NRP1 and EphrinB2, further differentiate these precursor cells into BECs, which then form the hierarchical network of blood vessels 4 . (nature.com)
  • This was associated with CaMKII activation and was blocked by the CaMKII inhibitor KN-93 (and were approved by the Institutional Animal Care and Use Committee of the Rosalind Franklin University of Medicine and Science. (bakingandbakingscience.com)
  • Indeed, it is now possible to identify various changes in biological components due to disease states directly on tissue as well as to analyze the effect of treated drugs. (koreascience.kr)