Search results for "Down-Regulation"
showing 10 items of 310 documents
1-ethyl-3-(6-methylphenanthridine-8-il) urea modulates TLR3/9 activation and induces selective pro-inflammatory cytokine expression in vitro.
2017
We have previously demonstrated the nucleic acid binding capacity of phenanthridine derivatives (PHTs). Because nucleic acids are potent inducers of innate immune response through Toll-like receptors (TLRs), and because PTHs bear a structural resemblance to commonly used synthetic ligands for TLR7/8, we hypothesized that PHTs could modulate/activate immune response. We found that compound M199 induces secretion of IL-6, IL-8 and TNFα in human PBMCs and inhibits TLR3/9 activation in different cellular systems (PBMCs, HEK293 and THP-1 cell lines).
Curcumin downregulates expression of opioid-related nociceptin receptor gene (OPRL1) in isolated neuroglia cells.
2018
Abstract Background: Curcumin (CC) exerts polyvalent pharmacological actions and multi-target effects, including pain relief and anti-nociceptive activity. In combination with Boswellia serrata extract (BS), curcumin shows greater efficacy in knee osteoarthritis management, presumably due to synergistic interaction of the ingredients. Aim: To elucidate the molecular mechanisms underlying the analgesic activity of curcumin and its synergistic interaction with BS. Methods: We performed gene expression profiling by transcriptome-wide mRNA sequencing in human T98G neuroglia cells treated with CC (Curamed), BS, and the combination of CC and BS (CC-BS; Curamin), followed by interactive pathways a…
Bumetanide prevents brain trauma-induced depressive-like behavior
2019
AbstractBrain trauma triggers a cascade of deleterious events leading to enhanced incidence of drug resistant epilepsies, depression and cognitive dysfunctions. The underlying mechanisms leading to these alterations are poorly understood and treatment that attenuates those sequels not available. Using controlled-cortical impact (CCI) as experimental model of brain trauma in adult mouse we found a strong suppressive effect of the sodium-potassium-chloride importer (NKCC1) specific antagonist bumetanide on appearance of depression-like behavior. We demonstrate that this alteration in behavior is associated with a block of CCI-induced decrease in parvalbumin-positive interneurons and impairmen…
Identification of novel drug resistance mechanisms by genomic and transcriptomic profiling of glioblastoma cells with mutation-activated EGFR.
2021
Abstract Aims Epidermal growth factor receptor (EGFR) is not only involved in carcinogenesis, but also in chemoresistance. We characterized U87.MGΔEGFR glioblastoma cells with constitutively active EGFR due to deletion at the ligand binding domain in terms of gene expression profiling and chromosomal aberrations. Wild-type U87.MG cells served as control. Materials and methods RNA sequencing and network analyses (Ingenuity Pathway Analysis) were performed to identify novel drug resistance mechanisms related to expression of mutation activated EGFR. Chromosomal aberrations were characterized by multicolor fluorescence in situ hybridization (mFISH) and array comparative genomic hybridization (…
Molecular mechanisms underlying the neuroprotective role of atrial natriuretic peptide in experimental acute ischemic stroke
2018
Abstract Along with its role in regulating blood pressure and fluid homeostasis, the natriuretic peptide system could be also part of an endogenous protective mechanism against brain damage. We aimed to assess the possibility that exogenous atrial natriuretic peptide (ANP) could protect against acute ischemic stroke, as well as the molecular mechanisms involved. Three groups of rats subjected to transient middle cerebral artery occlusion (tMCAO, intraluminal filament technique, 60 min) received intracerebroventricular vehicle, low-dose ANP (0.5 nmol) or high-dose ANP (2.5 nmol), at 30 min reperfusion. Neurofunctional condition, and brain infarct and edema volumes were measured at 24 h after…
NEGR1 and FGFR2 cooperatively regulate cortical development and core behaviours related to autism disorders in mice.
2018
See Contreras and Hippenmeyer (doi:10.1093/brain/awy218) for a scientific commentary on this article. Autism spectrum disorders (ASDs) are complex conditions with diverse aetiologies. Szczurkowska et al. demonstrate that two ASD-related molecules – FGFR2 and Negr1 – physically interact to act on the same downstream pathway, and regulate cortical development and ASD-relevant behaviours in mice. Identifying common mechanisms in ASDs may reveal targets for pharmacological intervention.
Unusual roles of caspase-8 in triple-negative breast cancer cell line MDA-MB-231
2015
Triple-negative breast cancer (TNBC) is a clinically aggressive form of breast cancer that is unresponsive to endocrine agents or trastuzumab. TNBC accounts for ~10-20% of all breast cancer cases and represents the form with the poorest prognosis. Patients with TNBC are at higher risk of early recurrence, mainly in the lungs, brain and soft tissue, therefore, there is an urgent need for new therapies. The present study was carried out in MDA-MB-231 cells, where we assessed the role of caspase-8 (casp-8), a critical effector of death receptors, also involved in non‑apoptotic functions. Analysis of casp-8 mRNA and protein levels indicated that they were up-regulated with respect to the normal…
NUPR1, a new target in liver cancer: implication in controlling cell growth, migration, invasion and sorafenib resistance
2016
AbstractSorafenib, an oral multikinase inhibitor, is the only approved agent for the treatment of advanced hepatocellular carcinoma (HCC). However, its benefits are modest, and as its mechanisms of action remain elusive, a better understanding of its anticancer effects is needed. Based on our previous study results, we investigated here the implication of the nuclear protein 1 (NUPR1) in HCC and its role in sorafenib treatment. NUPR1 is a stress-inducible protein that is overexpressed in various malignancies, but its role in HCC is not yet fully understood. We found that NUPR1 expression was significantly higher in primary human HCC samples than in the normal liver. Knockdown of NUPR1 signi…
Urinary- and Plasma-Derived Exosomes Reveal a Distinct MicroRNA Signature Associated With Albuminuria in Hypertension.
2021
Urinary albumin excretion (UAE) is a marker of cardiovascular risk and renal damage in hypertension. MicroRNAs (miRNAs) packaged into exosomes function as paracrine effectors in cell communication and the kidney is not exempt. This study aimed to state an exosomal miRNA profile/signature associated to hypertension with increased UAE and the impact of profibrotic TGF-β1 (transforming growth factor β1) on exosomes miRNA release. Therefore, exosomes samples from patients with hypertension with/without UAE were isolated and characterized. Three individual and unique small RNA libraries from each subject were prepared (total plasma, urinary, and plasma-derived exosomes) for next-generation sequ…
Targeting aurora kinase B alleviates spinal microgliosis and neuropathic pain in a rat model of peripheral nerve injury.
2019
Peripheral nerve injury elicits spinal microgliosis, contributing to neuropathic pain. The aurora kinases A (AURKA), B (AURKB), and C (AURKC) are potential therapeutic targets in proliferating cells. However, their role has not been clarified in microglia. The aim of this study was to examine the regulation of aurora kinases and their roles and druggability in spinal microgliosis and neuropathic pain. Sprague-Dawley rats received chronic constriction injury (CCI). Gene expression of aurora kinases A-C was evaluated by quantitative RT-PCR and western blot, respectively, in spinal cords at 1, 3, 7, and 14 days after CCI. AURKB gene and protein expression was up-regulated concomitantly with th…