miR-489-3p inhibits TLR4/NF-κB signaling to prevent inflammation in psoriasis

xlomafota13 shared this article with you from Inoreader miR-489-3p inhibits TLR4/NF-κB signaling to prevent inflammation in psoriasis Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):744. doi: 10.3892/etm.2021.10176. Epub 2021 May 11. ABSTRACT Psoriasis is a chronic inflammatory skin disease whose etiology has not yet been determined. MicroRNAs (miRs) regulate the early stages of psoriasis and are targets for therapeutic intervention. The present study aimed to investigate the functional role of miR-489-3p in psoriasis. The present study first assessed the expression levels of miR-489-3p and Toll-like receptor (TLR)4 mRNA using reverse transcription-quantitative PCR, and also detected the protein expression levels of TLR4 and NF-κB via western blot analysis. TargetScan and miRDB target gene prediction tools were used to confirm the regulation of Toll-like receptor (TLR)4 by miR-489-3p. Moreover, a Cell Counting Kit (CCK)-8 assay was conducted to evaluate cell viability, while cell cycle and colony formation assays were performed to evaluate cell proliferation. Human keratinocytes (HaCa T) were co-transfected with TLR4-small interfering RNA and miR-489-3p-inhibitor plasmids, and analysis of cell proliferation and inflammatory cytokine secretion was performed using CCK-8 assay and ELISA. It was found that miR-489-3p expression was downregulated in patients with psoriasis. Bioinformatics analysis identified that TLR4 was a direct target of miR-489-3p. This was confirmed via luciferase reporter assays in HaCaT cells. The overexpression of miR-489-3p inhibited the TLR4/NF-κB signaling pathway and reduced cell proliferation. TLR4 silencing alleviated the effects of miR-489-3p, and enhanced cell proliferation and inflammatory cytokine secretion. Taken together, these data suggested that miR-489-3p may be a key effector of psoriasis, which promotes inflammatory responses by direct targeting of TLR4. miR-489-3p therefore represents a promising prognostic biomarker and therapeutic target for psoriasis treatment. PMID:34055060 | PMC:PMC8138277 | DOI:10.3892/etm.2021.10176 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Curcumin ameliorates ischemic stroke injury in rats by protecting the integrity of the blood-brain barrier

xlomafota13 shared this article with you from Inoreader Curcumin ameliorates ischemic stroke injury in rats by protecting the integrity of the blood-brain barrier Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):783. doi: 10.3892/etm.2021.10215. Epub 2021 May 19. ABSTRACT The blood-brain barrier (BBB) is critical for proper cerebral homeostasis and its dysfunction during ischemic stroke can result in significant neurological injury. The major goal of the present study was to identify whether curcumin pretreatment possessed protective effects on BBB integrity during the 24 h of acute ischemic brain injury. To investigate the protective effects of curcumin, male Sprague-Dawley rats were divided into multiple groups, including sham, middle cerebral artery occlusion/reperfusion (MCAO/R) vehicle and curcumin pretreated MCAO/R groups. The effects of curcumin were measured by analyzing neurological deficits, infarct size, BBB permeability and expression levels of permeability-related proteins in the brain. It was found that curcumin pretreatment significantly improved neurological scores, decreased infarct size, and prote cted synaptic remodeling of hippocampal neurons and upregulated the protein expression level of tight junction proteins, ZO-1, occludin and claudin-5 in ischemic rat brains. Furthermore, curcumin pretreatment before stroke was shown to downregulate the phosphorylation of NF-κB and MMP-9, which are central mediators of inflammation. The results from the present study indicated that curcumin pretreatment ameliorated ischemic stroke injury by protecting BBB integrity and synaptic remodeling, as well as inhibiting inflammatory responses. PMID:34055082 | PMC:PMC8145684 | DOI:10.3892/etm.2021.10215 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Magnetic resonance imaging in schizophrenia: Luxury or necessity? (Review)

xlomafota13 shared this article with you from Inoreader Magnetic resonance imaging in schizophrenia: Luxury or necessity? (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):765. doi: 10.3892/etm.2021.10197. Epub 2021 May 14. ABSTRACT Schizophrenia, one of the most common psychiatric disorders, with a worldwide annual incidence rate of approximately 0.3-0.7%, known to affect the population below 25 years of age, is persistent throughout lifetime and includes people from all layers of society. With recent technological progress that allows better imaging techniques, such as the ones provided by computed tomography and particularly magnetic resonance imaging (MRI), research on schizophrenia imaging has grown considerably. The purpose of this review is to establish the importance of using imaging techniques in the early detection of brain abnormalities in patients diagnosed with schizophrenia. We reviewed all articles which reported on MRI imaging in schizophrenia. In order to do this, we used the PubMed database, using as search words 'MRI' and 'schizophrenia'. MRI studies of fir st episode patients and chronic patients, suggest reduction of the whole brain volume. Enlargement of lateral ventricles was described as positive in 15 studies out of 19 and was similar to findings in chronic patients. Moreover, for the first episode patients, all data collected point to important changes in medial temporal lobe structures, diminished hippocampal volume, the whole frontal lobe, asymmetry in prefrontal cortex, diminished volume in cingulate, corpus callosum, and cavum septum pellucidum reported abnormalities. MRI is recommended as an important tool in the follow-up process of patients with schizophrenia. Yet, it is still under debate whether the abnormalities described in this condition are able to be used as diagnostic biomarkers. PMID:34055064 | PMC:PMC8145262 | DOI:10.3892/etm.2021.10197 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Bioinformatics identification of hub genes and signaling pathways regulated by intravenous immunoglobulin treatment in acute Kawasaki disease

xlomafota13 shared this article with you from Inoreader Bioinformatics identification of hub genes and signaling pathways regulated by intravenous immunoglobulin treatment in acute Kawasaki disease Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):784. doi: 10.3892/etm.2021.10216. Epub 2021 May 19. ABSTRACT Kawasaki disease (KD) is an acute, self-limiting form of vasculitis commonly encountered in infants and young children. Intravenous immunoglobulin (IVIG) is the primary drug used for the treatment of KD, which may significantly reduce the occurrence of coronary artery lesions. However, the specific molecular profile changes of KD caused by IVIG treatment have remained elusive and require further research. The present study was designed to identify key genes, pathways and immune cells affected by IVIG treatment using multiple bioinformatics analysis methods. The results suggested that myeloid cells and neutrophils were affected by IVIG treatment. Kyoto Encyclopedia of Genes and Genomes pathway analysis identified that hematopoietic cell lineages and osteoclast differentiation may have an important role in the mechanism of action of IVIG treatment. Immune cell analysis indicated that the levels of monocytes, M1 macrophages, neutrophils and platelets were markedly changed in patients with KD after vs. prior to IVIG treatment. The key upregulated genes, including ZW10 interacting kinetochore protein, GINS complex subunit 1 and microRNA-30b-3p in whole blood cells of patients with KD following treatment with IVIG indicated that these IVIG-targeted molecules may have important roles in KD. In addition, these genes were further examined by literature review and indicated to be involved in cell proliferation, apoptosis and virus-related immune response in patients with KD. Therefore, the present results may provide novel insight into the mechanisms of action of IVIG treatment for KD. PMID:34055083 | PMC:PMC8145699 | DOI:10.3892/etm.2021.10216 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cascades between miRNAs, lncRNAs and the NF-κB signaling pathway in gastric cancer (Review)

xlomafota13 shared this article with you from Inoreader Cascades between miRNAs, lncRNAs and the NF-κB signaling pathway in gastric cancer (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):769. doi: 10.3892/etm.2021.10201. Epub 2021 May 17. ABSTRACT Gastric cancer is a common digestive tract malignancy that is mainly treated with surgery combined with perioperative adjuvant chemoradiotherapy and biological targeted therapy. However, the diagnosis rate of early gastric cancer is low and both postoperative recurrence and distant metastasis are thorny problems. Therefore, it is essential to study the pathogenesis of gastric cancer and search for more effective means of treatment. The nuclear factor-κB (NF-κB) signaling pathway has an important role in the occurrence and development of gastric cancer and recent studies have revealed that microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are able to regulate this pathway through a variety of mechanisms. Understanding these interrelated molecular mechanisms is helpful in guiding improvements in gastric cancer treatment. In the present review, the functional associations between miRNAs, lncRNAs and the NF-κB signaling pathway in the occurrence, development and prognosis of gastric cancer were discussed. It was concluded that miRNAs and lncRNAs have complex relations with the NF-κB signaling pathway in gastric cancer. miRNAs/target genes/NF-κB/target proteins, signaling molecules/NF-κB/miRNAs/target genes, lncRNAs/miRNAs/NF-κB/genes or mRNAs, lncRNAs/target genes/NF-Κb/target proteins, and lncRNAs/NF-κB/target proteins cascades are all important factors in the occurrence and development of gastric cancer. PMID:34055068 | PMC:PMC8145527 | DOI:10.3892/etm.2021.10201 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Etomidate attenuates hyperoxia-induced acute lung injury in mice by modulating the Nrf2/HO-1 signaling pathway

xlomafota13 shared this article with you from Inoreader Etomidate attenuates hyperoxia-induced acute lung injury in mice by modulating the Nrf2/HO-1 signaling pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):785. doi: 10.3892/etm.2021.10217. Epub 2021 May 19. ABSTRACT The present study aimed to investigate the protective effects of etomidate on hyperoxia-induced acute lung injury in mice, particularly on the nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway. Fifty specific pathogen-free mice were randomly divided into the blank control, model, high oxygen exposure + low etomidate dose (0.3 mg·kg-1), a high oxygen exposure + moderate etomidate dose (3 mg·kg-1), and a high oxygen exposure + high etomidate dose (10 mg·kg-1) groups, with ten mice allotted per group. After 72 h, the mice were sacrificed and the lung tissues were harvested, and the wet-to-dry (W/D) ratio of the tissues was calculated. Hematoxylin-eosin staining was performed to observe the pathological changes in the lung tissues, and the lung injury score (LIS) was calculated. The mRNA and protein expression levels of Nrf2 and HO-1 were measured. The malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD) and catalase (CAT) levels were also measured, and interleukin (IL)-1β, IL-6, tumor necrosis factor alpha (TNF-α) and IL-10 concentrations in the bronchoalveolar lavage fluid were determined. At low and moderate doses, etomidate decreased pathological damage in the lung tissue, decreased the LIS and W/D ratio, upregulated Nrf2 and HO-1 mRNA and protein expression, decreased IL-1β, IL-6, and TNF-α concentrations, increased MPO activity and IL-10 levels, suppressed the production of the oxidation product MDA, and enhanced the activities of the antioxidant enzymes CAT and SOD. Within a certain dose range, etomidate enhanced antioxidant and anti-inflammatory effects in mice, thereby decreasing lung injury induced by the chronic inhalation of oxygen at high concentrations. Furthermore, the underlying mechanism may be associate with the upregul ation of the Nrf2/HO-1 signaling pathway. PMID:34055084 | PMC:PMC8145798 | DOI:10.3892/etm.2021.10217 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Inhibition of the Wnt/β-catenin signaling pathway reduces autophagy levels in complement treated podocytes

xlomafota13 shared this article with you from Inoreader Inhibition of the Wnt/β-catenin signaling pathway reduces autophagy levels in complement treated podocytes Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):737. doi: 10.3892/etm.2021.10169. Epub 2021 May 9. ABSTRACT In idiopathic membranous nephropathy, the complement membrane attack complex, more commonly referred to as complement 5b-9 (C5b-9), induces glomerular epithelial cell injury and proteinuria. C5b-9 can also activate numerous mechanisms that restrict or facilitate injury. Recent studies suggest that autophagy and the canonical Wnt signaling pathway serve an important role in repairing podocyte injury. However, the effect of C5b-9 on these pathways and the relationship between them remains unclear. The aim of the present study was to show the effect of C5b-9 on the Wnt/β-catenin signaling pathway and autophagy in podocytes in vitro. Levels of relevant indicators were detected by immunofluorescence staining and capillary western immunoassay. C5b-9 serum significantly activated the Wnt/β-catenin signaling pathway and promoted autophagy. Treatme nt with Dickkopf-related protein 1 (DKK1), a Wnt/β-catenin pathway blocker, protected podocytes from injury and significantly inhibited autophagy. The results indicated that inhibition of the Wnt/β-catenin pathway physiologically activated autophagy. The results indicated that C5b-9 resulted in a decrease in Akt in podocytes. However, the podocytes preincubated with DKK1 and then attacked by C5b-9 showed an increase in Akt levels. This may explain the observation that blocking the Wnt/β-catenin signaling pathway attenuated C5b-9 podocyte damage, while inhibiting autophagy. The results of the present study also suggest that regulation of these two pathways may serve as a novel method for the treatment of idiopathic membranous nephropathy. PMID:34055054 | PMC:PMC8138266 | DOI:10.3892/etm.2021.10169 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.