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Recent announcements indicated, without sharing any distinct published set of results, that the corticosteroid dexamethasone may reduce mortality of severe COVID-19 patients only. The recent Coronavirus [severe acute respiratory syndrome (SARS)-CoV-2]-associated multiorgan disease, called COVID-19, has high morbidity and mortality due to autoimmune destruction of the lungs stemming from the release of a storm of pro-inflammatory cytokines. Defense against this Corona virus requires activated T cells and specific antibodies. Instead, cytokines are responsible for the serious sequelae of COVID-19 that damage the lungs. Dexamethasone is a synthetic corticosteroid approved by the FDA 1958 as a broad-spectrum immunosuppressor and it is about 30 times as active and with longer duration of action (2-3 days) than cortisone. Dexamethasone would limit the production of and damaging effect of the cytokines, but will also inhibit the protective function of T cells and block B cells from making antibodies, potentially leading to increased plasma viral load that will persist after a patient survives SARS. Moreover, dexamethasone would block macrophages from clearing secondary, nosocomial, infections. Hence, dexamethasone may be useful for the short-term in severe, intubated, COVID-19 patients, but could be outright dangerous during recovery since the virus will not only persist, but the body will be prevented from generating protective antibodies. Instead, a pulse of intravenous dexamethasone may be followed by administration of nebulized triamcinolone (6 times as active as cortisone) to concentrate in the lungs only. These corticosteroids could be given together with the natural flavonoid luteolin because of its antiviral and anti-inflammatory properties, especially its ability to inhibit mast cells, which are the main source of cytokines in the lungs. At the end, we should remember that "The good physician treats the disease; the great physician treats the patient who has the disease" [Sir William Osler's (1849-1919)].
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Idiopathic facial palsy is the most common disease of the VII cranial nerve. There are many treatments to facilitate recovery from this condition: pharmacological, surgical, rehabilitative, but the effectiveness of some of these treatments, especially the latter, is still under discussion. The purpose of this umbrella review of systematic reviews is to analyse the literature in order to investigate the different rehabilitation interventions in patients suffering from idiopathic facial palsy. A scientific literature search was carried out from January 2009 until August 2019, using Mesh the terms "facial palsy", "Bell's Palsy", "idiopathic facial nerve palsy", combined with "rehabilitation" and "therapy". Initially all the systematic reviews and meta-analyses of the last 10 years concerning rehabilitation treatments for the recovery of injured functions in facial palsy were included. Given the heterogeneity of the studies in the literature, which do not differentiate the different causes of facial palsy, all the causes of idiopathic facial palsy were included in the review. The research resulted in 94 published systematic reviews but only 6 were considered in respect to the inclusion criteria. All studies agree on the lack of high-quality scientific work to be able to say that Bell's physiotherapy treatments for facial palsy are effective, in particular with regard to recovery times during the rehabilitation process. Future studies are needed, in order to highlight the therapeutic implications of the different rehabilitation methods, with standardized protocols, in patients suffering from facial palsy of different aetiology.
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This study aimed to investigate the expression and biological functions of TRAF5 in colon cancer at tissue and cellular levels. Forty-two patients with colon cancer were included in the present study. Tumor tissues and tumor-adjacent tissues were collected from all patients. Bioinformatics was used to analyze how TRAF5 was related to metastasis and prognosis of colon cancer. Quantitative real-time polymerase chain reaction was carried out to determine the expression of mRNA. SW620 and SW480 cells were used to study the inhibition and overexpression of TRAF5, respectively. CCK-8 assay was used to examine cell proliferation. Flow cytometry was employed to investigate cell phase and apoptosis. Transwell assay was used to study migration and invasion of cells. Western blotting was utilized to test how TRAF5 expression affected the activities of PI3K/AKT/NF-κB signaling pathways. Bioinformatics showed that the expression of TRAF5 in colon cancer tissues was correlated with metastasis and prognosis of the tumor. TRAF5 mRNA expression was up-regulated in colon cancer tissues, and related to recurrence and metastasis of the cancer. In vitro experiments showed that TRAF5 expression promoted proliferation, migration, and invasion of colon cancer cells, but reduced apoptosis of the cells. Moreover, TRAF5 might exert its biological functions by activating PI3K/AKT/NF-κB signaling pathways in colon cancer cells. In conclusion, TRAF5 expression in colon cancer tissues is up-regulated and correlated with prognosis, lymphatic metastasis and clinical staging. TRAF5 promotes the occurrence and development of colon cancer by activating PI3K/ AKT/NF-κB signaling pathways, and acts as an oncogene.
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To uncover the potential influence of microRNA-589 (miRNA-589) on cerebral ischemia-reperfusion injury (IRI) and the underlying mechanism, BV2 cells were stimulated by lipopolysaccharide (LPS) or conditioned medium (CM) of primary cortical neurons undergoing oxygen-glucose deprivation (OGD). Regulatory effects of miRNA-589 on the release of inflammatory factors in BV2 cells induced with LPS or CM of primary cortical neurons undergoing OGD were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). The interaction between miRNA-589 and TRAF6 was finally assessed by dual-luciferase reporter gene assay. MiRNA-589 was downregulated in BV2 cells induced with LPS or CM of primary cortical neurons undergoing OGD. Overexpression of miRNA-589 reduced the release of inflammatory factors in LPS or CM-induced BV2 cells. TRAF6 was verified to be the downstream gene of miRNA-589, and its level was negatively regulated by miRNA-589. MiRNA-589 is downregulated following cerebral IRI and alleviates inflammatory response through negatively regulating TRAF6.
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The aim of this work was to study the effects of micro ribonucleic acid (miR)-20a on acute kidney injury (AKI) in sepsis rats and its key molecular mechanism. Sprague-Dawley rats were randomly divided into healthy rat group (H group, n=3), sham group (S group, n=3), sepsis rat group (D group, n=3), sepsis rat + negative control transfection group (N group, n=3) and sepsis rat + miR-20a inhibitor transfection group (M group, n=3). At 6 h, 12 h and 24 h, serum creatinine (Scr) and blood urea nitrogen (BUN) were detected, the changes in miR-20a expression in kidney tissues were determined via reverse transcription-polymerase chain reaction (RT-PCR), the expression of autophagy marker protein microtubule-associated protein 1 light chain 3 (LC3) was measured via Western blotting, and the inflammatory cell infiltration in kidney tissues was detected using hematoxylin-eosin (HE) staining. There was no obvious change in each index in S group compared with H group. D group, N group and M group had higher levels of Scr, BUN and LC3 in kidney tissues than S group. The levels of Scr, BUN and LC3 in kidney tissues were lower in M group than those in N group. MiR-20a may cause AKI in sepsis rats via activating autophagy.
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It has been reported that micro ribonucleic acid (miR)-424 is an important molecule in cerebral ischemia. However, the precise mechanism of action and biological effects of miR-424 remain to be further explored. miR-424 mimic and miR-424 inhibitor were injected via the caudal vein in rats, and the effect of miR-424 expression on brain tissue damage induced by middle cerebral artery occlusion (MCAO) was detected. The miR-424 mimic-induced changes in genomic levels were detected via the gene chip assay, and the signaling pathways regulated by miR-424 and its potential targets were explored combined with target prediction. Then the effect of miR-424 mimic on apoptosis of PC12 cells induced by oxygen-glucose deprivation (OGD) was determined using Annexin V/PI assay. Finally, drosophila mothers against decapentaplegic protein 7 (Smad7) was overexpressed to further verify the mechanism of action of miR-424 mimic. Compared with that in the sham group, the expression of miR-424 in brain tissues significantly declined in the model group. The results of 2,3,5-triphenyltetrazolium chloride (TTC) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay revealed that the miR-424 mimic obviously reduced the cerebral infarction area and apoptosis level of brain tissues, while the miR-424 inhibitor obviously increased the cerebral infarction area and apoptosis level of brain tissues. It was found, using bioinformatics and KEGG enrichment analysis, that differentially expressed genes induced by miR-424 were significantly enriched in the transforming growth factor-β (TGF-β) signaling pathway. According to the results of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting, the miR-424 mimic could evidently lower the expression of Smad7, thus activating the TGF-β1/Smad3 signaling pathway. Overexpression of Smad7 could weaken the protective effect of miR-424 mimic on ischemic-hypoxic cells. Increasing the expression of miR-424 can inhibit Smad7 to activate the TGF-β1/Smad3 signaling pathway, thereby exerting a protective effect against the brain tissue damage induced by MCAO.
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The aim of this study was to investigate the differential expression of micro ribonucleic acid (miR)- 125b in acute myocardial infarction (AMI) cases, and to explore the mechanism by which it affects cardiac function. Sprague-Dawley rats were used for AMI modeling, and the expression of miR-125b in the myocardial tissues of AMI rats was detected via fluorescence quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Thereafter, the target genes of miR-125b were collected and uploaded to WenGestalt for gene ontology (GO) and pathway enrichment analyses. In-vitro experiments were then applied to determine the p38-sirtuin 1 (Sirt1)-p53 expression change and cardiomyocyte apoptosis under down-regulation of miR-125b. Next, the interaction between miR-125b and its target genes was verified by luciferase reporter gene assay. The expression of miR-125b in the cardiac tissues was decreased in theAMI group compared with that in the Sham group (p< 0.05). The luciferase reporter gene assay confirmed that p38 was the target gene of miR-125b. Furthermore, the down-regulated expression of miR-125b in H9C2 cells up-regulated the protein expressions of p38 and phosphorylated p38, thus activating the Sirt1-p53 signaling pathway. Moreover, the down-regulation of miR-125b expression in H9C2 cells gave rise to the elevated apoptosis rate, and the down-regulated expression of miR-125b induced cardiomyocyte apoptosis through activating the p38-Sirt1-p53 signaling pathway.
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Melanoma, which originates from the transformation of normal melanocytes, is one of the three main types of skin cancer. We aimed to explore the functions of SNHG16 and miR-132 in melanoma. CCK-8, Transwell assays were used to measure the viability and migration, respectively. Spearman's correlation analysis was performed to analyze the relationship between the expression of SNHG16, miR-132 and LAPTM4B in melanoma tissues. SNHG16 was overexpressed, and miR-132 was low expressed in melanoma tissues and cell lines. Moreover, overexpression of SNHG16 was associated with poor prognosis of melanoma patients. The expression of SNHG16 had a negative connection with the expression of miR-132, and it had a positive relationship with the expression of LAPTM4B in melanoma tissues. Knockdown of SNHG16 or overexpression of miR-132 inhibited SK-MEL-2 cell proliferation and migration. In addition, we confirmed that SNHG16 directly binding to miR-132 promotes the expression of LAPTM4B, facilitating the tumorigenesis of melanoma. SNHG16 promotes the expression of LAPTM4B by sponging miR-132, thereby acting as an oncogene in melanoma. This study demonstrated that the lncRNA-miRNA-mRNA signal cascade existed in melanoma, which may help elucidate the tumorigenesis and development mechanism of melanoma.
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The purpose of this study was to investigate the expression and mechanism of miR-17 in gastric lym-phoma. miR-17mimics, miR-17 inhibitors and negative controls were transfected into human gastric lymphoma cell line cyp6d. The proliferation, invasion and apoptosis of cyp6d cells were detected by CCK-8, Transwell and TUNEL methods, respectively. The expression and clinicopathological features of miR-17 in gastric lymphoma were analyzed by real-time quantitative PCR. The target gene of miR-17 was predicted by targetscan 7.2, and the expression of miR-17 related protein was detected by Western blot. The results showed that the expression of miR-17 in gastric lymphoma was significantly higher than that in normal tissues (P < 0.05), which was closely related to lymph node metastasis, tumor size and distant metastasis (P < 0.05). The high expression of miR-17 significantly promoted the proliferation and invasion of cyp6d cells and inhibited apoptosis (P < 0.05). The high expression of miR-17 can regu¬late the expression of HSP60 and TNFR2. It has been found that miR-17 can promote the development of gastric lymphoma by regulating HSP60/TNFR2 pathway, which is a potential molecular target for the diagnosis and treatment of gastric lymphoma.
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The aim of this study was to investigate the effect of micro ribonucleic acid (miR)-195 on myocardial infarction (MI) in rats via regulating the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. A total of 36 Sprague-Dawley rats were randomly divided into a normal group (n=12), a model group (n=12) and an miR-195 antagomir group (n=12). In the normal group, the heart was exposed only, and normal saline was intraperitoneally injected after operation. In the model group, the acute MI model was established. In the miR-195 antagomir group, the acute MI model was also established, and miR- 195 antagomir was intraperitoneally injected. The samples were collected at 2 weeks after surgery. Then cardiac function was detected via echocardiography, and the morphology of heart tissues was observed via hematoxylin and eosin (H&E) staining. Moreover, the expression of Collagen I was determined using immunohistochemistry, the protein expressions of TGF-β1, Smad3 and Smad7 were detected using Western blotting, and the expression of miR-195 was detected via quantitative polymerase chain reaction (qPCR). It was found by echocardiography that, compared with those in the normal group, left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) significantly declined, while left ventricular end-diastolic diameter (LVDd) and left ventricular end-systolic diameter (LVDs) significantly rose in the other two groups (P<0.05). In comparison with the model group, the miR-195 antagomir group had significantly increased LVEF and LVFS, and significantly decreased LVDd and LVDs (P<0.05). The immunohistochemistry results showed that the mean optical density of tissues with positively expressed Collagen I was obviously higher in the other two groups than that in the normal group (P<0.05), while it was obviously lower in the miR-195 antagomir group than that in the model group (P<0.05). According to the results of Western blotting, the protein expressions of TGF-β1 and Smad3 were evidently increased, while the protein expression of Smad7 was evidently decreased in the other two groups compared with those in the normal group (P<0.05). The opposite results were found in the miR-195 antagomir group compared with those in the model group (P<0.05). The results of qPCR manifested that the expression of miR-195 was markedly higher in the other two groups than that in the normal group (P<0.05), while it was markedly lower in the miR-195 antagomir group than in the model group (P<0.05). Moreover, it was observed using H&E staining that the myocardial fibers in the normal group had normal arrangement and intact structure, without obvious morphological abnormalities. In the model group, the myocardial fibers were arranged disorderly, and there were massive proliferating fibrous tissues, with a high degree of fibrosis. In themiR-195 antagomir group, the myocardial fibers were damaged and arranged less disorderly, and proliferation and fibrosis could be seen in some fibrous tissues, but to a lesser extent than the model group. In conclusion, miR-195 promotes myocardial fibrosis in MI rats via up-regulating the TGF-β1/Smad signaling pathway.
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MicroRNAs (miRNAs) have pivotal roles in the initiation and progression of gastric cancer (GC), and miR-92a-3p has been proved to act as an oncogene in multiple malignancies. However, the molecular mechanisms by which miR-92a-3p contributes to GC remain unclear. The differentially expressed miRNAs were screened by GEO dataset, and the association of miR-92a-3p expression with clinicopathological characteristics and prognosis in patients with GC was analyzed by TCGA dataset. The target genes of miR-92a-3p were identified by bioinformatic analysis, and their interaction was confirmed by luciferase reporter assay. MTT, EdU and Transwell assays were conducted to determine the role of miR-92a-3p in GC cells. As a result, it was found that the expression levels of miR-92a-3p were increased in GC tissues and were associated with tumor size, lymph node infiltration and distant metastasis, acting as an independent prognostic factor of poor survival in patients with GC. Restored expression of miR-92a-3p facilitated cell proliferation, DNA synthesis and cell invasion, but its inhibitor reversed these effects. KLF2 was further identified as a direct target of miR-92a-3p, indicating a negative correlation with miR-92a-3p expression and harboring a favorable prognosis in GC. In addition, KLF2 repressed cell proliferation and invasion and attenuated the tumor-promoting effects of miR-92a-3p in GC cells. Altogether, our findings demonstrated that miR-92a-3p promoted the proliferation and invasion of GC cells by targeting KLF2.
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Hallux valgus is a common foot deformity disease caused by various extrinsic and intrinsic factors, and systemic conditions, but the etiopathogenesis and pathogenesis of this deformity are still unknown. Hallux valgus affects 10-20% of Chinese adults. Although considered highly heritable, the candidate gene is unclear. We conducted the first candidate gene study of hallux valgus to identify the biological mechanism. Between June 2015 and July 2018, the records and radiographs of 80 patients diagnosed with hallux valgus and 80 controls who were treated were analyzed. In order to compare the differences in severity associated with this deformity, the charts of 80 patients were divided into 3 groups from the angle of hallux valgus. Clinical and basic studies were also statistically compared by PCR and data analysis. Patients and controls had significant differences in age and gender, however, there were no significant differences in age and gender among the light, moderate and severe groups. Post-operative groups resulted in significant improvements in all of the measured radiographic parameters compared with pre-operative groups. BsmI seemed to show a specific variation, and may serve as a useful bio-marker for the disease (OR = 5.88, 95% CI 1.54-22.35, P <0.001). In this paper, the article which proved the VDR polymorphisms (BsmI) playing an important role in hallux valgus were studied to understand and manage the hallux valgus more scientifically.
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miR-382-3p can regulate apoptosis through multiple pathways, but the mechanism remains unknown. In this experiment, we explored whether miR-382-3p can modulate the N-methyL-D-aspartate (NMDA)- induced HT22 cell apoptosis by regulating the RhoC/ROCK1 signaling pathway. An excitatory neurotoxicity model of HT22 cells was induced in vitro with 2 mmol/L NMDA. The cells were divided into normal control, NMDA-induced, NMDA + miR-382-3p mimic, and NMDA + miR-382-3p inhibitor groups. The 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) method, Real-time PCR, Western blot, and flow cytometry were performed to investigate the mechanisms. The results found that NMDA can increase the oxidative stress of HT22 cells in a dose-dependent manner, downregulate the expression of miR-382-3p, upregulate the expression of mRNA and protein abundance of ROCK1 and RhoC, increase the expression levels of proapoptotic proteins Bax, Caspase-3, and Caspase-9, increase the apoptosis of HT22 cells, and reduce the activity and survival rate of HT22 cells. Compared with the NMDA-induced group, the miR-382-3p mimic-transfected HT22 cells increased the expression of miR- 382-3p, reduced the expression of the mRNA and protein abundance of ROCK1 and RhoC, inhibited the expression of proapoptotic proteins Bax, Caspase-3, and Caspase-9, reduced the apoptosis of HT22 cells, and increased the activity and survival rate of HT22 cells. The results suggest that increasing the expression of miR-382-3p can inhibit the activity of the RhoC/ROCK1 signaling pathway, reduce the expression of proapoptotic proteins, reduce the oxidative stress and apoptosis of HT22 cells, and increase the activity and survival rate of HT22 cells.
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The aim of this study was to observe the expression of Klotho in renal tissues of mice with diabetic ne¬phropathy (DN), and to further explore the effect of Klotho on DN in mice and its mechanism. The 10-week-old mice in this experiment were divided into three groups: heterozygous db/+ mouse group (db/+ group, n=20), homozygous db/db mouse group (db/db group, n=20) and homozygous db/db mice + Klotho group (db/db + Klotho group, n=20). Firstly, Western blotting and immunohistochemical staining were applied to detect the protein expression of Klotho in the renal tissues of diabetic and non-diabetic mice of different ages. Finally, the protein expressions of fibroblast growth factor 2 (FGF2) and E-cadherin in the renal tissues of mice in each group were examined by Western blotting. The protein expression level of Klotho in the renal tissues of mice aged 10 and 16 weeks in the db/db group was remarkably lower than that in yhedb/+ group. In addition, it was found that db/db + Klotho group exhibited a prominently lower degree of interstitial fi¬brosis and content of Collagen I and Collagen III in the renal tissues than db/db group. Furthermore, it was revealed that the overexpression of Klotho could significantly repress the protein expression level of FGF2 but elevate that of E-cadherin in the renal tissues of DN mice. Klotho protein may ameliorate the renal injury and fibrosis in diabetic mice by inhibiting FGF2, so it is expected to become a targeted drug for DN.
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Platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) are selective blood fractions obtained by cen¬trifugation. They act locally on inflammation and immunity as adjuvant homeostatic modulators during tissue regeneration. In recent years, many methods for achieving these blood concentrates have emerged, whose parameters of time and force of centrifugation presented themselves as critical, conflicting, and poorly understood points. Thus, the present study aimed to evaluate the effect of different centrifugal experimental parameters on the concentration of cells and platelets in samples of anticoagulated blood. Blood samples were centrifuged by forces of 200, 400 and 800 x g for 5, 10 and 15 minutes of centrifugation times to obtain three fractions: a) platelet-poor plasma (PPP), b) leukocyte-rich plasma (L- PRP) and c) red blood cell sed¬iment (RBC). The leukocyte and platelet content of each centrifuged fraction was measured by automated flow cytometry associated with the peroxidase reaction for differential leukocyte count. The application of 200 x g generated a more significant dispersive content of leukocytes and platelets in the supernatant fraction of PPP when compared to the other two strength ranges. However, it presented the highest concentration of platelets in the sediment (P <0.05 ANOVA), representing a loss of total mass during processing. The 400 and 800 x g forces showed leukocytes and platelets condensed in the L-PRP fraction and lower levels in the sedi¬ment, demonstrating the greater effectiveness of buoyancy in the resuspension of these sedimented elements. Our experimental data showed that the concentration and organization of leukocytes and platelets in the centrifuged blood matrices are very sensitive to variations in g force and centrifugation time, thus generating products with different biological composition and characteristics, and with specific potential therapeutic effects. The present study did not focus on comparing authoring methods, but on presenting the impact of methodological variations on the biological nature of centrifuged blood matrices. Further in vivo studies are needed to assess the specific clinical effect of each methodological change.
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This article has been retracted at the request of the Editor. After a thorough investigation the Editor-in-Chief has retracted this article as it showed evidence of substantial manipulation of the peer review
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