Increased expression of cyclooxygenase-2 in synovium tissues and synovial fluid from patients with knee osteoarthritis is associated with downregulated microRNA-758-3p expression

xlomafota13 shared this article with you from Inoreader Increased expression of cyclooxygenase-2 in synovium tissues and synovial fluid from patients with knee osteoarthritis is associated with downregulated microRNA-758-3p expression Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1001. doi: 10.3892/etm.2021.10433. Epub 2021 Jul 15. ABSTRACT Cyclooxygenase-2 (COX-2) is a common factor in inflammation, and its specific regulatory mechanism has not been fully elucidated. The present study aimed to investigate COX-2 mRNA and protein expression levels in synovium tissues and synovial fluid from patients with knee osteoarthritis (KOA), and determine the molecular mechanism by which microRNA (miRNA/miR)-758 regulates KOA via COX-2. A total of 37 patients with KOA and 29 patients with acute knee trauma (control group) were enrolled in the present study. Reverse transcription-quantitative PCR analysis was performed to detect miR-758-3p and COX-2 mRNA expression, while western blotting and ELISA were performed to detect COX-2 protein expression in synovium and synovial fluid, respectively. The dual-luciferase reporter assay was performed to verify the interaction between miR-758-3p and the 3' -untraslated region (UTR) of COX-2 mRNA. Synovial cells were transfected with agomiR-758-3p, and the MTT assay was performed to assess cell proliferation. The results demonstrated that COX-2 expression was higher in patients with KOA than those with acute knee trauma. Conversely, miR-758-3p expression was lower in patients with KOA than those with acute knee trauma. Notably, miR-758-3p interacted with the 3'-UTR of COX-2 mRNA to regulate its expression. Overexpression of miR-758-3p inhibited the expression and release of COX-2, as well as the proliferation of human KOA synovial cells. Taken together, these results suggest that COX-2 expression is upregulated in synovium tissues and synovial fluid from patients with KOA, which is associated with downregulated miR-758-3p expression. In addition, miR-758-3p affects the proliferation of synovial cells and the expression of relevant proteins in these cells, thus promoting the occurrence and development of KOA. PMID:34345283 | PMC:PMC8311242 | DOI:10.3892/etm.2021.10433 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

En-face optical coherence tomography analysis of gold and silver nanoparticles in endodontic irrigating solutions: An in vitro study

xlomafota13 shared this article with you from Inoreader <em>En-face</em> optical coherence tomography analysis of gold and silver nanoparticles in endodontic irrigating solutions: An <em>in vitro</em> study Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):992. doi: 10.3892/etm.2021.10424. Epub 2021 Jul 14. ABSTRACT Optical coherence tomography (OCT) is a non-invasive, non-radioactive optical diagnostic method based on low-coherence interferometry, which achieves images with different orientation. In dentistry, its major advantage is represented by the localization and characterization of the smallest defects in hard dental tissues, dental materials and of the smallest details in dental anatomy (supplementary canals, recesses, isthmuses, or intra-radicular connections). The aim of the present in vitro study was to evaluate using c-scan en-face optical coherence tomography, the optical opacity, and the distribution inside the root canal lumen of several extracted human teeth of silver and gold nanoparticles from special irrigating solutions used in endodontic treatment. Twelve root canals from 5 human teeth were instrumented using the ProTaper Un iversal system after initial negotiation with hand K-files ISO no. 10 and rotary nickel-titanium PathFile instruments. An initial c-scan OCT analysis was performed for each sample to confirm that the root canal lumen was empty from radiopaque materials (Group 1). Teeth were first irrigated with NanoCare Plus (Group 2) and then with NanoCare Gold (Group 3) and C-scans were repeated after each irrigation method. The OCT investigation started at the tooth apex, at a depth of 1 mm from its tip. Subsequently, 100 slices of 10 microns were obtained from each root canal. Images were captured and then analyzed with ImageJ software to calculate the level of grey inside the root canal lumen. The highest values of grey were obtained in the samples irrigated with NanoCare Gold after NanoCare Plus (Group 3). The present study proved that both nanoparticles inserted in root canal irrigants were evidenced through OCT imagistic analysis due to their optical opacity, which allowed their highlighting in an empty root canal lumen, after the endodontic treatment was performed and the root canal was cleaned and shaped using specific protocols. PMID:34345274 | PMC:PMC8311245 | DOI:10.3892/etm.2021.10424 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Whole-exome sequencing reveals MYH7 p.R671C mutation in three different phenotypes of familial hypertrophic cardiomyopathy

xlomafota13 shared this article with you from Inoreader Whole-exome sequencing reveals MYH7 p.R671C mutation in three different phenotypes of familial hypertrophic cardiomyopathy Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1002. doi: 10.3892/etm.2021.10434. Epub 2021 Jul 15. ABSTRACT Familial hypertrophic cardiomyopathy (HCM) is one of the most common types of genetic heart disorder and features high genetic heterogeneity. HCM is a major cause of sudden cardiac death and also an important cause of heart failure-related disability. A pedigree with suspected familial HCM was recruited for the present study to identify genetic abnormalities. HCM was confirmed by echocardiography and clinical data of the family members were collected. Genomic DNA was extracted from the peripheral blood and sequenced based on standard whole-exome sequencing (WES) protocols. Sanger sequencing was further performed to verify mutation sites and their association with HCM. WES and Sanger sequencing revealed a heterozygous missense mutation (c.2011C>T p.R671C) in myosin heavy chain 7 (MYH7) that was identified in three family members. The Arg671Cys mutation was located in exon 18 and, to the best of our knowledge, has not been previously reported in familial HCM. Furthermore, family members carrying the same mutated gene were of different sexes and clinical phenotypes. They included the proband, a 17-year-old survivor of sudden cardiac arrest with ventricular systolic dysfunction, the proband's maternal uncle, who presented with ventricular diastolic dysfunction and the proband's mother, who had no obvious clinical symptoms and did not present with cardiac dysfunction. However, echocardiology indicated that the proband's mother had an enlarged left atrium, slightly thicker right anterior wall and anterior septum and an expanded atrial septum. Therefore, HCM exhibited obvious genetic and phenotypic heterogeneity. To the best of our knowledge, the present study was the first to report such a mutation in the MYH7 gene in familial HCM. In addition, the present study demonstrated that WES is a powerful tool for identifying genetic variants in HCM. PMID:34345284 | PMC:PMC8311224 | DOI:10.3892/etm.2021.10434 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Predictive value of immunological markers in systemic sclerosis

xlomafota13 shared this article with you from Inoreader Predictive value of immunological markers in systemic sclerosis Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):994. doi: 10.3892/etm.2021.10426. Epub 2021 Jul 14. ABSTRACT Systemic sclerosis (SSc) is a collagenosis characterized by excessive deposition of collagen in the skin and viscera, in a background of immune disorder. The immunological profile of SSc often shows elevated levels of antinuclear antibodies (ANAs). However, many authors have identified cases of SSc having normal ANA levels, framed as paraneoplastic SSc. Among patients with negative ANAs in our group, we did not identify any neoplastic process that could support this hypothesis. The extended detection of autoantibodies is extremely useful in establishing the subset of SSc. Thus, anti-Scl70 antibodies are specific for the diffuse subset of SSc, while anticentromere antibodies (ACAs) have specificity for a limited subset. However, studies have shown the existence of cases of diffuse SSc having high titers of ACAs and cases of limited SSc with high ti ters of anti-Scl70 antibodies. This indicates an inconsistent association between the disease subset and the autoantibodies specific to each subset. Our study found a more balanced consistency between disease subsets and autoantibodies specific for each subset. Therefore, the percentages of patients having an immunological profile inconsistent with the subset of SSc, are lower than those found by other authors. This observation opens the perspective of larger studies on the immunological profile in SSc. PMID:34345276 | PMC:PMC8311248 | DOI:10.3892/etm.2021.10426 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Protein arginine methyltransferase 5 mediates THP-1-derived macrophage activation dependent on NF-κB in endometriosis

xlomafota13 shared this article with you from Inoreader Protein arginine methyltransferase 5 mediates THP-1-derived macrophage activation dependent on NF-κB in endometriosis Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1003. doi: 10.3892/etm.2021.10436. Epub 2021 Jul 15. ABSTRACT Macrophage-induced inflammation is a major factor in the pathogenesis of endometriosis. The underlying mechanisms, however, remain largely unknown. TNF-α, IL-6, IL-10 and C-C motif chemokine 20 (CCL20) levels in endometrial extracts were determined using Luminex cytokine kits. Additionally, protein arginine methyltransferase 5 (PRMT5) levels were measured using reverse transcription-quantitative PCR and western blotting. IL-6 and IP-10 levels in cells were measured using ELISA kits. In the present study, it was revealed that PRMT5 expression at both the mRNA and protein levels in THP-1-derived macrophages was significantly decreased following treatment with serum or extracts of endometrium from patients with endometriosis in the presence of lipopolysaccharide, compared with that in control cells, suggesting a possible role for macrophage-derived PRMT5 in mediating the interaction between macrophages and endometrium in endometriosis. Mechanistically, macrophage PRMT5 expression was regulated in an NF-κB-dependent and Smad2/3-independent manner, indicating that PRMT5 is a downstream target of NF-κB. Importantly, macrophage-derived PRMT5 was required for macrophage activation in endometriosis, as evidenced by the PRMT5-dependent secretion of IL-6 and IFN-γ-induced protein 10 from THP-1-derived macrophages. The present study identified NF-κB-dependent PRMT5 as a novel regulator of macrophage activation in endometriosis. Targeting PRMT5 in macrophages may be a potential therapeutic strategy against endometriosis. PMID:34345285 | PMC:PMC8311241 | DOI:10.3892/etm.2021.10436 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Oscillating field stimulation promotes recovery from spinal cord injury in rats by regulating the differentiation of endogenous neural stem cells

xlomafota13 shared this article with you from Inoreader Oscillating field stimulation promotes recovery from spinal cord injury in rats by regulating the differentiation of endogenous neural stem cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):979. doi: 10.3892/etm.2021.10411. Epub 2021 Jul 12. ABSTRACT The mammalian spinal cord (SC) has a limited self-repair capacity and exogenous treatments are yet to produce substantial functional recovery following SC injury (SCI). The SC contains endogenous neural stem cells (NSCs) with multi-lineage differentiation potential and it may be possible to restore function via interventions that promote NSC differentiation following SCI. Oscillating field stimulation (OFS) has been reported to regulate the Wnt signaling pathway, a known modulator of NSC differentiation. However, the effects of OFS on NSC differentiation following SCI and associated functional recovery have not been previously examined. In the current study, the Basso-Beattie-Bresnahan (BBB) score was used to assess locomotion recovery following SCI in rats and immunofluorescence double-staining was used to examine the regeneration of neurons and oligodendrocytes derived from NSCs. Furthermore, Nissl staining was performed to assess the viability and survival of neurons following SCI, while recovery of the myelin sheath was examined by uranium-lead staining under transmission electron microscopy. OFS delivered via an implanted stimulator enhanced the differentiation of NSCs into neurons and oligodendrocytes and accelerated the regeneration of myelinated axons. Additionally, BBB scores revealed superior locomotion recovery in OFS-treated rats compared with SCI controls. Collectively, these results indicated that OFS may be a feasible strategy to promote SCI recovery by regulating the differentiation of endogenous NSCs. PMID:34345261 | PMC:PMC8311232 | DOI:10.3892/etm.2021.10411 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Molecular mechanisms of opioid tolerance: From opioid receptors to inflammatory mediators (Review)

xlomafota13 shared this article with you from Inoreader Molecular mechanisms of opioid tolerance: From opioid receptors to inflammatory mediators (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1004. doi: 10.3892/etm.2021.10437. Epub 2021 Jul 15. ABSTRACT Opioids are considered the most effective analgesics for the treatment of both acute and chronic pain. However, prolonged opioid use can induce a certain level of tolerance to its analgesic effects, leading to a reduction in its effectiveness, addiction and abuse. A better understanding of the mechanisms underlying opioid tolerance may provide insights into this phenomenon and aid in the development of novel methods to combat the side effects of opioid tolerance. The present review focused on two major contributors to tolerance, opioid receptors and inflammatory mediators. The molecular mechanisms involved in the desensitization of the opioid receptors were briefly described, including their phosphorylation, internalisation and recycling. Subsequently, the effects of Toll like receptor 4/NOD-like receptor family pyrin domain containing 3-mediated proinflammatory responses in opioid tolerance were discussed, aiming in supporting the identification of novel therapeutic targets. PMID:34345286 | PMC:PMC8311239 | DOI:10.3892/etm.2021.10437 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Predictors of spontaneous bacterial peritonitis in Romanian adults with liver cirrhosis: Focus on the neutrophil-to-lymphocyte ratio

xlomafota13 shared this article with you from Inoreader Predictors of spontaneous bacterial peritonitis in Romanian adults with liver cirrhosis: Focus on the neutrophil-to-lymphocyte ratio Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):983. doi: 10.3892/etm.2021.10415. Epub 2021 Jul 12. ABSTRACT Spontaneous bacterial peritonitis (SBP) is a severe complication of liver cirrhosis whose diagnosis is based on a polymorphonuclear leukocyte (PMN) value >250 mm3, yet this PMN value cannot identify all existing types. The aim of our study was to determine the clinical and biological factors that were associated with SBP and predict its occurrence, focusing on the neutrophil-to-lymphocyte ratio (NLR) as one of them. Our retrospective study included 216 patients with liver cirrhosis who were hospitalized between December 2019 and January 2010 at the Emergency County Clinical Hospital of 'St. Apostle Andrew' in Constanta, Romania. Demographic, clinical, and laboratory data were collected from patient observation sheets. The patients were divided into two groups: One group of patients with SBP and the other without SBP. The diagnosis of SBP was made when patients presented with PMN >250 mm3 and other causes of secondary bacterial peritonitis were excluded. The mean age of the patients was 61.25±10.67 years, and the alcoholic etiology of liver cirrhosis was most common (44%). Univariate logistic regression analysis showed that there was an association between biological parameters, such as serum white blood cells, total platelet count, total bilirubin, serum albumin, international normalized ratio, creatinine, erythrocyte sedimentation rate (ESR), serum sodium, alkaline reserve, and NLR, and clinical parameters, such us upper gastrointestinal bleeding and cardiac comorbidities in the occurrence of SBP. Multivariate analysis identified ESR and NLR as predictive factors in the occurrence of SBP. The area under the curve (AUC) was 0.916 [P<0.001, 95% confidence interval (CI) 0.870-0.949] for ESR and AUC was 0.963 (P<0.001, 95% CI 0.928-0.984) for NLR, respectively. In conclusion, the combination o f these 2 biological parameters is useful in identifying or excluding SBP. PMID:34345265 | PMC:PMC8311228 | DOI:10.3892/etm.2021.10415 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Lactobacillus acidophilus and vitamin C attenuate ethanol-induced intestinal and liver injury in mice

xlomafota13 shared this article with you from Inoreader <em>Lactobacillus acidophilus</em> and vitamin C attenuate ethanol-induced intestinal and liver injury in mice Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1005. doi: 10.3892/etm.2021.10438. Epub 2021 Jul 15. ABSTRACT Ethanol exposure frequently induces intestinal and liver injury, dysbiosis of the gut microbiota and vitamin C (VC) deficiency. Gut microbiota-targeted therapy is emerging as an important adjuvant method for protecting the body against ethanol-induced injury, particularly probiotics containing Lactobacillus acidophilus (LA). However, the feasibility and efficiency of using synbiotics containing LA and VC against ethanol-induced injury remained largely undetermined. To examine the advantages of LA+VC, their effect was evaluated in an ethanol-fed mouse model. The results suggested that LA+VC restored gut microbiota homeostasis and reinstated the immune balance of colonic T-regulatory cells (CD4+CD45+forkhead box p3+). In addition, intestinal barrier disorders were improved via upregulating tight junction prot eins (claudin-2, zona occludens-1 and occludin) and mucus secretion, which prevented the translocation of lipopolysaccharide into circulatory systems and subsequently reduced the expression of Toll-like receptor 4 in liver tissues. In this context, LA+VC treatment reduced the inflammatory response in the liver, which was likely responsible for the improved liver function in ethanol-challenged mice. Collectively, these results indicated that LA+VC treatment significantly protected the intestine and liver from ethanol damage by enhancing intestinal barrier function and reducing systemic inflammation. The present study paved the way for further exploration of synbiotics based on Lactobacillus species and VC. PMID:34345287 | PMC:PMC8311231 | DOI:10.3892/etm.2021.10438 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

High serum level of interleukin-6 is linked with dyslipidemia in oral lichen planus

xlomafota13 shared this article with you from Inoreader High serum level of interleukin-6 is linked with dyslipidemia in oral lichen planus Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):987. doi: 10.3892/etm.2021.10419. Epub 2021 Jul 13. ABSTRACT Oral lichen planus (OLP) is a complex chronic inflammatory disorder in which autocytotoxic CD8+ T cells, locally present in the affected tissue, induce basal keratinocyte apoptosis, through the release of several cytokines, such as interleukin-6 (IL-6). IL-6 is a proinflammatory cytokine that is related to alterations in lipid metabolism in psoriasis patients. Impaired lipid metabolism together with high serum levels of triglycerides have been found in association with OLP. However, the correlation between serum levels of IL-6 and dyslipidemia has not yet been studied in this disorder. The present study aimed to demonstrate the association between OLP, systemic inflammation through increased release of inflammation mediators such as IL-6 and alteration of lipid metabolism, in order to support the concept of OLP as a marker of systemic i nflammation and a potential risk factor of cardiovascular morbidities. For this purpose, we designed a case-control study using a cohort of 18 patients with different clinical forms of OLP compared with 18 control group patients with other oral conditions, to identify a potential correlation between serum levels of IL-6 and serum lipid levels. High plasma serum levels of IL-6 were found to be correlated with cholesterol, high density lipoprotein cholesterol and triglyceride serum levels in the patients with OLP. There was a significant association between erosive and atrophic clinical forms of OLP and the pathological serum values of IL-6 and triglycerides, respectively, making these two parameters good predictive factors of the clinical form of OLP. Further studies of other biomarkers of systemic inflammation using larger cohorts of OLP patients are necessary in order to consider LP as a marker of systemic inflammation and to support the screening of these patients for lipid metabo lism changes and treatment with specific antagonists in order to prevent cardiovascular events. PMID:34345269 | PMC:PMC8311226 | DOI:10.3892/etm.2021.10419 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.