Dexmedetomidine alleviates inflammation in neuropathic pain by suppressing NLRP3 via Nrf2 activation

xlomafota13 shared this article with you from Inoreader Dexmedetomidine alleviates inflammation in neuropathic pain by suppressing NLRP3 via Nrf2 activation Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1046. doi: 10.3892/etm.2021.10479. Epub 2021 Jul 22. ABSTRACT The aim of the present study was to investigate the mechanism by which dexmedetomidine (DEX) alleviates neuropathic pain in a chronic constriction injury (CCI) model in rats. A CCI rat model was established through sciatic nerve ligation. CCI rats were treated with DEX, the nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML385, the NLR family pyrin domain containing 3 (NLRP3) antagonist MCC950 and/or the NLRP3 activator nigericin. The mechanical withdrawal threshold (MWT) was measured to assess the pain sensitivity of CCI rats. Hematoxylin and eosin staining and TUNEL staining were used to examine spinal injury and apoptosis, respectively. ELISA was used to quantify the levels of inflammatory factors. The expression levels of Nrf2 and NLRP3 were also examined. The results indicated that a decrease in MWT and increases in spinal cord injury, apoptosis and inflammatory factors were detected in CCI rats compared with control rats. Spinal inflammation was abrogated in DEX-treated CCI rats. Compared with the model group, an increase in MWT and decreases in spinal cord injury, apoptosis and inflammatory factors were detected in rats treated with MCC950, while the opposite effects were observed in rats treated with nigericin. The opposite effects on these indicators were observed in the DEX + ML385 and MCC950 + ML385 groups compared with the DEX and MCC950 groups, respectively. MWT was increased, while spinal cord injury, apoptosis and inflammation decreased in the nigericin + DEX group compared with the nigericin group. In summary, the results of the present study indicated that DEX reduced neuropathic pain in CCI rats by suppressing NLRP3 through Nrf2 activation. PMID:34434260 | PMC:PMC8353619 | DOI:10.3892/etm.2021.10479 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Role and dynamics of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in burn patients

xlomafota13 shared this article with you from Inoreader Role and dynamics of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in burn patients Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1062. doi: 10.3892/etm.2021.10496. Epub 2021 Jul 27. ABSTRACT Burn injuries can trigger tissue changes that can explain the variation in the level of different biochemical markers that can be recorded both locally or systemically. Some events observed in burn wounds such as vascular hyperpermeability have been associated with the release of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) after trauma. Because it is unknown whether the serum levels of MMP-9 and TIMP-1 are a consequence of these destructions or a local response to thermal damage, we decided to follow their dynamics. Twenty-five patients (mean age 49.40±17.55 years) with a total body surface area (TBSA) affected by a thermal burn of <25% and 30 healthy subjects (mean age 49.70±8.04 years) were enrolled in the present study. Enzyme immunoassays were used to measure the serum levels of MMP-9 and TIMP-1. Our results show ed that MMP-9 was increased 6.25-fold immediately after injury compared to the controls and remained on a plateau throughout the 7-day monitoring period. TIMP-1 showed an upward trend with an increase of 49.52% on the seventh day after triggering insult. The time-course of the MMP-9/TIMP-1 ratio followed the inverse dynamics of TIMP-1 starting from a ratio value measured at admission 3.82-fold higher than the one observed in the healthy volunteers and a highly statistically significant correlation between the values measured at different time-points during the monitoring period (P<0.001). The results of this retrospective study indicate that the MMP-9/TIMP-1 ratio may provide information on local changes over time, starting from the triggering insult, and may be considered as a predictive biomarker of burn evolutivity. PMID:34434276 | PMC:PMC8353633 | DOI:10.3892/etm.2021.10496 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Network pharmacology-based prediction of the active compounds and mechanism of Buyang Huanwu Decoction for ischemic stroke

xlomafota13 shared this article with you from Inoreader Network pharmacology-based prediction of the active compounds and mechanism of Buyang Huanwu Decoction for ischemic stroke Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1050. doi: 10.3892/etm.2021.10484. Epub 2021 Jul 23. ABSTRACT Buyang Huanwu Decoction (BYHWD) is used to promote blood circulation and is widely used in Chinese clinical practice for the treatment and prevention of ischemic cerebral vascular diseases. However, the mechanism and active compounds of BYHWD used to treat ischemic stroke are not well understood. The current study aimed to identify the potential active components of BYHWD and explore its mechanism using network pharmacology and bioinformatics analyses. The compounds of BYHWD were obtained from public databases. Oral bioavailability and drug-likeness were screened using the absorption, distribution, metabolism and excretion (ADME) criteria. Components of BYHWD, alongside the candidate targets of each component and the known therapeutic targets of ischemic stroke were collected. A network of target gene compounds and cerebral ischemia compounds was established using network pharmacology data sources. The enrichment of key targets and pathways was analyzed using STRING and DAVID databases. Moreover, three of key targets [IL6, VEGFA and hypoxia-inducible-factor-1α (HIF-1α)] were verified using western blot analysis. Network analysis determined 102 compounds in seven herbal medicines that were subjected to ADME screening. A total of 42 compounds as well as 79 genes formed the principal pathways associated with ischemic stroke. The 16 key compounds identified were baicalein, beta-carotene, baicalin, kaempferol, luteolin, quercetin, hydroxysafflor yellow A, isorhamnetin, bifendate, formononetin, calycosin, astragaloside IV, stigmasterol, sitosterol, Z-ligustilide, and dihydrocapsaicin. The core genes in this network were IL6, TNF, VEGFA, HIF-1α, MAPK1, MAPK3, JUN, STAT3, IL1B and IL10. Furthermore, the TNF, IL17, apoptosis, PI3K-Akt, toll-like receptor, MAPK, NF-κB and HIF-1 signaling pathways were identified to be associated with ischemic stroke. Compared with the control group (no treatment), BYHWD significantly inhibited the expression of IL6 and increase the expression of HIF-1α and VEGFA. Network pharmacology analyses can help to reveal close interactions between multi-components and multi-targets and enhance understanding of the potential effects of BYHWD on ischemic stroke. PMID:34434264 | PMC:PMC8353622 | DOI:10.3892/etm.2021.10484 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A multidisciplinary approach in the diagnostic challenge of GIST

xlomafota13 shared this article with you from Inoreader A multidisciplinary approach in the diagnostic challenge of GIST Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1063. doi: 10.3892/etm.2021.10497. Epub 2021 Jul 27. ABSTRACT Gastrointestinal stromal tumors (GISTs) are the most common malignant mesenchymal lesions of the gastrointestinal tract. They originate from the interstitial cells of Cajal and are characterized by overexpression of the tyrosine kinase receptor, protein product of c-KIT gene (KIT). In this retrospective study, conducted over a period of 10 years, we retrieved from our database, a total number of 57 patients, admitted and operated in the surgical department of 'Sf. Pantelimon' Emergency Clinical Hospital, Bucharest, for digestive tumors, histopathologically confirmed as GISTs. More than half of the cases presented as surgical emergencies and the tumors found during the surgical procedures, which proved to be GISTs, were sometimes difficult to differentiate from other mesenchymal tumors, both for the clinician and the pathologist. The diagnosis of GIST relies mostly on pathology and immunohistochemistry, but also on clinical and imagistic data. The most common emergencies were digestive hemorrhage (associated with gastric location), followed by intestinal obstruction (especially for the ileal localization). The largest dimensions corresponded to gastric location. For selected indications (upper digestive sites), upper digestive endoscopy approaches 100% sensitivity. This study focuses on diagnosis of GISTs sustained by both clinical and imagistic methods, along with histopathology and immunohistochemistry techniques, according to the World Health Organization 2019 criteria. Even though the differential diagnosis of these tumors is challenging, an interdisciplinary cooperation with a multiple approach increases the odds of a correct positive diagnosis. PMID:34434277 | PMC:PMC8353641 | DOI:10.3892/etm.2021.10497 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Inhibition of autophagy promotes human RSV NS1-induced inflammation and apoptosis in vitro

xlomafota13 shared this article with you from Inoreader Inhibition of autophagy promotes human RSV NS1-induced inflammation and apoptosis <em>in vitro</em> Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1054. doi: 10.3892/etm.2021.10488. Epub 2021 Jul 23. ABSTRACT Human respiratory syncytial virus (RSV) is a major health challenge due to the lack of a safe and effective vaccine and antiviral drugs. RSV non-structural protein 1 (NS1) is the main inhibitor of antiviral signaling pathways in RSV infection; however, the underlying mechanism is unclear. The aim of the present study was to investigate of the role of NS1 and its relationship with autophagy. NS1-Flag plasmid was transfected into A549 cells and the levels of inflammatory cytokines, autophagy markers and apoptosis were detected. In addition, the cells were treated with an autophagy inhibitor, 3-methyladenine for 12 h prior to transfection with the NS1 plasmid to explore the role of autophagy in NS1-transfected cells. The results showed that the production of inflammatory cytokines and autophagy was induced in NS1-transfected cells, and indicated tha t autophagy prevents the production of cytokines and the activation of apoptosis. Furthermore, the results demonstrated that NS1 activated autophagy partly through the mTOR-p70 S6 kinase signaling pathway. The results suggest that autophagy induced by NS1 transfection through the mTOR pathway can hinder the production of inflammatory cytokines and interferon-α and inhibit cell apoptosis, which may help to explain why autophagy has been shown to be beneficial to viral replication in most studies. PMID:34434268 | PMC:PMC8353648 | DOI:10.3892/etm.2021.10488 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Omega plate for the treatment of acetabular fractures involving the quadrilateral plate

xlomafota13 shared this article with you from Inoreader Omega plate for the treatment of acetabular fractures involving the quadrilateral plate Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1064. doi: 10.3892/etm.2021.10498. Epub 2021 Jul 27. ABSTRACT This retrospective study aimed to assess the outcome of a modified Stoppa approach using an anatomically precontoured plate for the treatment of acetabular fractures. In total, 30 patients (mean age 50.3 years; 25 men and 5 women) with acetabular fractures were treated between January 1, 2018 and December 31, 2019. In all 30 cases, fracture reduction was performed through a modified Stoppa approach and fixed with the omega plate. In specific fracture patterns, additional approaches were needed (lateral window in 4 cases and posterior Kocher-Langenbeck approach in 7 cases). Patients were assessed for restoration of the hip joint congruency, complications, and overall fracture reduction. Quality of reduction was categorized based on Matta's radiological principles and to assess functional outcome the Merle d'Aubigné-Postel and Harris hip score was used. The average anesthesia time was 253.6 min, the mean intraoperative blood lost was 266.6 ml and the mean intraoperative fluoroscopy dose was 3.21 mGy. According to Matta criteria for reduction quality, anatomical reduction was recorded in 22 cases, imperfect reduction in 6 cases and 2 cases had poor reduction. The average follow-up was 22.5 months. Malunion, loss of reduction or implant loosening were not recorded. Late complications included one case of avascular necrosis of the femoral head and post-traumatic arthritis changes in 5 cases. At the final follow-up, a mean Merle d'Aubigné-Postel score of 13.26±4.46 and a mean Harris score of 86.03±13.37 were recorded. The possibility of an anatomically precontoured plate with subsequent lower operative time combined with stable fixation of the primary acetabular fracture fragments and the quadrilateral plate makes the omega plate a viable option for treating acetabular fractures with a very low complication rate and good to e xcellent results in 89% of the cases. PMID:34434278 | PMC:PMC8353621 | DOI:10.3892/etm.2021.10498 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

CGFe and TGF-β1 enhance viability and osteogenic differentiation of human dental pulp stem cells through the MAPK pathway

xlomafota13 shared this article with you from Inoreader CGFe and TGF-β1 enhance viability and osteogenic differentiation of human dental pulp stem cells through the MAPK pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1048. doi: 10.3892/etm.2021.10482. Epub 2021 Jul 23. ABSTRACT The present study aimed to evaluate the effects of concentrated growth factor exudate (CGFe) and TGF-β1 on the viability and osteogenic differentiation of human dental pulp stem cells (hDPSCs). CGFe was prepared from the peripheral blood of healthy donors (obtained with informed consent). STRO-1+ hDPSCs were isolated from dental pulp tissues and treated in four groups: i) Control; ii) TGF-β1 (1 ng/ml); iii) 100% CGFe; and iv) TGF-β1 (1 ng/ml) + 100% CGFe group. hDPSC viability was measured via MTT assay. The osteogenic differentiation of hDPSCs was quantified via alkaline phosphatase (ALP) activity, western blotting and reverse transcription-quantitative PCR assays. CGFe and TGF-β1 enhanced hDPSC viability, upregulated ALP activity, upregulated the expression of phosphorylated (p)-ERK1/2, p-JNK and p-p38 in hDPSCs, and promoted tra nscription and protein expression of osteogenic-related genes (bone sialoprotein, Runt-related transcription factor 2 and osteocalcin) in hDPSCs. The present study demonstrated that CGFe and TGF-β1 facilitated the viability and osteogenic differentiation of hDPSCs potentially through activation of the MAPK signaling pathway. PMID:34434262 | PMC:PMC8353646 | DOI:10.3 892/etm.2021.10482 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

External cervical resorption: Radiological diagnosis and literature (Review)

xlomafota13 shared this article with you from Inoreader External cervical resorption: Radiological diagnosis and literature (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1065. doi: 10.3892/etm.2021.10499. Epub 2021 Jul 27. ABSTRACT External cervical resorption (ECR) is a relatively unknown and insidious pathology characterized by the loss of hard dental tissues such as: Enamel, cementum and dentine due to clastic function. It begins as a localized resorptive process that initiates on the area of the root beneath the epithelial attachment and the coronal part of the alveolar process, involving vital and non-vital tissues. Despite the fact that there are several potential predisposing factors related to ECR, its aetiology still remains poorly understood and more research is needed to establish the cause-and-effect relationship of all the etiological factors. Improved radiographic detection using cone-beam computed tomography (CBCT) is required in order to correctly classify and assess this entity. This provides a three-dimensional insight into the lesion, regarding the locati on, the size, the depth and the circumferential spread of the ECR defect. It also allows establishment of the most efficacious treatment plan and management. The purpose of this literature review is to cover the relevant literature concerning the etiology, pathogenesis, clinical and radiological presentation and management of ECRs (based on the CBCT findings). PMID:34434279 | PMC:PMC8353645 | DOI:10.3892/etm.2021.10499 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Bilirubin is a specific marker for the diagnosis of acute appendicitis

xlomafota13 shared this article with you from Inoreader Bilirubin is a specific marker for the diagnosis of acute appendicitis Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1056. doi: 10.3892/etm.2021.10490. Epub 2021 Jul 23. ABSTRACT Total serum bilirubin and other biochemical parameters have been associated with acute appendicitis, mainly in complicated cases. The present study aimed to evaluate the role of biochemical parameters in the diagnosis of acute appendicitis, and to further investigate the role of bilirubin as a diagnostic marker irrespective of the severity of the pathology. All recorded cases of appendicectomies in a 1-year period in a single institution were reviewed. The median values of white cell count, C-reactive protein and total serum bilirubin on admission were associated with final histology, and their respective rates of abnormal and normal values were compared between patients who were proven to have negative histology and patients who were proven to have acute appendicitis. A total of 300 patients were studied. Median total serum bilirubin, white cell count and C-reactive protein on admission were significantly associated with acute appendicitis (P<0.001). Respective rates of normal and abnormal values were significantly associated with final histology (P<0.001). Total serum bilirubin demonstrated higher specificity (0.88) but lower sensitivity (0.26) and diagnostic accuracy (0.40) for acute appendicitis. In conclusion, total serum bilirubin on admission should be considered in the diagnostic workup to confirm rather than exclude appendicitis, without focusing on subgroups of specific severity of the disease. White cell count and C-reactive protein may also contribute to the diagnostic work-up, although with limited accuracy. PMID:34434270 | PMC:PMC8353631 | DOI:10.3892/etm.2021.10490 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

IL-17F promotes osteoblastic osteogenesis via the MAPK/ERK1/2 signaling pathway

xlomafota13 shared this article with you from Inoreader IL-17F promotes osteoblastic osteogenesis via the MAPK/ERK1/2 signaling pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1052. doi: 10.3892/etm.2021.10486. Epub 2021 Jul 23. ABSTRACT Osteoimmunology is a field that focuses on the interactions between the skeletal and immune systems, and has become a focus of research over the years. The role of interleukin (IL)-17F, a proinflammatory cytokine, in bone regeneration and its signal transduction are not completely understood. The aim of the present study was to evaluate the function of IL-17F and the possible mechanisms underlying IL-17F in osteoblasts in vitro. Osteoblasts derived from newborn rats were treated with various concentrations of IL-17F. The pro-osteogenic effects of IL-17F were assessed at the cellular and molecular level. The results demonstrated that IL-17F promoted osteoblast proliferation, differentiation and mineralization. Reverse transcription-quantitative PCR and western blotting indicated that IL-17F treatment upregulated osteogenesis-related factors , including bone morphogenetic protein-2, Runt-related transcription factor-2 (Runx2) and Osterix, and downregulated Noggin compared with the control group. Subsequently, whether the IL-17F receptors, IL-17 receptor (IL-17R) A and IL-17RC, served a role in the effects of IL-17F on osteoblasts was investigated. The mRNA expression levels of IL-17RA and IL-17RC were upregulated in IL-17F-treated osteoblasts compared with control osteoblasts. Furthermore, U0126, a MAPK/ERK1/2 inhibitor, was utilized to investigate the mechanisms underlying IL-17F. The results indicated that compared with the control group, IL-17F increased the protein expression of phosphorylated-ERK1/2, Runx2 and Osterix, whereas U0126 reversed IL-17F-mediated effects. Collectively, the results of the present study suggested that IL-17F promoted osteoblastic osteogenesis via the MAPK/ERK1/2-mediated signaling pathway. IL-17F promoted osteogenesis, including proliferation, differentiation and mineralization activity, i ndicating that IL-17F may serve as a potential therapeutic target for osteoblast-mediated bone loss disease. PMID:34434266 | PMC:PMC8353634 | DOI:10.3892/etm.2021.10486 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Association between obstructive sleep apnea and thyroid cancer incidence: a national health insurance data study

xlomafota13 shared this article with you from Inoreader Association between obstructive sleep apnea and thyroid cancer incidence: a national health insurance data study Via http://link.springer.com/journal/405,European archives of oto-rhino-laryngology,The European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino Eur Arch Otorhinolaryngol. 2021 Aug 25. doi: 10.1007/s00405-021-07050-7. Online ahead of print. NO ABSTRACT PMID:34435245 | DOI:10.1007/s00405-021-07050-7 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.