Melatonin attenuates low shear stress-induced pyroptosis and endothelial cell dysfunction via the RORα/miR-223/STAT-3 signalling pathway

xlomafota13 shared this article with you from Inoreader Melatonin attenuates low shear stress-induced pyroptosis and endothelial cell dysfunction via the RORα/miR-223/STAT-3 signalling pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1392. doi: 10.3892/etm.2021.10828. Epub 2021 Sep 30. ABSTRACT Endothelial cells sense changes in blood flow shear stress and affect the progression of atherosclerotic plaques. Pyroptosis is an inflammatory form of cell death and has been implicated in cardiovascular diseases. Melatonin and its nuclear receptor retinoid-related orphan receptor α (RORα) have protective effects on the development of atherosclerosis. To date, whether melatonin can prevent endothelial cell pyroptosis and dysfunction in pathological shear stress remains unclear. In the present study, human umbilical vein endothelial cells (ECs) were cultured under low shear stress conditions (5 dyne/cm2) for 24 h and treated with or without melatonin (2 µmol/l). The binding sites of the microRNA (miR)-223 promoter and RORα were predicted using the JASPAR website. Expression of pyroptosis-related proteins, including cleaved N-termin al gasdermin D, caspase-1, intercellular adhesion molecule 1 (ICAM-1) and nitric oxide (NO) were assessed. The results indicated that low shear stress increased pyroptosis and ICAM-1 expression, whereas it decreased NO levels. Melatonin alleviated pyroptosis and ICAM-1 expression and increased the production of NO in ECs. Further assessment revealed that low-level shear stress decreased RORα protein and mRNA expression, whereas melatonin would bind to RORα and thereby promoted miR-223 transcription in ECs. The present study also identified signal transducer and activator of transcription 3 (STAT-3) as a potential target gene of miR-223-3p. When transfected with miR-223 inhibitor, ECs up-regulated the expression of pyroptosis-related proteins and ICAM-1, and down-regulated NO levels. By contrast, silencing STAT-3 expression diminished the protective effect of miR-223. These results indicated that melatonin prevented ECs from undergoing pyroptosis and alleviated dysfunction via the RORα/miR-223/STAT-3 signalling pathway. This information could aid in the development of novel therapeutic approaches and provide new insights into atherosclerosis. PMID:34650640 | PMC:PMC8506941 | DOI:10.3892/etm.2021.10828 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Ecto-5'-nucleotidase (CD73) inhibits dorsal root ganglion neuronal apoptosis by promoting the Ado/cAMP/PKA/CREB pathway

xlomafota13 shared this article with you from Inoreader Ecto-5'-nucleotidase (CD73) inhibits dorsal root ganglion neuronal apoptosis by promoting the Ado/cAMP/PKA/CREB pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1374. doi: 10.3892/etm.2021.10809. Epub 2021 Sep 28. ABSTRACT Spinal cord injury (SCI) is a serious affliction that can lead to insufficient blood supply to the spinal cord, resulting in nutrient and energy deficiency in nerve cells such as neurons. In the present study, a spinal cord injury mouse model was constructed using wild-type (WT) and ecto-5'-nucleotidase (CD73)-/- mice. The results of TUNEL and immunofluorescence assays indicated that the apoptosis of neurons in CD73-/- mice was increased after spinal cord injury. Dorsal root ganglion (DRG) neurons from WT and CD73-/- mice were cultured in low glucose and hypoxic conditions to simulate the effects of spinal cord injury on neurons. Subsequently, a western blot assay was used to detect the expression of CD73, caspase-3 and Bcl-2. Flow cytometry was used to detect cell apoptosis and the corresponding kits were used to detect changes in lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), reactive oxygen species (ROS), adenosine triphosphate (ATP) and cell activity. The results revealed that the apoptosis level of CD73-overexpressing DRG neurons was decreased under anoxia and glucose deficiency. The release of LDH, MDA and the production of ROS in CD73 DRG neurons was decreased, while the synthesis of ATP, the activity of SOD and cell activity increased after hypoxia-hypoglycemia treatment. Additional cellular studies demonstrated that blocking the expression and hydrolase activity of CD73 with α,β-methylene ADP (APCP) could counteract the protective effect of CD73 on neuronal apoptosis, while adenosine (Ado) could rescue the increased apoptosis caused by CD73 deletion. In addition, the cAMP/ protein kinase A (PKA)/cAMP response element-binding protein (CREB) signaling pathway was also positively regulated by CD73 and Ado. In conclusion, CD73 could inhibit DRG neurona l apoptosis by promoting the Ado/cAMP/PKA/CREB pathway. PMID:34650622 | PMC:PMC8506929 | DOI:10.3892/etm.2021.10809 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Tat-thioredoxin 1 reduces inflammation by inhibiting pro-inflammatory cytokines and modulating MAPK signaling

xlomafota13 shared this article with you from Inoreader Tat-thioredoxin 1 reduces inflammation by inhibiting pro-inflammatory cytokines and modulating MAPK signaling Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1395. doi: 10.3892/etm.2021.10831. Epub 2021 Oct 1. ABSTRACT Thioredoxin 1 (Trx1) serves a central role in redox homeostasis. It is involved in numerous other processes, including oxidative stress and apoptosis. However, to the best of our knowledge, the role of Trx1 in inflammation remains to be explored. The present study investigated the function and mechanism of cell permeable fused Tat-Trx1 protein in macrophages and a mouse model. Transduction levels of Tat-Trx1 were determined via western blotting. Cellular distribution of transduced Tat-Trx1 was determined by fluorescence microscopy. 2',7'-Dichlorofluorescein diacetate and TUNEL staining were performed to determine the production of reactive oxygen species and DNA fragmentation. Protein and gene expression were measured by western blotting and reverse transcription-quantitative PCR (RT-qPCR), respectively. Effects of skin inflammation were determine d using hematoxylin and eosin staining, changes in ear weight and ear thickness, and RT-qPCR in ear edema animal models. Transduced Tat-Trx1 inhibited lipopolysaccharide-induced cytotoxicity and activation of NF-κB, MAPK and Akt. Additionally, Tat-Trx1 markedly reduced the production of inducible nitric oxide synthase, cyclooxygenase-2, IL-1β, IL-6 and TNF-α in macrophages. In a 12-O-tetradecanoylphorbol-13-acetate-induced mouse model, Tat-Trx1 reduced inflammatory damage by inhibiting inflammatory mediator and cytokine production. Collectively, these results demonstrated that Tat-Trx1 could exert anti-inflammatory effects by inhibiting the production of pro-inflammatory mediators and cytokines and by modulating MAPK signaling. Therefore, Tat-Trx1 may be a useful therapeutic agent for diseases induced by inflammatory damage. PMID:34650643 | PMC:PMC8506951 | DOI:10.3892/etm.2021.10831 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Heparin alleviates LPS-induced endothelial injury by regulating the TLR4/MyD88 signaling pathway

xlomafota13 shared this article with you from Inoreader Heparin alleviates LPS-induced endothelial injury by regulating the TLR4/MyD88 signaling pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1397. doi: 10.3892/etm.2021.10833. Epub 2021 Oct 1. ABSTRACT Heparin is a commonly used in the clinic, however, Heparin's effect on endothelial injury remains unclear. The aim of the present study was to evaluate the effects and possible mechanisms of action underlying heparin treatment in lipopolysaccharide (LPS)-induced endothelial injury in vitro. TNF-α, IL-1β, IL-6 and IFN-γ levels were measured using ELISA. Cell proliferation was measured using a 5-ethynyl-2'-deoxyuridine (EdU) assay. The number of apoptotic cells and apoptotic rate were evaluated using TUNEL assays and flow cytometry, respectively. Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88) and NF-κB (p65) gene expression was evaluated using reverse transcription-quantitative PCR, whilst TLR4, MyD88 and p-NF-κB (p65) protein expression was evaluated using western blot analysis. The levels of phosphoryl ated NF-κB in the nucleus were evaluated using cellular immunofluorescence. Compared with those in the normal control group, TNF-α, IL-1β, IL-6 and IFN-γ levels were significantly increased in the LPS group (P<0.001). In addition, 5-ethynyl-2'-deoxyuridine (EdU)-positive cells were significantly increased and apoptosis was significantly decreased (P<0.001). TLR4, MyD88 and NF-κB (p65) expression was also significantly increased (P<0.001). Compared with those in the LPS group, following heparin treatment, TNF-α, IL-1β, IL-6 and IFN-γ levels were significantly decreased (P<0.05), whilst the number of EdU-positive cells was significantly increased and the level of apoptosis was significantly decreased (P<0.05). TLR4, MyD88 and NF-κB (p65) expression was also significantly decreased by heparin in a dose-dependent manner (P<0.001). Small interfering RNA-TLR4 transfection exerted similar effects to those mediated by heparin in alleviating endothelial injury. In conclusion, heparin suppressed LPS-induced endothelial injury through the regulation of TLR4/MyD88/NF-κB (p65) signaling in vitro. PMID:34650645 | PMC:PMC8506914 | DOI:10.3892/etm.2021.10833 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Electrostatic Discharge (ESD) as a Cause of Facial Nerve Stimulation After Cochlear Implantation: A Case Report

xlomafota13 shared this article with you from Inoreader Electrostatic Discharge (ESD) as a Cause of Facial Nerve Stimulation After Cochlear Implantation: A Case Report Via otol rhinol Ann Otol Rhinol Laryngol. 2021 Oct 15:34894211051229. doi: 10.1177/00034894211051229. Online ahead of print. ABSTRACT OBJECTIVE: To discuss persistent facial nerve stimulation (FNS) related to repeated electrostatic discharge (ESD) shock following cochlear implantation. METHODS: Single case report with literature review. RESULTS: FNS is a feared complication after cochlear implantation, occurring in approximately 7% of cases, with most patients having anatomic ab normalities. The presented case has no anatomical abnormalities but reported frequent environmental static shock. FNS during the first 1 to 3 seconds of processor attachment caused a significant decrease in the patient's quality of life, requiring subsequent re-implantation with full resolution. CONCLUSIONS: FNS is a complication of cochlear implantation that can cause a great deal of distress and discomfort. Frequent electrostatic discharge (ESD) contributed to device malfunctioning and FNS in a patient with otherwise normal anatomy and should be avoided if possible. PMID:34651510 | DOI:10.1177/0003489421105122 9 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Magnetic resonance angiographic study of variations in course of paraclival and parasellar internal carotid artery in relation to expanded endonasal endoscopic approaches

xlomafota13 shared this article with you from Inoreader Magnetic resonance angiographic study of variations in course of paraclival and parasellar internal carotid artery in relation to expanded endonasal endoscopic approaches 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 Oct 15. doi: 10.1007/s00405-021-07123-7. Online ahead of print. ABSTRACT AIMS: To study the variations in the course of the paraclival and parasellar carotid arteries in normal subjects using magnetic resonance angiography as is relevant from an endoscopic endonasal perspective. METHODS: Two hundred MR angiographies of normal subjects were analyzed in a prospective study. The intercarotid distances were measured at fixed points along the paraclival and parasellar segments of the internal carotid artery. The intercarotid spaces thus obtained were categorized into trapezoid, square and hourglass shapes. The angle between the posterior ascending vertical and horizontal bend of the parasellar ICA was also measured and analyzed. RESULTS: The trapezoid shape of intercarotid space is the most common (52.5%), followed by the square (35%) and the hourglass (12.5%) shaped spaces. Angle of < 80° bet ween the posterior ascending vertical and horizontal bend of the parasellar ICA was found in 39% of subjects, angle between 80° and 100° was found in 9% subjects, angle > 100° was found in 43% while asymmetric angles on the two sides was found in 9% of subjects. CONCLUSION: A thorough understanding of the course of the ICA is important in planning the approach and preventing injury to the ICA. PMID:34652526 | DOI:10.1007/s00405-021-07123-7 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Endoscopic Orientation of Juxta-Pituitary Carotid in Transsphenoidal Approaches: Critical Considerations for Clinical Applications

xlomafota13 shared this article with you from Inoreader Endoscopic Orientation of Juxta-Pituitary Carotid in Transsphenoidal Approaches: Critical Considerations for Clinical Applications Via Otolaryngology Indian Abstract Accidental injury of the internal carotid artery (ICA) remains one of the most challenging complications reported in the endoscopic endonasal transsphenoidal approaches (EETA) particularly, in sphenoid sinuses with ill-defined carotid bony landmarks. The purpose of this study was to describe an anatomical model for the endoscopic orientation of juxta-pituitary segment of ICA in relation to the lateral optico-carotid recess (OCR) as a nearby bony landmark. Cadaveric dissection was conducted progressively in twenty fresh adult cadavers simulating the EETA. After reducing posterior and lateral walls of sphenoid sinuses, various measurements were taken from both lateral OCRs to "contact points" of the juxta-pituitary segment of ICA and lateral margins of the pituitary gland. Current results have enabled us to divide the region between lateral OCRs into three compartments. Two lateral parasellar compartments contain juxta-pituitary segments of ICA showing a mean wid th of 8 mm; with a narrow range of 7–10 mm; and a central inter-carotid sellar compartment represents the safe region for bone drilling showing widely variable widths ranging between 9 to 20 mm. In all specimens; variation in the width of the inter-carotid compartment correlated with the distance between both lateral OCRs. This study improves surgeons' awareness of the ICA course variations in the EETA through sphenoid sinuses with ill-defined bony landmarks. An appreciation of the measurements gathered from this study can help in operative training, and can also provide a base for future studies to confirm ICA courses associated with higher risk of injury. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Influence of Life Style Factors on Oral Potentially Malignant and Malignant Disorders: A Cross Sectional Study

xlomafota13 shared this article with you from Inoreader Influence of Life Style Factors on Oral Potentially Malignant and Malignant Disorders: A Cross Sectional Study Via Otolaryngology Indian Abstract The incidence of oral cancer has risen in the past decades and is usually recognised when symptomatic and at a late stage. A premalignant lesion is like smoldering volcano, which if not taken care of, may erupt, often with disastrous consequences. Early detection is therefore very important to reduce morbidity and mortality. A descriptive cross-sectional study was done to assess the prevalence, clinical presentation, and association of various addiction habits in the patients who presented with potentially malignant and malignant lesions of the oral cavity in outdoor clinics of ENT and HNS department of a tertiary care center in Jaipur (Rajasthan). 351 patients of different oral mucosal lesions were examined from August 2019 to January 2020 among which 173(49.2%) patients of potentially malignant and malignant lesions comprise the study group. Clinical findings and detailed history including addiction habits with frequency and duration were noted. Cytological a nd histopathological examinations were done to conclude the diagnosis. Out of 173 patients of the study group, 146(84.4%) were diagnosed with potentially malignant lesions (PMLs) and 27(15.6%) with malignant lesions (MLs). The most prevalent PML was Oral submucous fibrosis (23%) followed by leukoplakia (7.6%). The most common involved site was buccal mucosa (45.0%) followed by the tongue (26.5%). Tobacco consumption was the most prevalent addiction habit (80%) in the study group. High prevalence of tobacco abuse in patients with potentially malignant and malignant lesions suggested a strong relationship between two. It necessitates adequate awareness in the general population as well as early detection and management of these lesions by an expert Otolaryngologist. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Head and Neck Malignant Paragangliomas: Experience from a Single Institution

xlomafota13 shared this article with you from Inoreader Head and Neck Malignant Paragangliomas: Experience from a Single Institution Via ear nose throat Ear Nose Throat J. 2021 Oct 15:1455613211052338. doi: 10.1177/01455613211052338. Online ahead of print. ABSTRACT Objectives: To summarize the clinicopathological and genetic features of malignant paragangliomas in head and neck cancer and to explore the appropriate treatment options for this rare lesion. Methods: Six patients harboring head and neck malignant paraganglioma from Beijing Tongren Hospital were retrospectively reviewed. The clinicopathological char acteristics, gene mutations, and prognosis of these patients were analyzed. Results: Of these 6 patients, 3 were male and 3 were female; 4 patients harbored malignant carotid body tumors, and two had malignant vagal paragangliomas. Three patients had cervical lymph node metastasis, two presented with lung and bone metastasis, and 1 had lung and liver metastasis. Of the 6 patients, four underwent surgical resection, and the other two patients denied surgery and instead received chemotherapy with paclitaxel, ifosfamide, and dacarbazine. These 2 patients with vagal paraganglioma received postoperative radiotherapy. All 6 patients are still alive at the present time, with a median follow-up time of 66 months. Positive Ki-67 expression in tumor tissue ranged from 1% to 40%. Genetic mutations in SDHD, SDHB, ATR, and MAP3K13 were identified in 4 patients. Conclusions: After comprehensive treatment, head and neck malignant paraganglioma can attain a favorable prognosis. Geneti c mutations are commonly detected in patients with malignant paragangliomas. This study also identified mutations in ATR and MAP3K13 in these patients. PMID:34654328 | DOI:10.1177/01455613211052338 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Coblation supraglottoplasty: a ten-year experience in a tertiary referral hospital

xlomafota13 shared this article with you from Inoreader Coblation supraglottoplasty: a ten-year experience in a tertiary referral hospital 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 Oct 16. doi: 10.1007/s00405-021-07130-8. Online ahead of print. ABSTRACT PURPOSE: The present study aims to review the outcomes of coblation supraglottoplasty performed for children with different types of laryngomalacia, and we discuss the factors affecting these outcomes. METHODS: We retrospectively reviewed the medical records of laryngomalacia patients admitted to the Otorhinolaryngology Department, Mansoura University, from 2010 to 2020. We examined the patient's demography, symptoms, comorbidities, type of laryngomalacia, oxygen saturation, and final outcomes. RESULTS: Our study included 235 patients; 122 patients responded to medical therapy, while 113 underwent surgical management. There is a significant relation between the types and therapy they underwent (p ≤ 0.001). Larger percentage within type I underwent medical therapy. There is a statistically significant difference between the studied groups regarding age at surgery. On pairwise comparison, patients with type II had the lowest age significantly at the surgery when compared with each other individual group (p ≤ 0.001). On multivariate regression analysis, the presence of comorbid congenital heart disease, neurological comorbidities significantly increased the risk of failure of surgical intervention by 17.32 and 5.803 folds, respectively. CONCLUSIONS: Coblation supraglottoplasty is effective and safe to treat severe laryngomalacia. Different morphological types of laryngomalacia require slight surgical variations of coblation supraglottoplasty. The presence of comorbid congenital heart disease, neurological comorbidities significantly increased the risk of failure of surgical intervention. PMID:34654950 | DOI:10.1007/s00405-021-07130-8 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Preclinical Implementation of a Steerable, Da Vinci Xi ® Compatible CO2‐Laser Fiber Carrier for Transoral Robotic Surgery (TORS): a Cadaveric Feasibility Study

xlomafota13 shared this article with you from Inoreader Preclinical Implementation of a Steerable, Da Vinci Xi ® Compatible CO2‐Laser Fiber Carrier for Transoral Robotic Surgery (TORS): a Cadaveric Feasibility Study Via The International Journal of Medical Robotics and Computer Assisted Surgery Abstract Introduction Monopolar electrocautery is the most common dissection and coagulation tool during transoral robotic surgery (TORS) but causes significant collateral tissue damage as opposed to CO2 laser. We aimed at combining both modalities in one robotic instrument arm. Methods We developed a steerable CO2-laser fiber carrier serving as an add-on to the existing Endowrist® monopolar spatula of the Da Vinci Xi. Feasibility and safety were assessed in a preclinical setting. Results One radical tonsillectomy with monopolar cautery and 3 with the instrument prototype were performed in 2 cadavers by 2 surgeons. No serious prototype-related intra-operative difficulties were observed. Safe and efficient switching between energy sources proved possible in all simulated intra-operative bleeding events. Prototype use allowed for the identification of the majority of key anatomical structures and was scored favorably on NASA-TLX ques tionnaires. Discussion The reported prototype successfully combines the advantages of CO2-laser with the advantages of TORS. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.