Κυριακή 17 Οκτωβρίου 2021

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

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

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

xlomafota13 shared this article with you from Inoreader

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

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

xlomafota13 shared this article with you from Inoreader

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

Head and Neck Malignant Paragangliomas: Experience from a Single Institution

xlomafota13 shared this article with you from Inoreader

pubmed-meta-image.png

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

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

xlomafota13 shared this article with you from Inoreader

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

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

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

The clinical and financial impact of introducing robotic‐assisted hysterectomy in a tertiary referral center: a direct cost analysis of consecutive hysterectomies during a decade

xlomafota13 shared this article with you from Inoreader

Abstract

Background

Economic data and the clinical impact of introducing robotic-assisted hysterectomy in a European setting are scarce with conflicting findings.

Methods

In this retrospective cohort study, the cost and complication rate of the different approaches of hysterectomy are investigated, both benign and (pre)malignant indications were included.

Results

844 patients were included: 323 (38.3%) patients underwent robotic-assisted hysterectomy (RAH), 317 (37.5%) total abdominal hysterectomy (TAH), and 204 (24.2%) total laparoscopic hysterectomy (TLH). TAH dropped from 67.2% to 25.5% of procedures, whilst RAH rose to 41.8% of cases. The total hospitalization cost was for RAH €5208.39 (± €916.91), for TAH €5846.61 (± €4464.37) and for TLH €3790.06 (± €1267.05). The postoperative complication rate of TAH (9.1%) was significantly higher in comparison with TLH and RAH (5.4% and 3.1% respectively, p=0.005).

Conclusions

RAH h as replaced TAH in most cases, especially for large uteri, early-stage endometrial cancer and in selected endometriosis cases, resulting in reduced morbidity with lower hospitalization costs. The indications for TLH remained, including menorrhagia, adenomyosis and persistent cervical dysplasia.

This article is protected by copyright. All rights reserved.

View on the web

Long-term swallowing-related outcomes in oral cancer patients receiving proactive swallowing therapy

xlomafota13 shared this article with you from Inoreader

pubmed-meta-image.png

Oral Oncol. 2021 Oct 13;122:105569. doi: 10.1016/j.oraloncology.2021.105569. Online ahead of print.

ABSTRACT

OBJECTIVES: The present study aimed to evaluate the impact of proactive swallowing rehabilitation on swallowing function and quality of life (QoL) in oral cancer patients in the first two years after definitive treatment.

MATERIALS AND METHODS: Consecutive adult patients with locally advanced oral cancer who received radical surgery, free flap reconstruction, and adjuv ant radiotherapy were recruited prospectively, to whom proactive swallowing rehabilitation was provided. Body weight (BW); fiberoptic endoscopic evaluation of swallowing (FEES), functional oral intake scale (FOIS), and diet level; 10-item eating assessment tool (EAT-10), and MD Anderson Dysphagia Inventory (MDADI); and adherence at baseline, 1, 3, 6, 12, and 24 months were evaluated.

RESULTS: A total of 104 patients were included during May 2018 to July 2020. Compared to the baseline, significant deterioration in BW, FOIS, and MDADI was noted at one month. However, a trend of recovery was observed in FOIS from one month, and in BW and MDADI from three months. A total of 94% patients were free of tube feeding at 12 months but with a diet requiring special preparations or compensation. Safe swallowing could be achieved in approximately 90% of the participants after six months with diet modification or compensatory maneuvers. BW at 18 and 24 months did not differ significantly fr om baseline.

CONCLUSION: Proactive swallowing therapy is feasible for patients with locally advanced oral cancer receiving definitive treatments. It facilitates safe oral intake and adequate nutrition. Patients who performed swallowing exercises had a faster and better recovery in swallowing function and swallowing-related QoL.

PMID:34656054 | DOI:10.1016/j.oraloncology.2021.105569

View on the web