Monday, March 15, 2021

Ethylparaben induces subconjunctival fibrosis via the Wnt/β-catenin signaling pathway

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Exp Ther Med. 2021 Apr;21(4):295. doi: 10.3892/etm.2021.9726. Epub 2021 Jan 28.

ABSTRACT

The aim of the present study was to explore the etiology of subconjunctival fibrosis (SCF) induced by ethylparaben, the most prevalent preservative in Chinese eye drops. Ethylparaben was administered to the left eyes of male Sprague-Dawley rats in the experimental group twice daily for 1 month, whereas the control group received PBS. Experimental group rats displayed a mild promotion in density of fibroblasts and a tighter deposition of collagen in the bulbar subepithelial connective tissue compared with the control group. Furthermore, the present findings revealed that extracellular matrix expression was promoted in murine bulbar conjunctival tissues in the experimental group. In primary conjunctival fibroblasts, expression of ECM triggered by ethylparaben was suppressed by XAV-939. Furthermore, stimulation of the Wnt/β-catenin axis triggered by ethylparaben was impaired by XAV-939. In conclusion, SCF triggered by ethylparaben results from extra ECM generation of conjunctival fibroblasts via the Wnt/β-catenin axis.

PMID:33717238 | PMC:PMC7885073 | DOI:10.3892/etm.2021.9726

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The miR-136-5p/ROCK1 axis suppresses invasion and migration, and enhances cisplatin sensitivity in head and neck cancer cells

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Exp Ther Med. 2021 Apr;21(4):317. doi: 10.3892/etm.2021.9748. Epub 2021 Feb 3.

ABSTRACT

Laryngeal squamous cell carcinoma (LSCC) and hypopharyngeal squamous cell carcinoma (HPSCC) are two types of head and neck cancers with high incidence rates and relatively poor prognoses. The aim of the present study was to determine the effects of microRNA (miR/miRNA)-136-5p and its downstream target, Rho-associated coiled-coil containing protein kinase 1 (ROCK1), on LSCC and HPSCC progression and cisplatin sensitivity. The miRNA and protein expression levels in head and neck cancer cell lines were evaluated using reverse transcription-quantitative PCR and western blotting, respectively. MTT, wound healing assays, transwell assays and flow cytometry analysis were performed to measure cell properties. The binding between miR-136-5p and ROCK1 was detected using a dual-luciferase reporter assay. Autophagy double-labeled adenoviral infection assays wer e used to assess cell autophagy. The results showed that miR-136-5p was expressed in LSCC and HPSCC cells. Functional experiments showed that the expression of miR-136-5p in LSCC and HPSCC cells was negatively correlated with cell viability, invasion and migration. Additionally, miR-136-5p overexpression inhibited epithelial-mesenchymal transition, whereas miR-136-5p knockdown had the opposite effect. Dual-luciferase reporter assays confirmed the targeting relationship between miR-136-5p and ROCK1. miR-136-5p overexpression increased the cisplatin sensitivity of LSCC and HPSCC cells by reducing cell viability, as well as promoting cell apoptosis and autophagy. miR-136-5p overexpression decreased the expression levels of its downstream target ROCK1 and attenuated activity of the Akt/mTOR signaling pathway in cisplatin-treated LSCC and HPSCC cells. Conversely, miR-136-5p knockdown increased ROCK1 levels and decreased cisplatin sensitivity of the LSCC and HPSCC cells by increasing cell viability and inhibiting cell apoptosis, which was reversed by ROCK1 inhibition using the ROCK1 inhibitor, Y27632. Taken together, the results showed that the miR-136-5p/ROCK1 axis inhibits cell invasion and migration, and increases the sensitivity of LSCC and HPSCC cells to cisplatin.

PMID:33717260 | PMC:PMC7885062 | DOI:10. 3892/etm.2021.9748

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Diammonium glycyrrhizinate lipid ligand ameliorates lipopolysaccharide-induced acute lung injury by modulating vascular endothelial barrier function

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Exp Ther Med. 2021 Apr;21(4):303. doi: 10.3892/etm.2021.9734. Epub 2021 Jan 29.

ABSTRACT

The aim of the present study was to investigate the effects of diammonium glycyrrhizinate lipid ligand (DGLL) treatment on acute lung injury (ALI) and pulmonary edema induced by lipopolysaccharide (LPS) in Sprague-Dawley rats. Rats orally received 30, 60 and 120 mg/kg DGLL. After 1 h, the rat ALI model was established by LPS (10 mg/kg) intraperitoneal injection. After 6 h, lung injury was evaluated using hematoxylin and eosin staining techniques. Pulmonary edema was evaluated using lung wet-dry weight ratio, protein concentrations in the bronchoalveolar lavage fluid (BALF) and Evans blue (EB) extravasation in lung tissue. The expression levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in lung tissues were measured using ELISA. Myeloperoxidase (MPO) expression levels were detected by immunohistochemical staining. Western blotting wa s used to measure the expression level changes of intercellular adhesion molecule (ICAM)-1, as well as adherent and tight junction proteins, including vascular endothelial (VE)-cadherin, zonula occludens (ZO)-1, occludin and junctional adhesion molecule (JAM)-1 that were associated with pulmonary inflammation and microvascular permeability. DGLL treatment significantly alleviated ALI induced by LPS, which was demonstrated by reduction of MPO-positive cells and expression levels of TNF-α, IL-1β and ICAM-1 in rat lung tissues. In addition, DGLL abrogated LPS-induced pulmonary edema, decreased the protein concentration in BALF and reduced EB extravasation. DGLL also reversed the reduced expression of VE-cadherin and tight junction proteins, including ZO-1, occludin and JAM-1 in the lung tissues caused by LPS. In conclusion, DGLL exhibits a protective effect on LPS-induced rat ALI, which is associated with the inhibition of inflammatory cell infiltration and microvascular barrier disr uption. The present results provide a theoretical basis for the application of DGLL for the potential clinical treatment of ALI.

PMID:33717246 | PMC:PMC7885082 | DOI:10.3892/etm.2021.9734

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Long-Term Outcomes and Prognoses of Elderly Patients (≥65-Years-Old) With Distant Metastases From Well-Differentiated Thyroid Cancer During Radioiodine Therapy and Follow-Up

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Front Endocrinol (Lausanne). 2021 Feb 25;11:588024. doi: 10.3389/fendo.2020.588024. eCollection 2020.

ABSTRACT

OBJECTIVE: The objective of this study was to investigate the clinicopathological characteristics, long-term outcomes, and prognostic factors of elderly patients with distant metastases at initial diagnosis from well-differentiated thyroid cancer (WDTC) during radioactive iodine (131I) treatment and follow-up.

METHODS: A retrospective review of medical rec ords identified 183 elderly patients with DTC who underwent 131I treatment at our institution between 2006 and 2019.

RESULTS: In total, 57 elderly WDTC patients with distant metastases were enrolled in this study. After 131I treatment, 32 (56.14%) patients had 131I avidity and 25 (43.86%) had non-131I avidity; 35 (61.40%) cases were classified as radioiodine refractory (RR)-WDTC and 22 (38.60%) as non-RR-WDTC. At the end of follow-up, 25 (43.86%) patients had died and 32 (56.14%) were alive. The 5- and 10-year overall survival (OS) rates were 71.50% and 30.49%, respectively, while the 5- and 10-year disease-specific survival (DSS) rates were 76.89% and 48.71%, respectively. Multivariate analyses showed that gross extrathyroidal extension and RR-DTC were independent prognostic factors for poor OS (P=0.04 and P=0.03, respectively), while gross extrathyroidal extension, extrapulmonary distant metastases, and RR-WDTC were independent pro gnostic factors for poor DSS at the end of follow-up (P=0.02, P=0.03, and P=0.02, respectively).

CONCLUSIONS: WDTC with distant metastases at initial diagnosis accounted for 31.15% of all elderly patients with DTC. Gross extrathyroidal extension and RR-DTC were the major factors associated with poor OS; gross extrathyroidal extension, extrapulmonary distant metastases, and RR-DTC were independent prognostic factors for poor DSS in elderly DTC patients with distant metastases.

PMID:33716950 | PMC:PMC7947854 | DOI:10.3389/fendo.2020.588024

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Utility of Stimulated Thyroglobulin in Reclassifying Low Risk Thyroid Cancer Patients' Following Thyroidectomy and Radioactive Iodine Ablation: A 7-Year Prospective Trial

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Front Endocrinol (Lausanne). 2021 Feb 24;11:603432. doi: 10.3389/fendo.2020.603432. eCollection 2020.

ABSTRACT

CONTEXT: Following total thyroidectomy and radioactive iodine (RAI) ablation, serum thyroglobulin levels should be undetectable to assure that patients are excellent responders and at very low risk of recurrence.

OBJECTIVE: To assess the utility of stimulated (sTg) and non-stimulated (nsTg) thyroglobulin levels in prediction of patients outcomes with differentiated t hyroid cancer (DTC) following total thyroidectomy and RAI ablation.

METHOD: A prospective observational study conducted at a University Hospital in Saudi Arabia. Patients diagnosed with differentiated thyroid cancer and were post total thyroidectomy and RAI ablation. Thyroglobulin levels (nsTg and sTg) were estimated 3-6 months post-RAI. Patients with nsTg <2 ng/ml were stratified based on their levels and were followed-up for 5 years and clinical responses were measured.

RESULTS: Of 196 patients, nsTg levels were <0.1 ng/ml in 122 (62%) patients and 0.1-2.0 ng/ml in 74 (38%). Of 122 patients with nsTg <0.1 ng/ml, 120 (98%) had sTg levels <1 ng/ml, with no structural or functional disease. sTg levels >1 occurred in 26 (35%) of patients with nsTg 0.1-2.0 ng/ml, 11 (15%) had structural incomplete response. None of the patients with sTg levels <1 ng/ml developed structural or functional disease over the follow-up period.

CONCLUSION: Suppressed thyrog lobulin (nsTg < 0.1 ng/ml) indicates a very low risk of recurrence that does not require stimulation. Stimulated thyroglobulin is beneficial with nsTg 0.1-2 ng/ml for re-classifying patients and estimating their risk for incomplete responses over a 7 years follow-up period.

PMID:33716951 | PMC:PMC7945948 | DOI:10.3389/f endo.2020.603432

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2021 European Thyroid Association Guideline on Thyroid Disorders prior to and during Assisted Reproduction

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Eur Thyroid J. 2021 Feb;9(6):281-295. doi: 10.1159/000512790. Epub 2021 Jan 21.

ABSTRACT

Severe thyroid dysfunction may lead to menstrual disorders and subfertility. Fertility problems may persist even after restoring normal thyroid function, and then an assisted reproductive technology (ART) may be a solution. Prior to an ART treatment, ovarian stimulation is performed, leading to high oestradiol levels, which may lead to hypothyroidism in women with thyroid autoimmunity (TAI), ne cessitating levothyroxine (LT4) supplements before pregnancy. Moreover, women with the polycystic ovarian syndrome and idiopathic subfertility have a higher prevalence of TAI. Women with hypothyroidism treated with LT4 prior to ART should have a serum TSH level <2.5 mIU/L. Subfertile women with hyperthyroidism planning an ART procedure should be informed of the increased risk of maternal and foetal complications, and euthyroidism should be restored and maintained for several months prior to an ART treatment. Fertilisation rates and embryo quality may be impaired in women with TSH >4.0 mIU/L and improved with LT4 therapy. In meta-analyses that mainly included women with TSH levels >4.0 mIU/L, LT4 treatment increased live birth rates, but that was not the case in 2 recent interventional studies in euthyroid women with TAI. The importance of the increased use of intracytoplasmic sperm injection as a type of ART on pregnancy outcomes in women with TAI deserves more investigatio n. For all of the above reasons, women of subfertile couples should be screened routinely for the presence of thyroid disorders.

PMID:33718252 | PMC:PMC7923920 | DOI:10.1159/000512790

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Update on molecular biomarkers for diagnosis and prediction of prognosis and treatment responses in gastric cancer

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Histol Histopathol. 2021 Mar 9:18326. doi: 10.14670/HH-18-326. Online ahead of print.

ABSTRACT

Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide, and its high mortality rate is a serious problem in many regions. To improve prognosis, it is necessary to identify novel biomarkers for the early detection of GC, along with its prognosis, risk of metastatic recurrence, and predicted response to chemotherapy, and to develop individualized treatment strategies. Advances in microarray and sequencing techniques have led to the elucidation of cancer-related gene mutations and aberrant expression levels, which have deepened our knowledge of GC. Further searches for sensitive biomarkers are needed to improve the management of patients with GC. In this review article, we update the current knowledge of GC biomarkers, examine recently published literature, and introduce some representative molecules.

PMID:33719028 | DOI:10.14670/HH-18-326

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The Thermal Damage of Canine Vocal Fold by CO2 Laser Under Different Laser Emission Mode

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Ear Nose Throat J. 2021 Mar 15:145561321999262. doi: 10.1177/0145561321999262. Online ahead of print.

ABSTRACT

OBJECTIVE: The purpose of this study is to review the differences between continuous wave (CW) and UltraPulse (UP) on thermal damage of the laser with different power.

METHODS: Four adult beagle dogs underwent transoral laser microsurgery (TLM) using CO2 laser. The laser emission mode and power was CW (3 W, 5 W, and 8 W) and UP (3 W and 5 W), respec tively. The tissue from 4 animals was evaluated histologically on postoperative days 1 and 3. The thermal damage of the laser was measured using slide scan system via SlideViewer version 1.5.5.2 software.

RESULTS: All dogs underwent TLM uneventfully. Under microscope examined, the laser damage area was composed of 2 parts: the vaporized zone (VPZ) and thermal damage area. The thermal damage area can be divided into thermal coagulative necrosis area (TCN) and hydropic degeneration area. The width of VPZ and TCN in UP mode was less than that in CW mode (P < .01). The data indicate that lower laser power created less thermal damage (P < .01). In addition, the width of VPZ on postoperative day 3 was less than that on postoperative day 1 (P < .01).

CONCLUSION: CO2 laser with UP and lower power could decrease the laser thermal damage and may offer more prompt wound healing.

PMID:33719628 | DOI:10.1177/0145561321999262

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Comparison of Endoscopic Cartilage Myringoplasty in Dry and Wet Ears With Chronic Suppurative Otitis Media

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Ear Nose Throat J. 2021 Mar 15:145561321999263. doi: 10.1177/0145561321999263. Online ahead of print.

ABSTRACT

OBJECTIVES: This study compared the rate of graft success, as well as hearing improvement and dry ear time between dry ears and wet ears with otomycosis or without otomycosis in patients with chronic suppurative otitis media (CSOM) after endoscopic cartilage myringoplasty.

METHODS: This retrospective study was conducted in a tertiary hospital in Shanghai. In t otal, 83 patients with CSOM (43 with dry ears and 40 with wet ears) were included. Among the 40 patients with CSOM and wet ears, 25 exhibited otomycosis. All patients underwent endoscopic myringoplasty, and perforations were repaired using tragal cartilage with a single-sided perichondrium. Patients were followed up for at least 6 months. Pure-tone hearing was examined preoperatively and at 3 months postoperatively. The graft uptake rate, hearing improvement, and dry ear time were compared between the groups.

RESULTS: The graft success rate did not differ significantly between the dry-ear and wet-ear groups (95.35% and 90.00%, respectively). Furthermore, the graft success rate also did not differ significantly between patients with wet ears and otomycosis and those with wet ears without otomycosis (92.00% and 86.67%, respectively). Hearing gain did not differ significantly between the dry-ear and wet-ear groups. No significant difference in hearing gain was also found in patie nts with wet ears with or without otomycosis. However, the time to dry ear was significantly longer in the wet-ear group than in the dry-ear group.

CONCLUSION: Patients with CSOM and wet ears required more time to achieve a completely healthy status. However, the graft success rate and hearing improvement were not affected by a wet middle ear and otomycosis. Thus, endoscopic myringoplasty using tragus cartilage is an effective treatment for refractory CSOM in patients with wet ears and otomycosis.

PMID:33719601 | DOI:10.1177/0145561321999263

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An Oropharyngeal Obstructive Lesion in a Neonate

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Ear Nose Throat J. 2021 Mar 15:145561321995014. doi: 10.1177/0145561321995014. Online ahead of print.

ABSTRACT

Neonatal HNT in the pharynx is a rare cause of respiratory distress and poor feeding in the newborn, but must be differentiated from teratoma, encephalocele, and nasal glioma. While surgical resection is the preferred treatment modality, we posit there is a role for sclerosis of the glial heterotopic cyst if complete surgical excision is not possible or carries risk of high morbidity. Here, we present a case of a 7-day-old neonate presenting with acute respiratory distress found to have a nasopharyngeal/oropharyngeal mass ultimately treated with sclerotherapy at 9 months of age.

PMID:33719614 | DOI:10.1177/0145561321995014

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