Τετάρτη 15 Σεπτεμβρίου 2021

Downregulation of NEAT1 sensitizes gemcitabine-resistant pancreatic cancer cells to gemcitabine through modulation of the miR-506-3p/ZEB2/EMT axis

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Am J Cancer Res. 2021 Aug 15;11(8):3841-3856. eCollection 2021.

ABSTRACT

Chemoresistance is a major cause of treatment failure in pancreatic cancer (PC). It has been demonstrated that epithelial-to-mesenchymal transition (EMT) is closely related to drug resistance in PC; however, the underlying mechanisms are not yet fully understood. Recently found evidence has suggested that nuclear-enriched abundant transcript 1 (NEAT1) is involved in the development of chemoresistance. However, the role and mechanism of NEAT1 in PC gemcitabine resistance remain unknown. In the present study, we first established two independent gemcitabine-resistant (GR) PC cell lines, PANC-1/GR and SW1990/GR. We found that GR cells displayed markedly enhanced migration and invasion abilities, decreased expression of E-cadherin, and upregulation of N-cadherin, Vimentin, Snail, ZEB1, and ZEB2. Our findings suggested that downregulation of NEAT1 enhanced the sensitiv ity of GR cells to gemcitabine by reversing the EMT process. Mechanistically, NEAT1 mediates ZEB2 mRNA expression through sponging miR-506-3p. Downregulation of NEAT1 can reverse the EMT process of GR PC cells by reducing the expression of ZEB2, thus enhancing the sensitivity of GR PC cells to gemcitabine. These findings were further confirmed in a nude mouse xenograft model. Taken together, downregulation of NEAT1 sensitized the GR PC cells to gemcitabine through modulation of the miR-506-3p/ZEB2/EMT axis. These results provide the novel evidence for understanding the function and molecular mechanism of NEAT1, and a new direction for improving the chemotherapeutic effects in PC.

PMID:34522453 | PMC:PMC8414385

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bFGF-mediated phosphorylation of δ-catenin increases its protein stability and the ability to induce the nuclear redistribution of β-catenin

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Am J Cancer Res. 2021 Aug 15;11(8):3877-3892. eCollection 2021.

ABSTRACT

Recently, we have shown that δ-catenin strengthened the epidermal growth factor receptor (EGFR)/Erk1/2 signaling pathway through the association between EGFR and δ-catenin. Now, we further analyzed the correlation between basic fibroblast growth factor (bFGF)/fibroblast growth factor receptor 1 (FGFR1) and δ-catenin in prostate cancer and investigated the molecular mechanism underlying the role of bFGF/FGFR1 modulation in CWR22Rv-1 (Rv-1) cells. Here, we demonstrated that bFGF phosphorylated the tyrosine residues of δ-catenin in Rv-1 cells and further proved that the bFGF mediated FGFR1/δ-catenin tyrosine phosphorylation was time dependent. Furthermore, we demonstrated that bFGF stabilized the expression of δ-catenin through weakening its association with GSK3β and enhancing its stability to induce β-catenin into the nuclear by strengthening the processing of E-cadherin. In a word, these results indicated that bFGF/FGFR1 signaling pathway could enhance the tumor progression of prostate cancer via δ-catenin.

PMID:34522455 | PMC:PMC8414378

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Phonosurgery Training in Human Larynx Preserved with Thiel’s Embalming Method

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Background: To describe the suitability of larynges preserved with Thiel's embalming method for phonosurgery training. Methods: A training model for phonosurgery techniques simulating vocal pathology and glottal insufficiency is developed to compare and evaluate the perception of embalmed vocal cords through a voluntary and anonymous survey rated on a scale of 1–5. A total of 10 residents and young otolaryngologists participated in the surgical training in phon osurgery. Results: Ten larynges preserved in formalin and 10 Thiel's embalmed larynges were used for the investigation. Phonosurgery procedures were performed following microflap and injection laryngoplasty techniques. The larynges preserved with Thiel's method demonstrated vocal cords that maintain their pliability and good tissue quality allowing a sensation of realism compared to the living body and providing suitable conditions for realistic laryngeal training. Participants held a positive experience, believed them to be useful and that these models of embalmed larynges were similar to the clinical setting and improved skills and confidence in performing phonosurgery. Conclusions: The human larynges embalmed with Thiel's method maintain the pliability of the vocal cords, thus representing a unique model to practice and reproduce training for endolaryngeal procedures without the risks of contamination, anatomical variation, or rigidity of other m odels.
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Τρίτη 14 Σεπτεμβρίου 2021

The impact of comorbid allergic airway disease on the severity and mortality of COVID-19: a systematic review and meta-analysis

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Eur Arch Otorhinolaryngol. 2021 Sep 14. doi: 10.1007/s00405-021-07072-1. Online ahead of print.

ABSTRACT

PURPOSE: To analyze the impact of AAD on the severity and mortality of COVID-19 patients and compare clinical outcomes between patients with and without AAD.

METHODS: In the systematic review and meta-analysis, we searched PubMed, Embase, Web of Science for studies reporting allergic rhinitis, asthma prevalence in COVID-19 patients and compared clinical outcomes, and excluded duplicate publications, reviews, comments, single or few cases reports (< 100 cases). We determined the pooled effect estimates using random effect model.

RESULTS: Thirty-four studies (345,091) were finally included for the meta-analysis. On the basis of 32 studies (337,821) involving with the severity of COVID-19, we did not find significant association between AAD and the severity of COVID-19 (p = 0.35, OR 1.10, 95% CI 0.90-1.35). Subgroup anal ysis indicated there was no the variability in the prevalence of AAD among COVID-19 patients in different study designs, disease categories, countries, the definition of severity, and population size of AAD. Based on 21 studies (306,331) involving with the mortality of COVID-19, AAD was significantly associated with the decreased mortality of COVID-19 (p < 0.05, OR 0.83, 95% CI 0.70-0.99). The subgroup analysis showed AAD was not associated with the mortality of COVID-19 in different countries or regions. Based on the population size of AAD, we found AAD within 100 cases was not associated with the mortality of COVID-19 (p = 0.63, OR 1.15, 95% CI 0.65-2.03). Moreover, study design was possible heterogeneity source as the heterogeneity I2 was reduced to 0 in prospective studies.

CONCLUSION: The preexisting AAD was not inclined to deteriorate the course of COVID-19. The prevalence of AAD was not associated with the severity of COVD-19 patients and inclined to be si gnificantly associated with the decreased mortality risk of COVID-19.

PMID:34519838 | DOI:10.1007/s00405-021-07072-1

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The prognostic value of before treatment neutrophil-to-lymphocyte ratio in nasopharyngeal carcinoma

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Eur Arch Otorhinolaryngol. 2021 Sep 12. doi: 10.1007/s00405-021-07070-3. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this analysis was to evaluate the prognostic significance of inflammatory biomarkers (NLR, dNLR, PLR and LMR) in NPC patients.

METHODS: This was a retrospective analysis of 111 NPC patients from January 2013 and December 2016. Receiver-operating characteristic (ROC) curve was plotted to determine the cut-off values of these inflammatory biomarkers. Univariate analysis and multivariate Cox regression model were used to evaluate the association between these parameters and progression-free survival (PFS) and overall survival (OS).

RESULTS: The optimal critical value of NLR was 2.02, by which cases were divided into high NLR group (NLR ≥ 2.02) and low NLR group (NLR < 2.02). The elevated NLR was significantly associated with decreased OS (P = 0.009) and remained significant in multivariate analysi s (HR 8.48, 95% CI 1.69-42.46, P = 0.009).

CONCLUSIONS: The before treatment NLR may be an independent prognostic biomarker for OS in patients with NPC. NLR, dNLR and PLR might be a useful complement to TNM staging in the prognosis evaluation of NPC patients.

PMID:34510259 | DOI:10.1007/s00405-021-07070-3

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Influences of GABAergic Inhibition in the Dorsal Medulla on Contralateral Swallowing Neurons in Rats

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Objectives

We aimed to examine the effect of unilateral inhibition of the medullary dorsal swallowing networks on the activities of swallowing-related cranial motor nerves and swallowing interneurons.

Methods

In 25 juvenile rats, we recorded bilateral vagal nerve activity (VNA) as well as unilateral phrenic and hypoglossal activity (HNA) during fictive swallowing elicited by electrical stimulation of the superior laryngeal nerve during control and following microinjection of the GABA agonist muscimol into the caudal dorsal medulla oblongata in a perfused brainstem preparation. In 20 animals, swallowing interneurons contralateral to the muscimol injection side were simultaneously recorded extracellularly and their firing rates were analyzed during swallowing.

Results

Integrated VNA and HNA to the injection side decreased to 49.0 ± 16.6% and 32.3 ± 17.9%, respectively. However, the VNA on the uninjected side showed little change after muscimol injection. Following local inhibition, 11 out of 20 contralateral swallowing interneurons showed either increased or decreased of their respective firing discharge during evoked-swallowing, while no significant changes in activity were observed in the remaining nine neurons.

Conclusion

The neuronal networks underlying the swallowing pattern generation in the dorsal medulla mediate the ipsilateral motor outputs and modulate the contralateral activity of swallowing interneurons, suggesting that the bilateral coordination of the swallowing central pattern generator regulates the spatiotemporal organization of pharyngeal swallowing movements.

Level of Evidence

NA Laryngoscope, 131:2187–2198, 2021

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A Case of Parotid Gland Fistula After Microtia Reconstruction Successfully Treated With Botulinum Toxin Type A

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Ear Nose Throat J. 2021 Sep 13:1455613211038325. doi: 10.1177/01455613211038325. Online ahead of print.

ABSTRACT

Parotid gland fistula after microtia reconstruction is relatively rare, with only 3 cases having been reported in the literature. It may be caused by the presence of an accessory parotid gland or surgical damage to parotid gland tissues. The principal treatment is dressing the wound. Here, we report the first case of parotid fistula after microtia reconstruction u sing a delayed retroauricular flap, which healed following wound dressing and an injection of botulinum toxin type A (CBTXA) into the parotid gland.

PMID:34510956 | DOI:10.1177/01455613211038325

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