Αρχειοθήκη ιστολογίου

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Πέμπτη 25 Νοεμβρίου 2021

Long non-coding RNA profiles in plasma exosomes of patients with gastric high-grade intraepithelial neoplasia

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Exp Ther Med. 2022 Jan;23(1):1. doi: 10.3892/etm.2021.10923. Epub 2021 Oct 26.

ABSTRACT

Long non-coding (lnc) RNAs in circulating exosomes are a new class of promising cancer biomarkers; however, their expression in exosomes derived from gastric high-grade intraepithelial neoplasia (GHGIN) has not been reported. In the present study, differentially expressed (DE) lncRNAs were analyzed in the peripheral blood collected from 5 patients with GHGIN and 5 healthy donors using high-throughput sequencing. Reverse transcription-quantitative PCR analysis was performed on 6 randomly selected DE lncRNAs to validate the reliability of the sequencing results. The potential roles of the DE lncRNAs in GHGIN were investigated using Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analyses. A total of 25,145 lncRNAs were identified in all the samples and 83 DE lncRNAs were further screened, including 76 upregulated and 7 downregulated DE lncRNAs. GO and KEGG analyses predicted that the DE lncRNAs played notable roles in 'protein/macromolecule glycosylation', 'regulation of protein ubiquitination', 'renin-angiotensin system' and 'MAPK signaling pathways'. A lncRNA-micro (mi)RNA-mRNA interaction network was constructed and used to perform association analyses. It was found that 83 lncRNAs were abnormally expressed in GHGIN, with some potential functions associated with gastric cancer. Furthermore, the lncRNA-miRNA-mRNA interaction network indicated that 7 DE lncRNAs may play a notable role in the occurrence and development of GHGIN. The results of the present study showed the expression profiles of lncRNAs in human GHGIN, elucidated some of the molecular changes associated with GHGIN and improved the understanding of the molecular mechanisms underlying GHGIN and gastric cancer.

PMID:34815753 | PMC:PMC8593877 | DOI:10.3892/etm.2021.10923

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Altered Wnt5a expression affects radiosensitivity of non-small cell lung cancer via the Wnt/β-catenin pathway

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Exp Ther Med. 2022 Jan;23(1):5. doi: 10.3892/etm.2021.10927. Epub 2021 Oct 26.

ABSTRACT

It has been reported that upregulation of wingless-type protein 5a (Wnt5a) is associated with poor prognosis in patients with non-small cell lung cancer (NSCLC). Wnt5a expression is often upregulated in radiation-resistant NSCLC cells. However, the biological functions or molecular mechanisms of radiosensitivity in NSCLC remain unknown. In the present study, MTT assay and flow cytometric analysis were performed to assess the effect of overexpression or knockdown of Wnt5a and/or radiation on the proliferation and apoptosis of NSCLC cells. Furthermore, western blot analysis was performed to detect canonical Wnt signaling (β-catenin) in H1650 and A549 cells. The results demonstrated that Wnt5a knockdown combined with irradiation inhibited proliferation and induced apoptosis in NSCLC cells compared with Wnt5a knockdown or radiotherapy alone. In additio n, the combination of Wnt5a knockdown and irradiation decreased nuclear and increased cytoplasmic β-catenin expression in H1650 and A549 cells, the effects of which were reversed following overexpression of Wnt5a. The combination of overexpressing Wnt5a and irradiation resulted in significant tumor regression, while β-catenin knockdown reversed Wnt5a overexpression-induced NSCLC cell proliferation. Taken together, these results suggest that Wnt5a may be involved in the activation of β-catenin-dependent canonical Wnt signaling, and thus may influence the effectiveness of radiation therapy in NSCLC.

PMID:34815757 | PMC:PMC8593861 | DOI:10.3892/etm.2021.10927

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Influence of pemphigoid gestationis on pregnancy outcome: A case report and review of the literature

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Exp Ther Med. 2022 Jan;23(1):23. doi: 10.3892/etm.2021.10945. Epub 2021 Nov 4.

ABSTRACT

Pemphigoid gestationis is considered to be a rare pregnancy exclusive bullous disease, which modifies the course of the pregnancy, with difficulties in the management of the pruritus and skin lesions as well as a possible change in the neonatal outcome. Differential diagnosis of skin lesions and pruritus in pregnancy is challenging, and complementary investigations such as skin biopsy or laboratory tests are indispensable. The correct diagnosis and proper treatment could change the natural course of a pregnancy at risk and could improve maternal and fetal morbidity. We present the case of a patient with pemfigoid gestationis with the aim to highlight: i) the management of this pregnancy-associated skin disorder which transfers this pregnancy into a category of high obstetrical risk pregnancy; ii) the particularities of the course of the pregnancy; a nd iii) the importance in the differential diagnosis of pregnancy dermatoses. The particularity of this case of pemphigoid gestationis was the acute fetal distress in the absence of intrauterine growth restriction that is frequently found in this pathology, and the management of a rare pregnancy skin condition that currently has no standard treatment.

PMID:34815775 | PMC:PMC8593916 | DOI:10.3892/etm.2021.10945

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Theaflavin-3,3'-digallate attenuates cigarette smoke extract-induced pulmonary emphysema in mice by suppressing necroptosis

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Exp Ther Med. 2022 Jan;23(1):11. doi: 10.3892/etm.2021.10933. Epub 2021 Oct 28.

ABSTRACT

Pulmonary emphysema is one of the most important pathological manifestations of chronic obstructive pulmonary disease and is commonly associated with cigarette smoking. Previous studies have indicated that necroptosis, a novel non-apoptotic cell death mechanism associated with inflammation and oxidative stress, may contribute to the development of pulmonary emphysema. Theaflavin-3,3'-digallate (TF-3), one of the theaflavins present in black tea, is known to possess several bioactive properties. In the present study, it was demonstrated that TF-3 significantly reduced the generation of reactive oxygen species and the mRNA expression levels of TNF-α, IL-1β and IL-6 in CSE-treated human normal lung epithelial BEAS-2B cells. To further explore the role of TF-3 in necroptosis, the necroptotic rates of BEAS-2B cells were examined via flow cytometry and immunofluorescence assays. The results demonstrated that TF-3 may suppress necroptosis in CSE-treated BEAS-2B cells. Furthermore, it was determined that TF-3 significantly inhibited the CSE-induced phosphorylation of p38 MAPK, receptor-interacting serine/threonine-protein kinase three (RIPK3) and mixed lineage kinase domain-like (MLKL) in BEAS-2B cells. Another experiment demonstrated that a pharmacological inhibitor of the p38 MAPK pathway, SB203580, significantly reduced the protein expression levels of phosphorylated (p)-RIPK3 and phosphorylated (p-)MLKL, which indicated that TF-3 suppressed necroptosis via the p38 MAPK/RIPK3/MLKL signaling pathways. In vivo, it was observed that TF-3 treatment significantly attenuated morphological lung injury in mice with CSE-induced emphysema. Moreover, TF-3 significantly reduced the levels of proinflammatory cytokines, TNF-α and IL-1β and significantly enhanced the antioxidant capacity of the lung tissues in mice with emphysema. TF- 3 also significantly inhibited the levels of p-RIPK3 and p-MLKL in the lungs of mice with emphysema. Therefore, the present study indicated that TF-3 may attenuate CSE-induced emphysema in mice by inhibiting necroptosis.

PMID:34815763 | PMC:PMC8593858 | DOI:10.3892/etm.2021.10933

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Dupilumab in CRSwNP: Responder Analysis Using Clinically Meaningful Efficacy Outcome Thresholds

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Objectives/Hypothesis

Dupilumab, a fully human monoclonal antibody that blocks the shared interleukin (IL)-4/IL-13 receptor component, significantly improved outcomes for patients with chronic rhinosinusitis with nasal polyps (CRSwNP) in the SINUS-24 and SINUS-52 studies. This post hoc analysis evaluated dupilumab's effect on patient-reported symptoms and objective outcome measures using thresholds of clinically meaningful within-patient change from baseline.

Methods

Patients with CRSwNP receiving subcutaneous dupilumab or placebo every 2 weeks in SINUS-24/SINUS-52 were analyzed. Patients recorded severity of nasal congestion (NC), loss of smell (LoS), and anterior/posterior rhinorrhea (each within range 0–3) daily. Total Symptom Score (TSS) was calculated as a composite severity score (0–9) for these symptoms. Objective measures included University of Pennsylvania Smell Identification Test (UPSIT; 0–40), nasal polyps score (NPS; 0–8), and Lund–Mackay computed tomography score (LMK-CT; 0–24). Thresholds of within-patient change in scores from baseline at weeks 24 and 52 considered clinically meaningful were ≥1.0 (NC, LoS), ≥3.0 (TSS), ≥8.0 (UPSIT), ≥1.0 (NPS), and ≥5.0 (LMK-CT).

Results

A total of 724 and 303 patients were included in the week 24 and 52 analyses, respectively. Responder rates were significantly higher with dupilumab versus placebo at week 24 for NC (64% vs. 24%), LoS (63% vs. 14%), TSS (62% vs. 15%), UPSIT (54% vs. 6%), NPS (63% vs. 14%), and LMK-CT (59% vs. 3%); all P < .0001. Results were consistent at week 52.

Conclusion

Significantly greater proportions of dupilumab-treated patients with CRSwNP compared with placebo demonstrated clinically meaningful improvements in patient-reported sinonasal symptoms and objective outcomes.

Level of Evidence

2 Laryngoscope, 2021

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Squamous cell papilloma-like presentation of multiple neurovascular hamartomas of the oral cavity

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Ear Nose Throat J. 2021 Nov 24:1455613211061623. doi: 10.1177/01455613211061623. Online ahead of print.

ABSTRACT

Significance Statement: Neurovascular hamartomas (NVH) is an uncommon tumor-like developmental anomaly. We hereby report the case of a 28-year-old woman presenting with multiple millimetric excrescences in the oral cavity that were clinically interpreted as squamous cell papilloma and histologically consistent with NVHs. Neurovascular hamartomas is rare in the oral cavity. To the best of our knowledge, multiple NVHs have never been reported at this site.

PMID:34818931 | DOI:10.1177/01455613211061623

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Machine learning-based voice assessment for the detection of positive and recovered COVID-19 patients

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Many virological tests have been implemented during the COVID-19 pandemic for diagnostic purposes, but they appear unsuitable for screening purposes. Furthermore, current screening strategies are not accurate enough to effectively curb the spread of the disease. Therefore, the present study was conducted within a controlled clinical environment to determine eventual detectable variations in the voice of COVID-19 patients, recovered and healthy subjects, and also to determine whether machine learning-based voice assessment (MLVA) can accurately discriminate between them, thus potentially serving as a more effective mass-screening tool.
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