Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Δευτέρα 20 Σεπτεμβρίου 2021

Role of miR-139-5p in ectopic endometrial stromal cells and the underlying molecular mechanism

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Exp Ther Med. 2021 Nov;22(5):1251. doi: 10.3892/etm.2021.10686. Epub 2021 Sep 2.

ABSTRACT

Endometriosis is an estrogen-dependent disease. Studies have shown that miR-139-5p is significantly upregulated in endometriosis lesions, but its specific role and molecule mechanism in endometriosis has not yet been reported. The malignant biological behavior of ectopic endometrial stromal cells (ESCs) is similar to that of malignant cancer cells. BBC3 (BCL2 binding component 3) is a known apoptosis inducer and it serves key roles in the regulation of cell behavior. However, the role of BBC3 in ectopic ESCs remains unknown. The present study aimed to investigate the role of miR-139-5p in the progression of endometriosis and to determine its underlying molecular mechanism of action. Ectopic, non-ectopic and normal endometrial stromal cells (ESCs) were extracted from endometrial samples, and reverse transcription-quantitative PCR was performed to d etermine microRNA (miR)-139-5p and Bcl-2 binding component 3 (BBC3) mRNA expression levels in endometrial tissue samples and ESCs. The target gene of miR-139-5p was predicted using TargetScan software and verified using a dual luciferase reporter assay. Western blotting was performed to determine BBC3 protein expression levels. Flow cytometry analysis, and MTT and Transwell assays were performed to assess cell apoptosis, viability, and migration and invasion of the cells transfected with inhibitor control, miR-139-5p inhibitor, miR-139-5p inhibitor + control-small interfering (si)RNA or miR-139-5p inhibitor + BBC3-siRNA, respectively. The results demonstrated that miR-139-5p expression levels were upregulated in ectopic endometrial samples and ESCs compared with the respective control groups. Furthermore, it was verified that BBC3 was a direct target of miR-139-5p, and both BBC3 mRNA and protein expression levels were downregulated in ectopic endometrial samples and ESCs. Both trans fection with the miR-139-5p inhibitor and BBC3-small interfering (si)RNA markedly downregulated miR-139-5p and BBC3 expression levels in ectopic ESCs, respectively. miR-139-5p inhibitor-induced upregulated BBC3 expression was reversed following transfection with BBC3-siRNA. Furthermore, the miR-139-5p inhibitor significantly decreased viability, migration and invasion, while inducing apoptosis in ectopic ESCs compared with the inhibitor control group. Notably, the aforementioned effects were reversed by knocking down BBC3 expression. In conclusion, the results of the present study suggested that miR-139-5p may play a key role in the progression of endometriosis by regulating the viability of ESCs and directly targeting BBC3.

PMID:34539847 | PMC:PMC8438670 | DOI:10.3892/etm.2021.10686

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Moxibustion improves ovarian function based on the regulation of the androgen balance

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Exp Ther Med. 2021 Nov;22(5):1230. doi: 10.3892/etm.2021.10664. Epub 2021 Aug 30.

ABSTRACT

The effect of androgens on follicular development and female reproduction has become an active research topic. Moxibustion is a Traditional Chinese Medicine therapy that has been reported to be able to prevent and treat numerous ovary-related problems. However, studies on the effect of moxibustion for diminished ovarian reserve (DOR) on androgen balance are still lacking. The present study aimed to assess the efficacy of moxibustion intervention prior to disease onset and at the early stage of disease in a rat model of DOR and explore the mechanisms of its effect on ovarian function. A total of 32 rats were randomly divided into four groups: Blank group, Model group (a drug-induced model of DOR), Moxibustion group 1 and Moxibustion group 2. Moxibustion was performed on the BL23 and RN4 acupoints of female rats daily for a total of 20 days (once a day, five times a week for a total of 4 weeks). The two moxibustion groups were established with different intervention times: One group was subjected to pre-disease intervention and the other group to early-disease intervention. The ovarian function was evaluated by detecting anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), estradiol (E2), testosterone (T), dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT) and androgen receptor (AR) levels in the serum or the ovary samples. To further investigate the downstream regulatory factors for AR after moxibustion treatment for pre-disease or early-disease intervention, FSH receptor (FSHR) and microRNA (miR)-125b expression in ovaries were also analyzed. The results indicated that AMH and DHT levels were reduced in the model group compared with those in the blank group, while FSH, T and DHEA levels were increased. AMH and DHT levels were increased in Moxibustion group 1 compared with those in the model group, while F SH, T and DHEA levels were reduced. There was no difference in E2 levels between Moxibustion group 1 and the model group. Compared with that in the model group, the AR content in the ovary was increased in Moxibustion group 1. There was no difference in FSHR mRNA in the ovaries between Moxibustion group 1 and the model group. miR-125b levels were significantly increased in Moxibustion group 1 as compared with those in the model group. Furthermore, AMH and DHT levels were increased in Moxibustion group 2 compared with those in the model group, while FSH, T and DHEA levels were reduced. E2 levels were significantly decreased in Moxibustion group 2 compared with those in the model group. The relative mRNA expression of AR, FSHR and miR-125b was decreased following establishment of the model. Compared with that in the model group, the AR content in the ovary was increased in Moxibustion group 2. In comparison with the blank and model groups, the FSHR content in the ovary of Moxibustion group 2 was significantly increased. miR-125b levels were not obviously altered in Moxibustion group 2 as compared with those in the model group. In addition, there was no significant difference in AMH, FSH, T and DHEA levels between the two moxibustion groups. E2 and DHT levels were higher in Moxibustion group 1 than in Moxibustion group 2. There was no difference in AR mRNA expression between the two moxibustion groups. FSHR mRNA levels were lower in Moxibustion group 1 than in Moxibustion group 2, while miR-125b mRNA levels were higher in Moxibustion group 1 than in Moxibustion group 2. In conclusion, the present study suggested that moxibustion intervention prior to disease onset and at the early disease stage was able to improve ovarian function via modulation of the AR-mediated stable equilibrium of androgens. However, the effects and mechanisms of moxibustion intervention for pre-disease and early-disease intervention of DOR appear to be different. The appropriate duration of treatment and the time-effect relationship require to be further studied.

PMID:34539826 | PMC:PMC8438671 | DOI:10.3892/etm.2021.10664

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Intratumor Epigenetic Heterogeneity-A Panel Gene Methylation Study in Thyroid Cancer

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Front Genet. 2021 Sep 3;12:714071. doi: 10.3389/fgene.2021.714071. eCollection 2021.

ABSTRACT

BACKGROUND: Thyroid cancer (TC) is the most common endocrine malignancy, and the incidence is increasing very fast. Surgical resection and radioactive iodine ablation are major therapeutic methods, however, around 10% of differentiated thyroid cancer and all anaplastic thyroid carcinoma (ATC) are failed. Comprehensive understanding the molecular mechanisms may provide new therapeutic strat egies for thyroid cancer. Even though genetic heterogeneity is rigorously studied in various cancers, epigenetic heterogeneity in human cancer remains unclear.

METHODS: A total of 405 surgical resected thyroid cancer samples were employed (three spatially isolated specimens were obtained from different regions of the same tumor). Twenty-four genes were selected for methylation screening, and frequently methylated genes in thyroid cancer were used for further validation. Methylation specific PCR (MSP) approach was employed to detect the gene promoter region methylation.

RESULTS: Five genes (AP2, CDH1, DACT2, HIN1, and RASSF1A) are found frequently methylated (>30%) in thyroid cancer. The five genes panel is used for further epigenetic heterogeneity analysis. AP2 methylation is associated with gender (P < 0.05), DACT2 methylation is associated with age, gender and tumor size (all P < 0.05), HIN1 methyl ation is associated to tumor size (P < 0.05) and extra-thyroidal extension (P < 0.01). RASSF1A methylation is associated with lymph node metastasis (P < 0.01). For heterogeneity analysis, AP2 methylation heterogeneity is associated with tumor size (P < 0.01), CDH1 methylation heterogeneity is associated with lymph node metastasis (P < 0.05), DACT2 methylation heterogeneity is associated with tumor size (P < 0.01), HIN1 methylation heterogeneity is associated with tumor size and extra-thyroidal extension (all P < 0.01). The multivariable analysis suggested that the risk of lymph node metastasis is 2.5 times in CDH1 heterogeneous methylation group (OR = 2.512, 95% CI 1.135, 5.557, P = 0.023). The risk of extra-thyroidal extension is almost 3 times in HIN1 heterogeneous methylation group (OR = 2.607, 95% CI 1.138, 5.971, P = 0.023).

CONCLUSION: Five of twenty-four genes were found frequently methylated in human thyroid cancer. Based on 5 genes panel analysis, epigenetic heterogeneity is an universal event. Epigenetic heterogeneity is associated with cancer development and progression.

PMID:34539742 | PMC:PMC8446600 | DOI:10.3389/fgene.2021.714071

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Bilateral vocal cord paralysis caused by accidental button battery ingestion in children: A case report and literature review

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Ear Nose Throat J. 2021 Sep 19:1455613211043678. doi: 10.1177/01455613211043678. Online ahead of print.

ABSTRACT

Button battery ingestion in pediatric populations is a common occurrence with severe sequelae. Multiple case reports have established the occurrence of death, fistula formation, mucosal erosion, esophageal perforation, and bleeding post-ingestion of button batteries. However, there is a gap in the literature on the occurrence of bilateral vocal cord paralysis post -lithium battery ingestion. We present a case in which a 12-month-old male developed bilateral vocal cord paralysis following ingestion of a button battery. We compare our case to eleven other reports that exist in the literature based on age, sex, time until removal, clinical presentation, day upon which vocal cord paralysis developed, anatomic location, and post-operative course. We conclude that bilateral vocal cord paralysis is a time-sensitive complication which requires prompt diagnosis. Any child with stridor following button battery ingestion should undergo consultation with pediatric otolaryngology immediately. In addition, long-term follow-up is necessary to evaluate return of normal vocal cord function.

PMID:34541933 | DOI:10.1177/01455613211043678

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Molecular alterations differentiate microinvasive carcinoma from ductal carcinoma in situ and invasive breast carcinoma: retrospective analysis of a large single-center series

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Int J Clin Exp Pathol. 2021 Aug 15;14(8):892-901. eCollection 2021.

ABSTRACT

Microinvasive carcinoma (MIC) of the breast is a rare lesion. The clinicopathologic features and biologic behavior of MIC are unclear. Whether MIC is a distinct entity or an interim stage in the progression from ductal carcinoma in situ (DCIS) to invasive breast carcinoma (IBC) remains to be determined. A retrospective review of clinicopathologic features and analysis of the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 in patients with MIC (90 cases), DCIS (268 cases) and IBC (1504 cases) was performed. Most MICs (93.3%) exhibited an intermediate to high nuclear grade, and this proportion was larger than that of DCIS (62.7%, P < 0.001) or IBC (85.4%, P = 0.036). The incidence of sentinel lymph node metastasis in MIC (12.5%) was higher than that of DCIS (1.6%, P < 0.001), but much lower than that of IBC (39.7%, P < 0.001). MICs had higher expression of HER-2 and lower expression of ER and PR compared to DCIS and IBC; and MIC was more likely to present with a HER-2+ subtype. Furthermore, DCIS exhibited greater HER-2 overexpression or gene amplification (P < 0.001) levels and lower proliferation index of Ki-67 (P < 0.001) compared to IBC. Our results suggest that the clinicopathologic and molecular phenotype of MIC are different from DCIS and IBC. Thus, MIC may be a distinct entity rather than an interim stage in the progression from DCIS to IBC. The prognosis of MIC and the biologic behavior of this uncommon subset need to be further explored.

PMID:34527132< /a> | PMC:PMC8414427

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Effects of acrylonitrile on apoptosis of rat cerebral nerve cells

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Int J Clin Exp Pathol. 2021 Aug 15;14(8):908-914. eCollection 2021.

ABSTRACT

The brain, especially the hippocampus, is sensitive to damage caused by anoxic chemicals. In this study, we established a rat model of acrylonitrile poisoning with administration by gavage, aiming to determine the influence of acrylonitrile on rat cerebral nerve cells. Transmission electron microscopy observation and TdT-mediated dUTP nick-end labelling (TUNEL) staining were used to explore preliminarily the apoptotic changes of cerebral nerve cells. The pathogenesis revealed by transmission electron microscopy indicated that apoptosis in the control group was more serious than that of the exposure groups. The results of TUNEL staining showed the apoptotic rate was significantly higher in the control group than that of other exposure groups. All the results indicated that acrylonitrile can inhibit the apoptosis of rat cerebral nerve cells, which is closely rel ated to its animal carcinogenicity.

PMID:34527134 | PMC:PMC8414433

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Adenoid cystic carcinoma. An indolent but aggressive tumour. Part B: treatment and prognosis

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Acta Otorhinolaryngol Ital. 2021 Aug;41(4):296-307. doi: 10.14639/0392-100X-N1729.

NO ABSTRACT

PMID:34533533 | DOI:10.14639/0392-100X-N1729

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How to predict the outcome of septorhinoplasty? A normative study of ROE and FROI-17 scores

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Acta Otorhinolaryngol Ital. 2021 Aug;41(4):327-335. doi: 10.14639/0392-100X-N1291.

ABSTRACT

OBJECTIVE: Normative values of patient-reported outcome instruments are needed to identify good candidates for rhinoplasty. Rhinoplasty Outcome Evaluation (ROE) and Functional Rhinoplasty Outcome Inventory-17 (FROI-17) are disease-specific questionnaires that evaluate quality of life in patients undergoing rhinoplasty.

METHODS: The reference cohort contained 1,000 participants, selected from a non-probability panel. Normative ROE and FROI-17 scores from this reference cohort were compared with ROE and FROI-17 scores from a patient cohort before (n = 104) and 6 (n = 55) and 12 months (n = 32) after septorhinoplasty.

RESULTS: Mean FROI-17 scores (± SD) were: overall score, 20.8 ± 17; nasal symptoms, 16.8 ± 7; general symptoms, 24.8 ± 22; and self-confidence, 16.4 ± 21. The ROE total score was 73.1 ± 16. Normative values differed significantly from the preoperative ROE and FROI-17 scores of septorhinoplasty patients (p < 0.01). Except for the FROI-17 general score at 12 months postoperatively (p = 0.004), there were no significant differences between normative ROE/FROI-17 and septorhinoplasty scores postoperatively, indicating that they returned to normalcy.

CONCLUSIONS: Normative scores for ROE and FROI-17 provide a reference point from which to identify patients who are most likely to benefit from rhinoplasty.

PMID:34533536 | DOI:10.14639/0392-100X-N1291

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Development of a questionnaire to investigate socio-cultural differences in the perception of smell, taste and flavour

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Acta Otorhinolaryngol Ital. 2021 Aug;41(4):336-347. doi: 10.14639/0392-100X-N0766.

ABSTRACT

OBJECTIVES: Clinical experience and daily life indicate that the importance of smell, taste and flavour is variable among individuals. Therefore, the aim of this research was to develop a questionnaire to investigate the importance attributed to smell, taste and flavour and socio-cultural differences among individuals.

METHODS: Cross-cultural adaptation of the questionnaire was executed by two professional translators and one bilingual investigator and pre-tested on a pilot group of 25 subjects with normal smell and taste abilities. The final version of the questionnaire was sent by e-mail to 850 healthy subjects. The Google form consisted of three parts: "The importance of olfaction" developed by Croy et al. in 2010, "The importance of taste and flavour" developed by our team and a section to collect demographic data. The questions were classified into "association", "application", "consequence" and "aggravation". Statistical differences were assessed using t-test with p ≤ 0.05. Correlations were calculated using Spearman's test. Internal consistency was assessed using the Cronbach's Alpha, while test-retest reliability was analysed by calculating the Intraclass Correlation Coefficients (ICC2k).

RESULTS: The questionnaire received a non-response rate of 10.7%. Calculation of Cronbach's alpha showed good internal reliabi lity (a = 0.87). Test-retest evaluation was satisfactory for all subscales, with an overall ICC2k = 0.84 (CI 0.79-0.89). Statistical analysis showed that smell, taste and flavour appeared to be more important for women when compared to men (p < 0.001). No statistical differences were seen between individuals with various educational background (p > 0.05), and the importance of smell (r = 0.16; p < 0.01), taste and flavour (r = 0.08; p < 0.05) did not decline with age.

CONCLUSIONS: The development of this original test provides an overview into the importance of smell, taste and flavour among individuals. Although further research is needed, it can help in the evaluation and investigation of aspects that influence people to seek medical attention in the presence of sensory alterations.

PMID:34533537 | DOI:10.14639/0392-100X-N0766

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Sound frequency spectra of snore in relation to the site of obstruction among snorers

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Acta Otorhinolaryngol Ital. 2021 Aug;41(4):348-355. doi: 10.14639/0392-100X-N1202.

ABSTRACT

OBJECTIVE: This study aimed to describe the sound frequency of snoring in relation to the site of upper airway vibration among snorers.

METHODS: 383 snores from 40 participants who complained of snoring were digitally recorded during natural and induced sleep using a level III polysomnography monitor with a built-in microphone. During drug-induced sleep endoscopy (DISE), the rea l-time site of upper airway obstruction was assessed, and the sound frequency of snoring was recorded synchronously.

RESULTS: The mean peak of snoring frequency for unilevel palatal, oropharynx and epiglottis obstruction were 522.5, 482.4 and 300.0 Hz, respectively. Most participants showed multilevel obstruction at the palate and oropharynx, in which the mean for bi-peak snoring frequency were 402.90 Hz and 1086.96 Hz, respectively. Severity of OSA was significantly associated with multilevel obstruction.

CONCLUSIONS: There was a significant association between the snoring sound frequency and site of unilevel obstruction. Palatal or oropharyngeal obstruction produced sound at mid-frequency range, while the epiglottis produced a low frequency range. Multilevel obstruction documented a bi-peak snoring frequency.

PMID:34533538 | DOI:10.14639/0392-100X-N1202

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