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Δευτέρα 11 Οκτωβρίου 2021

Blood glucose control contributes to protein stability of Ski-related novel protein N in a rat model of diabetes

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Exp Ther Med. 2021 Nov;22(5):1341. doi: 10.3892/etm.2021.10776. Epub 2021 Sep 22.

ABSTRACT

Ski-related novel protein N (SnoN) negatively regulates the transforming growth factor-β1 (TGF-β1)/Smads signaling pathway and is present at a low level during diabetic nephropathy (DN), but its underlying regulatory mechanism is currently unknown. The present study aimed to assess the effects of insulin-controlled blood glucose on renal SnoN expression and fibrosis in rats with diabetes mellitus (DM). Streptozotocin-induced DM rats were treated with insulin glargine (INS group) following successful model establishment. Blood samples were collected and centrifuged for biochemical indexes and the kidneys were collected for morphological analysis. In vitro, rat renal proximal tubular epithelial cells were treated with high-glucose medium for 24 h and transferred to normal glucose medium for 24 h. The expression levels of TGF-β1, SnoN, Sma d ubiquitin regulatory factor 2 (Smurf2), Arkadia, Smads, E-cadherin, α-smooth muscle actin and collagen III were assessed by western blotting and immunohistochemistry. The ubiquitylation of SnoN was detected by immunoprecipitation, and the expression levels of SnoN mRNA were evaluated by reverse transcription-quantitative PCR. The biochemical parameters and morphology indicated that renal fibrosis was notable in the DM group and mitigated in the INS group. Compared with the control group, TGF-β1, phosphor (p)-Smad2, p-Smad3, Smurf2 and Arkadia levels were enhanced in the DM group, and the levels of SnoN protein were decreased, whereas the levels of SnoN mRNA and ubiquitylation were increased in renal tissues. Notably, treatment with insulin reversed this trend. Furthermore, changing the glucose levels in the medium from high to normal glucose suppressed the epithelial-mesenchymal transition of NRK-52E cells by restoring the SnoN protein levels, and this phenomenon was impaired by the knockout of SnoN. SnoN protein levels were likely reduced through a mechanism enhanced by the ubiquitin proteasome system, which reversed the transcriptional activation of SnoN during DN progression. In addition, controlling blood glucose may delay DN fibrosis by rescuing the protein stability of SnoN.

PMID:34630695 | PMC:PMC8495591 | DOI:10.3892/etm.2021.10776< /a>

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Dermatological and endocrine elements in Carney complex (Review)

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Exp Ther Med. 2021 Nov;22(5):1313. doi: 10.3892/etm.2021.10748. Epub 2021 Sep 17.

ABSTRACT

Carney complex (CΝC) is a very rare, autosomal dominant, hereditary syndrome. Seventy percent of individuals with CNC have germline inactivating or deleting mutations of the CNC1 gene [currently known as protein kinase cAMP-dependent type I regulatory subunit α (PRKAR1A), located at the 17q22-24 chromosome level], with 30% of cases presenting with phosphodiesterase gene mutations. A member of the lentiginosis family, dermatological features include: skin pigmentation, cutaneous/mucosal myxomas, usually diagnosed by the age of 20 years (neonatal presentation is exceptional, requiring a meticulous differential diagnosis). Melanocyte-derived tumors such as epithelioid blue nevi (with different levels of pigmentation) and pigmented epithelioid melanocytoma (previously 'animal-type melanoma') are often found. Myxomas, mesenchymal tumor s with mostly a benign pattern, may be recurrent. Primary cutaneous melanotic schwannoma are atypical, while non-skin sites are frequent. Corticotropinomas or somatotropinomas are part of the hereditary syndrome-related pituitary adenomas (representing 5% of all). Primary pigmented nodular adrenocortical disease involves bilateral cortical hyperplasia causing Cushing syndrome (CS) at an earlier age than non-CNC cases; osteoporotic fractures seem more prevalent compare to CS of other etiologies. Typically benign, a few cases of adrenocortical carcinoma have been identified. A total of 5% of familial non-medullary thyroid cancer is syndromic, also including CNC. CNC-related thyroid frame includes: hyperthyroidism, follicular hyperplasia/adenomas, follicular carcinoma (usually aggressive, bilateral or multifocal). Large cell calcifying Sertoli cell tumors of the testes have malignant behavior in adults; in children these may induce precocious puberty. Two particular mammary tumors are found: myxoid fibroadenomas and breast myxomatosis. Cutaneous/subcutaneous lesions, pigmented or not, or any focal swelling of non-identified cause needs careful examination, since dermatological elements are among the earliest and most discernable by which to detect lesions in CNC, a systemic condition with multi-level endocrine involvement.

PMID:34630667 | PMC:PMC8461626 | DOI:10.3892/etm.2021.10748

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Pheochromocytoma as a rare hypertensive complication rarely associated with pregnancy: Diagnostic difficulties (Review)

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Exp Ther Med. 2021 Nov;22(5):1345. doi: 10.3892/etm.2021.10780. Epub 2021 Sep 22.

ABSTRACT

This review provides a brief clinically relevant review of pheochromocytoma in pregnancy, to raise awareness among doctors in obstetrics and the aim is to serve as the first point of reference when confronted by their presence. Pheochromocytomas are neuroendocrine, catecholamine-secreting tumours. Despite having the highest incidence rate among other hormone-secreting adrenal tumours, they remain rare especially when associated with pregnancy. The non-specific presentation of pheochromocytomas, the difficulties in their diagnosis during pregnancy as well as the high maternal and fetal mortality rates associated with them, present a challenge. Clinical suspicion and meticulous patient history-taking remain the primary lines of defense, while biochemical proof of catecholamine excess (or their metabolites) and imaging-based localisation of the tumo ur are required for diagnosis. Antenatal diagnosis and complete localisation of the tumour increase the likelihood of successful outcomes for both mother and newborn. Magnetic resonance imaging (MRI) remains the method of choice during pregnancy without excluding the use of ultrasound. Treatment goals should include the avoidance of hypertensive crises while maintaining adequate uteroplacental circulation. The target blood pressure is not strictly defined but is in line with the general guideline addressing chronic hypertension during pregnancy. Antihypertensive medications remain the cornerstone in managing pheochromocytoma. As a first-line, the α-adrenergic, nonselective antagonist phenoxybenzamine is the most frequently used agent, while α1-selective adrenergic antagonists with or without the addition of β- or β1-blockers are also prescribed in certain cases, rendering calcium channel blockers as 'second-choice'. Blood-pressure control of the mother and the well-being of the fetus are determining factors in deciding the time of delivery, which is preferably conducted by Caesarean section. Excision of the tumour(s) remains the final treatment goal. Lifelong biochemical testing is required with or without medical treatment, to address mineralocorticoid or glucocorticoid deficits. Despite ever-improving positive outcome rates, pheochromocytoma associated with pregnancy remains a pathology with high mortality and morbidity rates.

PMID:34630699 | PMC: PMC8495583 | DOI:10.3892/etm.2021.10780

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Gigantol inhibits cell proliferation and induces apoptosis by regulating DEK in non-small cell lung cancer

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Exp Ther Med. 2021 Nov;22(5):1317. doi: 10.3892/etm.2021.10752. Epub 2021 Sep 17.

ABSTRACT

Non-small cell lung cancer (NSCLC) is a common type of cancer, with a mortality of >80% worldwide. Gigantol is a bibenzyl compound that displays anticancer activity. The aim of the present study was to determine the biological activity of gigantol in NSCLC and to elucidate the underlying molecular mechanism of its action. The expression of DEK proto-oncogene (DEK) was measured in NSCLC tissues and cell lines by reverse transcription-quantitative PCR (RT-qPCR). The results suggested that DEK levels were significantly increased in NSCLC tissues and cell lines compared with adjacent non-tumor tissues and BEAS-2B normal bronchial epithelial cells, respectively. A549 cells were exposed to a series of gigantol concentrations (0, 25, 50 and 100 µM) and transfected with DEK small interfering RNA. The results of cell viability measured by MTT assay in dicated that gigantol significantly decreased cell viability. Additionally, cell proliferation was assessed by CCK-8 and apoptosis was measured by flow cytometry. In comparison with the control group, gigantol treatment inhibited cell proliferation and promoted apoptosis, whereas DEK knockdown increased gigantol-induced suppression of proliferation and acceleration of apoptosis. Additionally, DEK overexpression reversed gigantol-induced effects on proliferation and apoptosis. Moreover, compared with the control group, gigantol treatment decreased Ki-67 and Bcl-2 expression levels, increased Bax expression levels and inactivated the Wnt/β-catenin signaling pathway, as assessed by RT-qPCR and/or western blot. DEK knockdown further increased gigantol-induced effects, but DEK overexpression reversed gigantol-induced effects. To conclude, the results of the present study suggested that gigantol inhibited cell proliferation and induced apoptosis by decreasing Ki-67 and Bcl-2 expression, increasing Bax expression and activating the Wnt/β-catenin signaling pathway by regulating DEK. The present study indicated the therapeutic potential of gigantol in patients with NSCLC. In addition, DEK may serve as a novel therapeutic target to enhance the effects of gigantol treatment.

PMID:34630671 | PMC:PMC8495587 | DOI:10.3892/etm.2021.10752

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Testing A Hypothesis: Tinnitus Control by Enhancing Physiological Inhibition

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Abstract

Background

Deficit in cognitive functions and central executive function is one of the popular hypotheses on the underlying cause of tinnitus. Some studies expressed the effect of tinnitus on the inhibitory cognitive tasks, referring to the slower inhibitory results such as in the Stroop task in the people suffering from tinnitus as compared to normal subjects. Since Stroop engages the network overlapping the attention and tinnitus distress networks, it seems likely that Stroop exercises can effectively contribute to controlling the tinnitus and its consequent distress through improvement of the cognitive function and increasing the physiological inhibition.

Method

A total of 25 patients with chronic tinnitus (> 6 months) were randomly divided into two groups: an intervention group of 15 patients and a control group of 10 patients. Both groups were subjected to initial evaluations including pure tone audiometry, psychoacoustic measurements, tinnitus handicap inventory (THI) survey, and visual analogue scale (VAS) of annoyance and loudness. The intervention group underwent a rehabilitation program consisting of 6 Stroop training sessions. The control group didn't receive any training. Afterwards, both groups were reevaluated and the results were compared to those of initial evaluations.

Results

Results of this study indicated significant differences in THI scores and VAS of annoyance, before and after Stroop training in the intervention group, although no significant difference was observed when it came to VAS of loudness.

Conclusion

Successive sessions of conflict processing training can improve the annoyance of tinnitus by enhancing the patient's inhibition control, making this task a safe practice for tinnitus treatment.

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A Scoping Review of Ongoing Fluorescence‐Guided Surgery Clinical Trials in Otolaryngology

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Objective

Fluorescence-guided surgery (FGS) is a rapidly developing intraoperative technology, and many contrast agents are currently under investigation. We sought to provide a review of the current state of FGS clinical trials in Otolaryngology, emphasizing its oncologic applications.

Methods

According to the preferred reporting Items for systematic reviews and meta-analyses (PRISMA) workflow for scoping reviews, a clinical trial search was performed across multiple international clinical trials registries, searching for permutations of "fluorescence," "tumor," "surgery," and "nerve" to identify all relevant studies. Studies that were active, enrolling, or soon to be enrolling patients undergoing head and neck surgery were included.

Results

Nineteen studies were eligible for inclusion. Seventeen studies are focused on FGS for oncologic resection and lymph node detection. One study assesses peripheral nerve fluorescence, and one evaluates normal parathyroid function after thyroidectomy. Contrast agents under development are conjugated to fluorophores that excite in the 800 nm (indocyanine green), 410 nm (5-aminolevulinic acid), 700 nm (Cyanine 5.5), and 525 nm ranges (fluorescein derivatives).

Conclusion

Presently, there are 19 ongoing trials investigating novel FGS contrast agents for their safety, efficacy, and utility in Otolaryngology—Head and Neck Surgery. These agents rely on unique fluorophores and absorption ranges in the near-infrared and visible light spectra. FGS studies are expanding within Otolaryngology—Head and Neck Surgery with profound implications in oncologic surgery, lymph node detection, and anatomic and functional assessment. Laryngoscope, 2021

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Physiological Effects of Voice Therapy for Aged Vocal Fold Atrophy Revealed by EMG Study

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Age-related voice changes are characterized as breathy, weak and strained, and a deterioration in vocal function in the elderly has been putatively linked to a reduced intensity of speech. They contribute to undesirable voice changes known as presbyphonia. These changes are caused by histological alterations in the lamina propria of the vocal fold mucosa and atrophy of the thyroarytenoid muscle, as well as by decreased respiratory support. There are several clinical studies on presbylarynx dysphonia showing the effectiveness of voice therapy.
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Endoscopic measurement of nasal septum perforations

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HNO. 2021 Oct 11. doi: 10.1007/s00106-021-01102-4. Online ahead of print.

ABSTRACT

BACKGROUND: Nasal septum perforations (NSP) have many uncomfortable symptoms for the patient and a highly negative impact on quality of life. NSPs are closed using patient-specific implants or surgery. Implants are created either under anesthesia using silicone impressions or using 3D models from CT data. Disadvantages for patient safety are the increased risk of morbidity or radiation exposur e.

MATERIALS AND METHODS: In the context of otorhinolaryngologic surgery, we present a gentle approach to treating NSP with a new image-based, contactless, and radiation-free measurement method using a 3D endoscope. The method relies on image information only and makes use of real-time capable computer vision algorithms to compute 3D information. This endoscopic method can be repeated as often as desired in the clinical course and has already proven its accuracy and robustness for robotic-assisted surgery (RAS) and surgical microscopy. We expand our method for nasal surgery, as there are additional spatial and stereoperspective challenges.

RESULTS: After measuring 3 relevant parameters (NSP extension: axial, coronal, and NSP circumference) of 6 patients and comparing the results of 2 stereoendoscopes with CT data, it was shown that the image-based measurements can achieve comparable accuracies to CT data. One patient could be only partially evaluated because the NSP was larger than the endoscopic field of view.

CONCLUSION: Based on the very good measurements, we outline a therapeutic procedure which should enable the production of patient-specific NSP implants based on endoscopic data only.

PMID:34633475 | DOI:10.1007/s00106-021-01102-4

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Πέμπτη 7 Οκτωβρίου 2021

Expression of epithelial membrane protein (EMP) 1, EMP 2, and EMP 3 in thyroid cancer

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Histol Histopathol. 2021 Oct 7:18378. doi: 10.14670/HH-18-378. Online ahead of print.

ABSTRACT

Purpose Epithelial membrane protein (EMP) 1, EMP2, and EMP3 are expressed in various types of tumors and have been reported to be involved in carcinogenesis. In this study, we aimed to investigate the expression of these proteins in primary and metastatic thyroid cancer and its clinical implication. Methods EMP1, EMP2, and EMP3 immunohistochemistry was performed using tissue microarrays of 545 primary thyroid carcinomas [338 papillary thyroid carcinoma (PTC), 111 follicular carcinoma (FC), 69 medullary carcinoma (MC), 23 poorly differentiated carcinoma (PDC), and 4 anaplastic carcinoma (AC)] and 59 recurrent or metastatic PTCs. Results EMP1 showed high expression in AC, PTC, FC (P<0.001), and EMP2 was highly expressed in AC (P<0.001). EMP1 and EMP2 were not expressed in stromal cells. Expression of EMP3 in tumor cells [EMP3 (T)] was hig her in PDC, PTC, and AC (P<0.001), and expression in stromal cells [EMP3 (S)] was observed only in AC and PTC (P=0.001). The expression of EMP1 (P=0.002) and EMP3 (T) (P<0.001) was higher in conventional PTC than in follicular variant PTC. PTC with BRAF V600E mutation showed higher expression of EMP1 (P<0.001), EMP3 (T) (P<0.001), and EMP3 (S) (P=0.012) than PTC without BRAF V600E mutation. In the PTC without BRAF V600E mutation group, expression of EMP3 (S) was associated with shorter disease free survival (P=0.004). Metastatic PTC showed higher EMP2 (3.4% vs. 0%, P=0.022) and lower EMP3 (T) (44.1% vs. 66%, P=0.001) than primary PTC. Conclusions Expression of EMP1, EMP2, and EMP3 is different according to the subtypes of thyroid cancer. Further studies are needed to determine their role as prognostic markers and treatment target in thyroid cancer.

PMID:34617578 | DOI:10.14670/HH-18-378

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Hybrid [18F]FDG PET/MR Has High Sensitivity and Specificity in the Detection of Recurrent Differentiated Thyroid Cancer

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Clinical Thyroidology, Volume 33, Issue 10, Page 447-451, October 2021.
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Temporal bone computed tomography checklist-TeSLANO: introduction of a standardized preoperative imaging evaluation for middle ear surgery

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Eur Arch Otorhinolaryngol. 2021 Oct 7. doi: 10.1007/s00405-021-07112-w. Online ahead of print.

ABSTRACT

PURPOSE: Aim of the study was to evaluate if the introduction of the imaging checklist TeSLANO would improve the identification of crucial anatomical findings from temporal bone computed tomography (TBCT) scans among a cohort of Otolaryngology residents.

STUDY DESIGN: Single-blinded prospective cohort study.

SETTING: Tertiary care university hospital and referral center for otology and skull base surgery.

METHODS: The cohort was composed by eight Otorhinolaryngology residents (four junior and four senior) that were individually asked to identify all relevant anatomic findings from preoperative TBCT scans. Supervising surgeon showed to each resident four TBCT scans before and four after the introduction of a systematic checklist evaluation system based on the TeSLANO acronym. Statistical analysis was performed using McNemar's test and results were considered significant with a P value < 0.05.

RESULTS: Introduction of the checklist improved global identification of critical anatomical structures from 48.75 to 89.17% (P < 0.05). The postimplementation identification percentage improved for both the senior and junior groups (P < 0.05).

CONCLUSIONS: The imaging checklist TeSLANO allows a systematic approach to review TBCT scans and significantly improves identification of critical anatomical structures in Otorhinolaryngology residents.

PMID:34618226 | DOI:10.1007/s00405-021-07112-w

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