Overexpression of circulating MiR-30b-5p identifies advanced breast cancer

Breast cancer (BrC) remains the leading cause of cancer-related death in women, mainly due to recurrent and/or metastatic events, entailing the need for biomarkers predictive of progression to advanced disease. MicroRNAs hold promise as noninvasive cancer biomarkers due to their inherent stability and resilience in tissues and bodily fluids. There is increasing evidence that specific microRNAs play a functional role at different steps of the metastatic cascade, behaving as signaling mediators to enable the colonization of a specific organ. Herein, we aimed to evaluate the biomarker performance of microRNAs previously reported as associated with prognosis for predicting BrC progression in liquid biopsies. Background Breast cancer (BrC) remains the leading cause of cancer-related death in women, mainly due to recurrent and/or metastatic events, entailing the need for biomarkers predictive of progression to advanced disease. MicroRNAs hold promise as noninvasive cancer biomarkers due to their inherent stability and resilience in tissues and bodily fluids. There is increasing evidence that specific microRNAs play a functional role at different steps of the metastatic cascade, behaving as signaling mediators to enable the colonization of a specific organ. Herein, we aimed to evaluate the biomarker performance of microRNAs previously reported as associated with prognosis for predicting BrC progression in liquid biopsies. Methods Selected microRNAs were assessed using a quantitative reverse transcription-polymerase chain reaction in a testing cohort of formalin-fixed paraffin-embedded primary (n = 16) and metastatic BrC tissues (n = 22). Then, miR-30b-5p and miR-200b-3p were assessed in a validation cohort #1 of formalin-fixed paraffin-embedded primary (n = 82) and metastatic BrC tissues (n = 93), whereas only miR-30b-5p was validated on a validation cohort #2 of liquid biopsies from BrC patients with localized (n = 20) and advanced (n = 25) disease. ROC curve was constructed to evaluate prognostic performance. Results MiR-30b-5p was differentially expressed in primary tumors and paired metastatic lesions, with bone metastases displaying significantly higher miR-30b-5p expression levels, paralleling the corresponding primary tumors. Interestingly, patients with advanced disease disclosed increased circulating miR-30b-5p expression compared to patients with localized BrC. Conclusions MiR-30b-5p might identify BrC patients at higher risk of disease progression, thus, providing a useful clinical tool for patients’ monitoring, entailing earlier and more effective treatment. Nonetheless, validation in larger multicentric cohorts is mandatory to confirm these findings.Research Center of Portuguese Oncology Institute of Porto (PI 74-CI-IPOP-19-2016). JL and CSG are supported by a PhD fellowship from FCT - Fundação para a Ciência e Tecnologia (SFRH/ BD/132751/2017 and SFRH/BD/92786/2013, respectively). SS is supported by a PhD fellowship IPO/ESTIMA-1 NORTE-01-0145-FEDER-000027. BMC is funded by FCT-Fundação para a Ciência e a Tecnologia (IF/00601/2012

Prevalence of Developmental Anomalies of Oral Mucosa within Patients Referred to Oral Medicine Department of Hamadan ِDentistry Faculty in 2014

Introduction: Developmental anomalies of oral mucosa are not necessarily related to a specific disease, that  may be demonstrated in differential diagnosis of oral disease and premalignant lesions. Mucosal anomalies incidence may be varied in different individuals, which can be related to many genetic and environmental elements. Therefore, this study aimed to evaluate the developmental anomalies of oral mucosa in the patients referred to department of Oral Medicine of Hamadan Dentistry faculty in 2014. Methods: In this cross-sectional study, the developmental anomalies of oral mucosa were studied in 800 patients, who referred to Hamadan School of Dentistry in Iran. All the 800 patients were clinically examined using dental mirrors on the dentistry unit in regard with diagnosis of mucosal anomalies. Demographic data and types of mucosal anomalies were recorded in a predesigned questionnaire. In order to analyze the study data, SPSS software (ver, 16) was applied via chi-square test at significance level of 0.05. Results: Oral developmental lesions were observed in 700 patients (87.5%). The most common lesion was reported as fissured tongue (50.9%), followed by Fordyce granules (49.5%), Macroglossia (17%), torousplatinus (13.4%). A significant association was detected between fissured tongue, macroglosia ,fordice granule with gender and age, Varicosities and furred tongue with age and Torus palatines , Comissural lip pit and hairy tongue with gender . Conclusion: The findings of the present study revealed high prevalence of oral mucosal anomalies. As a result, dentists and medical practitioners are demanded to attend to the oral mucosal anomalies

The Effect of the MicroRNA-183 Family on Hair Cell-Specific Markers of Human Bone Marrow-Derived Mesenchymal Stem Cells

Hearing loss is considered the most common sensory disorder across the world. Nowadays, a cochlear implant can be an effective treatment for patients. Moreover, it is often believed that sensorineural hearing loss in humans is caused by loss or disruption of the function of hair cells in the cochlea. In this respect, mesenchymal cells can be a good candidate for cell-based therapeutic approaches. To this end, the potential of human bone marrow-derived mesenchymal stem cells to differentiate into hair cells with the help of transfection of microRNA in vitro was investigated. MicroRNA mimics (miRNA-96, 182, and 183) were transfected to human bone marrow-derived mesenchymal stem cells using Lipofec-tamine as a common transfection reagent following the manufacturer's instructions at 50 nM for microRNA mimics and 50 nM for the scramble. The changes in cell morphology were also observed under an inverted microscope. Then, the relative expression levels of SOX2, POU4F3, MYO7A, and calretinin were assayed using real-time polymerase chain reaction according to the ΔΔCt method. The ATOH1 level was similarly measured via real-time polymerase chain reaction and Western blotting. The results showed that increased expression of miRNA-182, but neither miRNA-96 nor miRNA-183, could lead to higher expression levels in some hair cell markers. The morphology of the cells also did not change in this respect, but the evaluation of gene expression at the levels of mRNA could promote the expression of the ATOH1, SOX2, and POU4F3 markers. Furthermore, miRNA-182 could enhance the expression of ATOH1 at the protein level. According to the results of this study, it was concluded that miRNA-182 could serve as a crucial function in hair cell differentiation by the upregulation of SOX2, POU4F3, and ATOH1 to promote a hair cell's fate

Randomized controlled trial of astaxanthin impacts on antioxidant status and assisted reproductive technology outcomes in women with polycystic ovarian syndrome

Purpose: Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women, is typically accompanied by a defective oxidative defense system. Here, we investigated the effect of astaxanthin (AST) as a powerful antioxidant on the oxidative stress (OS) response and assisted reproductive technology (ART) outcomes in PCOS patients. Methods: In this double-blind, randomized, placebo-controlled trial, PCOS patients were randomly assigned into two groups. The intervention group received 8 mg AST, and the control group received the placebo daily for 40 days. The primary outcomes were the serum and follicular fluid (FF) levels of the OS biomarkers and the expression levels of the specific genes and proteins in the oxidative stress response pathway. The secondary outcomes were considered ART outcomes. Results: According to our findings, a 40-day course of AST supplementation led to significantly higher levels of serum CAT and TAC in the AST group compared to the placebo group. However, there were no significant intergroup differences in the serum MDA and SOD levels, as well as the FF levels of OS markers. The expression of Nrf2, HO-1, and NQ-1 was significantly increased in the granulosa cells (GCs) of the AST group. Moreover, the MII oocyte and high-quality embryo rate were significantly increased in the AST group compared to the placebo group. We found no significant intergroup difference in the chemical and clinical pregnancy rates. Conclusion: AST treatment has been shown to increase both serum TAC levels and activation of the Nrf2 axis in PCOS patients� GCs. Trial Registration: ClincialTrials.gov Identifier: NCT03991286. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature

An overview on tumor treating fields (TTFields) technology as a new potential subsidiary biophysical treatment for COVID-19

COVID-19 pandemic situation has affected millions of people with tens of thousands of deaths worldwide. Despite all efforts for finding drugs or vaccines, the key role for the survival of patients is still related to the immune system. Therefore, improving the efficacy and the functionality of the immune system of COVID-19 patients is very crucial. The potential new, non-invasive, FDA-approved biophysical technology that could be considered in this regard is tumor treating fields (TTFields) based on an alternating electric field has great biological effects. TTFields have significant effects in improving the functionality of dendritic cell, and cytotoxic T-cells, and these cells have a major role in defense against viral infection. Hence, applying TTFields could help COVID-19 patients against infection. Additionally, TTFields can reduce viral genomic replication, by reducing the expressions of some of the vital members of DNA replication complex genes from the minichromosome maintenance family (MCMs). These genes not only are involved in DNA replication but it has also been proven that they have a crucial role in viral replication. Also, TTFields suppress the formation of the network of tunneling nanotubes (TNTs) which is knows as filamentous (F)-actin-rich tubular structures. TNTs have a critical role in promoting the spread of viruses through improving viral entry and acting as a protective agent for viral components from immune cells and even pharmaceuticals. Moreover, TTFields enhance autophagy which leads to apoptosis of virally infected cells. Thus, it can be speculated that using TTFields may prove to be a promising approach as a subsidiary treatment of COVID-19. Graphical abstract: [Figure not available: see fulltext.