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BACKGROUND: Ovarian cancer is one of the most lethal gynecological cancers among women worldwide. Cisplatin (Cis) is an effective chemotherapeutic agent used to treat several types of cancer. Silymarin (SLM) is an extract of medicinal plant Silybum marianum (milk thistle) with anti-inflammatory, anti-angiogenesis, antioxidant, and anticancer properties used alone or in combination with other drugs. OBJECTIVE: This study aimed to explore the effects of co-treatment with SLM and Cis on A2780 human ovarian cancer cell lines. METHODS: In this study, A2780 cells were treated with various concentrations of SLM and Cis, separately and in combination. Cell cytotoxicity, scratch, clonogenic, and flow-cytometry assays were accomplished to estimate cell viability, migration, colony formation, and apoptosis, respectively. Real-time PCR was utilized to determine the expression levels of miR-155 and miR-27a. RESULTS: SLM significantly reduced the proliferation of A2780 cells in a concentration- and time-dependent manner. Combination treatment with SLM and Cis was more potent than either single treatment in reducing viability, suppressing migration, inhibiting colony formation, and promoting the induction of apoptosis. Additionally, gene expression analysis revealed a significant decline in the expression levels of miR-155 and miR-27a in response to all separate and combined treatments, and co-treatment was more effective than individual treatments in altering miRNAs expression. CONCLUSION: Based on our findings, SLM boosts the anticancer activity of Cis and mitigates its side effects. Thus, the co-treatment of SLM and Cis can be proposed as a promising therapeutic strategy for further investigation.
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MicroRNAs , Neoplasias Ovarianas , Silimarina , Feminino , Humanos , Cisplatino/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Silimarina/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Apoptose , MicroRNAs/genéticaRESUMO
INTRODUCTION: MicroRNAs, or miRNAs, with regulatory performance in inflammatory responses and infection are the prevalent manifestations of severe coronavirus disease (COVID-19). This study aimed to evaluate whether PBMC miRNAs are diagnostic biomarkers to screen the ICU COVID-19 and diabetic COVID-19 subjects. METHODS: Candidate miRNAs were selected through previous studies, and then the PBMC levels of selected miRNAs (miR-28, miR-31, miR-34a, and miR-181a) were measured via quantitative reverse transcription PCR. The diagnostic value of miRNAs was determined by the receiver operating characteristic (ROC) curve. The bioinformatics analysis was utilized to predict the DEM genes and relevant bio-functions. RESULTS: The COVID-19 patients admitted to ICU had significantly greater levels of selected miRNAs compared to non-hospitalized COVID-19 and healthy people. Besides, the mean miR-28 and miR-34a expression levels in the diabetic COVID-19 group were significantly upregulated when compared with the non-diabetic COVID-19 group. ROC analyses demonstrated the role of miR-28, miR-34a, and miR-181a as new biomarkers to discriminate the non-hospitalized COVID-19 group from the COVID-19 patients admitted to ICU samples, and also miR-34a can probably act as a useful biomarker for screening diabetic COVID-19 patients. Using bioinformatics analyses, we found the performance of target transcripts in many bioprocesses and diverse metabolic routes such as the regulation of multiple inflammatory parameters. DISCUSSION: The difference in miRNA expression patterns between the studied groups suggested that miR-28, miR-34a, and miR-181a could be helpful as potent biomarkers for diagnosing and controlling COVID-19.
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COVID-19 , Diabetes Mellitus , MicroRNAs , Humanos , Leucócitos Mononucleares , COVID-19/diagnóstico , MicroRNAs/genética , Biomarcadores , Unidades de Terapia IntensivaRESUMO
Salinity energy generation (SEG) studies have only been done under isothermal conditions at ambient temperature. The production of salinity energy can be improved under non-isothermal conditions, albeit preserving the energy efficiency. In the current study, the effects of gradients of temperature and concentration on the salinity energy generation process were examined simultaneously. Based on the temperature-dependent properties resulting from both temperature and concentration gradients, a numerical study was carried out to determine the maximum efficiency of salinity energy generation in funnel-shaped soft nanochannels. It was presumed that a dense layer of negative charge, called a polyelectrolyte layer (PEL), is coated on the walls of the nanochannels. Co-current and counter-current modes were used to obtain temperature and concentration gradients. Under steady-state conditions, the Poisson-Nernst-Planck, Stokes-Brinkman, and energy equations were numerically solved using equivalent approaches. The results revealed that by increasing the temperature and concentration ratios in both co-current and counter-current modes of operation, the salinity energy generation increased appreciably. The salinity energy generation increased from 30 to 80 pW upon increasing the temperature ratio from 1 to 8 at a constant concentration ratio of 1000 in counter-current mode. As verified from this analysis, low-grade heat sources (<100 °C) provide considerable energy conversion in PEL grafted nanofluidic confinement when placed between electrolyte solutions of different temperatures.
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MicroRNAs (miRNAs) are fundamental post-transcriptional modulators of several critical cellular processes, a number of which are involved in host defense mechanisms. In particular, miRNA let-7 functions as an essential regulator of the function and differentiation of both innate and adaptive immune cells. Let-7 is involved in several human diseases, including cancer and viral infections. Several viral infections have found ways to dysregulate the expression of miRNAs. Extracellular vesicles (EV) are membrane-bound lipid structures released from many types of human cells that can transport proteins, lipids, mRNAs, and miRNAs, including let-7. After their release, EVs are taken up by the recipient cells and their contents released into the cytoplasm. Let-7-loaded EVs have been suggested to affect cellular pathways and biological targets in the recipient cells, and can modulate viral replication, the host antiviral response, and the action of cancer-related viruses. In the present review, we summarize the available knowledge concerning the expression of let-7 family members, functions, target genes, and mechanistic involvement in viral pathogenesis and host defense. This may provide insight into the development of new therapeutic strategies to manage viral infections.
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Vesículas Extracelulares , MicroRNAs , Viroses , Vesículas Extracelulares/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Viroses/genética , Viroses/metabolismo , Replicação ViralRESUMO
Autophagy is known as a conserved self-eating mechanism that contributes to cells to degrade different intracellular components (i.e., macromolecular complexes, aggregated proteins, soluble proteins, organelles, and foreign bodies). Autophagy needs formation of a double-membrane structure, which is composed of the sequestered cytoplasmic contents, called autophagosome. There are a variety of internal and external factors involved in initiation and progression of autophagy process. Viruses as external factors are one of the particles that could be associated with different stages of this process. Viruses exert their functions via activation and/or inhibition of a wide range of cellular and molecular targets, which are involved in autophagy process. Besides viruses, a variety of cellular and molecular pathways that are activated and inhibited by several factors (e.g., genetics, epigenetics, and environment factors) are related to beginning and developing of autophagy mechanism. Exosomes and microRNAs have been emerged as novel and effective players anticipated in various stages of autophagy. More knowledge in these pathways and identification of accurate roles of them could help to provide better therapeutic approaches in several diseases such as cancer. We highlighted the roles of viruses, exosomes, and microRNAs in the autophagy processes.
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Exossomos , MicroRNAs , Vírus , Exossomos/metabolismo , MicroRNAs/metabolismo , Autofagia/fisiologia , Autofagossomos/metabolismoRESUMO
Cervical cancer (CC) is the fourth most common cause of cancer death in women. The most important risk factor for the development of CC is cervical infection with human papilloma virus (HPV). Inflammation is a protective strategy that is triggered by the host against pathogens such as viral infections that acts rapidly to activate the innate immune response. Inflammation is beneficial if it is brief and well controlled; however, if the inflammation is excessive or it becomes of chronic duration, it can produce detrimental effects. HPV proteins are involved, both directly and indirectly, in the development of chronic inflammation, which is a causal factor in the development of CC. However, other factors may also have a potential role in stimulating chronic inflammation. MicroRNAs (miRNAs) (a class of noncoding RNAs) are strong regulators of gene expression. They have emerged as key players in several biological processes, including inflammatory pathways. Abnormal expression of miRNAs may be linked to the induction of inflammation that occurs in CC. Exosomes are a subset of extracellular vesicles shed by almost all types of cells, which can function as cargo transfer vehicles. Exosomes contain proteins and genetic material (including miRNAs) derived from their parent cells and can potentially affect recipient cells. Exosomes have recently been recognized to be involved in inflammatory processes and can also affect the immune response. In this review, we discuss the role of HPV proteins, miRNAs and exosomes in the inflammation associated with CC.
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Exossomos/imunologia , Inflamação/imunologia , MicroRNAs/metabolismo , Infecções por Papillomavirus/imunologia , Neoplasias do Colo do Útero/imunologia , Feminino , Regulação da Expressão Gênica/imunologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Inflamação/patologia , Inflamação/virologia , Papillomaviridae/imunologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Fatores de Risco , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Proteínas Virais/imunologia , Proteínas Virais/metabolismoRESUMO
Cellular microRNAs (miRNAs) were identified as a key player in the posttranscriptional regulation of cellular-genes regulatory pathways. They also emerged as a significant regulator of the immune response. In particular, miR-146a acts as an importance modulator of function and differentiation cells of the innate and adaptive immunity. It has been associated with disorder including cancer and viral infections. Given its significance in the regulation of key cellular processes, it is not surprising which virus infection have found ways to dysregulation of miRNAs. miR-146a has been identified in exosomes (exosomal miR-146a). After the exosomes release from donor cells, they are taken up by the recipient cell and probably the exosomal miR-146a is able to modulate the antiviral response in the recipient cell and result in making them more susceptible to virus infection. In this review, we discuss recent reports regarding miR-146a expression levels, target genes, function, and contributing role in the pathogenesis of the viral infection and provide a clue to develop the new therapeutic and preventive strategies for viral disease in the future.
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MicroRNAs/fisiologia , Viroses/genética , Exossomos/genética , Regulação da Expressão Gênica , Infecções por HIV/genética , Infecções por HIV/imunologia , Hepatite B/genética , Hepatite B/imunologia , Hepatite C/genética , Hepatite C/imunologia , Infecções por Herpesviridae/genética , Infecções por Herpesviridae/imunologia , Interações Hospedeiro-Patógeno/genética , Humanos , Influenza Humana/genética , Influenza Humana/imunologia , Viroses/imunologiaRESUMO
Autophagy has a crucial role in many cancers, including brain tumors. Several types of endogenous molecules (e.g. microRNAs, AKT, PTEN, p53, EGFR, and NF1) can modulate the process of autophagy. Recently miRNAs (small non-coding RNAs) have been found to play a vital role in the regulation of different cellular and molecular processes, such as autophagy. Deregulation of these molecules is associated with the development and progression of different pathological conditions, including brain tumors. It was found that miRNAs are epigenetic regulators, which influence the level of proteins coded by the targeted mRNAs with any modification of the genetic sequences. It has been revealed that various miRNAs (e.g., miR-7-1-3p, miR-340, miR-17, miR-30a, miR-224-3p, and miR-93), as epigenetic regulators, can modulate autophagy pathways within brain tumors. A deeper understanding of the underlying molecular targets of miRNAs, and their function in autophagy pathways could contribute to the development of new treatment methods for patients with brain tumors. In this review, we summarize the various miRNAs, which are involved in regulating autophagy in brain tumors. Moreover, we highlight the role of miRNAs in autophagy-related pathways in different cancers. Video abstract.
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Autofagia , Neoplasias Encefálicas/metabolismo , MicroRNAs/fisiologia , Animais , HumanosRESUMO
Joubert syndrome (JS) disease is a clinically and genetically heterogeneous disorder with mutations in more than 35 genes involved in its pathogenicity. Molecular genetic methods including next generation sequencing (NGS) and Sanger sequencing are effective techniques used for identifying rare genetic variants that have a strong effect on disease pathogenesis. In this study, we tested a large pedigree with a history of several affected members with JS. At first the proband was sequenced by NGS technique then, confirmed by sanger sequencing method. After this, all available members of the pedigree were subjected to molecular analysis by sanger sequencing technique. The results of this study showed a novel variant in the C5ORF42 gene c.3080A > T: p. D1027V leading to a substitution of a valine for aspartic acid (D1027V) and may be associated with JS. This variant was present in proband compatible with autosomal recessive pattern. Also this variant was present in all parents (both father and mother) of affected individuals in a heterozygous state. It seems that mutations in C5ORF42 gene are associated with JS. However, the substantial mechanism requires further investigation.
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Anormalidades Múltiplas/genética , Cerebelo/anormalidades , Anormalidades do Olho/genética , Doenças Renais Císticas/genética , Proteínas de Membrana/genética , Retina/anormalidades , Anormalidades Múltiplas/fisiopatologia , Adulto , Encéfalo/fisiologia , Cerebelo/fisiologia , Cerebelo/fisiopatologia , Pré-Escolar , Anormalidades do Olho/fisiopatologia , Feminino , Heterozigoto , Humanos , Lactente , Doenças Renais Císticas/fisiopatologia , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Mutação , Linhagem , Retina/fisiopatologia , Sequenciamento do Exoma/métodosRESUMO
Cervical cancer is as a kind of cancer beginning from the cervix. Given that cervical cancer could be observed in women who infected with papillomavirus, regular oral contraceptives, and multiple pregnancies. Early detection of cervical cancer is one of the most important aspects of the therapy of this malignancy. Despite several efforts, finding and developing new biomarkers for cervical cancer diagnosis are required. Among various prognostic, diagnostic, and therapeutic biomarkers, miRNA have been emerged as powerful biomarkers for detection, treatment, and monitoring of response to therapy in cervical cancer. Here, we summarized various miRNAs as an employable platform for prognostic, diagnostic, and therapeutic biomarkers in the treatment of cervical cancer.
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Biomarcadores Tumorais/genética , MicroRNAs , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Animais , Detecção Precoce de Câncer , Feminino , Humanos , PrognósticoRESUMO
Hepatocellular carcinoma (HCC) is known as one of the major health problems worldwide. Pathological analysis indicated that a variety of risk factors including genetical (i.e., alteration of tumor suppressors and oncogenes) and environmental factors (i.e., viruses) are involved in beginning and development of HCC. The understanding of these risk factors could guide scientists and clinicians to design effective therapeutic options in HCC treatment. Various viruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV) via targeting several cellular and molecular pathways involved in HCC pathogenesis. Among various cellular and molecular targets, microRNAs (miRNAs) have appeared as key players in HCC progression. miRNAs are short noncoding RNAs which could play important roles as oncogenes or tumor suppressors in several malignancies such as HCC. Deregulation of many miRNAs (i.e., miR-222, miR-25, miR-92a, miR-1, let-7f, and miR-21) could be associated with different stages of HCC. Besides miRNAs, exosomes are other particles which are involved in HCC pathogenesis via targeting different cargos, such as DNAs, RNAs, miRNAs, and proteins. In this review, we summarize the current knowledge of the role of miRNAs and exosomes as important players in HCC pathogenesis. Moreover, we highlighted HCV- and HBV-related miRNAs which led to HCC progression.
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Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , MicroRNAs/genética , Animais , Carcinoma Hepatocelular/etiologia , Hepacivirus/patogenicidade , Hepatite B/complicações , Hepatite B/virologia , Vírus da Hepatite B/patogenicidade , Hepatite C/complicações , Humanos , Neoplasias Hepáticas/etiologiaRESUMO
Additive Manufacturing (AM) is a transformative manufacturing technology enabling direct fabrication of complex parts layer-by-layer from 3D modeling data. Among AM applications, the fabrication of Functionally Graded Materials (FGMs) has significant importance due to the potential to enhance component performance across several industries. FGMs are manufactured with a gradient composition transition between dissimilar materials, enabling the design of new materials with location-dependent mechanical and physical properties. This study presents a comprehensive review of published literature pertaining to the implementation of Machine Learning (ML) techniques in AM, with an emphasis on ML-based methods for optimizing FGMs fabrication processes. Through an extensive survey of the literature, this review article explores the role of ML in addressing the inherent challenges in FGMs fabrication and encompasses parameter optimization, defect detection, and real-time monitoring. The article also provides a discussion of future research directions and challenges in employing ML-based methods in the AM fabrication of FGMs.
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Background and aims: MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are well-known types of noncoding RNAs (ncRNAs), which have been known as the key regulators of gene expression. They can play critical roles in viral infection by regulating the host immune response and interacting with genes in the viral genome. In this regard, ncRNAs can be employed as biomarkers for viral diseases. The current study aimed to evaluate peripheral blood mononuclear cell (PBMC) ncRNAs (lncRNAs-homeobox C antisense intergenic RNA [HOTAIR], -H19, X-inactive-specific transcript [XIST], plasmacytoma variant translocation 1 [PVT-1], and miR-34a) as diagnostic biomarkers to differentiate severe COVID-19 cases from mild ones. Methods: Candidate ncRNAs were selected according to previous studies and assessed by real-time polymerase chain reaction in the PBMC samples of patients with severe coronavirus disease 2019 (COVID-19) (n = 40), healthy subjects (n = 40), and mild COVID-19 cases (n = 40). Furthermore, the diagnostic value of the selected ncRNAs was assessed by analyzing the receiver-operating characteristic (ROC). Results: The results demonstrated that the expression pattern of the selected ncRNAs was significantly different between the studied groups. The levels of HOTAIR, XIST, and miR-34a were remarkably overexpressed in the severe COVID-19 group in comparison with the mild COVID-19 group, and in return, the PVT-1 levels were lower than in the mild COVID-19 group. Interestingly, the XIST expression level in men with severe COVID-19 was higher compared to women with mild COVID-19. ROC results suggested that HOTAIR and PVT-1 could serve as useful biomarkers for screening mild COVID-19 from severe COVID-19. Conclusions: Overall, different expression patterns of the selected ncRNAs and ROC curve results revealed that these factors can contribute to COVID-19 pathogenicity and can be considered diagnostic markers of COVID-19 severe outcomes.
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Despite recent medical advancements, breast cancer remains one of the most prevalent and deadly diseases among women. Although machine learning-based Computer-Aided Diagnosis (CAD) systems have shown potential to assist radiologists in analyzing medical images, the opaque nature of the best-performing CAD systems has raised concerns about their trustworthiness and interpretability. This paper proposes MT-BI-RADS, a novel explainable deep learning approach for tumor detection in Breast Ultrasound (BUS) images. The approach offers three levels of explanations to enable radiologists to comprehend the decision-making process in predicting tumor malignancy. Firstly, the proposed model outputs the BI-RADS categories used for BUS image analysis by radiologists. Secondly, the model employs multitask learning to concurrently segment regions in images that correspond to tumors. Thirdly, the proposed approach outputs quantified contributions of each BI-RADS descriptor toward predicting the benign or malignant class using post-hoc explanations with Shapley Values.
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This study aimed to investigate the effects of glycyrrhizic acid (GL) on the anticancer activity of cisplatin in A2780 ovarian cancer cells. Cultured A2780 cells were treated with different concentrations of GL and cisplatin individually and in combination. The MTT assay, flow cytometry, wound-healing, and clonogenic assay, were used to determine cell viability, apoptosis, migration, and colony formation, respectively. The effects on superoxide dismutase (SOD) activity were also evaluated. QPCR was used to study the effects of individual and combined treatments with GL and cisplatin on the expression levels of migration genes (MMP2 and MMP9), and some apoptosis pathway genes (caspase-3, -8, -9, and BCL2). A synergistic effect was observed between GL and cisplatin (CI < 1). Combination therapy was significantly more effective in reducing cell viability, suppressing migration and colony formation, inducing apoptosis, and altering gene expression compared to single therapies. GL significantly increased SOD activity. The relative expression of caspase -3, -8, and - 9 increased significantly, and the expression levels of MMP2 and MMP9 decreased significantly in the treated cells. Our results indicate that GL enhances the anticancer activity of cisplatin in the A2780 cell line. Therefore, the combination of GL and cisplatin can be proposed as a promising therapeutic strategy for ovarian cancer.
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Antineoplásicos , Neoplasias Ovarianas , Humanos , Feminino , Cisplatino/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Ácido Glicirrízico/farmacologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Apoptose , Superóxido Dismutase/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proliferação de CélulasRESUMO
Aims: Investigate the association between oral and dental health (ODH) and metabolic syndrome (MetS) in adults aged 35-70 years. Methods: The study utilized data from the enrollment phase of Dehgolan prospective cohort study in the west of Iran. A cross-sectional assessment was conducted on a total of 3996 participants, involving a comprehensive oral examination and the assessment of their oral hygiene behavior (ODH). MetS was defined according to the updated National Cholesterol Education Program Adult Treatment Panel III. Logistic regression used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for sociodemographic characteristics. Results: MetS was more prevalent among those who not daily brushing and flossing. Participants with missing teeth (MT) show higher prevalent of MetS. Being female, lower age, illiteracy, family history of diabetes, low physical activity, and salt at table were independently associated with increase odds of MetS (p < 0.05). Odds of MetS were significantly decreased with use flossing (OR = 0.75; CI = 0.60-0.93), decayed (OR = 0.83; CI = 0.72-0.97), filled (OR = 0.84; CI = 0.71-0.99), and increased with MT (OR = 1.45; CI = 1.16-1.81) as long as adjusted for ODH factors. When other potential confounder such as sociodemographic, personal and nutritional habits were adjusted, daily flossing was the only factor that still statistically decreased (OR = 0.79; CI = 0.62-0.99) the odds of MetS. Conclusion: Daily flossing was the only factor that independently associated with MetS. Relationship of other ODH factors with Mets were confounded by sociodemographic characteristics of the participants.
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Aim: We predicted the modulation of autophagy and apoptosis in response to temozolomide (TMZ) and IFN-γ based on changes in the expression of non-coding RNAs in C6-induced glioblastoma (GBM). Materials & methods: Each rat received an intraperitoneal injection of TMZ (7.5 mg/kg) and/or IFN-γ (50,000 IU). Results: The reduced expression of H19 and colorectal neoplasia differentially expressed (CRNDE) was associated with a reduction in autophagy in response to TMZ, IFN-γ and TMZ + IFN-γ therapy, whereas the decreased level of miR-29a (proapoptotic miRNA) was associated with an increase in apoptosis. Conclusion: It appears that H19 promotes switching from autophagy to apoptosis in response to combination therapy of TMZ and IFN-γ through the miR-29a/autophagy-related protein 9A (ATG9A) pathway in C6-induced GBM.
Temozolomide (TMZ) is a drug for people with brain cancer. It can make it hard for patients to learn and think, and it can also make the drug stop working, which lets the tumor keep growing. Researchers are looking for other drugs or things that can be taken with TMZ to stop this from happening. In this study, we used a protein called interferon (IFN), which helps fight cancer. We gave mice with brain cancer both TMZ and IFN, and saw that the tumor cells died and the tumor got smaller. We also looked at how IFN and TMZ changed the genetic material of the mouse brain, called RNA. But we need to test this on people to be sure it works.
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Neoplasias Encefálicas , Glioblastoma , MicroRNAs , Ratos , Animais , Temozolomida/uso terapêutico , Temozolomida/farmacologia , Glioblastoma/tratamento farmacológico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , MicroRNAs/genética , Autofagia , Apoptose , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêuticoRESUMO
PURPOSE: To compare the IVF outcome of clomiphene citrate/gonadotropin/antagonist (mild protocol) and microdose GnRH agonist flare protocols for poor responders undergoing in vitro fertilization. METHODS: 159 poor responder patients were randomized and ovarian stimulation was performed with clomiphene citrate, gonadotropin and antagonist (group I) or microdose GnRH agonist flare (group II) protocols. Main outcome was clinical pregnancy rate and secondary outcomes were doses of gonadotropin administration and duration of stimulation. RESULTS: There were no significant differences in age, causes of infertility, basal FSH, BMI, duration of infertility, E(2) level on the day of hCG injection in both groups. Although the cancellation, fertilization, and clinical pregnancy rates were similar in both groups, the endometrial thickness, number of retrieved oocytes, mature oocytes and implantation rate were significantly higher in mild protocol. The doses of gonadotropin administration and duration of stimulation were significantly lower in mild protocol. CONCLUSION: We recommend mild protocol in assisted reproductive technology cycles for poor responders based on our results regarding less doses of used gonadotropin and a shorter duration of stimulation.
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Busserrelina/administração & dosagem , Fármacos para a Fertilidade Feminina/administração & dosagem , Hormônio Liberador de Gonadotropina/agonistas , Indução da Ovulação/métodos , Adulto , Clomifeno/administração & dosagem , Feminino , Hormônio Foliculoestimulante/administração & dosagem , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Humanos , Menotropinas/administração & dosagem , Gravidez , Taxa de Gravidez , Estudos Prospectivos , Injeções de Esperma IntracitoplásmicasRESUMO
Cohen syndrome is caused by homozygous mutation in the vacuolar protein sorting 13 homolog B (VPS13B, also referred to as COH1) gene on chromosome 8q22.2. The VPS13B protein is involved in transmembrane transport, Golgi integrity, and neuritogenesis. Clinical manifestations of Cohen syndrome are mainly intellectual disability, developmental delay, facial abnormalities, and eye disorders. This study aimed to identify the causative variant in two unrelated families with Cohen syndrome. To this end, whole-exome sequencing (WES) was performed to identify the pathogenic variants. A homozygous nonsense variant (NM_017890:c.10369C > T; NP_060360.3: p.Q3457X) in the VPS13B gene was identified and co-segregated with all affected individuals in both families. In silico analysis highly suggested this variant as damaging for protein function. The present study increases the mutation spectrum of the VPS13B gene and could be useful in genetic diagnosis and genetic counseling in Cohen syndrome patients.
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Dedos/anormalidades , Deficiência Intelectual/genética , Microcefalia/genética , Hipotonia Muscular/genética , Miopia/genética , Obesidade/genética , Degeneração Retiniana/genética , Proteínas de Transporte Vesicular/genética , Criança , Códon sem Sentido , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/patologia , Dedos/patologia , Homozigoto , Humanos , Deficiência Intelectual/patologia , Masculino , Microcefalia/patologia , Hipotonia Muscular/patologia , Miopia/patologia , Obesidade/patologia , Fenótipo , Degeneração Retiniana/patologia , Sequenciamento do Exoma , Adulto JovemRESUMO
OBJECTIVE: Great attention is currently paid to both the pathogenetic mechanisms and non-invasive prenatal diagnosis (NIPD) of Down syndrome (DS). It has been posited that dysregulation of epigenetic signatures including DNA methylation and microRNAs (miRNAs) crucially contribute to the pathomechanism of DS. Therefore, we aimed to perform a systematic review of case-control publications that have examined the differences in epigenetic landscape between pregnancies bearing euploid fetuses and those affected with DS to provide a focused insight into the pathophysiology of DS and also novel biomarkers for NIPD of DS. STUDY DESIGN: Pertinent keywords were utilized to search into PubMed, Scopus, and Google Scholar. We enrolled studies that have compared the pattern of miRNAs expression profile or DNA methylation between pregnant women who carries DS fetuses and those with euploid fetuses. RESULTS: An assessment of 599 articles resulted in, finally, 18 eligible studies (12 miRNAs and 6 DNA methylation). The most investigated miRNAs were those that are encoded by genes on chromosome 21 and more hypermethylation regions in DS fetuses than euploids with nearly evenly distribution on all chromosomes were found. Distinct mechanisms with potential therapeutic purposes have been put forward for the involvement of epigenetic perturbations in the etiopathogenesis of DS. CONCLUSION: There is a disagreement in the recruiting of epigenetic biomarkers for NIPD of DS. This heterogeneity in results of the qualified publications emanates from confounding factors such as differences in demographic data of participants, analytical platforms, and study design. Hence, before harnessing epigenetic signatures for NIPD of DS, more experiments are required.