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1.
Health Sci Rep ; 7(2): e1861, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38332929

RESUMO

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.

2.
Mol Biol Rep ; 51(1): 118, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38227082

RESUMO

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.


Assuntos
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/genética
3.
Health Sci Rep ; 6(10): e1602, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37841941

RESUMO

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.

4.
Toxicol In Vitro ; 93: 105687, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37659683

RESUMO

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.


Assuntos
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 Células
5.
Immunotherapy ; 15(14): 1157-1169, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37584216

RESUMO

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.


Assuntos
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 terapêutico
6.
Intervirology ; 66(1): 63-76, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36882006

RESUMO

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.


Assuntos
COVID-19 , Diabetes Mellitus , MicroRNAs , Humanos , Leucócitos Mononucleares , COVID-19/diagnóstico , MicroRNAs/genética , Biomarcadores , Unidades de Terapia Intensiva
7.
Artigo em Inglês | MEDLINE | ID: mdl-38572141

RESUMO

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.

8.
Phys Chem Chem Phys ; 24(34): 20303-20317, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-35979759

RESUMO

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.

9.
Adv Exp Med Biol ; 1401: 97-162, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35781219

RESUMO

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.


Assuntos
Exossomos , MicroRNAs , Vírus , Exossomos/metabolismo , MicroRNAs/metabolismo , Autofagia/fisiologia , Autofagossomos/metabolismo
10.
Cell Mol Biol Lett ; 27(1): 14, 2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-35164678

RESUMO

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.


Assuntos
Vesículas Extracelulares , MicroRNAs , Viroses , Vesículas Extracelulares/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Viroses/genética , Viroses/metabolismo , Replicação Viral
11.
Eur J Obstet Gynecol Reprod Biol ; 264: 189-199, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34325214

RESUMO

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.


Assuntos
Síndrome de Down , MicroRNAs , Estudos de Casos e Controles , Metilação de DNA , Síndrome de Down/genética , Epigênese Genética , Feminino , Humanos , MicroRNAs/genética , Gravidez
12.
J Mol Neurosci ; 71(12): 2566-2574, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34041686

RESUMO

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.


Assuntos
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 Jovem
13.
Asian Pac J Cancer Prev ; 22(1): 257-266, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33507707

RESUMO

INTRODUCTION: Central nervous system tumors are a diverse group of tumors that account for 2% of all adult cancers and 17% of childhood malignancies. Several internal and external risk factors are involved in the development of this cancer such as viral infections. The aim of this study was to the determination of the EBV infection frequency and the expression level of miR-122 and miR-BART in CNS tumors samples. METHODS: One hundred and thirty-eight  fresh tissue sample (106 case and 32 control) was collected from CNS specimens. The presence of Epstein-Barr virus (EBV) DNA was examined by PCR assay and the expression level of miR-122 and miR-BART were evaluated by using real-time PCR assay in CNS tissue samples. RESULTS: EBV DNA was detected in 17% (18 of 106) of tumors tissue samples and 6.4% (2 of 32) of control samples. according to results, there was a significant relationship between the presence of EBV-DNA with CNS tumors. Additionally, the expression level of miR-122 was significantly downregulated in the EBV-positive sample compared to that of the EBV-negative sample. Also, the level of EBV-BART1-3p expression was significantly higher in EBV-positive tumors samples than EBV-positive normal samples. CONCLUSION: The results of this study suggest that the EBV could change the condition of cancer cells by altering the expression of miR-122 and EBV-BART1-3p and maybe contribute to the development of cancer cells. However, the role of viral infections in CNS cancer requires further studies. 
.


Assuntos
Neoplasias Encefálicas/patologia , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/isolamento & purificação , MicroRNAs/genética , RNA Viral/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/virologia , Estudos de Casos e Controles , DNA Viral/análise , DNA Viral/genética , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/virologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
14.
J Immunother Cancer ; 9(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33472857

RESUMO

Exosomes, as the main group of extracellular vesicles, are biologically active lipid-bilayer vesicles that are naturally released from different types of normal or tumor cells. These vesicles play an important role in intercellular communication and influence the extracellular environment and the immune system. Emerging evidence demonstrates that cancer-derived exosomes are enriched in immunosuppressive proteins, such as the programmed death-ligand 1 (PD-L1). PD-L1 and its receptor programmed cell death protein 1 (PD-1) are the key immune checkpoint molecules that promote tumor progression via negative regulation of immune responses. PDL-1 is highly expressed on the surface of tumor cells and binds to PD-1 on the surface of activated T cells, leading to suppression of T cells, which consequently enables cancer cells to escape antitumor immunity. Currently, there are several Food and Drug Administration-approved monoclonal antibodies blocking PD-1/PD-L1 interaction, which are clinically used for cancer treatment. However, despite impressive treatment outcomes, some patients show poor response to PD-1/PD-L1 blockade. Of note, tumor-derived exosomes containing PD-L1 can recapitulate the effect of cell-surface PD-L1. There is evidence that reveals a significant association between levels of circulating exosomal PD-L1 and rate of response to anti-PD-1/PD-L1 antibody therapy. The present article reviews the role of exosomal PDL-1 in the therapeutic resistance to anti-PD-1/PD-L1 treatment. Importantly, it is suggested that the removal of exosomal PDL-1 could serve as a therapeutic adjuvant for enhancing the efficacy of anti-PD-1/PD-L1 therapy in patients with cancer.


Assuntos
Antígeno B7-H1/metabolismo , Resistencia a Medicamentos Antineoplásicos , Exossomos/metabolismo , Neoplasias/imunologia , Antígeno B7-H1/efeitos dos fármacos , Progressão da Doença , Exossomos/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias/tratamento farmacológico , Receptor de Morte Celular Programada 1/efeitos dos fármacos , Receptor de Morte Celular Programada 1/metabolismo , Regulação para Cima/efeitos dos fármacos
15.
Cancer Gene Ther ; 28(3-4): 157-174, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32773776

RESUMO

Disruption in DNA methylation processes can lead to alteration in gene expression and function that would ultimately result in malignant transformation. In this way, studies have shown that, in cancers, methylation-associated silencing inactivates tumor suppressor genes, as effectively as mutations. DNA methylation machinery is composed of several genes, including those with DNA methyltransferases activity, proteins that bind to methylated cytosine in the promoter region, and enzymes with demethylase activity. Based on a prominent body of evidence, DNA methylation machinery could be regulated by microRNAs (miRNAs) called epi-miRNAs. Numerous studies demonstrated that dysregulation in DNA methylation regulators like upstream epi-miRNAs is indispensable for carcinogenesis; consequently, the malignant capacity of these cells could be reversed by restoring of this regulatory system in cancer. Conceivably, recognition of these epi-miRNAs in cancer cells could not only reveal novel molecular entities in carcinogenesis, but also render promising targets for cancer therapy. In this review, at first, we have an overview of the methylation alteration in cancers, and the effect of this phenomenon in miRNAs expression and after that, we conduct an in-depth discussion about the regulation of DNA methylation regulators by epi-miRNAs in cancer cells.


Assuntos
MicroRNAs/genética , Neoplasias/terapia , Metilação de DNA , Humanos , Neoplasias/genética
16.
J Oncol ; 2020: 7630197, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33224198

RESUMO

Lung cancer is the most common cause of cancer-related deaths worldwide. Annually, millions of people die from lung cancer because of late detection and ineffective therapies. Recently, exosomes have been introduced as new therapeutic players with the potential to improve upon current diagnostic and treatment options. Exosomes are small membranous vesicles produced during endosomal merging. This allows for cell packaging of nucleic acids, proteins, and lipids and transfer to adjacent or distant cells. While exosomes are a part of normal intercellular signaling, they also allow malignant cells to transfer oncogenic material leading to tumor spread and metastasis. Exosomes are an interesting field of discovery for biomarkers and therapeutic targets. Among exosomal materials, lncRNAs have priority; lncRNAs are a class of noncoding RNAs longer than 200 base pairs. In the case of cancer, primary interest regards their oncogene and tumor suppressor functions. In this review, the advantages of exosomal lncRNAs as biomarkers and therapeutic targets will be discussed in addition to reviewing studies of their application in lung cancer.

17.
Int Rev Immunol ; 39(6): 264-279, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32552273

RESUMO

There is a high level of heterogeneity in symptom manifestations and response to disease-modifying therapies (DMTs) in multiple sclerosis (MS), an immune-based neurodegenerative disease with ever-increasing prevalence in recent decades. Because of unknown aspects of the etiopathology of MS and mechanism of action of DMTs, the reason for this variability is undetermined, and much remains to be understood. Traditionally, physicians consider switching to other DMTs based on the exacerbation of symptoms and/or change in the results of magnetic resonance imaging and biochemical factors. Therefore, identifying biological treatment response markers that help us recognizing non-responders rapidly and subsequently choosing another DMTs is necessary. microRNAs (miRNAs) are micromanagers of gene expression which have been profiled in different samples of MS patients, highlighting their role in pathogenetic of MS. Recent studies have investigated expression profiling of miRNAs after treatment with DMTs to clarify possible DMTs-mediated mechanism and obtaining response to therapy biomarkers. In this review, we will discuss the modulation of miRNAs by DMTs in cells and pathways involved in MS.


Assuntos
Regulação da Expressão Gênica , Fatores Imunológicos/uso terapêutico , MicroRNAs/genética , Esclerose Múltipla/genética , Esclerose Múltipla/terapia , Animais , Biomarcadores , Gerenciamento Clínico , Suscetibilidade a Doenças , Humanos , Fatores Imunológicos/farmacologia , Imunomodulação/efeitos dos fármacos , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/imunologia , Resultado do Tratamento
18.
Cell Commun Signal ; 18(1): 88, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32517694

RESUMO

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.


Assuntos
Autofagia , Neoplasias Encefálicas/metabolismo , MicroRNAs/fisiologia , Animais , Humanos
19.
Mol Biol Rep ; 47(5): 4099-4103, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32367316

RESUMO

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.


Assuntos
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/métodos
20.
Cancer Gene Ther ; 27(12): 854-868, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32418986

RESUMO

Cancer immunotherapy emerged as a novel therapeutic option that employs enhanced or amended native immune system to create a robust response against malignant cells. The systemic therapies with immune-stimulating cytokines have resulted in substantial dose-limiting toxicities. Targeted cytokine immunotherapy is being explored to overcome the heterogeneity of malignant cells and tumor cell defense with a remarkable reduction of systemic side effects. Cell-based strategies, such as dendritic cells (DCs), fibroblasts or mesenchymal stem cells (MSCs) seek to minimize the numerous toxic side effects of systemic administration of cytokines for extended periods of time. The usual toxicities comprised of a vascular leak, hypotension, and respiratory insufficiency. Natural and strong tropism of MSCs toward malignant cells made them an ideal systemic delivery vehicle to direct the proposed therapeutic genes to the vicinity of a tumor where their expression could evoke an immune reaction against the tumor. Compared with other methods, the delivery of cytokines via engineered MSCs is safer and renders a more practical, and promising strategy. Large numbers of genes code for cytokines have been utilized to reengineer MSCs as therapeutic cells. This review highlights the recent findings on the cytokine gene therapy for human malignancies by focusing on MSCs application in cancer immunotherapy.


Assuntos
Engenharia Genética/métodos , Imunomodulação/imunologia , Imunoterapia/métodos , Células-Tronco Mesenquimais/metabolismo , Neoplasias/imunologia , Animais , Modelos Animais de Doenças , Humanos , Camundongos
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