A comprehensive overview of miRNA targeting drought stress resistance in plants / Uma visão geral abrangente do miRNA visando a resistência ao estresse hídrico em plantas

MicroRNAs (miRNAs) are essential nonprotein-coding genes. In a range of organisms, miRNAs has been reported to play an essential role in regulating gene expressions at post-transcriptional level. They participate in most of the stress responsive processes in plants. Drought is an ultimate abiotic stress that affects the crop production. Therefore understanding drought stress responses are essential to improve the production of agricultural crops. Throughout evolution, plants have developed their own defense systems to cope with the adversities of environmental stresses. Among defensive mechanisms include the regulations of gene expression by miRNAs. Drought stress regulates the expression of some of the functionally conserved miRNAs in different plants. The given properties of miRNAs provide an insight to genetic alterations and enhancing drought resistance in cereal crops. The current review gives a summary to regulatory mechanisms in plants as well as miRNAs response to drought stresses in cereal crops. Some possible approaches and guidelines for the exploitation of drought stress miRNA responses to improve cereal crops are also described.

MicroRNAs (miRNAs) são genes essenciais não codificadores de proteínas. Em uma variedade de organismos, foi relatado que miRNAs desempenham papel essencial na regulação da expressão gênica em nível pós-transcricional. Eles participam da maioria dos processos responsivos ao estresse nas plantas. A seca é um estresse abiótico final que afeta a produção agrícola. Portanto, compreender as respostas ao estresse da seca é essencial para melhorar a produção de safras agrícolas. Ao longo da evolução, as plantas desenvolveram seus próprios sistemas de defesa para lidar com as adversidades do estresse ambiental. Entre os mecanismos de defesa está a regulação da expressão gênica por miRNAs. O estresse hídrico regula a expressão de alguns dos miRNAs funcionalmente conservados em diferentes plantas. As propriedades dadas dos miRNAs fornecem uma visão das alterações genéticas e aumentam a resistência à seca nas safras de cereais. A revisão atual apresenta um resumo dos mecanismos regulatórios nas plantas, bem como a resposta dos miRNAs ao estresse hídrico nas plantações de cereais. Algumas abordagens e diretrizes possíveis para a exploração das respostas do miRNA ao estresse da seca para melhorar as safras de cereais também são descritas.

A comprehensive overview of miRNA targeting drought stress resistance in plants / Uma visão geral abrangente do miRNA visando a resistência ao estresse hídrico em plantas

MicroRNAs (miRNAs) are essential nonprotein-coding genes. In a range of organisms, miRNAs has been reported to play an essential role in regulating gene expressions at post-transcriptional level. They participate in most of the stress responsive processes in plants. Drought is an ultimate abiotic stress that affects the crop production. Therefore understanding drought stress responses are essential to improve the production of agricultural crops. Throughout evolution, plants have developed their own defense systems to cope with the adversities of environmental stresses. Among defensive mechanisms include the regulations of gene expression by miRNAs. Drought stress regulates the expression of some of the functionally conserved miRNAs in different plants. The given properties of miRNAs provide an insight to genetic alterations and enhancing drought resistance in cereal crops. The current review gives a summary to regulatory mechanisms in plants as well as miRNAs response to drought stresses in cereal crops. Some possible approaches and guidelines for the exploitation of drought stress miRNA responses to improve cereal crops are also described.(AU)

MicroRNAs (miRNAs) são genes essenciais não codificadores de proteínas. Em uma variedade de organismos, foi relatado que miRNAs desempenham papel essencial na regulação da expressão gênica em nível pós-transcricional. Eles participam da maioria dos processos responsivos ao estresse nas plantas. A seca é um estresse abiótico final que afeta a produção agrícola. Portanto, compreender as respostas ao estresse da seca é essencial para melhorar a produção de safras agrícolas. Ao longo da evolução, as plantas desenvolveram seus próprios sistemas de defesa para lidar com as adversidades do estresse ambiental. Entre os mecanismos de defesa está a regulação da expressão gênica por miRNAs. O estresse hídrico regula a expressão de alguns dos miRNAs funcionalmente conservados em diferentes plantas. As propriedades dadas dos miRNAs fornecem uma visão das alterações genéticas e aumentam a resistência à seca nas safras de cereais. A revisão atual apresenta um resumo dos mecanismos regulatórios nas plantas, bem como a resposta dos miRNAs ao estresse hídrico nas plantações de cereais. Algumas abordagens e diretrizes possíveis para a exploração das respostas do miRNA ao estresse da seca para melhorar as safras de cereais também são descritas.(AU)

A comprehensive overview of miRNA targeting drought stress resistance in plants / Uma visão geral abrangente do miRNA visando a resistência ao estresse hídrico em plantas

Abstract MicroRNAs (miRNAs) are essential nonprotein-coding genes. In a range of organisms, miRNAs has been reported to play an essential role in regulating gene expressions at post-transcriptional level. They participate in most of the stress responsive processes in plants. Drought is an ultimate abiotic stress that affects the crop production. Therefore understanding drought stress responses are essential to improve the production of agricultural crops. Throughout evolution, plants have developed their own defense systems to cope with the adversities of environmental stresses. Among defensive mechanisms include the regulations of gene expression by miRNAs. Drought stress regulates the expression of some of the functionally conserved miRNAs in different plants. The given properties of miRNAs provide an insight to genetic alterations and enhancing drought resistance in cereal crops. The current review gives a summary to regulatory mechanisms in plants as well as miRNAs response to drought stresses in cereal crops. Some possible approaches and guidelines for the exploitation of drought stress miRNA responses to improve cereal crops are also described.

Resumo MicroRNAs (miRNAs) são genes essenciais não codificadores de proteínas. Em uma variedade de organismos, foi relatado que miRNAs desempenham papel essencial na regulação da expressão gênica em nível pós-transcricional. Eles participam da maioria dos processos responsivos ao estresse nas plantas. A seca é um estresse abiótico final que afeta a produção agrícola. Portanto, compreender as respostas ao estresse da seca é essencial para melhorar a produção de safras agrícolas. Ao longo da evolução, as plantas desenvolveram seus próprios sistemas de defesa para lidar com as adversidades do estresse ambiental. Entre os mecanismos de defesa está a regulação da expressão gênica por miRNAs. O estresse hídrico regula a expressão de alguns dos miRNAs funcionalmente conservados em diferentes plantas. As propriedades dadas dos miRNAs fornecem uma visão das alterações genéticas e aumentam a resistência à seca nas safras de cereais. A revisão atual apresenta um resumo dos mecanismos regulatórios nas plantas, bem como a resposta dos miRNAs ao estresse hídrico nas plantações de cereais. Algumas abordagens e diretrizes possíveis para a exploração das respostas do miRNA ao estresse da seca para melhorar as safras de cereais também são descritas.

A comprehensive overview of miRNA targeting drought stress resistance in plants

Abstract MicroRNAs (miRNAs) are essential nonprotein-coding genes. In a range of organisms, miRNAs has been reported to play an essential role in regulating gene expressions at post-transcriptional level. They participate in most of the stress responsive processes in plants. Drought is an ultimate abiotic stress that affects the crop production. Therefore understanding drought stress responses are essential to improve the production of agricultural crops. Throughout evolution, plants have developed their own defense systems to cope with the adversities of environmental stresses. Among defensive mechanisms include the regulations of gene expression by miRNAs. Drought stress regulates the expression of some of the functionally conserved miRNAs in different plants. The given properties of miRNAs provide an insight to genetic alterations and enhancing drought resistance in cereal crops. The current review gives a summary to regulatory mechanisms in plants as well as miRNAs response to drought stresses in cereal crops. Some possible approaches and guidelines for the exploitation of drought stress miRNA responses to improve cereal crops are also described.

Resumo MicroRNAs (miRNAs) são genes essenciais não codificadores de proteínas. Em uma variedade de organismos, foi relatado que miRNAs desempenham papel essencial na regulação da expressão gênica em nível pós-transcricional. Eles participam da maioria dos processos responsivos ao estresse nas plantas. A seca é um estresse abiótico final que afeta a produção agrícola. Portanto, compreender as respostas ao estresse da seca é essencial para melhorar a produção de safras agrícolas. Ao longo da evolução, as plantas desenvolveram seus próprios sistemas de defesa para lidar com as adversidades do estresse ambiental. Entre os mecanismos de defesa está a regulação da expressão gênica por miRNAs. O estresse hídrico regula a expressão de alguns dos miRNAs funcionalmente conservados em diferentes plantas. As propriedades dadas dos miRNAs fornecem uma visão das alterações genéticas e aumentam a resistência à seca nas safras de cereais. A revisão atual apresenta um resumo dos mecanismos regulatórios nas plantas, bem como a resposta dos miRNAs ao estresse hídrico nas plantações de cereais. Algumas abordagens e diretrizes possíveis para a exploração das respostas do miRNA ao estresse da seca para melhorar as safras de cereais também são descritas.

Circular RNA protein tyrosine kinase 2 aggravates pyroptosis and inflammation in septic lung tissue by promoting microRNA-766/eukaryotic initiation factor 5A axis-mediated ATP efflux

Purpose: Sepsis is characterized by an acute inflammatory response to infection, often with multiple organ failures, especially severe lung injury. This study was implemented to probe circular RNA (circRNA) protein tyrosine kinase 2 (circPTK2)-associated regulatory mechanisms in septic acute lung injury (ALI). Methods: A cecal ligation and puncture-based mouse model and an lipopolysaccharides (LPS)-based alveolar type II cell (RLE-6TN) model were generated to mimic sepsis. In the two models, inflammation- and pyroptosisrelated genes were measured. Results: The degree of lung injury in mice was analyzed by hematoxylin and eosin (H&E) staining and the apoptosis was by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining. In addition, pyroptosis and toxicity were detected in cells. Finally, the binding relationship between circPTK2, miR-766, and eukaryotic initiation factor 5A (eIF5A) was detected. Data indicated that circPTK2 and eIF5A were up-regulated and miR-766 was down-regulated in LPS-treated RLE-6TN cells and lung tissue of septic mice. Lung injury in septic mice was ameliorated after inhibition of circPTK2. Conclusion: It was confirmed in the cell model that knockdown of circPTK2 effectively ameliorated LPS-induced ATP efflux, pyroptosis, and inflammation. Mechanistically, circPTK2 mediated eIF5A expression by competitively adsorbing miR-766. Taken together, circPTK2/ miR-766/eIF5A axis ameliorates septic ALI, developing a novel therapeutic target for the disease.

Mecanismos epigenéticos nos espermatozoides e o impacto sobre a fertilidade masculina / Epigenetic mechanisms on sperm cells and the impact on male fertility

Por ser uma célula altamente especializada, o espermatozoide apresenta diferentes mecanismos epigenéticos, sendo os principais as metilações do DNA, o código de histonas, os ncRNAs (RNAs não codificadores), e a alta condensação da cromatina pela presença das protaminas. Estes mecanismos interagem entre si, contribuindo para a formação do epigenoma espermático, que modela a carga molecular espermática, que, por sua vez, pode impactar sobre as características do desenvolvimento embrionário e da progênie. Dessa forma, atualmente é consenso que o papel do espermatozoide ultrapassa a entrega de DNA de qualidade para o oócito no momento da fecundação. Pesquisas recentes de diversos grupos, incluindo o nosso, mostram que além da contribuição com DNA de qualidade, o espermatozoide entrega moléculas ao oócito no momento da fecundação que influenciam o desenvolvimento do embrião. Recentemente, essas moléculas de origem espermática (Em inglês: sperm-borne) também são associadas com alterações metabólicas e cognitivas da progênie. Embora ainda pouco se entenda como esses mecanismos podem persistir mesmo com o ciclo de reprogramação celular que ocorre logo após a fecundação, é evidente que estes podem impactar as características da progênie. Nesta revisão abordaremos sobre a modulação do epigenoma espermático e seus efeitos no desenvolvimento embrionário.(AU)

Since it is a highly specialized cell, the spermatozoa display different epigenetic mechanisms; the main ones are DNA methylation, histone code, ncRNAs (non-coding RNAs), and high chromatin condensation by the presence of protamines. These mechanisms act in synergy contributing to forming the sperm epigenome, which modulates the spermatic molecular cargo, and, may impact embryo and offspring development features. Thus, it is currently a consensus that the role of spermatozoa goes beyond delivering quality DNA to the oocyte at fertilization. Relevant findings from several research groups, including ours, have shown that sperm delivers several molecules to the oocyte at fertilization, beyond the contribution to DNA, which influences the development of the embryo. Recently, these sperm-borne molecules have also been associated with metabolic and cognitive changes in the offspring. Although the mechanism by which these changes can persist even after embryo reprogramming is not completely understood, evidence shows that sperm cell molecular content impacts embryo and offspring development. This review will mainly focus on the modulation of the sperm epigenome and its effects on embryo development.(AU)

Expression of LIN28A/B and Let-7 miRNAs in canine mammary carcinomas / Expressão de LIN28A/B e Let-7 miRNAs em carcinomas mamários caninos

LIN28 is a RNA-binding protein including two highly conserved homologous, LIN28A and LIN28B. Proto-oncogenes such as LIN28A and LIN28B are generally targeted by the let-7 miRNAs in different types of human cancers. Here, we determined the expression of LIN28A in canine mammary tumor samples and the LIN28/let-7 pathway in canine mammary cell lines. In those cell lines, we identified a functional LIN28/let-7 pathway which exhibited high expression of let-7 members and low expression of its targets, including LIN28A and LIN28B. However, the mammary carcinoma tissue samples showed a frequent expression of LIN28A being expressed mainly in the epithelial cells. No association was observed between LIN28A expression and histopathological classification and grade, TNM and survival time. Our results suggested a possible role of the LIN28A protein in the development of canine mammary carcinomas due to the high frequency observed in the tumor samples (28 of 32). The in vitro experiments suggested that the LIN28/let-7 pathway is active in the tumor cells evaluated. However, more studies are necessary to elucidate the exact role of LIN28/let-7 pathway in canine mammary carcinomas.

LIN28 é uma proteína de ligação ao RNA, com duas formas homólogas altamente conservadas, LIN28A e LIN28B. Os proto-oncogenes LIN28A e LIN28B são regulados pela família de miRNAs let-7 em diferentes tipos de cânceres em humanos. No presente trabalho, o objetivo foi determinar a expressão de LIN28A em amostras de tumor mamário de cadelas e a via LIN28/let-7 em linhagens celulares mamárias caninas. Nestas linhagens, através das técnicas de qPCR e RNAseq, foi identificado que a via LIN28/let-7 apresenta-se funcional, com alta expressão dos membros da família let-7 e baixa expressão de seus alvos, entre eles LIN28A e LIN28B. No entanto, as amostras de tecidos de carcinomas mamários caninos demonstraram expressão frequente de LIN28A, sendo observada principalmente em células epiteliais. Não foram observadas associações entre expressão de LIN28A com classificação e gradação histopatológicas, TNM e tempo de sobrevida. Nossos resultados sugerem uma possível relação da proteína LIN28A no desenvolvimento de carcinomas mamários caninos devido à alta frequência observada nas amostras tumorais (28 de 32). Os experimentos in vitro sugerem que a via LIN28/let-7 é ativa nas linhagens celulares caninas avaliadas. Entretanto, estudos funcionais ainda são necessários para elucidar a função exata da via LIN28/let-7 nos carcinomas mamários caninos.

Morphological and molecular analysis of apoptosis in the corpus cavernosum of rats submitted to a chronic alcoholism model

Purpose To evaluate the effect of chronic alcoholism on morphometry and apoptosis mechanism and correlate with miRNA-21 expression in the corpus cavernosum of rats. Methods Twenty-four rats were divided into two experimental groups: Control (C) and Alcoholic group (A). After two weeks of an adaptive phase, rats from group A received only ethanol solution (20%) during 7 weeks. The morphometric and caspase-3 immunohistochemistry analysis were performed in the corpus cavernosum. The miRNA-21 expression was analyzed in blood and cavernous tissue. Results Chronic ethanol consumption decreased cavernosal smooth muscle area of alcoholic rats. The protein expression of caspase 3 in the corpus cavernosum was higher in A compared to the C group. There was no difference in the expression of miRNA-21 in serum and cavernous tissue between the groups. Conclusion Chronic ethanol consumption reduced smooth muscle area and increased caspase 3 in the corpus cavernosum of rats, without altered serum and cavernosal miR-21 gene expression.(AU)

Bothrops moojeni L-amino acid oxidase induces apoptosis and epigenetic modulation on Bcr-Abl+ cells

Resistance to apoptosis in chronic myeloid leukemia (CML) is associated with constitutive tyrosine kinase activity of the Bcr-Abl oncoprotein. The deregulated expression of apoptosis-related genes and alteration in epigenetic machinery may also contribute to apoptosis resistance in CML. Tyrosine kinase inhibitors target the Bcr-Abl oncoprotein and are used in CML treatment. The resistance of CML patients to tyrosine kinase inhibitors has guided the search for new compounds that may induce apoptosis in Bcr-Abl+ leukemic cells and improve the disease treatment. Methods: In the present study, we investigated whether the L-amino acid oxidase isolated from Bothrops moojeni snake venom (BmooLAAO-I) (i) was cytotoxic to Bcr-Abl+ cell lines (HL-60.Bcr-Abl, K562-S, and K562-R), HL-60 (acute promyelocytic leukemia) cells, the non-tumor cell line HEK-293, and peripheral blood mononuclear cells (PBMC); and (ii) affected epigenetic mechanisms, including DNA methylation and microRNAs expression in vitro. Results: BmooLAAO-I induced ROS production, apoptosis, and differential DNA methylation pattern of regulatory apoptosis genes. The toxin upregulated expression of the pro-apoptotic genes BID and FADD and downregulated DFFA expression in leukemic cell lines, as well as increased miR-16 expression - whose major predicted target is the anti-apoptotic gene BCL2 - in Bcr-Abl+ cells. Conclusion: BmooLAAO-I exerts selective antitumor action mediated by H2O2 release and induces apoptosis, and alterations in epigenetic mechanisms. These results support future investigations on the effect of BmooLAAO-I on in vivo models to determine its potential in CML therapy.(AU)

Bothrops moojeni L-amino acid oxidase induces apoptosis and epigenetic modulation on Bcr-Abl+ cells

Resistance to apoptosis in chronic myeloid leukemia (CML) is associated with constitutive tyrosine kinase activity of the Bcr-Abl oncoprotein. The deregulated expression of apoptosis-related genes and alteration in epigenetic machinery may also contribute to apoptosis resistance in CML. Tyrosine kinase inhibitors target the Bcr-Abl oncoprotein and are used in CML treatment. The resistance of CML patients to tyrosine kinase inhibitors has guided the search for new compounds that may induce apoptosis in Bcr-Abl+ leukemic cells and improve the disease treatment. Methods: In the present study, we investigated whether the L-amino acid oxidase isolated from Bothrops moojeni snake venom (BmooLAAO-I) (i) was cytotoxic to Bcr-Abl+ cell lines (HL-60.Bcr-Abl, K562-S, and K562-R), HL-60 (acute promyelocytic leukemia) cells, the non-tumor cell line HEK-293, and peripheral blood mononuclear cells (PBMC); and (ii) affected epigenetic mechanisms, including DNA methylation and microRNAs expression in vitro. Results: BmooLAAO-I induced ROS production, apoptosis, and differential DNA methylation pattern of regulatory apoptosis genes. The toxin upregulated expression of the pro-apoptotic genes BID and FADD and downregulated DFFA expression in leukemic cell lines, as well as increased miR-16 expression - whose major predicted target is the anti-apoptotic gene BCL2 - in Bcr-Abl+ cells. Conclusion: BmooLAAO-I exerts selective antitumor action mediated by H2O2 release and induces apoptosis, and alterations in epigenetic mechanisms. These results support future investigations on the effect of BmooLAAO-I on in vivo models to determine its potential in CML therapy.(AU)

Análise estatística multivariada da expressão de microRNAs no exercício exaustivo em Rattus norvegicus / Multivariate statistical analysis of expression of microRNAs in the exhaustive exercise in Rattus norvegicus

MicroRNAs são pequenas moléculas de RNA que atuam na regulação e silenciamento gênico em organismos eucariotos. Na atividade física a compreensão da expressão de microRNAs pode ser relevante para entendimento da sua fisiologia. Feito o transcriptoma do exercício exaustivo agudo em Rattus norvegicus, buscou-se analisar a expressão diferencial (através do valor obtido de Fold-Change) de microRNAs, com o auxílio de avaliação estatística multivariada, em ambiente R. Os métodos usados mostraram expressão de 71 miRNAs. Destes, destacaram-se 6 (por análise PCoA) e dois microRNAs: mir145 e mir186 (por análise de expressão diferencial, EBseq). Concluiu-se que com os métodos usados (PCoA, Permanova e Simper) foi possível analisar a expressão diferencial de microRNAs e destacar possíveis alvos de estudo para o exercício experimental extenuante.

MicroRNAs are small molecules of RNA that act on the regulation and gene silencing in eukaryotic organisms. In physical activity the understanding of the expression of microRNAs may be relevant to understanding their physiology. The transcriptome of acute exhaustive exercise in Rattus norvegicus was used to analyze the differential expression (through the Fold-Change value obtained) of microRNAs, with the aid of multivariate statistical evaluation, in the R environment. The methods used showed expression of 71 miRNAs. Of these, six (by PCoA analysis) and two microRNAs: mir145 and mir186 (by differential expression analysis, EBseq) were highlighted. It was concluded that with the methods used (PCoA, Permanova and Simper) it was possible to analyze the differential expression of microRNAs and to highlight possible study targets for the strenuous experimental exercise.

Análise estatística multivariada da expressão de microRNAs no exercício exaustivo em Rattus norvegicus / Multivariate statistical analysis of expression of microRNAs in the exhaustive exercise in Rattus norvegicus

MicroRNAs são pequenas moléculas de RNA que atuam na regulação e silenciamento gênico em organismos eucariotos. Na atividade física a compreensão da expressão de microRNAs pode ser relevante para entendimento da sua fisiologia. Feito o transcriptoma do exercício exaustivo agudo em Rattus norvegicus, buscou-se analisar a expressão diferencial (através do valor obtido de Fold-Change) de microRNAs, com o auxílio de avaliação estatística multivariada, em ambiente R. Os métodos usados mostraram expressão de 71 miRNAs. Destes, destacaram-se 6 (por análise PCoA) e dois microRNAs: mir145 e mir186 (por análise de expressão diferencial, EBseq). Concluiu-se que com os métodos usados (PCoA, Permanova e Simper) foi possível analisar a expressão diferencial de microRNAs e destacar possíveis alvos de estudo para o exercício experimental extenuante.(AU)

MicroRNAs are small molecules of RNA that act on the regulation and gene silencing in eukaryotic organisms. In physical activity the understanding of the expression of microRNAs may be relevant to understanding their physiology. The transcriptome of acute exhaustive exercise in Rattus norvegicus was used to analyze the differential expression (through the Fold-Change value obtained) of microRNAs, with the aid of multivariate statistical evaluation, in the R environment. The methods used showed expression of 71 miRNAs. Of these, six (by PCoA analysis) and two microRNAs: mir145 and mir186 (by differential expression analysis, EBseq) were highlighted. It was concluded that with the methods used (PCoA, Permanova and Simper) it was possible to analyze the differential expression of microRNAs and to highlight possible study targets for the strenuous experimental exercise.(AU)

Effect of miR-134 against myocardial hypoxia/reoxygenation injury by directly targeting NOS3 and regulating PI3K/Akt pathway

Abstract Purpose To reveal the function of miR-134 in myocardial ischemia. Methods Real-time PCR and western blotting were performed to measure the expression of miR-134, nitric oxide synthase 3 (NOS3) and apoptotic-associated proteins. Lactic dehydrogenase (LDH) assay, cell counting kit-8 (CCK-8), Hoechst 33342/PI double staining and flow cytometry assay were implemented in H9c2 cells, respectively. MiR-134 mimic/inhibitor was used to regulate miR-134 expression. Bioinformatic analysis and luciferase reporter assay were utilized to identify the interrelation between miR-134 and NOS3. Rescue experiments exhibited the role of NOS3. The involvement of PI3K/AKT was assessed by western blot analysis. Results MiR-134 was high regulated in the myocardial ischemia model, and miR-134 mimic/inhibitor transfection accelerated/impaired the speed of cell apoptosis and attenuated/exerted the cell proliferative prosperity induced by H/R regulating active status of PI3K/AKT signaling. LDH activity was also changed due to the different treatments. Moreover, miR-134 could target NOS3 directly and simultaneously attenuated the expression of NOS3. Co-transfection miR-134 inhibitor and pcDNA3.1-NOS3 highlighted the inhibitory effects of miR-134 on myocardial H/R injury. Conclusion This present work puts insights into the crucial effects of the miR-134/NOS3 axis in myocardial H/R injury, delivering a potential therapeutic technology in future.(AU)

MiR-106a aggravates sepsis-induced acute kidney injury by targeting THBS2 in mice model

Purpose: To investigate the role and related mechanisms of miR-106a in sepsis-induced AKI.Methods: Serum from sepsis and healthy patients was collected, sepsis mouse model was established by cecal ligation and puncture (CLP). TCMK-1 cells were treated with lipopolysaccharide (LPS) and transfected with THBS2-small interfering RNA (siTHBS2), miR-106a inhibitor, miR-106a mimics and their negative controls (NCs). The expression of miR-106a, thrombospondin 2 (THBS2), Bax, cleaved caspase-3 and Bcl-2, cell viability, relative caspase-3 activity and TNF-α, IL-1β, IL-6 content were respectively detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, Cell Counting Kit-8 (CCK-8) and enzyme linked immunosorbent assay (ELISA). The relationship between miR-106a and THBS2 was confirmed by dual luciferase reporter assay. Results: MiR-106a was up-regulated in serum of sepsis patients, CLP-induced mice models and LPS-induced TCMK-1 cells. LPS reduced cell viability and Bcl-2 expression, and increased caspase-3 activity, Bax expression, the content of TNF-α, IL-1β, IL-6. THBS2 was a target of miR-106a. The decreases of caspase-3 activity, TNF-α, IL-1β, IL-6, Bax expression and the increases of cell viability, Bcl-2 expression caused by miR-106a knockdown were reversed when THBS2 silencing in LPS-stimulated TCMK-1 cells. Conclusion: MiR-106a aggravated LPS-induced inflammation and apoptosis of TCMK-1 cells via regulating THBS2 expression.(AU)

MicroRNA and cancer: a focus on mammary tumors in female dogs / MicroRNA e o câncer: um enfoque em tumores mamários de cadelas

Mammary tumors are the most frequent tumors reported in female dogs and have great relevance in veterinary oncology; however, little is known about the molecular mechanisms involved in the development of metastasis. An increasing number of human studies have suggested that epigenetic alterations, such as DNA methylation, miRNA, and histone modifications, are the predominant events leading to the metastatic phenotype in tumor cells and participate in regulating oncogenic signals associated with tumor spread. Among these epigenetic alterations, miRNAs have stood out in recent years, presenting a fundamental role in tumorigenesis. There are still few studies evaluating the role of miRNAs in canine mammary tissues. Thus, this paper aims to review the role of miRNAs in cancer with a special focus on canine mammary tumors.(AU)

Os tumores mamários caninos são considerados os mais frequentes em cadelas, além de apresentarem grande relevância na oncologia veterinária, porém a doença metastática ainda é um desafio que compreende mecanismos moleculares não totalmente esclarecidos. Um número crescente de estudos na medicina humana tem sugerido que alterações epigenéticas, tais como metilação do DNA e modificação das histonas são eventos predominantes na célula tumoral para aquisição do fenótipo metastático, participando da regulação de sinais oncogênicos associados com a disseminação do tumor. Dentre as alterações epigenéticas, os miRNAs se destacaram nos últimos anos apresentando um papel fundamental na tumorigênese. Ainda existem poucos estudos avaliando o papel dos miRNAs em tecidos mamários caninos. Assim, com este trabalho objetiva-se revisar o papel dos miRNAs no câncer com foco especial nos tumores de mama de cadelas.(AU)

The life and death of the dominant follicle

Much work has been conducted over the years to determine the major factors that control follicle growth, including the role of FSH, LH and IGF1. These factors permit the dominant follicle to grow while subordinate follicles regress. The dominant follicle enters a phase of growth, and then that growth slows as the follicle reaches maximum size. The dominant follicle remains morphologically larger for a few days in the static phase, before starting to regress with the loss of functional dominance. Few studies have addressed the factors that determine follicle fate during the static phase. In this review, we summarize the differences in gene expression between growing and non-growing (static or early regressing) dominant follicles, highlighting areas that require further study. Potential factors that may help survival of the dominant follicle include IGF1, estradiol and BMP4/BMP7, and intrafollicular factors that likely initiate regression and apoptosis include FGF18 and AMH acting through FASLG. It is also very likely that the influence of microRNAs, especially miR-21, play a role in determining the fate of the dominant follicle.(AU)

The life and death of the dominant follicle

Much work has been conducted over the years to determine the major factors that control follicle growth, including the role of FSH, LH and IGF1. These factors permit the dominant follicle to grow while subordinate follicles regress. The dominant follicle enters a phase of growth, and then that growth slows as the follicle reaches maximum size. The dominant follicle remains morphologically larger for a few days in the static phase, before starting to regress with the loss of functional dominance. Few studies have addressed the factors that determine follicle fate during the static phase. In this review, we summarize the differences in gene expression between growing and non-growing (static or early regressing) dominant follicles, highlighting areas that require further study. Potential factors that may help survival of the dominant follicle include IGF1, estradiol and BMP4/BMP7, and intrafollicular factors that likely initiate regression and apoptosis include FGF18 and AMH acting through FASLG. It is also very likely that the influence of microRNAs, especially miR-21, play a role in determining the fate of the dominant follicle.

MicroRNAs: uma nova abordagem para a predição da fertilidade em touros / MicroRNAs: a new approach to predict fertility in bulls

Atualmente, a predição da fertilidade masculina é realizada avaliando diversos aspectosmorfofuncionais (MFF) espermáticos. Em geral, estas características MFF possuem alta correlação com afertilidade. No entanto, existem ejaculados que embora possuam características MFF consideradas adequadasapresentam fertilidade insatisfatória. Assim, há demanda pela busca de novos marcadores que consigam predizera fertilidade dessas amostras seminais. Dentre estes, estão os microRNAs (miRNAs), reguladores póstranscricionais,que desempenham funções importantes na espermatogênese, na maturação espermática e nodesenvolvimento embrionário. Estudos com humanos e bovinos têm mostrado que essas moléculas possuemrelação com a fertilidade. Além disso, já foi descrito também que os miRNAs são altamente regulados nosistema reprodutivo masculino, e principalmente, ao longo da cabeça, corpo e cauda do epidídimo. Atualmenteexistem mais de 790 sequências maduras de miRNAs conhecidas em bovinos e o estabelecimento destes comomarcadores se torna cada vez mais real. Entretanto, o grande desafio destes estudos está em mostrar como estesmiRNAs efetivamente regulam a fertilidade e qual o papel deles nas funções espermáticas e no desenvolvimentoembrionário. Dessa forma, o objetivo desta revisão é compilar os dados existentes na literatura sobre os miRNAse a fertilidade masculina.(AU)

Fertility prediction is performed evaluating several sperm morphological and functional aspects(MFF). In general, MFF features present high correlation with fertility. However, there are ejaculates that,although present normal MFF features, have poor fertility results. So, there is necessity to investigate potentialfertility molecular markers which are able to predict fertility rates. Among them are the microRNAs (miRNAs),which are post-transcriptional regulators molecules that are important to spermatogenesis, sperm maturationand also embryo development. Besides, miRNAs are related with men and bull fertility and are highly regulatedon masculine tract. Currently, there are around 790 mature miRNA sequences in bovine, which could be used asbiomarkers. Nevertheless, the big challenge is to show how miRNAs regulate fertility and their functions onsperm and embryo development. Thus, the goal of this review is to compile the data of scientific literature aboutmiRNAs and male fertility.(AU)

MicroRNAs: uma nova abordagem para a predição da fertilidade em touros / MicroRNAs: a new approach to predict fertility in bulls

Atualmente, a predição da fertilidade masculina é realizada avaliando diversos aspectosmorfofuncionais (MFF) espermáticos. Em geral, estas características MFF possuem alta correlação com afertilidade. No entanto, existem ejaculados que embora possuam características MFF consideradas adequadasapresentam fertilidade insatisfatória. Assim, há demanda pela busca de novos marcadores que consigam predizera fertilidade dessas amostras seminais. Dentre estes, estão os microRNAs (miRNAs), reguladores póstranscricionais,que desempenham funções importantes na espermatogênese, na maturação espermática e nodesenvolvimento embrionário. Estudos com humanos e bovinos têm mostrado que essas moléculas possuemrelação com a fertilidade. Além disso, já foi descrito também que os miRNAs são altamente regulados nosistema reprodutivo masculino, e principalmente, ao longo da cabeça, corpo e cauda do epidídimo. Atualmenteexistem mais de 790 sequências maduras de miRNAs conhecidas em bovinos e o estabelecimento destes comomarcadores se torna cada vez mais real. Entretanto, o grande desafio destes estudos está em mostrar como estesmiRNAs efetivamente regulam a fertilidade e qual o papel deles nas funções espermáticas e no desenvolvimentoembrionário. Dessa forma, o objetivo desta revisão é compilar os dados existentes na literatura sobre os miRNAse a fertilidade masculina.

Fertility prediction is performed evaluating several sperm morphological and functional aspects(MFF). In general, MFF features present high correlation with fertility. However, there are ejaculates that,although present normal MFF features, have poor fertility results. So, there is necessity to investigate potentialfertility molecular markers which are able to predict fertility rates. Among them are the microRNAs (miRNAs),which are post-transcriptional regulators molecules that are important to spermatogenesis, sperm maturationand also embryo development. Besides, miRNAs are related with men and bull fertility and are highly regulatedon masculine tract. Currently, there are around 790 mature miRNA sequences in bovine, which could be used asbiomarkers. Nevertheless, the big challenge is to show how miRNAs regulate fertility and their functions onsperm and embryo development. Thus, the goal of this review is to compile the data of scientific literature aboutmiRNAs and male fertility.

MicroRNAs em cardiologia veterinária / MicroRNAs in veterinary cardiology

The use of biomarkers is an important recent development in veterinary medicine. Biomarkers allow non-invasive quantification of substances with diagnostic and prognostic potential in several diseases. The microRNAs are small, non-coding RNAs that regulate gene expression and are expressed in different forms in many diseases. Reduced or over-expression of microRNAs showed to be part of the pathogenesis of some heart diseases in humans and animals. Diagnostic and therapeutic value of measuring microRNAs in veterinary cardiology is increased because abnormal expression can be managed by the use of antagonists (in the case of overexpression) and mimicking (in the case of underexpression). Thus, this literature review aimed to compile scientific evidence of dysregulation of microRNAs expression in different cardiac diseases being one of the promises in the therapeutic field and diagnosis of veterinary cardiology. MicroRNAs not only have potential as a biomarker but may also help in elucidation of aspects of the pathogenesis of a variety of diseases.

Os biomarcadores vêm crescendo na medicina veterinária, pois permitem, de forma não invasiva, a quantificação de substâncias com potencial para avaliação prognóstica e diagnóstica em diversas doenças. Os microRNAs são pequenos RNAs não codificantes que regulam a expressão de genes e são expressos de diferentes formas em diversas doenças. A sua super ou subexpressão já foi evidenciada como parte da patogênese de cardiopatias em seres humanos e animais. O controle dessa anormalidade de expressão pode ser obtido pela utilização de antagonistas (em casos de superexpressão) e mimetizadores (em casos de subexpressão). Dessa forma, esta revisão de literatura tem como objetivo compilar as evidências científicas da desregulação da expressão de microRNAs nas diferentes doenças cardíacas, sendo essa uma das promessas no campo terapêutico e diagnóstico da cardiologia veterinária, permitindo não só a sua utilização como biomarcador, mas também com aspecto elucidativo da patogênese de diversas doenças.