miR-221 and miR-222 Expression Affects the Proliferation Potential of Human Prostate Carcinoma Cell Lines by Targeting p27Kip1

MicroRNAs are short regulatory RNAs that negatively modulate protein expression at a post-transcriptional level and are deeply involved in the pathogenesis of several types of cancers. Here we show that miR-221 and miR-222, encoded in tandem on chromosome X, are overexpressed in the PC3 cellular model of aggressive prostate carcinoma, as compared with LNCaP and 22Rv1 cell line models of slowly growing carcinomas. In all cell lines tested, we show an inverse relationship between the expression of miR-221 and miR-222 and the cell cycle inhibitor p27(Kip1). We recognize two target sites for the microRNAs in the 3' untranslated region of p27 mRNA, and we show that miR-221/222 ectopic overexpression directly results in p27 down-regulation in LNCaP cells. In those cells, we demonstrate that the ectopic overexpression of miR-221/222 strongly affects their growth potential by inducing a G(1) to S shift in the cell cycle and is sufficient to induce a powerful enhancement of their colony-forming potential in soft agar. Consistently, miR-221 and miR-222 knock-down through antisense LNA oligonucleotides increases p27(Kip1) in PC3 cells and strongly reduces their clonogenicity in vitro. Our results suggest that miR-221/222 can be regarded as a new family of oncogenes, directly targeting the tumor suppressor p27(Kip1), and that their overexpression might be one of the factors contributing to the oncogenesis and progression of prostate carcinoma through p27(Kip1) down-regulation

Phylogenomic analysis for Campylobacter fetus ocurring in Argentina

Background and Aim: Campylobacter fetus is one of the most important pathogens that severely affects livestock industry worldwide. C. fetus mediated bovine genital campylobacteriosis infection in cattle has been associated with significant economic losses in livestock production in the Pampas region, the most productive area of Argentina. The present study aimed to establish the genomic relationships between C. fetus strains, isolated from the Pampas region, at local and global levels. The study also explored the utility of multi‐locus sequence typing (MLST) as a typing technique for C. fetus. Materials and Methods: For pangenome and phylogenetic analysis, whole genome sequences for 34 C. fetus strains, isolated from cattle in Argentina were downloaded from GenBank. A local maximum likelihood (ML) tree was constructed and linked to a Microreact project. In silico analysis based on MLST was used to obtain information regarding sequence type (ST) for each strain. For global phylogenetic analysis, a core genome ML‐tree was constructed using genomic dataset for 265 C. fetus strains, isolated from various sources obtained from 20 countries. Results: The local core genome phylogenetic tree analysis described the presence of two major clusters (A and B) and one minor cluster (C). The occurrence of 82% of the strains in these three clusters suggested a clonal population structure for C. fetus. The MLST analysis for the local strains revealed that 31 strains were ST4 type and one strain was ST5 type. In addition, a new variant was identified that was assigned a novel ST, ST70. In the present case, ST4 was homogenously distributed across all the regions and clusters. The global analysis showed that most of the local strains clustered in the phylogenetic groups that comprised exclusively of the strains isolated from Argentina. Interestingly, three strains showed a close genetic relationship with bovine strains obtained from Uruguay and Brazil. The ST5 strain grouped in a distant cluster, with strains obtained from different sources from various geographic locations worldwide. Two local strains clustered in a phylogenetic group comprising intercontinental Campylobacter fetus venerealis strains. Conclusion: The results of the study suggested active movement of animals, probably due to economic trade between different regions of the country as well as with neighboring countries. MLST results were partially concordant with phylogenetic analysis. Thus, this method did not qualify as a reliable subtyping method to assess C. fetus diversity in Argentina. The present study provided a basic platform to conduct future research on C. fetus, both at local and international levels.Fil: Farace, Pablo Daniel. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Irazoqui, José Matías. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Santa Fe. Instituto de Investigacion de la Cadena Lactea. - Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Santa Fe. Estacion Experimental Agropecuaria Rafaela. Instituto de Investigacion de la Cadena Lactea.; ArgentinaFil: Morsella, Claudia Graciela. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce; ArgentinaFil: García, Juan Agustín. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Méndez, Maria Alejandra. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Paolicchi, Fernando Alberto. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Amadio, Ariel Fernando. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Santa Fe. Instituto de Investigacion de la Cadena Lactea. - Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Santa Fe. Estacion Experimental Agropecuaria Rafaela. Instituto de Investigacion de la Cadena Lactea.; ArgentinaFil: Gioffré, Andrea Karina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular; Argentin

The inhibition of the highly expressed miR-221 and miR-222 impairs the growth of prostate carcinoma xenografts in mice

MiR-221 and miR-222 are two highly homologous microRNAs whose upregulation has been recently described in several types of human tumors, for some of which their oncogenic role was explained by the discovery of their target p27, a key cell cycle regulator. We previously showed this regulatory relationship in prostate carcinoma cell lines in vitro, underlying the role of miR-221/222 as inducers of proliferation and tumorigenicity

Cadmium modifies the cell cycle and apoptotic profiles of human breast cancer cells treated with 5-fluorouracil

Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd), which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU) is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd

Editing of HIV-1 RNA by the double-stranded RNA deaminase ADAR1 stimulates viral infection

Adenosine deaminases that act on dsRNA (ADARs) are enzymes that target double-stranded regions of RNA converting adenosines into inosines (A-to-I editing) thus contributing to genome complexity and fine regulation of gene expression. It has been described that a member of the ADAR family, ADAR1, can target viruses and affect their replication process. Here we report evidence showing that ADAR1 stimulates human immuno deficiency virus type 1 (HIV-1) replication by using both editing-dependent and editing-independent mechanisms. We show that over-expression of ADAR1 in HIV-1 producer cells increases viral protein accumulation in an editing-independent manner. Moreover, HIV-1 virions generated in the presence of over-expressed ADAR1 but not an editing-inactive ADAR1 mutant are released more efficiently and display enhanced infectivity, as demonstrated by challenge assays performed with T cell lines and primary CD4+ T lymphocytes. Finally, we report that ADAR1 associates with HIV-1 RNAs and edits adenosines in the 5′ untranslated region (UTR) and the Rev and Tat coding sequence. Overall these results suggest that HIV-1 has evolved mechanisms to take advantage of specific RNA editing activity of the host cell and disclose a stimulatory function of ADAR1 in the spread of HIV-1

COVID-19 in Brazilian children and adolescents: findings from 21 hospitals / COVID-19 em crianças e adolescentes brasileiros: registros de 21 hospitais

Introdução: Crianças e adolescentes com Covid-19 apresentam menor mortalidade e sintomas menos intensos quando comparados aos adultos. Os estudos no Brasil baseiam-se apenas no sistema de notificação compulsória. Objetivo: Analisar as características clínicas, laboratoriais, radiológicas e desfechos de pacientes hospitalizados com menos de 20 anos de idade com Covid-19. Métodos: Série de casos de pacientes internados com Covid-19, confirmado, com idade inferior a 20 anos, obtida em estudo de coorte em 21 hospitais de cinco estados brasileiros. Resultados: Dos 36 pacientes, 20 (55,5%) eram adolescentes, 20 (55,5%) eram do sexo masculino, 18 (50,0%) apresentavam comorbidades, 2 estavam grávidas; e em 7 (19,4%) os sintomas iniciais ocorreram durante a internação por outras causas, dos quais 3 foram possivelmente infectados no hospital. Febre (61,1%), dispneia (33,3%) e sintomas neurológicos (33,0%) foram as queixas mais comuns. A proteína C reativa estava acima de 50mg / L em 16,7% e o dímero-D estava acima do limite de referência em 22,2%. Radiografias de tórax foram realizadas em 20 (55,5%) pacientes, 9 apresentavam anormalidades; e tomografias computadorizadas de tórax em 5. O tempo de internação variou de 1-40 dias (mediana 5 [intervalo interquartil 3-10]), 16 (44,4%) necessitaram de cuidados intensivos, 6 (16,7%) necessitaram de ventilação mecânica e um paciente (2,8%) faleceu. Conclusão: Em uma amostra de pacientes menores de 20 anos, procedentes de hospitais de 5 estados do Brasil, as comorbidades foram frequentes e os sintomas mais comuns foram febre, dispneia e sintomas neurológicos. Quarenta e quatro por cento dos pacientes necessitaram de cuidados intensivos, mostrando que na amostra avaliada a doença não era tão leve quanto o esperado, e um paciente morreu. 

THE ROLE OF DIGITAL PLATFORMS IN AGRI-FOOD ECOSYSTEMS RESILIENCE: A SYSTEMATIC LITERATURE REVIEW

Continued global population growth coupled with the effects of climate change leading to the exacerbation of phenomena such as droughts, extreme events, and desertification, create an extremely challenging situation for agri-food ecosystems. The challenges concern the economic conditions of rural people on the one hand, and the climate change impact of agribusiness-related activities on the other. The answer to these challenges converges in the concept of resilience of agri-food ecosystems and the impact that new digital technologies, specifically digital platforms, can have on this. The purpose of this review is to outline the different types of platforms currently used with the aim of pursuing resilience of agri-food ecosystems their core working mechanisms, and the strategies behind their use

THE ROLE OF DIGITAL PLATFORMS IN AGRI-FOOD ECOSYSTEMS RESILIENCE: A SYSTEMATIC LITERATURE REVIEW

Continued global population growth coupled with the effects of climate change leading to the exacerbation of phenomena such as droughts, extreme events, and desertification, create an extremely challenging situation for agri-food ecosystems. The challenges concern the economic conditions of rural people on the one hand, and the climate change impact of agribusiness-related activities on the other. The answer to these challenges converges in the concept of resilience of agri-food ecosystems and the impact that new digital technologies, specifically digital platforms, can have on this. The purpose of this review is to outline the different types of platforms currently used with the aim of pursuing resilience of agri-food ecosystems their core working mechanisms, and the strategies behind their us

Interpretazione scientifica del diritto e umanesimo giuridico

approfondimento interpretazione giuridica in relazione all'Umanesimo Giuridic