The World Health Organization has estimated the annual occurrence of approximately 392 million dengue virus (DENV) infections in more than 100 countries where the virus is endemic, which represents a serious threat to humanity. DENV is a serologic group with four distinct serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) belonging to the genus Flavivirus, in the family Flaviviridae. Dengue is the most widespread mosquito-borne disease in the world. The ~10.7 kb DENV genome encodes three structural proteins (capsid (C), pre-membrane (prM), and envelope (E)) and seven non-structural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5). The NS1 protein is a membrane-associated dimer and a secreted, lipid-associated hexamer. Dimeric NS1 is found on membranes both in cellular compartments and cell surfaces. Secreted NS1 (sNS1) is often present in patient serum at very high levels, which correlates with severe dengue symptoms. This study was conducted to discover how the NS1 protein, microRNAs-15/16 (miRNAs-15/16), and apoptosis are related during DENV-4 infection in human liver cell lines. Huh 7.5 and HepG2 cells were infected with DENV-4, and miRNAs-15/16, viral load, NS1 protein, and caspases-3/7 were quantified after different durations of infection. This study demonstrated that miRNAs-15/16 were overexpressed during the infection of HepG2 and Huh 7.5 cells with DENV-4 and had a relationship with NS1 protein expression, viral load, and the activity of caspases-3/7, thus making these miRNAs potential injury markers during DENV infection in human hepatocytes.
The World Health Organization has estimated an annual occurrence of approximately 392 million Dengue virus (DENV) infections in more than 100 countries where the virus is endemic, and this represents a serious threat to humanity. DENV is a serologic group with four distinct serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) belonging to the genus Flavivirus, in the family Flaviviridae. Dengue is the most widespread mosquito-borne disease in the world. The ~10.7 kb DENV genome encodes three structural proteins (capsid [C], pre-membrane [prM], and envelope [E]) and seven non-structural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5). The NS1 protein is a membrane-associated dimer and a secreted, lipid-associated hexamer. Dimeric NS1 is found on membranes both in cellular compartments and cell surfaces. Secreted NS1 (sNS1) is often present in patient serum at very high levels, which correlates with severe dengue symptoms. This study was conducted to discover how NS1 protein, microRNAs-15/16 (miRNAs-15/16), and apoptosis are related during DENV-4 infection in human liver cell lines. Huh 7.5 and HepG2 cells were infected with DENV-4, and miRNAs-15/16, viral load, NS1 protein, and caspases-3/7 were quantified after different times of infection. This study demonstrated that miRNAs-15/16 are overexpressed during infection of HepG2 and Huh 7.5 cells by DENV-4 and have a relationship with NS1 protein expression, viral load, and activity of caspases-3/7, thus making these miRNAs potential injury markers during DENV infection in human hepatocytes.
Brain stroke is an acute neural disorder characterized by obstruction (ischemic) or rupture (hemorrhagic) of blood vessels causing neural damage and subsequent functional impairment. Its pathophysiology is complex and involves a multitude of pathological events including energetic collapse, excitotoxicity, oxidative stress, metabolic acidosis, cell death and neuroinflammation. Despite its clinical importance, there is no effective pharmacological therapies available to diminish secondary damage avowing functional deficits. Considering the failure of pharmacological approaches for stroke, cell therapy came as promising alternative. Different cell types have been investigated in different experimental models with promising results. An important issue regarding the transplantation of stem cells into the damaged CNS tissue is how the pathological environment influences the transplanted cells. It has been established that an exacerbated inflammation in the pathological environment is detrimental to the survival of the transplanted stem cells. This prompted us to develop an experimental strategy to improve the therapeutic actions of bone marrow mononuclear cells (BMMCs) transplanted into the acute phase of brain stroke by modulating microglial activation with minocycline. In this chapter, we first review the basic pathophysiology of ischemic stroke with emphasis on the role of microglia to the pathological outcome. We then review the experimental approach of modulating microglia activation in order to enhance therapeutic actions of BMMCS for experimental stroke. We suggest that such an approach may be applied as an adjuvant therapy to control excessive neuroinflammation in the pathological environment allowing acute transplants and improving therapeutic actions of different kind of stem cells.
The Zika virus (VZIK) is a Flavivirus of the Flaviviridae family. With the ability to infect neural progenitor cells, microcephaly is the most serious and irreversible neurological complication associated with ZIKV. In this work, we evaluated the mRNA expression of cytokines involved in the inflammatory process that occurred during Zika virus infection in Mesocricetus auratus. The samples came from the real tissue of animals infected through sexual transmission and comprising 3 different groups of animals (TS-01, TS-02 and ZP-01).The project started with the extraction of viral RNA and mRNA from the kidneys of ZIKV-infected animals. After this step, RT-qPCR was carried out to quantify both the viral load and the expression of cytokines associated with the inflammatory process that occurred during the ZIKV infection. As can be seen in our results, this work corroborates different studies that demonstrate that ZIKV can infect and cause an inflammatory response to the kidneys, even causing a high viral load.
The World Health Organization has estimated an annual occurrence of approximately 392 million dengue virus (DENV) infections in more than 100 countries where the virus is endemic, and this represents a serious threat to humanity. DENV is a serologic group with four distinct serotypes (DENV1, DENV2, DENV3, and DENV4) belonging to the genus Flavivirus, family Flaviviridae. Dengue is the most widespread mosquito-borne disease in the world. The ~10.7 kb DENV genome encodes three structural proteins (capsid [C], pre-membrane [prM], and envelope [E]) and seven non-structural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5). The NS1 protein is found both as a membrane-associated dimer and as a secreted, lipid-associated hexamer. Dimeric NS1 is found on membranes both in cellular compartments and on the cell surface. Secreted NS1 (sNS1) is often present in patient serum at very high levels, which correlates with severe dengue symptoms. This study was carried out to find out how the NS1 protein, miRNAs 15 and 16, and apoptosis are related to each other during DENV4 infection in human liver cell line culture. The Huh 7.5 and HepG2 strains were infected with DENV4, and after different times of infection, miRNA-15 and miRNA-16, viral load, NS1 protein, and caspases 3 and 7 were quantified. This study demonstrated that miRNAs 15 and 16 are overexpressed during infection of HepG2 and HuH7.5 cells by DENV4 and have a relationship with NS1 protein expression, VDEN4 viral load, and caspase pathways 3 and 7, thus making these miRNAs interesting targets for markers of injuries during VDEN infection in human hepatocyte cells.
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