Aedes-Chikungunya virus interaction : key role of vector midguts microbiota and its saliva in the host infection

Aedes mosquitoes are important vectors for emerging diseases caused by arboviruses, such as chikungunya (CHIKV). These viruses’ main transmitting species are Aedes aegypti and Ae. albopictus, which are present in tropical and temperate climatic areas all over the globe. Knowledge of vector characteristics is fundamentally important to the understanding of virus transmission. Only female mosquitoes are able to transmit CHIKV to the vertebrate host since they are hematophagous. In addition, mosquito microbiota is fundamentally important to virus infection in the mosquito. Microorganisms are able to modulate viral transmission in the mosquito, such as bacteria of the Wolbachia genus, which are capable of preventing viral infection, or protozoans of the Ascogregarina species, which are capable of facilitating virus transmission between mosquitoes and larvae. The competence of the mosquito is also important in the transmission of the virus to the vertebrate host, since their saliva has several substances with biological effects, such as immunomodulators and anticoagulants, which are able to modulate the host’s response to the virus, interfering in its pathogenicity and virulence. Understanding the Aedes vector-chikungunya interaction is fundamentally important since it can enable the search for new methods of combating the virus’ transmission

Salivary gland extract from Aedes aegypti improves survival in murine polymicrobial sepsis through oxidative mechanisms

Sepsis is a systemic disease with life-threatening potential and is characterized by a dysregulated immune response from the host to an infection. The organic dysfunction in sepsis is associated with the production of inflammatory cascades and oxidative stress. Previous studies showed that Aedes aegypti saliva has anti-inflammatory, immunomodulatory, and antioxidant properties. Considering inflammation and the role of oxidative stress in sepsis, we investigated the effect of pretreatment with salivary gland extract (SGE) from Ae. aegypti in the induction of inflammatory and oxidative processes in a murine cecum ligation and puncture (CLP) model. Here, we evaluated animal survival for 16 days, as well as bacterial load, leukocyte migration, and oxidative parameters. We found that the SGE pretreatment improved the survival of septic mice, reduced bacterial load and neutrophil influx, and increased nitric oxide (NO) production in the peritoneal cavity. With regard to oxidative status, SGE increased antioxidant defenses as measured by Trolox equivalent antioxidant capacity (TEAC) and glutathione (GSH), while reducing levels of the oxidative stress marker malondialdehyde (MDA). Altogether, these data suggest that SGE plays a protective role in septic animals, contributing to oxidative and inflammatory balance during sepsis. Therefore, Ae. aegypti SGE is a potential source for new therapeutic molecule(s) in polymicrobial sepsis, and this effect seems to be mediated by the control of inflammation and oxidative damage

Aedes–Chikungunya Virus Interaction: Key Role of Vector Midguts Microbiota and Its Saliva in the Host Infection

Aedes mosquitoes are important vectors for emerging diseases caused by arboviruses, such as chikungunya (CHIKV). These viruses’ main transmitting species are Aedes aegypti and Ae. albopictus, which are present in tropical and temperate climatic areas all over the globe. Knowledge of vector characteristics is fundamentally important to the understanding of virus transmission. Only female mosquitoes are able to transmit CHIKV to the vertebrate host since they are hematophagous. In addition, mosquito microbiota is fundamentally important to virus infection in the mosquito. Microorganisms are able to modulate viral transmission in the mosquito, such as bacteria of the Wolbachia genus, which are capable of preventing viral infection, or protozoans of the Ascogregarina species, which are capable of facilitating virus transmission between mosquitoes and larvae. The competence of the mosquito is also important in the transmission of the virus to the vertebrate host, since their saliva has several substances with biological effects, such as immunomodulators and anticoagulants, which are able to modulate the host’s response to the virus, interfering in its pathogenicity and virulence. Understanding the Aedes vector-chikungunya interaction is fundamentally important since it can enable the search for new methods of combating the virus’ transmission

Dynamical mechanism for sharp orientation tuning in an integrate-and-fire model of a cortical hypercolumn

Orientation tuning in a ring of pulse-coupled integrate-and-fire (IF) neurons is analyzed in terms of spontaneous pattern formation. It is shown how the ring bifurcates from a synchronous state to a non-phase-locked state whose spike trains are characterized by clustered but irregular fluctuations of the interspike intervals (ISIs). The separation of these clusters in phase space results in a localized peak of activity as measured by the time-averaged firing rate of the neurons. This generates a sharp orientation tuning curve that can lock to a slowly rotating, weakly tuned external stimulus. Under certain conditions, the peak can slowly rotate even to a fixed external stimulus. The ring also exhibits hysteresis due to the subcritical nature of the bifurcation to sharp orientation tuning. Such behavior is shown to be consistent with a corresponding analog version of the IF model in the limit of slow synaptic interactions. For fast synapses, the deterministic fluctuations of the ISIs associated with the tuning curve can support a coefficient of variation of order unity.<br/

Action mechanism and cardiovascular effect of anthocyanins: a systematic review of animal and human studies

Abstract Cardiovascular diseases (CVD) are an important cause of death worldwide. Anthocyanins are a subgroup of flavonoids found in berries, flowers, fruits and leaves. In epidemiological and clinical studies, these polyphenols have been associated with improved cardiovascular risk profiles as well as decreased comorbidities. Human intervention studies using berries, vegetables, parts of plants and cereals (either fresh or as juice) or purified anthocyanin-rich extracts have demonstrated significant improvements in low density lipoproteins oxidation, lipid peroxidation, total plasma antioxidant capacity, and dyslipidemia as well as reduced levels of CVD molecular biomarkers. This review discusses the use of anthocyanins in animal models and their applications in human medicine, as dietary supplements or as new potent drugs against cardiovascular disease

Resveratrol Role in Autoimmune Disease—A Mini-Review

Autoimmune diseases are still considered to be pressing concerns due the fact that they are leaders in death and disability causes worldwide. Resveratrol is a polyphenol derived from a variety of foods and beverages, including red grapes and red wine. Anti-inflammatory, antioxidant, and antiaging properties of resveratrol have been reported, and in some animal and human studies this compound reduced and ameliorated the progression of autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, psoriasis, inflammatory bowel disease, and type 1 diabetes mellitus. Thus, this review aims to summarize and critically analyze the role of resveratrol in the modulation of several organ-specific or systemic autoimmune diseases

Flavopereirine—An Alkaloid Derived from <i>Geissospermum vellosii</i>—Presents Leishmanicidal Activity In Vitro

Chemotherapy is limited in the treatment of leishmaniasis due to the toxic effects of drugs, low efficacy of alternative treatments, and resistance of the parasite. This work assesses the in vitro activity of flavopereirine on promastigote cultures of Leishmania amazonensis. In addition, an in silico evaluation of the physicochemical characteristics of this alkaloid is performed. The extract and fractions were characterized by thin-layer chromatography and HPLC-DAD, yielding an alkaloid identified by NMR. The antileishmanial activity and cytotoxicity were assayed by cell viability test (MTT). The theoretical molecular properties were calculated on the Molinspiration website. The fractionation made it possible to isolate a beta-carboline alkaloid (flavopereirine) in the alkaloid fraction. Moreover, it led to obtaining a fraction with greater antileishmanial activity, since flavopereirine is very active. Regarding the exposure time, a greater inhibitory effect of flavopereirine was observed at 24 h and 72 h (IC50 of 0.23 and 0.15 &#956;g/mL, respectively). The extract, fractions, and flavopereirine presented low toxicity, with high selectivity for the alkaloid. Furthermore, flavopereirine showed no violation of Lipinski&#8217;s rule of five, showing even better results than the known inhibitor of oligopeptidase B, antipain, with three violations. Flavopereirine also interacted with residue Tyr-499 of oligopeptidase B during the molecular dynamics simulations, giving a few insights of a possible favorable mechanism of interaction and a possible inhibitory pathway. Flavopereirine proved to be a promising molecule for its antileishmanial activity

Aedes-Chikungunya virus interaction : key role of vector midguts microbiota and its saliva in the host infection

Aedes mosquitoes are important vectors for emerging diseases caused by arboviruses, such as chikungunya (CHIKV). These viruses’ main transmitting species are Aedes aegypti and Ae. albopictus, which are present in tropical and temperate climatic areas all over the globe. Knowledge of vector characteristics is fundamentally important to the understanding of virus transmission. Only female mosquitoes are able to transmit CHIKV to the vertebrate host since they are hematophagous. In addition, mosquito microbiota is fundamentally important to virus infection in the mosquito. Microorganisms are able to modulate viral transmission in the mosquito, such as bacteria of the Wolbachia genus, which are capable of preventing viral infection, or protozoans of the Ascogregarina species, which are capable of facilitating virus transmission between mosquitoes and larvae. The competence of the mosquito is also important in the transmission of the virus to the vertebrate host, since their saliva has several substances with biological effects, such as immunomodulators and anticoagulants, which are able to modulate the host’s response to the virus, interfering in its pathogenicity and virulence. Understanding the Aedes vector-chikungunya interaction is fundamentally important since it can enable the search for new methods of combating the virus’ transmission

Salivary gland extract from Aedes aegypti improves survival in murine polymicrobial sepsis through oxidative mechanisms

Sepsis is a systemic disease with life-threatening potential and is characterized by a dysregulated immune response from the host to an infection. The organic dysfunction in sepsis is associated with the production of inflammatory cascades and oxidative stress. Previous studies showed that Aedes aegypti saliva has anti-inflammatory, immunomodulatory, and antioxidant properties. Considering inflammation and the role of oxidative stress in sepsis, we investigated the effect of pretreatment with salivary gland extract (SGE) from Ae. aegypti in the induction of inflammatory and oxidative processes in a murine cecum ligation and puncture (CLP) model. Here, we evaluated animal survival for 16 days, as well as bacterial load, leukocyte migration, and oxidative parameters. We found that the SGE pretreatment improved the survival of septic mice, reduced bacterial load and neutrophil influx, and increased nitric oxide (NO) production in the peritoneal cavity. With regard to oxidative status, SGE increased antioxidant defenses as measured by Trolox equivalent antioxidant capacity (TEAC) and glutathione (GSH), while reducing levels of the oxidative stress marker malondialdehyde (MDA). Altogether, these data suggest that SGE plays a protective role in septic animals, contributing to oxidative and inflammatory balance during sepsis. Therefore, Ae. aegypti SGE is a potential source for new therapeutic molecule(s) in polymicrobial sepsis, and this effect seems to be mediated by the control of inflammation and oxidative damage