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Dengue (DENV) and Chikungunya (CHIKV) viruses can be transmitted simultaneously by Aedes mosquitoes, and there may be co-infections in humans. However, how the adaptive immune response is modified in the host has yet to be known entirely. In this study, we analyzed the cross-reactivity and neutralizing activity of IgG antibodies against DENV and CHIKV in sera of patients from the Mexican Institute of Social Security in Veracruz, Mexico, collected in 2013 and 2015 and using IgG antibodies of BALB/c mice inoculated with DENV and/or CHIKV. Mice first inoculated with DENV and then with CHIKV produced IgG antibodies that neutralized both viruses. Mice were inoculated with CHIKV, and then with DENV; they had IgG antibodies with more significant anti-CHIKV IgG antibody neutralizing activity. However, the inoculation only with CHIKV resulted in better neutralization of DENV2. In sera obtained from patients in 2013, significant cross-reactivity and low anti-CHIKV IgG antibody neutralizing activity were observed. In CHIKV-positive 2015 sera, the anti-DENV IgG antibody neutralizing activity was high. These results suggest that CHIKV stimulates DENV2-induced memory responses and vice versa. Furthermore, cross-reactivity between the two viruses generated neutralizing antibodies, but exchanging CHIKV for DENV2 generated a better anti-CHIKV neutralizing response.

Amoebiasis is produced by the parasite Entamoeba histolytica; this disease affects millions of people throughout the world who may suffer from amoebic colitis or amoebic liver abscess. Metronidazole is used to treat this protozoan, but it causes important adverse effects that limit its use. Studies have shown that riluzole has demonstrated activity against some parasites. Thus, the present study aimed, for the first time, to demonstrate the in vitro and in silico anti-amoebic activity of riluzole. In vitro, the results of Entamoeba histolytica trophozoites treated with IC50 (319.5 μM) of riluzole for 5 h showed (i) a decrease of 48.1% in amoeba viability, (ii) ultrastructural changes such as a loss of plasma membrane continuity and alterations in the nuclei followed by lysis, (iii) apoptosis-like cell death, (iv) the triggering of the production of reactive oxygen species and nitric oxide, and (v) the downregulation of amoebic antioxidant enzyme gene expression. Interestingly, docking studies have indicated that riluzole presented a higher affinity than metronidazole for the antioxidant enzymes thioredoxin, thioredoxin reductase, rubrerythrin, and peroxiredoxin of Entamoeba histolytica, which are considered as possible candidates of molecular targets. Our results suggest that riluzole could be an alternative treatment against Entamoeba histolytica. Future studies should be conducted to analyze the in vivo riluzole anti-amoebic effect on the resolution of amebic liver abscess in a susceptible model, as this will contribute to developing new therapeutic agents with anti-amoebic activity.

Dengue and Zika viruses cocirculate annually in endemic areas of Mexico, causing outbreaks of different magnitude and severity every year, suggesting a continuous selection of Flavivirus variants with variable phenotypes of transmissibility and virulence. To evaluate if Flavivirus variants with different phenotypes cocirculate during outbreaks, we isolated dengue and Zika viruses from blood samples of febrile patients from Oaxaca City during the 2016 and 2019 epidemic years. We compared their replication kinetics in human cells, susceptibility to type I interferon antiviral response, and the accumulation of subgenomic RNA on infected cells. We observed correlations between type I interferon susceptibility and subgenomic RNA accumulation, with high hematocrit percentage and thrombocytopenia. Our results suggest that Flaviviruses that cocirculate in Oaxaca, Mexico, have variable sensitivity to the antiviral activity of type I interferons, and this phenotypic trait correlates with the severity of the disease.

Dengue (DENV) and Chikungunya (CHIKV) viruses can be transmitted simultaneously by Aedes mosquitoes, and there may be co-infections in humans. However, how the adaptive immune response is modified in the host has yet to be known entirely. In this study, we analyzed the cross-reactivity and neutralizing activity of IgG antibodies against DENV and CHIKV in sera of patients from the Mexican Institute of Social Security in Veracruz, Mexico, collected in 2013 and 2015 and using IgG antibodies of BALB/c mice inoculated with DENV and/or CHIKV. Mice first inoculated with DENV and then with CHIKV produced IgG antibodies that neutralized both viruses. Mice were inoculated with CHIKV, and then with DENV; they had IgG antibodies with more significant anti-CHIKV IgG antibody neutralizing activity. However, the inoculation only with CHIKV resulted in better neutralization of DENV2. In sera obtained from patients in 2013, significant cross-reactivity and low anti-CHIKV IgG antibody neutralizing activity were observed. In CHIKV-positive 2015 sera, the anti-DENV IgG antibody neutralizing activity was high. These results suggest that CHIKV stimulates DENV2-induced memory responses and vice versa. Furthermore, cross-reactivity between the two viruses generated neutralizing antibodies, but exchanging CHIKV for DENV2 generated a better anti-CHIKV neutralizing response. [ABSTRACT FROM AUTHOR]

Spirulina (formerly Arthrospira) maxima (SP) is a cyanobacterium reported to have great nutritional and pharmacological potential. The objective of this study was to evaluate the protective properties of SP against ethanol-induced toxicity. Male Wistar rats were used in the study and subjected to a 70% partial hepatectomy (PH); they were then divided into five groups. During the experiment, animals in two groups drank an aqueous solution of ethanol (EtOH) (40%, v/v). Additionally, they were administered an SP extract daily at a dose of 200 mg/kg body weight intragastrically. To explore possible mechanisms of action, we examined antioxidant defense enzymes, as well as serum biochemical parameters and histopathological changes in the liver. SP administration normalized elevated glutathione reductase (GR), glutathione (GSH), and superoxide dismutase (SOD) levels, in addition to increased catalase (CAT) and glutathione peroxidase (GPX) enzymes. Alterations in biochemical parameters were observed in the groups with PH treated with EtOH associated with a reduction in cholesterol and albumin levels, while glucose and triglyceride levels increased. The histological study supported the protective activity of SP, reducing apoptosis, necrosis, and congestion in the liver. Our findings demonstrated a protective effect of SP against EtOH that is related to less inflammation, a lesser antioxidant effect, and less free radical scavenging activity.

Dengue manifestations range from a mild form, dengue fever (DF), to more severe forms such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The ability of the host to present one of these clinical forms could be related to polymorphisms located in genes of the Toll-like receptors (TLRs) which activate the pro-inflammatory response. Therefore, the genotyping of single nucleotide genetic polymorphisms (SNPs) in TLR3 (rs3775291 and rs6552950), TLR4 (rs2737190, rs10759932, rs4986790, rs4986791, rs11536865, and rs10983755), TLR7 (rs179008 and rs3853839), and TLR8 (rs3764880, rs5741883, rs4830805, and rs1548731) was carried out in non-genetically related DHF patients, DF patients, and general population (GP) subjects. The SNPs were analyzed by real-time PCR by genotyping assays from Applied Biosystems®. The codominance model showed that dengue patients had a lower probability of presenting the TLR4-rs2737190-G/G genotype (odds ratio (OR) (95% CI) = 0.34 (0.14–0.8), p = 0.038). Dengue patients showed a lower probability of presenting TLR4-rs11536865-G/C genotype (OR (95% CI) = 0.19 (0.05–0.73), p = 0.0092) and had a high probability of presenting the TACG haplotype, but lower probability of presenting the TGCG haplotype in the TLR4 compared to GP individuals (OR (95% CI) = 0.55 (0.35–0.86), p = 0.0084). In conclusion, the TLR4-rs2737190-G/G and TLR4-rs11536865-G/C genotypes and TGCG haplotype were associated with protection from dengue.

In the oil industry, many reservoirs produce from partially penetrated wells, either to postpone the arrival of undesirable fluids or to avoid problems during drilling operations. The majority of these reservoirs are heterogeneous and anisotropic, such as naturally fractured reservoirs. The analysis of pressure-transient tests is a very useful method to dynamically characterize both the heterogeneity and anisotropy existing in the reservoir. In this paper, a new analytical solution for a partially penetrated well based on a fractal approach to capture the distribution and connectivity of the fracture network is presented. This solution represents the complexity of the flow lines better than the traditional Euclidean flow models for single-porosity fractured reservoirs, i.e., for a tight matrix. The proposed solution takes into consideration the variations in fracture density throughout the reservoir, which have a direct influence on the porosity, permeability, and the size distribution of the matrix blocks as a result of the fracturing process. This solution generalizes previous solutions to model the pressure-transient behavior of partially penetrated wells as proposed in the technical literature for the classical Euclidean formulation, which considers a uniform distribution of fractures that are fully connected. Several synthetic cases obtained with the proposed solution are shown to illustrate the influence of different variables, including fractal parameters.

Chikungunya fever is an acute viral disease caused by the Chikungunya Virus (CHIKV), which is transmitted to humans through infected Aedes aegypti and Aedes albopictus vectors. Spirulina (formerly Arthrospira) maxima (SP) is a filamentous cyanobacterium containing different molecules, some of which per se have shown antiviral activities. It has been reported that SP has a great participation in the viral replication cycle, a property that is very advantageous for therapeutic use, in addition to reducing the appearance of drug-resistant viruses. The purpose of this study was to analyze the antiviral effect and cytotoxicity of SP algae against the CHIKV virus in Vero cells. The determination of SP cytotoxicity was performed by the method based on the metabolic reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazole (MTT) bromide. The evaluation of SP antiviral activity against CHIKV, was observed in the reduction percentage was estimated by counting the plates. All assays were carried out in triplicate. Untreated infected cells were used as a positive control and dimethyl sulfoxide (DMSO), SP diluent, was added as a negative control. In the present study, the antiviral activity of SP against the CHIKV virus obtained ≥ 50 % inhibition of virus in cell culture, presenting a reduction of plaques (≥ 48.3 %). The results suggest that SP is an algae with great antiviral potential against CHIKV. [ABSTRACT FROM AUTHOR]

The neutralizing capacity of anti-CHIKV (chikungunya virus) antibodies against dengue virus (DENV) is currently unknown. In this study, the identification and titration of anti-DENV2 and anti-CHIKV antibodies was carried out in sera from patients from Veracruz during 2013 and 2015. In addition, anti-CHIKV antibodies were obtained in BALB/c mice and evaluated for their neutralizing capacity against DENV. An increase of 100 AU (arbitrary units) of anti-CHIKV antibodies was observed in the group of mice that were inoculated with DENV with respect to the control group (P < 0.0001); an increase of 250 AU was also observed in the group of mice that were initially inoculated with CHIKV and subsequently with DENV with respect to the control group (P < 0.0001). In the neutralization assay against dengue the group of mice that were inoculated only with CHIKV showed 50 % reduction of PFUs (Plaque forming units), in comparison the group of mice that were inoculated initially with dengue and subsequently with CHIKV had 65 % reduction of PFUs. The serum of patients positive for anti-CHIKV IgG and negative for anti-DENV2 IgG had a neutralizing antibody titer against DENV2 of 2 log2, in contrast those positive for anti-CHIKV IgG and anti-DENV showed a higher titer (7.5 log2, P < 0.0001). [ABSTRACT FROM AUTHOR]

The objective was to determine the regulatory dynamic of Nrf2 during liver regeneration and the administration of EtOH and/or the G. schiedeanum extract. Male Wistar rats weighing 200-230 g were subjected to a 70% partial hepatectomy; they were then divided into three groups (groups 1-3). During the experiment, animals in Group 1 drank only water. The other two groups (2-3) received an intragastric dose of ethanol (1.5 g/kg BW, solution at 40% in isotonic saline solution). Additionally, rats in group 3 received a geranium extract daily at a dose of 300 mg/kg BW i.g. EtOh and/or Geranium schiedeanum was administered to rats with regenerating livers for 7 days. At the end of treatment, the activity was determined of the antioxidant enzymes, DNA concentration, TBARS, and TAC, in addition to the expression of Nrf-2, Cyclin D1, and Nqo1. EtOH increased ROS and Nrf-2, which activated the antioxidant defenses and delayed liver proliferation. On the other hand, Geranium schiedeanum exerted an antioxidant effect, diminishing ROS, but Nrf-2 expression increased, favoring liver proliferation through the increase of DNA concentration and the overexpression of Cyclin D1, however it did not activate the antioxidant defenses. In sum, it can be concluded that Nrf-2 possesses a regulatory dynamic that is evident in the presence of a toxic agent (EtOH) and/or a phytochemical agent with antioxidant capacity ( Geranium schiedeanum ) during liver regeneration., Competing Interests: None., (IJCEP Copyright © 2017.)

Aim: To evaluate the effect of an extract of Geranium schiedeanum (Gs) as a hepatoprotective agent against ethanol (EtOH)-induced toxicity in rats., Methods: Male Wistar rats weighing 200-230 g were subjected to a 70% partial hepatectomy (PH); they were then divided into three groups (groups 1-3). During the experiment, animals in group 1 drank only water. The other two groups (2-3) drank an aqueous solution of EtOH (40%, v/v). Additionally, rats in group 3 received a Gs extract daily at a dose of 300 mg/kg body weight intragastically. Subsequently, to identify markers of liver damage in serum, alanine aminotransferase, aspartate aminotransferase, albumin and bilirubin were measured by colorimetric methods. Glucose, triglyceride and cholesterol concentrations were also determined. In addition, oxidative damage was estimated by measuring lipid peroxidation [using thiobarbituric-acid reactive substances (TBARS)] in both plasma and the liver and by measuring the total concentration of antioxidants in serum and the total antioxidant capacity in the liver. In addition, a liver mass gain assessment, total DNA analysis and a morpho-histological analysis of the liver from animals in all three groups were performed and compared. Finally, the number of deaths observed in the three groups was analyzed., Results: Administration of the Geranium shiedeanum extract significantly reduced the unfavorable effect of ethanol on liver regeneration (restitution liver mass: PH-EtOH group 60.68% vs PH-Gs-EtOH group 69.22%). This finding was congruent with the reduced levels of hepatic enzymes and the sustained or increased levels of albumin and decreased bilirubin in serum. The extract also modified the metabolic processes that regulate glucose and lipid levels, as observed from the serum measurements. Lower antioxidant levels and the liver damage induced by EtOH administration appeared to be mitigated by the extract, as observed from the TBARs (PH-EtOH group 200.14 mmol/mg vs PH-Gs-EtOH group 54.20 mmol/mg; P < 0.05), total status of antioxidants (PH-EtOH group 1.43 mmol/L vs PH-Gs-EtOH group 1.99 mmol/L; P < 0.05), total antioxidant capacity values, liver mass gain and total DNA determination (PH-EtOH group 4.80 mg/g vs PH-Gs-EtOH 9.10 mg/g; P < 0.05). Overall, these processes could be related to decreased mortality in these treated animals., Conclusion: The administered extract showed a hepatoprotective effect, limiting the EtOH-induced hepatotoxic effects. This effect can be related to modulating oxido-reduction processes.