Anthocyanins-rich interventions on oxidative stress, inflammation and lipid profile in patients undergoing hemodialysis: meta-analysis and meta-regression.

The aim of this systematic review and meta-analysis was to evaluate the effects of anthocyanins-interventions on oxidative stress, inflammation, and lipid profile in patients undergoing hemodialysis. This systematic review and meta-analysis were registered on the International Prospective Register of Systematic Reviews (PROSPERO CRD42020209742). The primary outcome was anthocyanins-rich intervention on OS parameters and secondary outcome was anthocyanins-rich intervention on inflammation and dyslipidemia. RevMan 5.4 software was used to analyze the effect size of anthocyanins-rich intervention on OS, inflammation and dyslipidemia. Meta-analysis effect size calculations incorporated random-effects model for both outcomes 1 and 2. Eight studies were included in the systematic review (trials enrolling 715 patients; 165 men and 195 women; age range between 30 and 79 years). Anthocyanin intervention in patients undergoing hemodialysis decrease the oxidant parameters (std. mean: -2.64, 95% CI: [-3.77, -1.50], P ≤ 0.0001, I2 = 97%). Specially by reduction of malondialdehyde products in favor of anthocyanins-rich intervention (std. mean: -14.58 µmol.L, 95% CI: [-26.20, -2.96], P ≤ 0.0001, I2 = 99%) and myeloperoxidase (std. mean: -1.28 ηg.mL, 95% CI: [-2.11, -0.45], P = 0.003, I2 = 77%) against placebo group. Decrease inflammatory parameters (std. mean: -0.57, 95% CI: [-0.98, -0.16], P = 0.007, I2 = 79%), increase HDL cholesterol levels (std. mean: 0.58 mg.dL, 95% CI: [0.23, 0.94], P = 0.001, I2 = 12%) against placebo group. Anthocyanins-rich intervention seems to reduce oxidative stress, inflammatory parameters and improve lipid profile by increasing HDL cholesterol levels in patients with chronic kidney disease undergoing hemodialysis.

Genetic Susceptibility to Neurodegeneration in Amazon: Apolipoprotein E Genotyping in Vulnerable Populations Exposed to Mercury.

Human exposure to mercury is a serious problem of public health in Amazon. As in other vulnerable populations throughout the world, Amazonian riverine populations are chronically exposed to this metal and some symptoms of mercury intoxication were already detected in these populations. However, studies on the genetic susceptibility to mercury toxicity in the Amazon are scarce, and they tested a limited number of individuals. In this context, apolipoprotein E gene (APOE) is a key element with a well-established association among their alleles and the neurodegenerative consequences of mercury intoxication. However, no studies have addressed APOE genotyping in Amazonian exposed populations. Additionally, epidemiological studies with APOE genotyping in Amazon have been restricted to indigenous populations. Therefore, this work analyzed for the first time the genotypic and allelic profiles of APOE in Amazonian riverine populations chronically exposed to mercury. Eight hundred and twenty three individuals were enrolled in our study donating blood (794) and/or hair (757). APOE genotyping was analyzed by real-time PCR. Total mercury and mercury species were quantified by ICP-MS and GC-pyro-AFS, respectively. Genomic ancestry markers were evaluated by multiplex-PCR reaction, separated by capillary electrophoresis on the ABI 3130 Genetic Analyzer instrument and analyzed on GeneMapper ID v3.2. The 𝜀3 and 𝜀3/𝜀3 were the most frequent allele and genotype, respectively, followed by 𝜀4 allele and 𝜀3/𝜀4 genotype. Only 𝜀2/𝜀2 genotype was not found, suggesting that the absence of this genotype is a generalized phenomenon in Amazon. Also, our data supported an association between the presence of APOE4 and the Amerindian origin in these populations. Fifty-nine individuals were identified at maximum risk with levels of mercury above 10 µg/g and the presence of APOE4. Interestingly, among individuals with high mercury content, APOE4-carriers had high mercury levels than APOE2-carriers, pointing to a different heavy metal accumulation according to the APOE allele. These data suggest that APOE4, in addition to a possible pharmacodynamic effect, may influence pharmacokinetically the mercury exposure causing its higher accumulation and leading to worse deleterious consequences. Our results may aid in the development of prevention strategies and health policy decision-making regarding these at-risk vulnerable populations.

The value of the Brazilian açai fruit as a therapeutic nutritional strategy for chronic kidney disease patients.

Açai (Euterpe oleracea Mart.) fruit from the Amazon region in Brazil contains bioactive compounds such as α-tocopherol, anthocyanins (cyanidin 3-glycoside and cyanidin 3-rutinoside), and other flavonoids with antioxidant and anti-inflammatory properties. Moreover, the prebiotic activity of anthocyanins in modulating the composition of gut microbiota has emerged as an additional mechanism by which anthocyanins exert health-promoting effects. Açai consumption may be a nutritional therapeutic strategy for chronic kidney disease (CKD) patients since these patients present with oxidative stress, inflammation, and dysbiosis. However, the ability of açai to modulate these conditions has not been studied in CKD, and this review presents recent information about açai and its possible therapeutic effects in CKD.

Cerebral malaria induces electrophysiological and neurochemical impairment in mice retinal tissue: possible effect on glutathione and glutamatergic system.

BACKGROUND: Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparum infection. This condition has usually been associated with cognitive, behavioural and motor dysfunctions, being the retinopathy the most serious consequence resulting from the disease. The pathophysiological mechanisms underlying this complication remain incompletely understood. Several experimental models of CM have already been developed in order to clarify those mechanisms related to this syndrome. In this context, the present work has been performed to investigate which possible electrophysiological and neurochemistry alterations could be involved in the CM pathology. METHODS: Experimental CM was induced in Plasmodium berghei-infected male and female C57Bl/6 mice. The survival and neurological symptoms of CM were registered. Brains and retina were assayed for TNF levels and NOS2 expression. Electroretinography measurements were recorded to assessed a- and b-wave amplitudes and neurochemicals changes were evaluated by determination of glutamate and glutathione levels by HPLC. RESULTS: Susceptible C57Bl/6 mice infected with ≈ 106 parasitized red blood cells (P. berghei ANKA strain), showed a low parasitaemia, with evident clinical signs as: respiratory failure, ataxia, hemiplegia, and coma followed by animal death. In parallel to the clinical characterization of CM, the retinal electrophysiological analysis showed an intense decrease of a- and-b-wave amplitude associated to cone photoreceptor response only at the 7 days post-infection. Neurochemical results demonstrated that the disease led to a decrease in the glutathione levels with 2 days post inoculation. It was also demonstrated that the increase in the glutathione levels during the infection was followed by the increase in the 3H-glutamate uptake rate (4 and 7 days post-infection), suggesting that CM condition causes an up-regulation of the transporters systems. Furthermore, these findings also highlighted that the electrophysiological and neurochemical alterations occurs in a manner independent on the establishment of an inflammatory response, once tumour necrosis factor levels and inducible nitric oxide synthase expression were altered only in the cerebral tissue but not in the retina. CONCLUSIONS: In summary, these findings indicate for the first time that CM induces neurochemical and electrophysiological impairment in the mice retinal tissue, in a TNF-independent manner.

Inhibition of tyrosinase by 4H-chromene analogs: Synthesis, kinetic studies, and computational analysis.

Inhibition of mushroom tyrosinase was observed with synthetic dihydropyrano[3,2-b]chromenediones. Among them, DHPC04 displayed the most potent tyrosinase inhibitory activity with a Ki value of 4 µm, comparable to the reference standard inhibitor kojic acid. A kinetic study suggested that these synthetic heterocyclic compounds behave as competitive inhibitors for the L-DOPA binding site of the enzyme. Furthermore, molecular modeling provided important insight into the mechanism of binding interactions with the tyrosinase copper active site.

Cinnamaldehyde modulates LPS-induced systemic inflammatory response syndrome through TRPA1-dependent and independent mechanisms.

Cinnamaldehyde is a natural essential oil suggested to possess anti-bacterial and anti-inflammatory properties; and to activate transient receptor potential ankyrin 1 (TRPA1) channels expressed on neuronal and non-neuronal cells. Here, we investigated the immunomodulatory effects of cinnamaldehyde in an in vivo model of systemic inflammatory response syndrome (SIRS) induced by lipopolysaccharide. Swiss mice received a single oral treatment with cinnamaldehyde 1 h before LPS injection. To investigate whether cinnamaldehyde effects are dependent on TRPA1 activation, animals were treated subcutaneously with the selective TRPA1 antagonist HC-030031 5 min prior to cinnamaldehyde administration. Vehicle-treated mice were used as controls. Cinnamaldehyde ameliorated SIRS severity in LPS-injected animals. Diminished numbers of circulating mononuclear cells and increased numbers of peritoneal mononuclear and polymorphonuclear cell numbers were also observed. Cinnamaldehyde augmented the number of peritoneal Ly6C(high) and Ly6C(low) monocyte/macrophage cells in LPS-injected mice. Reduced levels of nitric oxide, plasma TNFα and plasma and peritoneal IL-10 were also detected. Additionally, IL-1ß levels were increased in the same animals. TRPA1 antagonism by HC-030031 reversed the changes in the number of circulating and peritoneal leukocytes in cinnamaldehyde-treated animals, whilst increasing the levels of peritoneal IL-10 and reducing peritoneal IL-1ß. Overall, cinnamaldehyde modulates SIRS through TRPA1-dependent and independent mechanisms.

First isolation of Cryptococcus gattii molecular type VGII and Cryptococcus neoformans molecular type VNI from environmental sources in the city of Belém, Pará, Brazil.

Cryptococcus neoformans and Cryptococcus gattii are important agents of meningoencephalitis in humans in the city of Belém. This clinical data suggests that the region may be a highly endemic area for the pathogenic Cryptococcus species within the state of Pará (PA), Northern Brazil. Preliminary analysis of 11 environmental samples from the city of Belém showed two positive locations, including a hollow of a kassod tree (Senna siamea) colonized simultaneously by C. gattii molecular type VGII and C. neoformans molecular type VNI, and a birdcage in a commercial aviary positive for C. neoformans, molecular type VNI. This is the first evidence of an environmental occurrence of molecular types VNI and VGII in PA.

First isolation of Cryptococcus gattii molecular type VGII and Cryptococcus neoformans molecular type VNI from environmental sources in the city of Belém, Pará, Brazil

Cryptococcus neoformans and Cryptococcus gattii are important agents of meningoencephalitis in humans in the city of Belém. This clinical data suggests that the region may be a highly endemic area for the pathogenic Cryptococcus species within the state of Pará (PA), Northern Brazil. Preliminary analysis of 11 environmental samples from the city of Belém showed two positive locations, including a hollow of a kassod tree (Senna siamea) colonized simultaneously by C. gattii molecular type VGII and C. neoformans molecular type VNI, and a birdcage in a commercial aviary positive for C. neoformans, molecular type VNI. This is the first evidence of an environmental occurrence of molecular types VNI and VGII in PA.

Estradiol, but not dehydroepiandrosterone, decreases parasitemia and increases the incidence of cerebral malaria and the mortality in plasmodium berghei ANKA-infected CBA mice.

OBJECTIVE: The effect of castration and subsequent replacement of dehydroepiandrosterone (DHEA) or estradiol on parasitemia, mortality and incidence of cerebral malaria (CM) was evaluated in CBA mice infected with Plasmodium berghei ANKA. METHODS: Female mice were castrated, and groups of 12-15 animals received daily injections of DHEA, estradiol or saline. Four days after the start of treatment, mice were inoculated with 1 x 10(6)P. berghei ANKA-parasitized erythrocytes. DHEA treatment was continued during the 5 days after infection, and estradiol was administered during the follow-up. Parasitemia was evaluated daily in Giemsa-stained blood smears. Signs of CM were determined by the manifestation of coma, limb paralysis and/or convulsions. Plasma TNF-alpha levels were evaluated by sandwich ELISA. Nitric oxide synthase (NOS) activity in the brain of moribund mice was measured by the method of Bredt and Snyder. RESULTS: In non-castrated infected mice, the incidence of CM was 50%, and plasma TNF-alpha increased and brain NOS activity decreased compared to non-infected controls. Castration had no major effect on the parameters analyzed (parasitemia, mortality, CM incidence, TNF-alpha levels or NOS activity). Estradiol replacement caused a decrease in parasitemia but resulted in higher CM incidence and faster mortality, with an increase in NOS activity. CONCLUSIONS: Estradiol modulated the immune response of P. berghei ANKA-infected CBA mice, decreasing parasitemia and increasing NOS activity, and impacted negatively on survival and CM incidence, showing that neuroimmunoendocrine interactions are important in the physiopathogenesis of malaria infections.