Volatile Constituents of Some Myrtaceous Edible and Medicinal Fruits from the Brazilian Amazon.

Native and exotic fruits from the Amazon have varied characteristics, with aroma being a decisive factor in their acceptance for medicinal use as a nutraceutical supplement. This work aimed to analyze the chemical constituents of the volatile concentrates of some Myrtaceous fruit species sampled in the Brazilian Amazon. The fruit's pulps were subjected to simultaneous distillation-extraction, and gas chromatography-mass spectrometry was used to analyze their volatile chemical composition. In the volatile concentrate of Eugenia stipitata (Araçá-boi) α-pinene (17.5%), citronellyl butanoate (15.6%), and pogostol (13.5%) were identified as primary constituents; Eugenia uniflora (Ginja) concentrate comprised curzerene (30.5%), germacrone (15.4%), atractylone (13.1%), and (E)-ß-ocimene (11.1%); in Myrciaria dubia (Camu-Camu), α-pinene (55.8%), (E)-ß-ocimene (13.1%), and α-terpineol (10.0%) were present; in Psidium guajava (Goiaba) were (2E)-hexenal (21.7%), hexanal (15.4%), caryophylla-4(12),8(13)-dien-5-ß-ol (10.5%), caryophyllene oxide (9.2%), and pogostol (8.3%); and in Psidium guineense (Araçá), limonene (25.2%), ethyl butanoate (12.1%), epi-ß-bisabolol (9.8%), and α-pinene (9.2%) were the main constituents. The analyzed volatile concentrates of these fruit species presented a significant diversity of constituents with a predominance of functional groups, such as monoterpenes, sesquiterpenes, and fatty acid derivatives, originating from the plant's secondary metabolism and playing an important role in their nutritional and medicinal uses.

What Happens to the Immune System after Vaccination or Recovery from COVID-19?

Due to its leading role in fighting infections, the human immune system has been the focus of many studies in the context of Coronavirus disease 2019 (COVID-19). In a worldwide effort, the scientific community has transitioned from reporting about the effects of the novel coronavirus on the human body in the early days of the pandemic to exploring the body's many immunopathological and immunoprotecting properties that have improved disease treatment and enabled the development of vaccines. The aim of this review is to explain what happens to the immune system after recovery from COVID-19 and/or vaccination against SARS-CoV-2, the virus that causes the disease. We detail the way in which the immune system responds to a SARS-CoV-2 infection, including innate and adaptive measures. Then, we describe the role of vaccination, the main types of COVID-19 vaccines and how they protect us. Further, we explain the reason why immunity after COVID-19 infection plus a vaccination appears to induce a stronger response compared with virus exposure alone. Additionally, this review reports some correlates of protection from SARS-CoV-2 infection. In conclusion, we reinforce that vaccination is safe and important in achieving herd immunity.

Benchmarking for using an acoustic Doppler current profiler for bathymetric survey.

This research aims to improve data post-processing from an acoustic Doppler current profiler (ADCP) to obtain additional depth information with a high-quality bathymetric result. To validate the depth, dataset in a control area was used a scaled rod, the RTK (Real-Time Kinematic) positioning technique, and a single beam echo sounder (SBES). The developed post-processing and validation in the control area applied to a small region of a water supply reservoir in Brazil. A robust local regression method eliminated outliers from the raw data. Subsequently, a linear regression model was generated for the beams from the ADCP to adjust depths and improve the dataset. The statistical hypothesis test performed before and after the adjustment supported the validation of data processing. The resulting volumes calculated from the ADCP raw data showed a difference of 30% with SBES, which is usually the standard equipment used for bathymetric surveys. The proposed post-processing techniques declined to < 1% of the volume discrepancy. The raw dataset standard deviation was 0.15 m on average for Doppler beams, and after adjusts, this value dropped to 0.03 m. The results showed the necessity of a post-processing method to improve depth data quality from ADCP. Thus, the procedure described in this document can be used for bathymetric surveys using ADCP for analysis concerning the estimation of reservoir volume.

Genotoxic and cytotoxic effects of the drug dipyrone sodium in African green monkey kidney (Vero) cell line exposed in vitro.

Dipyrone or metamizole is one of the most used analgesics, mainly due to its low financial cost. However, in some countries, the sale of dipyrone is prohibited due to reported severe cases of agranulocytosis as a result of its use. Despite its high use, studies showing genotoxic and cytotoxic effects of dipyrone in mammalian cells are scarce. Therefore, in the present study, we assessed cell viability, genotoxic effects, cytotoxic effects (by apoptosis and necrosis induction), and the induction of reactive oxygen species (ROS) in Vero cells (a cell line obtained from the red kidney of green monkey) exposed to dipyrone. Our results showed a significant reduction in viability of cells exposed to dipyrone by the MTT assay. A significant increase in damage index evaluated by a comet assay was also observed, which indicates its genotoxic effects. In which concerns the cytotoxic effects of dipyrone, we observed a significant increase in the number of apoptotic cells using fluorescent dyes after 24 h and 48 h of treatment with the drug. Our results also showed that there was no significant difference in the induction of ROS generation after treatment of the cells with the drug assessed by the DCFH-DA assay. Thus, our work showed that dipyrone is both a genotoxic and cytotoxic drug to Vero cells in the assessed conditions.

Antagonistic role of IL-1ß and NLRP3/IL-18 genetics in chronic HIV-1 infection.

Host genetics affects both susceptibility and progression of HIV-1 infection. NLRP3 inflammasome provides a first-line defense in viral infections, and, accordingly, gain-of-function variants in NLRP3 have been associated with protection against HIV-1. Despite antiretroviral treatment (ART), HIV-infected patients continue to present systemic inflammation with a heterogeneous prognosis. As NLRP3 inflammasome is involved in several chronic diseases by amplifying "sterile" inflammation, its role in chronic phase of HIV infection has been postulated. Little is known about inflammasome genetics in HIV-infected patients and whether it may play a role in the different clinical outcomes. Therefore, we questioned whether NLRP3 inflammasome genetics could affect the clinical course of HIV-1 infection as it does in host/virus interaction. For this purpose, we analyzed selected single nucleotide polymorphisms (SNPs) in ART-treated HIV-infected patients (n = 300), in Long Term Non-Progressors/Elite Controllers and progressors (n = 133), and in HIV-infected individuals submitted to dendritic cell (DC)-based immunotherapy (n = 19). SNPs leading to increased activation of NLRP3 inflammasome are beneficial for patients, while SNPs that negatively affect NLRP3 activation or IL-18 production, detrimental. In contrast, gain-of-function variant in IL1B is also detrimental for patients, suggesting that while IL-1ß possible contributes to immune exhaustion, the axis NLRP3-inflammasome/IL-18 could act positively in chronic infection. Functional assays supported genetic results: NLRP3 variants associated with good quality HIV+ DC, and IL1B -511C > T with a poor one. Loss-of-function SNPs affect HIV+ T cells proliferation. These findings proposed for the first time that NLRP3 inflammasome, mainly through IL-18, play a protective role in chronic HIV infection.

Markers of oxidative-nitrosative stress induced by artesunate are followed by clastogenic and aneugenic effects and apoptosis in human lymphocytes.

Artesunate (ARS) is a semi-synthetic derivative of artemisinin, used as an outstanding antimalarial drug, which also displays antitumor, anti-inflammatory and immunosuppressive effects. In spite of the numerous reports showing the antitumor activity of ARS, the particular mechanisms associated with its cytotoxicity and genotoxicity in non-neoplastic human cells remain unclear. Here we aimed to verify the specific chromosome damages and the changes in markers of oxidative-nitrosative stress and apoptosis triggered by ARS exposure in human peripheral blood lymphocytes. Cultures were incubated in the presence of ARS and the number of binucleated cells was determined. To discriminate between micronuclei (MN) containing a whole chromosome or an acentric chromosome, the MN test was employed in combination with the fluorescence in situ hybridization assay. Alterations in the levels of superoxide anion (O2- ) and nitric oxide (NO) were measured by the nitroblue tetrazolium and Griess assay, respectively. Changes in the expression of the apoptotic markers were assessed by immunocytochemistry. We found that ARS induced a significant formation of both centromere-positive MN (C+ MN) and centromere-negative MN (C- MN). These alterations were accompanied by an increase in both cellular levels of O2- and total NO production, and a remarkable enhancement in the expression of the apoptotic markers cytochrome c and caspases 8 and 9. Together these findings reveal that ARS induces changes in the oxidative-nitrosative status of human lymphocytes, which are followed by apoptosis and clastogenic and aneugenic effects.

Host genetics contributes to the effectiveness of dendritic cell-based HIV immunotherapy.

Systems biological analysis has recently revealed how innate immune variants as well as gut microbiota impact the individual response to immunization. HIV-infected (HIV+) patients have a worse response rate after standard vaccinations, possibly due to the immune exhaustion, increased gut permeability and microbial translocation. In the last decade, dendritic cells (DC)-based immunotherapy has been proposed as an alternative approach to control HIV plasma viral load, however clinical trials showed a heterogeneity of immunization response. Hypothesizing that host genetics may importantly affects the outcome of immunotherapy in HIV+ patients, genetic polymorphisms' distribution and gene expression modulation were analyzed in a phase I/II clinical trial of DC-based immunotherapy according to immunization response, and quality of vaccine product (DC). Polymorphisms in genes previously associated with progression of HIV infection to AIDS (i.e.: PARD3B, CCL5) contribute to a better response to immunotherapy in HIV+ individuals, possibly through a systemic effect on host immune system, but also directly on vaccine product. Genes expression profile after immunization correlates with different degrees of immune chronic activation/exhaustion of HIV+ patients (i.e. PD1, IL7RA, EOMES), but also with anti-viral response and DC quality (i.e.: APOBEC3G, IL8, PPIA), suggested that an immunocompetent individual would have a better vaccine response. These findings showed once more that host genetics can affect the response to DC-based immunotherapy in HIV+ individuals, contributing to the heterogeneity of response observed in concluded trials; and it can be used as predictor of immunization success.

Direct, Metal-free C(sp2 )-H Chalcogenation of Indoles and Imidazopyridines with Dichalcogenides Catalysed by KIO3.

Herein, we report a greener protocol for the synthesis of 3-Se/S-indoles and imidazo[1,2-a]pyridines through direct C(sp2 )-H bond chalcogenation of heteroarenes with half molar equivalents of different dichalcogenides, using KIO3 as a non-toxic, easy-to-handle catalyst and a stoichiometric amount of glycerol. The reaction features are high yields, based on atom economy, easy performance on gram-scale, metal- and solvent-free conditions as well as applicability to different types of N-heteroarenes.

Pilocarpine-induced seizures trigger differential regulation of microRNA-stability related genes in rat hippocampal neurons.

Epileptogenesis in the temporal lobe elicits regulation of gene expression and protein translation, leading to reorganization of neuronal networks. In this process, miRNAs were described as being regulated in a cell-specific manner, although mechanistics of miRNAs activity are poorly understood. The specificity of miRNAs on their target genes depends on their intracellular concentration, reflecting the balance of biosynthesis and degradation. Herein, we confirmed that pilocarpine application promptly (<30 min) induces status epilepticus (SE) as revealed by changes in rat electrocorticogram particularly in fast-beta range (21-30 Hz). SE simultaneously upregulated XRN2 and downregulated PAPD4 gene expression in the hippocampus, two genes related to miRNA degradation and stability, respectively. Moreover, SE decreased the number of XRN2-positive cells in the hilus, while reduced the number of PAPD4-positive cells in CA1. XRN2 and PAPD4 levels did not change in calretinin- and CamKII-positive cells, although it was possible to determine that PAPD4, but not XRN2, was upregulated in parvalbumin-positive cells, revealing that SE induction unbalances the accumulation of these functional-opposed proteins in inhibitory interneurons that directly innervate distinct domains of pyramidal cells. Therefore, we were able to disclose a possible mechanism underlying the differential regulation of miRNAs in specific neurons during epileptogenesis.

Growth of aluminum-free porous oxide layers on titanium and its alloys Ti-6Al-4V and Ti-6Al-7Nb by micro-arc oxidation.

The growth of oxides on the surfaces of pure Ti and two of its ternary alloys, Ti-6Al-4V and Ti-6Al-7Nb, by micro-arc oxidation (MAO) in a pH 5 phosphate buffer was investigated. The primary aim was to form thick, porous, and aluminum-free oxide layers, because these characteristics favor bonding between bone and metal when the latter is implanted in the human body. On Ti, Ti-6Al-4 V, and Ti-6Al-7Nb, the oxides exhibited breakdown potentials of about 200 V, 130 V, and 140 V, respectively, indicating that the oxide formed on the pure metal is the most stable. The use of the MAO procedure led to the formation of highly porous oxides, with a uniform distribution of pores; the pores varied in size, depending on the anodizing applied voltage and time. Irrespective of the material being anodized, Raman analyses allowed us to determine that the oxide films consisted mainly of the anatase phase of TiO2, and XPS results indicated that this oxide is free of Al and any other alloying element.

HIV-1 induces NALP3-inflammasome expression and interleukin-1ß secretion in dendritic cells from healthy individuals but not from HIV-positive patients.

OBJECTIVE: NALP3-inflammasome is an innate mechanism, alternative to type-1 interferon, which is able to recognize nucleic acids and viruses in the cytoplasm and to induce pro-inflammatory response. Here, we hypothesized the involvement of inflammasome in the early defense against HIV-1 and in the full maturation of dendritic cells: for this, we evaluated the response of dendritic cells pulsed with HIV-1 in terms of inflammasome activation in healthy donors. Moreover, inflammasome response to HIV was evaluated in HIV-infected individuals. DESIGN AND METHODS: Monocyte-derived dendritic cells isolated from 20 healthy individuals (HC-DC) and 20 HIV-1-infected patients (HIV-DC) were pulsed with alditrithiol-2-inactivated HIV-1. We then analyzed inflammasome genes expression and interleukin-1ß (IL-1ß) secretion. RESULTS: In HC-DC, HIV-1 induced higher NLRP3/NALP3 mRNA expression compared with other inflammasome genes such as NALP1/NLRP1 or IPAF/NLRC4 (P < 0.001). This augmented expression was accompanied by CASP1-increased and IL1B-increased mRNA levels and by a significant increment of IL-1ß secretion (P < 0.05). Otherwise, HIV-1 failed to activate inflammasome and cytokine production in HIV-DC. HIV-DC showed an increased NLRP3/NALP3 basal expression, suggesting a chronic inflammatory profile of patients' immune cells. CONCLUSION: HIV-1 was able to induce a NALP3-inflammasome response in healthy individuals, indicating that this inflammasome could play a role in the first steps of HIV-1 infection; the consequent inflammatory process may be important for directing host immune response against the virus and/or disease progression. HIV-DC seemed to be chronically activated, but unresponsive against pathogens. Our findings could be of interest considering the ongoing research about dendritic cell manipulation and therapeutic strategies for AIDS involving dendritic cell-based immune-vaccines.

Preparation and characterization of biomimetically and electrochemically deposited hydroxyapatite coatings on micro-arc oxidized Ti-13Nb-13Zr.

Surface properties and corrosion resistance analyses of Ti-13Nb-13Zr coated by an oxide film (obtained by micro-arc oxidation at 300 V) or an oxide/hydroxyapatite (HA) film are reported. HA films were biomimetically or electrochemically deposited on the alloy/oxide surface, and their properties compared. Both the biomimetic and the electrochemical method yielded rough and globular apatite surfaces (10-20 µm globules for the former and 1-2 µm for the latter). As inferred from XRD data, the electrochemical method yielded more biologic-like HA films, while the biomimetic method yielded films containing a mixture of calcium phosphate phases. Coated Ti-13Nb-13Zr samples were immersed in an aerated PBS solution and continuously analyzed during 49 days. Considering that, after immersion, the biomimetically deposited films presented smaller variations in thickness and morphology and higher electric resistance (determined by electrochemical impedance spectroscopy), they clearly provide significantly better protection to the Ti-13Nb-13Zr alloy when in PBS solution.

Influence of hydroxyapatite on the corrosion resistance of the Ti-13Nb-13Zr alloy.

Electrochemical analyses on the biocompatible alloy Ti-13Nb-13Zr wt% in an electrolyte simulating physiological medium (PBS solution) are reported. Hydroxyapatite (HA) films were obtained on the alloy by electrodeposition at constant cathodic current. Samples of the alloy covered with an anodic-oxide film or an anodic-oxide/HA film were analyzed by open circuit potential and electrochemical impedance spectroscopy measurements during 180 days in the PBS electrolyte. Analyses of the open-circuit potential (E (oc)) values indicated that the oxide/HA film presents better protection characteristics than the oxide only. This behavior was corroborated by the higher film resistances obtained from impedance data, indicating that, besides improving the alloy osteointegration, the hydroxyapatite film may also increase the corrosion protection of the biomaterial.

Responses of the bovine infundibulum to noradrenaline during the oestrous cycle.

An experiment was conducted to investigate the responses of the bovine infundibulum to noradrenaline in vitro. Twelve beef heifers were killed and examined in equal numbers during pro-oestrus and dioestrus (day 12 of the oestrous cycle). A jugular blood sample was collected from each heifer immediately before killing, and the sera were subsequently analysed by radioimmunoassay for progesterone and oestradiol. A strip of each infundibulum (ipsilateral and contralateral to the ovary bearing the largest follicle or functional corpus luteum) was placed into a tissue bath and sequentially exposed to increasing concentrations of noradrenaline (0.4, 0.8 and 1.6 micrograms ml-1). Changes in frequency and amplitude of isometric contractions and tissue tone were recorded. Infundibula ipsilateral to ovaries bearing the largest follicle in pro-oestrous heifers responded to all concentrations of noradrenaline with greater frequency of contractions than did either contralateral infundibula or both ipsilateral and contralateral infundibula of dioestrous animals (stage of cycle x tissue location interaction, P < 0.01). Changes in the amplitude of contractions induced by noradrenaline did not differ between stages of the cycle studied or the location of the infundibulum within the animal. Mean tone of ipsilateral and contralateral infundibula of pro-oestrous and dioestrous animals increased linearly with exposure to all concentrations of noradrenaline tested (P < 0.05). However, the response of infundibula of dioestrous animals was greater than that of infundibula of pro-oestrous heifers (P < or = 0.06). These data demonstrate that the bovine infundibulum is responsive to noradrenaline, and suggest that responses to this neurotransmitter may be governed by concentrations of oestrogen and progesterone to which the infundibulum is exposed.