Search Results (13)

Plant compounds that inhibit snake venom activities are relevant and can provide active molecules to counteract snake venom effects. Numerous studies on snake viperid venoms found that metalloproteinases play a significant role in the pathophysiology of hemorrhage that occurs on envenomation. Preclinical studies using vitro and in vivo protocols investigated natural compounds and viperid snake venoms, evaluating the enzymatic, procoagulant, hemorrhagic, edematogenic, myotoxic, and lethal activities. Many studies focused on Bothrops venoms and ascribed that angiorrhexis and hemorrhage resulted from the metalloproteinase action on collagen in the basal lamina. This effect resulted in a combined action with phospholipase A2 and hyaluronidase, inducing hemorrhage, edema, and necrosis. Due to the lack of efficient antivenoms in remote areas, traditional native plant treatments remain common, especially in the Amazon. Our group studied plant extracts, isolated compounds, and lapachol synthetic derivative analogs with selective inhibition for Bothrops venom proteolytic and hemorrhagic activity and devoid of phospholipase activity. We highlight those new synthetic naphthoquinones which inhibit snake venom metalloproteinases and that are devoid of other venom enzyme inhibition. This review shows the potential use of snake venom effects, mainly Bothrops venom metalloproteinase activity, as a tool to identify and develop new active molecules against hemorrhagic effects. Full article

Zika virus (ZIKV) is an arbovirus with maternal, sexual, and TORCH-related transmission capabilities. After 2015, Brazil had the highest number of ZIVK-infected pregnant women who lost their babies or delivered them with Congenital ZIKV Syndrome (CZS). ZIKV triggers an immune defense in the placenta. This immune response counts with the participation of interleukins and transcription factors. Additionally, it has the potential involvement of human endogenous retroviruses (HERVS). Interleukins are immune response regulators that aid immune tolerance and support syncytial structure development in the placenta, where syncytin receptors facilitate vital cell-to-cell fusion events. HERVs are remnants of ancient viral infections that integrate into the genome and produce syncytin proteins crucial for placental development. Since ZIKV can infect trophoblast cells, we analyzed the relationship between ZIKV infection, HERV, interleukin, and transcription factor modulations in the placenta. To investigate the impact of ZIKV on trophoblast cells, we examined two cell types (BeWo and HTR8) infected with ZIKV-MR766 (African) and ZIKV-IEC-Paraíba (Asian–Brazilian) using Taqman and RT2 Profiler PCR Array assays. Our results indicate that early ZIKV infection (24–72 h) does not induce differential interleukins, transcription factors, and HERV expression. However, we show that the expression of a few of these host defense genes appears to be linked independently of ZIKV infection. Future studies involving additional trophoblastic cell lineages and extended infection timelines will illuminate the dynamic interplay between ZIKV, HERVs, interleukins, and transcription factors in the placenta. Full article

The Amapá margin, part of the Brazilian Equatorial Margin (BEM), is a key region that plays a strategic role in the global climate balance between the North and South Atlantic Ocean as it is strictly tied to equatorial heat conveyance and the fresh/salt water equilibrium with the Amazon River. We performed a new scientific expedition on the Amapá continental shelf (ACS, northern part of the Amazon continental platform) collecting sediment and using instrumental observation at an unstudied site. We show here the preliminary outcomes following the applied methodologies for investigation. Geophysical, geological, and biological surveys were carried out within the ACS to (1) perform bathymetric and sonographic mapping, high-resolution sub-surface geophysical characterization of the deep environment of the margin of the continental platform, (2) characterize the habitats and benthic communities through underwater images and biological sampling, (3) collect benthic organisms for ecological and taxonomic studies, (4) define the mineralogical and (5) elemental components of sediments from the study region, and (6) identify their provenance. The geophysical data collection included the use of bathymetry, a sub-bottom profiler, side scan sonar, bathythermograph acquisition, moving vessel profiler, and a thermosalinograph. The geological data were obtained through mineralogical, elemental, and grain size analysis. The biological investigation involved epifauna/infauna characterization, microbial analysis, and eDNA analysis. The preliminary results of the geophysical mapping, shallow seismic, and ultrasonographic surveys endorsed the identification of a hard substrate in a mesophotic environment. The preliminary geological data allowed the identification of amphibole, feldspar, biotite, as well as other minerals (e.g., calcite, quartz, goethite, ilmenite) present in the substrata of the Amapá continental shelf. Silicon, iron, calcium, and aluminum composes ~85% of sediments from the ACS. Sand and clay are the main fraction from these sediments. Within the sediments, Polychaeta (Annelida) dominated, followed by Crustacea (Arthropoda), and Ophiuroidea (Echinodermata). Through TowCam videos, 35 taxons with diverse epifauna were recorded, including polychaetes, hydroids, algae, gastropods, anemones, cephalopods, crustaceans, fishes, and sea stars. Full article

Mugil liza juveniles (6.69 ± 0.06 g) were subjected to dietary citral (0-control, 0.5, 1.0 and 2.0 mL per kg feed) for 45 days, and its possible effects on zootechnical and metabolic parameters, digestive enzymes, innate immunity, oxidative status and liver damage were evaluated. At the end of the experiment, fish fed 2.0 mL citral per kg feed showed a greater weight gain and protein retention efficiency, as well as enhanced activities of pepsin (stomach) and amylase (intestine) compared with control fish. Citral supplementation decreased liver lipoperoxidation and increased the activities of glutathione peroxidase, glutathione-S-transferase and superoxide dismutase in the gills, liver and brain. The highest level of citral inclusion augmented non-protein thiol content in the brain and gills. Myeloperoxidase activity was lower in fish offered 1.0 and 2.0 mL citral per kg feed. Dietary citral did not influence the plasma levels of aspartate aminotransferase and alanine aminotransferase or the hepatic histology. As it improved growth, the activity of digestive enzymes and general health, dietary citral may be recommended for M. liza at 2.0 mL per kg feed. Full article

Ceramic detachment is a serious problem that persists in modern building constructions despite technological advances and updated regulatory documents. Most of these detachments occur at the interface between the adhesive mortar and the ceramic tile, due to the action of simultaneous tensile and shearing efforts. However, despite this understanding, experimental studies that evaluate the integrity of the adhesion of façades covering materials subjected to simultaneous stress are scarce. In this sense, this study proposes to evaluate the integrity of adhesive mortar joints using the mixed-mode flexure (MMF) crack propagation test. Force and elastic and dissipated energy data were used in this analysis. Prismatic specimens, with a size of 160 × 40 mm² and a thickness of 6 mm, were produced consisting of two ceramic plates joined by a layer of adhesive mortar at 5 ± 0.5 mm. An acetate film was inserted into one of the mortar–ceramic interfaces in order to simulate the presence of a previous crack, and different crack sizes were used. The results showed the high stress-concentrating effect that the existence of flaws in the interface region has on fracture resistance, as well as the importance of effective contact between the materials. The energy parameters confirmed the analyses carried out based on the load values. The elastic energy of the system fell in the cracked samples, showing that there is a close relationship between the interface energy and the adhesive strength of the material. An energy release of the order of 0.053 ± 0.031 J was required for a 15 mm crack to propagate, creating a fracture surface. Full article

The innate immune system is the first line of defense against pathogens such as the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The type I-interferon (IFN) response activation during the initial steps of infection is essential to prevent viral replication and tissue damage. SARS-CoV and SARS-CoV-2 can inhibit this activation, and individuals with a dysregulated IFN-I response are more likely to develop severe disease. Several mutations in different variants of SARS-CoV-2 have shown the potential to interfere with the immune system. Here, we evaluated the buffy coat transcriptome of individuals infected with Gamma or Delta variants of SARS-CoV-2. The Delta transcriptome presents more genes enriched in the innate immune response and Gamma in the adaptive immune response. Interactome and enriched promoter analysis showed that Delta could activate the INF-I response more effectively than Gamma. Two mutations in the N protein and one in the nsp6 protein found exclusively in Gamma have already been described as inhibitors of the interferon response pathway. This indicates that the Gamma variant evolved to evade the IFN-I response. Accordingly, in this work, we showed one of the mechanisms that variants of SARS-CoV-2 can use to avoid or interfere with the host Immune system. Full article

SARS-CoV-2 infection triggers distinct patterns of disease development characterized by significant alterations in host regulatory responses. Severe cases exhibit profound lung inflammation and systemic repercussions. Remarkably, critically ill patients display a “lipid storm”, influencing the inflammatory process and tissue damage. Sphingolipids (SLs) play pivotal roles in various cellular and tissue processes, including inflammation, metabolic disorders, and cancer. In this study, we employed high-resolution mass spectrometry to investigate SL metabolism in plasma samples obtained from control subjects (n = 55), COVID-19 patients (n = 204), and convalescent individuals (n = 77). These data were correlated with inflammatory parameters associated with the clinical severity of COVID-19. Additionally, we utilized RNAseq analysis to examine the gene expression of enzymes involved in the SL pathway. Our analysis revealed the presence of thirty-eight SL species from seven families in the plasma of study participants. The most profound alterations in the SL species profile were observed in patients with severe disease. Notably, a predominant sphingomyelin (SM d18:1) species emerged as a potential biomarker for COVID-19 severity, showing decreased levels in the plasma of convalescent individuals. Elevated SM levels were positively correlated with age, hospitalization duration, clinical score, and neutrophil count, as well as the production of IL-6 and IL-8. Intriguingly, we identified a putative protective effect against disease severity mediated by SM (d18:1/24:0), while ceramide (Cer) species (d18:1/24:1) and (d18:1/24:0)were associated with increased risk. Moreover, we observed the enhanced expression of key enzymes involved in the SL pathway in blood cells from severe COVID-19 patients, suggesting a primary flow towards Cer generation in tandem with SM synthesis. These findings underscore the potential of SM as a prognostic biomarker for COVID-19 and highlight promising pharmacological targets. By targeting sphingolipid pathways, novel therapeutic strategies may emerge to mitigate the severity of COVID-19 and improve patient outcomes. Full article

This work presents a multi-parameter optical fiber monitoring solution applied to an underground power distribution network. The monitoring system demonstrated herein uses Fiber Bragg Grating (FBG) sensors to measure multiple parameters, such as the distributed temperature of the power cable, external temperature and current of the transformers, liquid level, and intrusion in the underground manholes. To monitor partial discharges of cable connections, we used sensors that detect radio frequency signals. The system was characterized in the laboratory and tested in underground distribution networks. We present here the technical details of the laboratory characterization, system installation, and the results of 6 months of network monitoring. The data obtained for temperature sensors in the field tests show a thermal behavior depending on the day/night cycle and the season. The temperature levels measured on the conductors indicated that in high-temperature periods, the maximum current specified for the conductor must be reduced, according to the applied Brazilian standards. The other sensors detected other important events in the distribution network. All the sensors demonstrated their functionality and robustness in the distribution network, and the monitored data will allow the electric power system to have a safe operation, with optimized capacity and operating within tolerated electrical and thermal limits. Full article

In recent decades, waves of yellow fever virus (YFV) from the Amazon Rainforest have spread and caused outbreaks in other regions of Brazil, including the Cerrado, a savannah-like biome through which YFV usually moves before arriving at the Atlantic Forest. To identify the vectors involved in the maintenance of the virus in semiarid environments, an entomological survey was conducted after confirmation of yellow fever (YF) epizootics at the peak of the dry season in the Cerrado areas of the state of Minas Gerais. In total, 917 mosquitoes from 13 taxa were collected and tested for the presence of YFV. Interestingly, mosquitoes of the Sabethes genus represented 95% of the diurnal captured specimens, displaying a peak of biting activity never previously recorded, between 4:30 and 5:30 p.m. Molecular analysis identified three YFV-positive pools, two from Sabethes chloropterus—from which near-complete genomes were generated—and one from Sa. albiprivus, whose low viral load prevented sequencing. Sa. chloropterus was considered the primary vector due to the high number of copies of YFV RNA and the high relative abundance detected. Its bionomic characteristics allow its survival in dry places and dry time periods. For the first time in Brazil, Sa. albiprivus was found to be naturally infected with YFV and may have played a role as a secondary vector. Despite its high relative abundance, fewer copies of viral RNA were found, as well as a lower Minimum Infection Rate (MIR). Genomic and phylogeographic analysis showed that the virus clustered in the sub-lineage YFV_PA-MG, which circulated in Pará in 2017 and then spread into other regions of the country. The results reported here contribute to the understanding of the epidemiology and mechanisms of YFV dispersion and maintenance, especially in adverse weather conditions. The intense viral circulation, even outside the seasonal period, increases the importance of surveillance and YFV vaccination to protect human populations in affected areas. Full article

3D bioprinting has gained visibility in regenerative medicine and tissue engineering due to its applicability. Over time, this technology has been optimized and adapted to ensure a better printability of bioinks and biomaterial inks, contributing to developing structures that mimic human anatomy. Therefore, cross-linked polymeric materials, such as hydrogels, have been highly targeted for the elaboration of bioinks, as they guarantee cell proliferation and adhesion. Thus, this short review offers a brief evolution of the 3D bioprinting technology and elucidates the main hydrogels used in the process. Full article

Epidermal growth factor receptor antibodies (EGFR-Abs) confer a survival benefit in patients with RAS wild-type metastatic colorectal cancer (mCRC), but resistance invariably occurs. Previous data showed that only a minority of cancer cells harboured known genetic resistance drivers when clinical resistance to single-agent EGFR-Abs had evolved, supporting the activity of non-genetic resistance mechanisms. Here, we used error-corrected ctDNA-sequencing (ctDNA-Seq) of 40 cancer genes to identify drivers of resistance and whether a genetic resistance-gap (a lack of detectable genetic resistance mechanisms in a large fraction of the cancer cell population) also occurs in RAS wild-type mCRCs treated with a combination of EGFR-Abs and chemotherapy. We detected one MAP2K1/MEK1 mutation and one ERBB2 amplification in 2/3 patients with primary resistance and KRAS, NRAS, MAP2K1/MEK1 mutations and ERBB2 aberrations in 6/7 patients with acquired resistance. In vitro testing identified MAP2K1/MEK1 P124S as a novel driver of EGFR-Ab resistance. Mutation subclonality analyses confirmed a genetic resistance-gap in mCRCs treated with EGFR-Abs and chemotherapy, with only 13.42% of cancer cells harboring identifiable resistance drivers. Our results support the utility of ctDNA-Seq to guide treatment allocation for patients with resistance and the importance of investigating further non-canonical EGFR-Ab resistance mechanisms, such as microenvironmentally-mediated resistance. The detection of MAP2K1 mutations could inform trials of MEK-inhibitors in these tumours. Full article

Background: Previous studies found a high prevalence of pathogens among female sex workers (FSWs) in the Amazon region, and established their parenteral and sexual transmission. This study estimated the prevalence of hepatitis C virus (HCV) infection and associated risk factors, and the frequency of HCV genotypes and resistance-associated substitutions (RASs) in this vulnerable group. Methods: Distinct sampling methods were used to access 412 FSWs in cities and riverside communities in the Amazon region from 2015 to 2018. Three methods for HCV diagnosis were used to determine infection status. HCV genotypes and RASs were identified by sequencing and nucleotide fragment analysis. An association between HCV infection and exposure factors was determined by bivariate and multivariate analysis. Results: In total, 44 (10.7%) FSWs were exposed to HCV, and 32 (7.8%) of them had active infection. Nine socioeconomic characteristics and risky sexual behaviors were associated with HCV exposure, particularly unprotected sex and condom exemption for the clients who paid extra money. Genotype 1 (81.3%) and 3 (18.7%) were detected. The frequency of FSWs with RASs was 23.1% (6/26) for grazoprevir related to the occurrence of substitutions Y56F and S122G. Conclusions: HCV infection among FSWs is highly prevalent and dominated by genotype I. Urgent preventive and treatment measures are required to reduce HCV infection in FSWs and the general population. Full article

Six pimarane-type diterpenes isolated from Viguiera arenaria Baker and two semi-synthetic derivatives were evaluated in vitro against a panel of representative microorganisms responsible for dental root canal infections. The microdilution method was used for the determination of the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Porphyromonas gingivalis, Prevotella nigrescens, Prevotella intermedia, Prevotella buccae, Fusobacterium nucleatum, Bacteroides fragilis, Actinomyces naeslundii, Actinomyces viscosus, Peptostreptococcus micros, Enterococcus faecalis and Aggregatibacter actinomycetemcomitans. The compounds ent-pimara-8(14),15-dien-19-oic acid, its sodium salt and ent-8(14),15-pimaradien-3β-ol were the most active, displaying MIC values ranging from 1 to 10 μg mL^-1. The results also allow us to conclude that minor structural differences among these diterpenes significantly influence their antimicrobial activity, bringing new perspectives to the discovery of new chemicals for use as a complement to instrumental endodontic procedures. Full article