Eosinophils have been long associated with helminthic infections, although their functions in these diseases remain unclear. During schistosomiasis caused by the trematode
, eosinophils are ...specifically recruited and migrate to sites of granulomatous responses where they degranulate. However, little is known about the mechanisms of eosinophil secretion during this disease. Here, we investigated the degranulation patterns, including the cellular mechanisms of major basic protein-1 (MBP-1) release, from inflammatory eosinophils in a mouse model of
infection (acute phase). Fragments of the liver, a major target organ of this disease, were processed for histologic analyses (whole slide imaging), conventional transmission electron microscopy (TEM), and immunonanogold EM using a pre-embedding approach for precise localization of major basic protein 1 (MBP-1), a typical cationic protein stored pre-synthesized in eosinophil secretory (specific) granules. A well-characterized granulomatous inflammatory response with a high number of infiltrating eosinophils surrounding
eggs was observed in the livers of infected mice. Moreover, significant elevations in the levels of plasma Th2 cytokines (IL-4, IL-13, and IL-10) and serum enzymes (alanine aminotransferase and aspartate aminotransferase) reflecting altered liver function were detected in response to the infection. TEM quantitative analyses revealed that while 19.1% of eosinophils were intact, most of them showed distinct degranulation processes: cytolysis (13.0%), classical and/or compound exocytosis identified by granule fusions (1.5%), and mainly piecemeal degranulation (PMD) (66.4%), which is mediated by vesicular trafficking. Immunonanogold EM showed a consistent labeling for MBP-1 associated with secretory granules. Most MBP-1-positive granules had PMD features (79.0 ± 4.8%). MBP-1 was also present extracellularly and on vesicles distributed in the cytoplasm and attached to/surrounding the surface of emptying granules. Our data demonstrated that liver-infiltrating mouse eosinophils are able to degranulate through different secretory processes during acute experimental
infections with PMD being the predominant mechanism of eosinophil secretion. This means that a selective secretion of MBP-1 is occurring. Moreover, our study demonstrates, for the first time, a vesicular trafficking of MBP-1 within mouse eosinophils elicited by a helminth infection. Vesicle-mediated secretion of MBP-1 may be relevant for the rapid release of small concentrations of MBP-1 under cell activation.
Triple-negative breast cancers (TNBCs) lack progesterone and estrogen receptors and do not have amplified human epidermal growth factor receptor 2, the main therapeutic targets for managing breast ...cancer. TNBCs have an altered metabolism, including an increased Warburg effect and glutamine dependence, making the glutaminase inhibitor CB-839 therapeutically promising for this tumor type. Accordingly, CB-839 is currently in phase I/II clinical trials. However, not all TNBCs respond to CB-839 treatment, and the tumor resistance mechanism is not yet fully understood. Here we classified cell lines as CB-839–sensitive or –resistant according to their growth responses to CB-839. Compared with sensitive cells, resistant cells were less glutaminolytic and, upon CB-839 treatment, exhibited a smaller decrease in ATP content and less mitochondrial fragmentation, an indicator of poor mitochondrial health. Transcriptional analyses revealed that the expression levels of genes linked to lipid metabolism were altered between sensitive and resistant cells and between breast cancer tissues (available from The Cancer Genome Atlas project) with low versus high glutaminase (GLS) gene expression. Of note, CB-839–resistant TNBC cells had increased carnitine palmitoyltransferase 2 (CPT2) protein and CPT1 activity levels. In agreement, CB-839–resistant TNBC cells mobilized more fatty acids into mitochondria for oxidation, which responded to AMP-activated protein kinase and acetyl-CoA carboxylase signaling. Moreover, chemical inhibition of both glutaminase and CPT1 decreased cell proliferation and migration of CB-839–resistant cells compared with single inhibition of each enzyme. We propose that dual targeting of glutaminase and CPT1 activities may have therapeutic relevance for managing CB-839–resistant tumors.
Studies carried out by Russo and collaborators (2021) brought a warning that the development of bloodstream infections caused by MDR A. baumannii in patients with COVID-19 further complicates the ...hospital course and contributes to the high mortality rate of the population in the study.6 Unfortunately, this is not an isolated case. The report highlights that the possible factors that contributed to this were the exponential increase in the number of more debilitated patients, especially in intensive care units, the more extended period of hospitalization, and even the shortage of personnel and protective equipment.13 In Brazil, some recent studies have already reported that in the post-pandemic period, there was an increased incidence of CRAB infections in different hospitals compared to pre-pandemic periods.14 Another point directly linked to antibiotic resistance deserves to be highlighted. Apart for this, the funding sources had no role in study design, or in the collection, management, analysis, and interpretation of data. Risk factors and effect on mortality of superinfections in a newly established COVID-19 respiratory sub-intensive care unit at University Hospital in Rome.
Purpose: Compare the safety and efficacy of wavefront-guided photorefractive keratotomy (PRK) 6 months after cross-linking (CXL) to wavefront-guided PRK alone for refractive correction in patients ...with bilateral asymmetric corneal topography. Methods: Prospective randomized clinical trial with 16 patients (32 eyes). CXL with subsequent PRK after 6 months in one eye, and PRK alone was performed in contralateral eyes. The follow-up was 10 years. We analyzed visual outcomes, Scheimpflug topography, and corneal haze evaluation. Results: Eyes in the PRK group showed better results than in the CXL + PRK group. Mean postoperative CDVA was 0.044 logmar (SD, 0.073) in the PRK group and 0.1 logmar (SD, 0.21) in the CXL + PRK group, the mean sphere was + 0.21 (SD, 0.6) D in the PRK group and 0.87 (SD, 2.3) D in the CXL + PRK group, and mean SE was −0.35 (SD, 0.65) D in the PRK group and 0.62 (SD, 2.32) D in the CXL + PRK group. In one patient, a steepening of 2.5 D and a thinning of 17 μm occurred in PRK alone group. Two patients in the CXL + PRK group presented corneal haze. The overall complication rate was 18,75% (haze and ectasia). Conclusion: Non-simultaneous CXL and PRK procedures yielded good refractive results, but worse than those obtained with PRK alone. Although one patient in the PRK group developed corneal ectasia, the CXL + PRK group had a higher loss of vision lines, indicating less safety.
High salt intake is related to an increase in blood pressure and development of hypertension. However, currently, there are no national representative data in Brazil using the gold standard method of ...24-h urine collection to measure sodium consumption. This study aimed to determine salt intake based on 24-h urine collection in a sample of 272 adults of both genders and to correlate it with blood pressure levels. We used a rigorous protocol to assure an empty bladder prior to initiating urine collection. We excluded subjects with a urine volume <500 mL, collection period outside of an interval of 23-25 h, and subjects with creatinine excretion that was not within the range of 14.4-33.6 mg/kg (men) and 10.8-25.2 mg/kg (women). The mean salt intake was 10.4±4.1 g/day (d), and 94% of the participants (98% of men and 90% of women) ingested more than the recommended level of 5 g/d. We found a positive association between salt and body mass index (BMI) categories, as well as with salt and blood pressure, independent of age and BMI. The difference in systolic blood pressure reached 13 mmHg between subjects consuming less than 6 g/d of salt and those ingesting more than 18 g/d. Subjects with hypertension had a higher estimated salt intake than normotensive subjects (11.4±5.0 vs 9.8±3.6 g/d, P<0.01), regardless of whether they were under treatment. Our data indicate the need for interventions to reduce sodium intake, as well the need for ongoing, appropriate monitoring of salt consumption in the general population.
Alzheimer's disease (AD) is considered the leading cause of dementia in the elderly worldwide. It results in progressive memory loss and impairment of cognitive and motor skills, leading to a high ...degree of disability and dependence. The development of AD is associated with the accumulation of senile plaques in the brain, caused by the amyloidogenic pathway of the disease. Several genetic and biochemical events are linked to AD development, with oxidative stress being one of them. Due to the scarcity of drugs aimed at treating AD, antioxidant compounds are increasingly studied as therapeutic targets for the disease. In this study, we investigate the antioxidant and anti-Alzheimer potential of the Tetragonisca angustula (Jataí) pollen extract in a Drosophila melanogaster Alzheimer's model. For this purpose, we utilized a D. melanogaster AD-like model, which expresses genes related to the amyloidogenic pathway of Alzheimer's disease. We explored the floral origin of the collected pollen, conducted phytochemical prospecting, and evaluated its antioxidant capacity in vitro. In vivo experiments involved assessing the survival and climbing ability of the D. melanogaster AD-like model with various concentrations of the pollen extract. Our findings revealed that the pollen extract of Tetragonisca angustula exhibits a significant antioxidant response and high concentrations of important phytochemicals, such as flavonoids and polyphenols. Furthermore, it enhanced the survival rate of D. melanogaster, and across all concentrations tested, it improved the climbing ability of the flies after 15 days of treatment with methanolic pollen extract. Additionally, the pollen extract reduced the neurodegeneration index in histopathological analysis. Thus, our study demonstrates the potential of Tetragonisca angustula pollen as an important subject for further investigation, aiming to isolate molecules that could potentially serve as therapeutic targets for Alzheimer's disease.
Summary
Background
One of the effects of the coronavirus disease 2019 (COVID‐19) pandemic is the risk of shortages in Blood Centres.
Objectives
To verify the impact of the COVID‐19 pandemic on the ...blood donor's attendance and production of blood components in Fundação Hemominas, a Brazilian public institution was formed by several Blood Centres.
Methods
A cross‐sectional study was carried out from January to June 2020. Data collected were compared to a historical series from 2016 to 2019.
Results
The study showed a reduction in the attendance of blood donors, whole blood collections and blood component production from March 2020, when the first case of COVID‐19 was notified in Minas Gerais, Brazil. The results evidenced that Hemominas Blood Centres were affected in a very distinct way by the pandemic with a general mean reduction around 17% in attendance of blood donors and in production of blood components in the period of March to June. On the other hand, the return of blood donors rate increased.
Conclusion
The reduction in blood donation during the pandemic period was significant, despite the measures adopted. Still, the recruitment of return donors appears to be an important measure to be considered to decrease the pandemic's effect on blood stocks.
Cellulolytic enzymes have wide use in several industrial segments (e.g. biofuels, pulp and paper, food, and cosmetics). However, one of the challenges is their large-scale production with high ...specific activity to eliminate the dependence of the purchase of enzymatic cocktails produced by commercial parties. The aims of this study were (1) isolation, selection, and partial characterization of bacterial cellulases present in the intestinal tract of the sugarcane borer and (2) to identify cellulase-producing bacteria by analyzing the 16S rDNA gene. Cellulase production and purification assays resulted in similar electrophoretic profiles between four bacterial strains. These strains were identified as Klebsiella pneumoniae, Klebsiella sp., and Bacillus sp. K. pneumoniae was the main cellulase-producing microorganism. Our results show the possibility of finding cellulolytic microorganisms that inhabit the gut of herbivorous animals, especially those that are predators of important crops of economic value. Furthermore, K. pneumoniae cellulase is of medical importance. In hospitals, health professionals, hospital technicians, patients and visitors wear clothes containing cellulose. Thus, K. pneumoniae within hospitals can contaminate these clothes and be spread to the environment. In that case, it would be important for the hospital's chemical sterilization products to have at least one cellulase inhibitor.
•Cellulolytic bacteria from the sugarcane borer were Klebsiella sp. and Bacillus sp.•K. pneumoniae was the main cellulase-producing microorganism.•This enzyme was able to hydrolyze sodium carboxymethylcellulose•K. pneumoniae cellulase is of medical importance.
In Brazil, Dengue (DENV) and Zika (ZIKV) viruses are reported as being transmitted exclusively by Aedes aegypti in urban settings. This study established the vectors and viruses involved in an ...arbovirus outbreak that occurred in 2019 in a rural area of Espírito Santo state, Brazil. Mosquitoes collected were morphologically identified, sorted in samples, and submitted to molecular analysis for arboviruses detection. Phylogenetic reconstruction was performed for the viral sequence obtained. All 393 mosquitoes were identified as Aedes albopictus. DENV-1 genotype V was present in one sample and another sample was positive for ZIKV. The DENV-1 clustered with viruses that have circulated in previous years in large urban centers of different regions in Brazil. This is the first report of A. albopictus infected by DENV and ZIKV during an outbreak in a rural area in Brazil, indicating its involvement in arboviral transmission. The DENV-1 strain found in the A. albopictus was not new in Brazil, being involved previously in epidemics related to A. aegypti, suggesting the potential to A. albopictus in transmitting viruses already circulating in the Brazilian population. This finding also indicates the possibility of these viruses to disperse across urban and rural settings, imposing additional challenges for the control of the diseases.
The UN Decade of Ecosystem Restoration is poised to trigger the recovery of ecosystem services and transform structural injustices across the world in a way unparalleled in human history. The ...inclusion of diverse Indigenous and local communities to co-create robust native seed supply systems is the backbone to achieve the goals for the Decade. Here we show how community-based organizations have co-developed native seed supply strategies for landscape restoration from the bottom-up. We draw on the interconnections over two decades of seed networks in Brazil and the emerging Indigenous participation in native seed production in Australia. From an environmental justice perspective, we provide a participatory seed supply approach for local engagement, noting local geographical, social and cultural contexts. Meeting large-scale restoration goals requires the connection between local seed production and collaborative platforms to negotiate roles, rights and responsibilities between stakeholders. An enduring native seed supply must include a diversity of voices and autonomy of community groups that builds equitable participation in social, economic, and environmental benefits.
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