causes heavy burdens of disease across malarious regions worldwide. Mature
asexual and transmissive gametocyte stages occur in the blood circulation, and it is often assumed that ...accumulation/sequestration in tissues is not an important phase in their development. Here, we present a systematic study of
stage distributions in infected tissues of nonhuman primate (NHP) malaria models as well as in blood from human infections. In a comparative analysis of the transcriptomes of
and
blood-stage parasites, we found a conserved cascade of stage-specific gene expression despite the greatly different gametocyte maturity times of these two species. Using this knowledge, we validated a set of conserved asexual- and gametocyte-stage markers both by quantitative real-time PCR and by antibody assays of peripheral blood samples from infected patients and NHP (
sp.). Histological analyses of
parasites in organs of 13 infected NHP (
and
species) demonstrated a major fraction of immature gametocytes in the parenchyma of the bone marrow, while asexual schizont forms were enriched to a somewhat lesser extent in this region of the bone marrow as well as in sinusoids of the liver. These findings suggest that the bone marrow is an important reservoir for gametocyte development and proliferation of malaria parasites.
malaria continues to cause major public health burdens worldwide. Yet, significant knowledge gaps in the basic biology and epidemiology of
malaria remain, largely due to limited available tools for research and diagnostics. Here, we present a systematic examination of tissue sequestration during
infection. Studies of nonhuman primates and malaria patients revealed enrichment of developing sexual stages (gametocytes) and mature replicative stages (schizonts) in the bone marrow and liver, relative to those present in peripheral blood. Identification of the bone marrow as a major
tissue reservoir has important implications for parasite diagnosis and treatment.
Translational research (TR) is an interdisciplinary branch of the biomedical field that seeks to connect its three supporting pillars: basic research on the bench, the hospital beds and other health ...system services, and the delivery of products for the well-being and health of the community. Here, we review the five transition stages of the TR spectrum, registering the lessons learned during > 20 years leading to the first clinical trial designed and performed in Brazil for testing a complementary treatment for Chagas disease (CD): the selenium trial (STCC). Lessons learned were: (1) to consider all the TR spectrum since the beginning of the project; (2) to start simultaneously animal studies and translation to humans; (3) to ensure a harmonious interaction between clinical and basic research teams; (4) to include MSc and PhD students only in pre-clinical and basic studies (TR0) or vertical clinical studies using retrospective samples and data (TR1); (5) to identify potential suppliers in the national commercial market for a future final treatment since the pre-clinical stage; (6) to keep an international network of experts as permanent advisers on the project. In the whole process, some perspectives were created: a complementary clinical trial for the opened questions and the construction of a Brazilian clinical CD platform.
The Pbcn orthorhombic phase of Y2Mo3O12 has been examined through high-resolution X-ray powder diffraction (10−450 K), heat capacity determination (2−390 K), and differential scanning calorimetry ...(103−673 K). No phase transition was found over this temperature range. The overall thermal expansion is negative, and the average linear thermal expansion coefficient, αl, is −9.02 × 10−6 K−1 averaged over T = 20−450 K. From a thorough analysis of the structure of Y2Mo3O12, we find that the YO6 octahedra and MoO4 tetrahedra are increasingly distorted with increasing temperature. The inherent volume distortion parameter (υ) of AO6 has been introduced to quantitatively evaluate polyhedral distortion and it is observed that this parameter is strongly correlated with the linear coefficient thermal expansion (αl) of different members of the A2M3O12 family. We attribute the negative thermal expansion to the reduction of the mean Y−Mo nonbonded distances and Y−O−Mo bond angles with increasing temperature, the joint action of high-energy optical and low-energy translational and librational modes.
For over 60 years, selenium (Se) has been known as an essential microelement to many biological functions, including cardiovascular homeostasis. This review presents a compilation of studies ...conducted in the past 20 years related to chronic Chagas disease cardiomyopathy (CCC), caused by
infection, a neglected disease that represents a global burden, especially in Latin America. Experimental and clinical data indicate that Se may be used as a complementary therapy to prevent heart failure and improve heart function. Starting from the main questions "
?" and "
?", we show evidence implicating the complex and multidetermined CCC physiopathology, discussing its possible interplays with the multifunctional cytokine TGF-β as regulators of immune response and fibrosis. We present two new proposals to face this global public health challenge in vulnerable populations affected by this parasitic disease: fibrosis modulation mediated by TGF-β pathways and the possible use of selenoproteins as antioxidants regulating the increased reactive oxygen stress present in CCC inflammatory environments. We assess the opportunity to consider the beneficial effects of Se in preventing heart failure as a concept to be applied for CCC patients.
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the causative agent of the COVID-19 pandemic, a global public health problem. Despite the numerous studies for drug ...repurposing, there are only two FDA-approved antiviral agents (Remdesivir and Nirmatrelvir) for non-hospitalized patients with mild-to-moderate COVID-19 symptoms. Consequently, it is pivotal to search for new molecules with anti-SARS-CoV-2 activity and to study their effects in the human immune system. Ebselen (Eb) is an organoselenium compound that is safe for humans and has antioxidant, anti-inflammatory, and antimicrobial properties. Diphenyl diselenide ((PhSe)
) shares several pharmacological properties with Eb and is of low toxicity to mammals. Herein, we investigated Eb and (PhSe)
anti-SARS-CoV-2 activity in a human pneumocytes cell model (Calu-3) and analyzed their toxic effects on human peripheral blood mononuclear cells (PBMCs). Both compounds significantly inhibited the SARS-CoV-2 replication in Calu-3 cells. The EC
values for Eb and (PhSe)
after 24 h post-infection (hpi) were 3.8 µM and 3.9 µM, respectively, and after 48 hpi were 2.6 µM and 3.4 µM. These concentrations are safe for non-infected cells, since the CC
values found for Eb and (PhSe)
on Calu-3 were greater than 200 µM. Importantly, the concentration rates tested on viral replication were not toxic to human PBMCs. Therefore, our findings reinforce the efficacy of Eb and demonstrate (PhSe)
as a new candidate to be tested in future trials against SARS-CoV-2 infection/inflammation conditions.
Transforming growth factor β1 (TGF-β1) and tumour necrosis factor (TNF) have been implicated in Chagas disease pathophysiology and may correlate with left ventricular (LV) function.
We determined ...whether TGF-β1 and TNF serum levels correlate with LV systolic and diastolic functions and brain natriuretic peptide (BNP) serum levels in chronic Chagas disease.
This cross-sectional study included 152 patients with Chagas disease (43% men; 57 ± 12 years old), classified as 53 patients with indeterminate form and 99 patients with cardiac form (stage A: 24, stage B: 25, stage C: 44, stage D: 6). TGF-β1, TNF, and BNP were determined by enzyme-linked immunosorbent assay ELISA. Echocardiogram was used to determine left atrial and LV diameters, as well as LV ejection fraction and diastolic function.
TGF-b1 serum levels were lower in stages B, C, and D, while TNF serum levels were higher in stages C and D of the cardiac form. TGF-β1 presented a weak correlation with LV diastolic function and LV ejection fraction. TNF presented a weak correlation with left atrial and LV diameters and LV ejection fraction.
TNF is increased, while TGF-β1 is decreased in the cardiac form of chronic Chagas disease. TNF and TGF-β1 serum levels present a weak correlation with LV systolic and diastolic function in Chagas disease patients.
The coffee processing wastewater (CPWW) requires treatment before being disposed of in the environment or reused due to its high organic and inorganic composition and a low pH. The indigenous ...microbiota from CPWW is highly diverse and could be selected as inoculums in treatment waste plants. Considering the physico-chemical characteristics of wastewater coffee, we elaborate on steps to select the microbial consortium that showed positive impact via decreasing the pollutant parameters of this effluent. The effectiveness was confirmed using wastewater from different origins with different chemical characteristics. A bacterial consortium composed by Serratia marcescens CCMA 1010 and CCMA 1012, Corynebacterium flavescens CCMA 1006, and Acetobacter indonesiensis CCMA 1002 was selected as the inoculums-based phenotypic assays. The mixed inoculum showed a highly active population (11.18 log CFU mL−1), promoting an 85% decrease in biochemical oxygen demand and a 60% decrease in chemical oxygen demand. There was also an 80% reduction in phosphorus and nitrogen. The final pH changed from 6.0 to 7.5. Additionally, the eco-toxicity using Daphnia similis was reduced by more than 59%. The microbial inoculum was efficient in the biological treatment in CPWWs, demonstrating the efficiency and robustness of the selected strains, independent of the physico-chemical characteristics of wastewater.
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•The post-harvest coffee process generates large volume of wastewater.•Wastewater must be treated before launch in the freshwater sources.•Serratia marcescens, Corynebacterium flavescens and Acetobacter indonesiensis were selected for the bio-treatment.•The effectiveness of bio-treatment was certificated in different physical-chemical composition and origin of the wastewater.•BOD, COD, P and N values had decreased after the biological treatment.•The inoculums has potential to use in any chemical coffee wastewater composition.
Background Chagas disease (CD) presents an ominous prognosis. The predictive value of biomarkers and new echocardiogram parameters in adjusted models have not been well studied. Methods and Results ...There were 361 patients with chronic CD (57.6% men, 61±11 years of age, clinical forms: indeterminate 27.1%, cardiac 56.6%, digestive 3.6%, cardiodigestive 12.7%) included in this single-center, observational, prospective longitudinal study. Echocardiographic evaluation included strain analyses of left atrial, left ventricular (LV), and right ventricular and 3-dimensional analyses of left atrial and LV volumes. Biomarkers included cardiac troponin I, brain natriuretic peptide, transforming growth factor β1, tumor necrosis factor, matrix metalloproteinases, and
polymerase chain reaction. The studied end point was a composite of CD-related mortality, heart transplant, hospital admission due to worsening heart failure, or new cardiac device insertion. Event-free survival was analyzed by multivariable regression analyses adjusted for competing risks.
values <0.05 were considered significant. The composite event occurred in 79 patients after 4.9±2.0 years follow-up. LV end-diastolic volume (hazard ratio HR, 1.01 95% CI, 1.00-1.02;
=0.02), peak negative global atrial strain (HR, 1.08 95% CI, 1.00-1.17;
=0.04), LV global circumferential strain (HR, 1.12 95% CI, 1.04-1.21;
=0.003), LV torsion (HR, 0.55 95% CI, 0.35-0.81;
=0.003), brain natriuretic peptide (HR, 2.03 95% CI, 1.23-3.34;
=0.005), and positive
polymerase chain reaction (HR, 1.80 95% CI, 1.12-2.91;
=0.01) were end point predictors independent from age, sex, 2-dimensional echocardiographic indexes, hypertension, previous cardiac device, and CD cardiac form. Conclusions Two-dimensional strain- and 3-dimensional-derived parameters, brain natriuretic peptide, and positive
polymerase chain reaction can be useful for prediction of CD cardiovascular events.
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