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From a systematic review framework, we assessed the preclinical evidence on the effectiveness of drug combinations for visceral leishmaniasis (VL) treatment. Research protocol was based on the PRISMA guideline. Research records were identified from Medline, Scopus and Web of Science. Animal models, infection and treatment protocols, parasitological and immunological outcomes were analysed. The SYRCLE's (SYstematic Review Center for Laboratory Animal Experimentation) toll was used to evaluate the risk of bias in all studies reviewed. Fourteen papers using mice, hamster and dogs were identified. Leishmania donovani was frequently used to induce VL, which was treated with 23 drugs in 40 different combinations. Most combinations allowed to reduce the effective dose, cost and time of treatment, in addition to improving the parasitological control of Leishmania spp. The benefits achieved from drug combinations were associated with an increased drug's half-life, direct parasitic toxicity and improved immune defences in infected hosts. Selection, performance and detection bias were the main limitations identified. Current evidence indicates that combination chemotherapy, especially those based on classical drugs (miltefosine, amphotericin B antimony-based compounds) and new drugs (CAL-101, PAM3Cys, tufisin and DB766), develops additive or synergistic interactions, which trigger trypanocidal and immunomodulatory effects associated with reduced parasite load, organ damage and better cure rates in VL.
The diagnosis of visceral leishmaniasis (VL) has improved with the search of novel antigens; however, their performance is limited when samples from VL/human immunodeficiency virus (HIV)-coinfected patients are tested. In this context, studies conducted to identify more suitable antigens to detect both VL and VL/HIC coinfection cases should be performed. In the current study, phage display was performed using serum samples from healthy subjects and VL, HIV-infected and VL/HIV-coinfected patients; aiming to identify novel phage-exposed epitopes to be evaluated with this diagnostic purpose. Nine non-repetitive and valid sequences were identified, synthetized and tested as peptides in enzyme-linked immunosorbent assay experiments. Results showed that three (Pep2, Pep3 and Pep4) peptides showed excellent performance to diagnose VL and VL/HIV coinfection, with 100% sensitivity and specificity values. The other peptides showed sensitivity varying from 50.9 to 80.0%, as well as specificity ranging from 60.0 to 95.6%. Pep2, Pep3 and Pep4 also showed a potential prognostic effect, since specific serological reactivity was significantly decreased after patient treatment. Bioinformatics assays indicated that Leishmania trypanothione reductase protein was predicted to contain these three conformational epitopes. In conclusion, data suggest that Pep2, Pep3 and Pep4 could be tested for the diagnosis of VL and VL/HIV coinfection.
Despite evidence showing that the intake of ultra-processed food has a negative impact on health, diet quality and dietary vitamin E, its impact on vitamin E nutritional status and breast milk remains unknown. This study aimed to assess the influence of the consumption of ultra-processed foods on vitamin E biomarkers of lactating women. A cross-sectional study was performed with 294 lactating women. Food consumption was obtained by 24-h dietary recall, and foods were grouped according to the NOVA classification. Levels of α-tocopherol were analysed by HPLC. Breast milk vitamin E (BMVE) adequacy was based on the quantity of the vitamin in the estimated intake volume. The Kruskal–Wallis test was used to compare the tertiles and linear regression to association between ultra-processed food consumption and biomarkers. Ultra-processed foods accounted for 16 % of energy intake and vitamin E intakes by all women were considered low. Serum α-tocopherol was 26·55 (sd 7·98) µmol/l, 5 % (n 11) showed inadequate vitamin E (< 12 µmol/l) and 78 % had an inadequate BMVE content (< 4 mg/780 ml). The regression showed that a higher dietary share of ultra-processed foods was associated with lower concentrations of serum α-tocopherol (β = –0·168, 95 % CI –0·047, 0·010, P = 0·003) and inadequate BMVE content (β = –0·144, 95 % CI = –0·505, 0·063, P = 0·012) (adjustment for income and maternal age). Thus, higher dietary shares of ultra-processed foods had an impact on vitamin E biomarkers, suggesting that inadequate dietary intake practices during lactation may reduce the supply of vitamin E to women and breast milk.
We aimed at evaluating the association of maternal pre-pregnancy nutritional status with offspring anthropometry and body composition. We also evaluated whether these associations were modified by gender, diet and physical activity and mediated by birth weight.
Birth cohort study.
Waist circumference was measured with an inextensible tape, and fat and lean mass were measured using dual-energy X-ray absorptiometry. Multiple linear regression was used to adjust for possible confounders and allele score of BMI. We carried out mediation analysis using G-formula.
In 1982, 1993 and 2004, all maternity hospitals in Pelotas (South Brazil) were visited daily and all live births whose families lived in the urban area of the city were evaluated. These subjects have been followed up at different ages.
Offspring of obese mothers had on average higher BMI, waist circumference and fat mass index than those of normal weight mothers, and these differences were higher among daughters. The magnitudes of the association were similar in the cohorts, except for height, where the association pattern was not clear. In the 1982 cohort, further adjustment for a BMI allele score had no material influence on the magnitude of the associations. Mediation analyses showed that birth weight captured part of this association.
Our findings suggest that maternal pre-pregnancy nutritional status is positively associated with offspring BMI and adiposity in offspring. And this association is higher among daughters whose mother was overweight or obese and, birth weight explains part of this association.
The co-infection between visceral leishmaniasis (VL) and human immunodeficiency virus (HIV) has increased in several countries in the world. The current serological tests are not suitable since they present low sensitivity to detect the most of VL/HIV cases, and a more precise diagnosis should be performed. In this context, in the present study, an immunoproteomics approach was performed using Leishmania infantum antigenic extracts and VL, HIV and VL/HIV patients sera, besides healthy subjects samples; aiming to identify antigenic markers for these clinical conditions. Results showed that 43 spots were recognized by antibodies in VL and VL/HIV sera, and 26 proteins were identified by mass spectrometry. Between them, β-tubulin was expressed, purified and tested in ELISA experiments as a proof of concept for validation of our immunoproteomics findings and results showed high sensitivity and specificity values to detect VL and VL/HIV patients. In conclusion, the identified proteins in the present work could be considered as candidates for future studies aiming to improvement of the diagnosis of VL and VL/HIV co-infection.
Asthma-obesity is a multifactorial disease with specific asthma phenotypes that aggravate due to overweight and an unbalanced diet. Furthermore, obese asthmatic patients are corticotherapy-resistant. Therefore, the aims of the present study were to evaluate the effects of an interdisciplinary intervention on food consumption, body composition, lung function and adipokines in asthmatic and non-asthmatic obese adolescents and to investigate the influence of nutrients on lung function. Obese non-asthmatic (n 42) and obese asthmatic (n 21) adolescents of both sexes were enrolled in the present study. Food intake, adipokine levels, body composition, asthma symptoms and lung function were assessed across the study. After the intervention of 1 year, there was a reduction (P ≤ 0·01) in BMI, body fat percentage, visceral and subcutaneous fat and an increase (P ≤ 0·01) in lean mass and all lung function variables in both groups, except the relation between forced expiratory volume in 1 s and forced vital capacity (FEV1:FVC) in non-asthmatic patients. Moreover, both groups decreased lipid and cholesterol consumption (P ≤ 0·01). The highest energy consumption (β = −0·021) was associated with lower values of FVC. Similarly, carbohydrate consumption (β = −0·06) and cholesterol were negative predictors (β = −0·05) in FEV1:FVC. However, the consumption of Ca (β = 0·01), fibres (β = 1·34) and vitamin A (β = 0·01) were positive predictors of FEV1:FVC. Asthma-obesity interdisciplinary treatment promoted an improvement on food consumption and lung function in adolescents and demonstrated that the consumption of nutrients influenced an increase in lung function.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
This study aimed to evaluate the transcriptional changes occurring in isolated perfused mammary alveolar tissue in response to inoculation with S. agalactiae and to identify the most affected biological functions and pathways after 3 h. Four udders taken at slaughter from cows with healthy mammary gland were perfused ex situ with warmed and gassed Tyrode's solution. Mammary alveolar tissue samples were taken from the left fore and rear quarters (IQ-inoculated quarters) before inoculation (hour 0) and at 3 h post inoculation (hpi) and at the same times from control right fore and rear quarters (not inoculated: NIQ). A total of 1756 differentially expressed genes (DEGs) were identified between IQ and NIQ at 3 hpi using edgeR package. Within this set of DEGs, 952 were up regulated and mainly involved with innate immune response and inflammatory response, e.g., CD14, CCL5, TLR2, IL-8, SAA3, as well as in transcriptional regulation such as FOS, STAT3 and NFKBIA. Genes down-regulated (804) included those involved with lipid synthesis e.g., APOC2, SCD, FABP3 and FABP4. The most affected pathways were chemokine signaling, Wnt signaling and complement and coagulation cascades, which likely reflects the early stage response of mammary tissue to S. agalactiae infection. No significant gene expression changes were detected by RNA-Seq in the others contrasts. Real time-PCR confirmed the increase in mRNA abundance of immune-related genes: TLR2, TLR4, IL-1β, and IL-10 at 3 hpi between IQ and NIQ. The expression profiles of Casp1 and Bax for any contrasts were unaffected whereas Bcl2 was increased in IQ, which suggests no induction of apoptosis during the first hours after infection. Results provided novel information regarding the early functional pathways and gene network that orchestrate innate immune responses to S. agalactiae infection. This knowledge could contribute to new strategies to enhance resistance to this disease, such as genomic selection.
In the current study, phage-exposed mimotopes as targets against tegumentary leishmaniasis (TL) were selected by means of bio-panning cycles employing sera of TL patients and healthy subjects, besides the immune stimulation of peripheral blood mononuclear cells (PBMCs) collected from untreated and treated TL patients and healthy subjects. The clones were evaluated regarding their specific interferon-γ (IFN-γ) and interleukin-4 (IL-4) production in the in vitro cultures, and selectivity and specificity values were calculated, and those presenting the best results were selected for the in vivo experiments. Two clones, namely A4 and A8, were identified and used in immunization protocols from BALB/c mice to protect against Leishmania amazonensis infection. Results showed a polarized Th1 response generated after vaccination, being based on significantly higher levels of IFN-γ, IL-2, IL-12, tumour necrosis factor-α (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF); which were associated with lower production of specific IL-4, IL-10 and immunoglobulin G1 (IgG1) antibodies. Vaccinated mice presented significant reductions in the parasite load in the infected tissue and distinct organs, when compared with controls. In conclusion, we presented a strategy to identify new mimotopes able to induce Th1 response in PBMCs from TL patients and healthy subjects, and that were successfully used to protect against L. amazonensis infection.
We show that superlattice (SL) of PbS quantum dots (QD) can be easily prepared by drop casting of colloidal QD solution onto glass substrate and the ordering level can be controlled by the substrate temperature. A QD solution was dropped on glass and dried at 25, 40, 70 and 100°C resulting in formation of different SL structures. X-ray diffractograms (XRD) of deposited films show a set of sharp and intense peaks that are higher order satellites of a unique peak at 1.8 degrees (two theta), which corresponds, using the Bragg’s Law, to an interplanar spacing of 5.3 nm. The mean particles diameter, calculated through the broadening of the (111) peak of PbS using the Scherrer’s formula, were in agreement with the interplanar spacing. Transmission electron microscopy (TEM) measurements were also used to study the SL structure, which showed mainly a face centered cubic (FCC) arrangement of the QD. The photoluminescence (PL) spectrum of QD in the SL showed a shift toward lower energy compared to one in solution. It can be attributed to the fluorescence resonant energy transfer (FRET) between neighbors QD´s. Moreover, we observed greater redshift of PL peak for film with lower drying temperature, suggesting that it has a more organized structure.
Diabetes mellitus (DM) is a major public health problem and its incidence is rising dramatically. The brain, particularly the cerebral cortex, is very susceptible to glucose fluctuations and hyperglycaemia-induced oxidative stress. Tea (Camellia sinensis (L.)) is widely consumed; however, the antidiabetic properties of white tea remain largely unexplored. In the present study, we investigated the effects of daily consumption of white tea on the cerebral cortex of prediabetic rats. The cerebral cortex metabolic profile was evaluated, and the expression levels of GLUT, phosphofructokinase-1, lactate dehydrogenase (LDH) and monocarboxylate transporter 4 were assessed. LDH activity was also determined. The cerebral cortex oxidative profile was determined by evaluating its antioxidant power, lipid peroxidation and protein oxidation levels. Catalase, glutathione, glutamate, N-acetylaspartate, aspartate, choline, γ-aminobutyric acid, taurine and valine contents were determined. Daily consumption of white tea ameliorated glucose tolerance and insulin sensitivity. Moreover, white tea altered the cortex glycolytic profile, modulating GLUT expression and lactate and alanine contents. Finally, white tea consumption restored protein oxidation and lipid peroxidation levels and catalase expression, and improved antioxidant capacity. In conclusion, daily consumption of white tea improved the cerebral cortex metabolic and oxidative profile in prediabetic rats, suggesting it as a good, safe and inexpensive strategy to prevent DM-related effects in the cerebral cortex.