Leishmaniasis is a group of infectious diseases caused by protozoan parasites that belong to the genus Leishmania. Currently, there is no human vaccine, and the available treatments are associated ...with toxicity, high cost, and the emergence of resistant strains. These factors highlight the need to identify new antileishmanial candidates. In this study, we synthesized twenty-four methoxylated cinnamides containing 1,2,3-triazole fragments and evaluated their antileishmanial activity against the Leishmania braziliensis species, which is the main etiological agent responsible for American Tegumentary Leishmaniasis (ATL). The cinnamides were synthetically prepared using nucleophilic acyl substitution and copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reactions. The compounds were characterized using infrared, nuclear magnetic resonance, and high-resolution mass spectrometry techniques. We performed preliminary studies to evaluate the biological activity of these compounds against L. braziliensis promastigotes and axenic amastigotes. Compound 28, N-((1-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)-1H-1,2,3-triazole-4-yl) methyl)-3,4-dimethoxy cinnamide, demonstrated relevant antileishmanial activity with low toxicity in murine cells. The selectivity index values for this compound were superior compared with data obtained using amphotericin B. Furthermore, this cinnamide derivative reduced the infection percentage and number of recovered amastigotes in L. braziliensis-infected macrophages. It also induced an increase in reactive oxygen species production, depolarization of the mitochondrial potential, and disruption of the parasite membrane. Taken together, these findings suggest that this synthetic compound holds potential as an antileishmanial candidate and should be considered for future studies in the treatment of ATL.
Erythema Nodosum Leprosum (ENL) is an immune reaction in leprosy that aggravates the patient´s clinical condition. ENL presents systemic symptoms of an acute infectious syndrome with high ...leukocytosis and intense malaise clinically similar to sepsis. The treatment of ENL patients requires immunosuppression and thus needs to be early and efficient to prevent both disabilities and permanent nerve damage. Some patients experience multiple episodes of ENL and prolonged use of immunosuppressive drugs may lead to serious adverse effects. Thalidomide treatment is extremely effective at ameliorating ENL symptoms. Several mechanisms have been proposed to explain the efficacy of thalidomide in ENL, including the inhibition of TNF production. Given its teratogenicity, thalidomide is prohibitive for women of childbearing age. A rational search for molecular targets during ENL episodes is essential to better understand the disease mechanisms involved, which may also lead to the discovery of new drugs and diagnostic tests. Previous studies have demonstrated that IFN-γ and GM-CSF, involved in the induction of CD64 expression, increase during ENL. The aim of the present study was to investigate CD64 expression during ENL and whether thalidomide treatment modulated its expression. Leprosy patients were allocated to one of five groups: (1) Lepromatous leprosy, (2) Borderline leprosy, (3) Reversal reaction, (4) ENL, and (5) ENL 7 days after thalidomide treatment. The present study demonstrated that CD64 mRNA and protein were expressed in ENL lesions and that thalidomide treatment reduced CD64 expression and neutrophil infiltrates-a hallmark of ENL. We also showed that ENL blood neutrophils exclusively expressed CD64 on the cell surface and that thalidomide diminished overall expression. Patient classification based on clinical symptoms found that severe ENL presented high levels of neutrophil CD64. Collectively, these data revealed that ENL neutrophils express CD64, presumably contributing to the immunopathogenesis of the disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Understanding which strategies have been recommended for the promotion of active and healthy lifestyles through physical education (PE) classes can guide PE policies and practice. Therefore, we ...summarized worldwide recommendations regarding strategies for PE classes that have aimed to promote active and healthy lifestyles among school-aged children and adolescents.
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines were utilized. A literature search was carried out in June 2020 in eight peer-reviewed literature databases, in addition to searches in institutional and personal libraries. The eligibility criteria included any online document that included recommendations targeting any dimension of PE classes (e.g., policy and environment, curriculum, appropriate instruction, student assessment, and strategies that interact with PE) published since 2000.
In total, 2,408 potentially eligible documents were screened. Of these, 63 were included in the final analysis. The recommended strategies were as follows: six referred to policy and environment (valuing PE, higher frequency and duration of classes, inclusive PE classes, mandatory daily classes, evaluation of PE classes, and qualified teachers), five to curriculum (structure, type of content, cross-cutting themes, and components that improve PE classes), four to appropriate instruction (promotion of physical activities, inclusion of social issues, employment of the use of innovative technologies, and organization of the teaching-learning process), and three to student assessment (understanding human movement concepts, evaluation of contents, and assessment methods to develop an active and healthy lifestyle).
Twenty-one strategies recommended for PE classes linked to five dimensions aimed at different target populations were identified. Over half were linked to the dimensions of policy and environment and appropriate instruction. PE is recommended to be mandatory and valued at all educational levels, with weekly frequency that contributes to an active and healthy lifestyle. This review shows that guaranteeing different experiences beyond sports, improving social inclusion, using innovative technologies, and providing adequate materials and spaces to be important challenges and ways to guide policies, programs, and new research in this field of knowledge. Open Science Framework Registration: https://osf.io/harwq/.
interacts with host cells, including cardiomyocytes, and induces the production of cytokines, chemokines, metalloproteinases, and glycan-binding proteins. Among the glycan-binding proteins is ...Galectin-3 (Gal-3), which is upregulated after
infection. Gal-3 is a member of the lectin family with affinity for β-galactose containing molecules; it can be found in both the nucleus and the cytoplasm and can be either membrane-associated or secreted. This lectin is involved in several immunoregulatory and parasite infection process. Here, we explored the consequences of Gal-3 deficiency during acute and chronic
experimental infection. Our results demonstrated that lack of Gal-3 enhanced
replication of intracellular parasites, increased
systemic parasitaemia, and reduced leukocyte recruitment. Moreover, we observed decreased secretion of pro-inflammatory cytokines in spleen and heart of infected Gal-3 knockout mice. Lack of Gal-3 also led to elevated mast cell recruitment and fibrosis of heart tissue. In conclusion, galectin-3 expression plays a pivotal role in controlling
infection, preventing heart damage and fibrosis.
Purpose
Regular physical activity is a good strategy to maintain the health of athletes, and prevent pain and decreased joint flexibility during the pandemic. On the other hand, higher sedentary time ...during the pandemic period can have deleterious effects. The objective of this study was to compare physical activity levels, sedentary time, and sleep parameters during the pre-COVID period and the COVID-19 pandemic period in young badminton athletes.
Methods
Fifteen young badminton athletes were evaluated during a pre-COVID period (July 2019) and during the COVID-19 period (July 2020). Sleep parameters, physical activity level, and sedentary time were measured using a tri-axial accelerometer. Participants wore the accelerometer on their dominant wrist for 7 days consecutively. In addition, the average of each sleep parameter time in bed and total sleep time in hours per day, sleep efficiency (%), wake after sleep onset (WASO, total per day), and sleep latency (minutes per day) was reported over the 7-day period.
Results
Athletes presented increased sedentary time (pre-COVID = 7.0 ± 1.1 vs.COVID-19 = 8.9 ± 1.9 h/day,
p
= 0.004,
d
= 1.30) and significant decreases in the total PA observed in counts per day (pre-COVID = 2,967,064.4 ± 671,544.1 vs. COVID-19 = 1,868,210.2 ± 449,768.4 counts/day,
p
= 0.001,
d
= 1.99), time in vigorous PA (pre-COVID = 7.7 ± 0.9 vs. COVID-19 = 6.1 ± 1.2 h/day,
p
= 0.001,
d
= 1.56), and time in moderate-to-vigorous PA (pre-COVID = 8.1 ± 0.9 vs. COVID-19 = 6.5 ± 1.3 h/day,
p
= 0.001,
d
= 1.48). There were no significant differences for time in light and moderate PA or in sleep parameters (
p
> 0.05).
Conclusion
Young badminton athletes presented increased sedentary time, and decreased total physical activity, time in MVPA, and time in vigorous activities during the COVID-19 pandemic compared to the pre-COVID period, however, there were no significant differences in sleep parameters.
Cassava (Manihot esculenta Crantz) has significant socioeconomic relevance in Brazil and other developing countries, as one of the main sources of carbohydrates for human and animal consumption (De ...Oliviera et al., 2011). Among the cassava crop diseases, anthracnose is one of the main limiting factors for production and may be caused by species like Colletotrichum plurivorum, C. karstii, C. fructicola, and C. siamense (Bragança et al., 2016; Liu et al., 2019; Oliveira et al., 2016; Sangpueak; Phansak; Buensanteai, 2018). Severity in the field is variable, depending on the resistance of the variety used and is also highly influenced by the climate, being the most severe disease under high humidity and high temperature. Under these conditions, it can cause losses of up to 100%. In 2019, cassava leaves presenting dark brown necrotic injuries of different sizes and irregular borders-typical anthracnose symptoms- were collected from commercial plantations in the states of Pará and Tocantins, Brazil. Symptomatic tissue fragments were superficially disinfected, placed in plates with potato dextrose agar (PDA), and incubated under 25 ± 2 °C for seven days. In the 56 isolates used in the morphological identification, the colonies were white and gray at the top and dark gray in the bottom with sector formation. The conidia were hyaline, cylindrical, and aseptic, 10.04 to 17.83 μm long × 3.29 to 5.75 μm wide. These phenotypical characteristics were similar to those of C. gloeosporioides lato sensu species (Weir et al., 2012). Genomic DNA was extracted from two representative isolates (UFT/Coll69, collected in the municipality of Casa de Tábua-PA; UFT/Coll82, collected in Pau Darco-PA) and the APN2 / MAT-IGS, DNA lyase (Apn2), and glyceraldehyde-3-phosphate dehydrogenase-IGS (GAP2-IG) intergenic spacers were amplified and sequenced. The nucleotide sequences were deposited in the GenBank (accession numbers: MT409462, MT396231, MT759633, MT396239, MT396232, MT800846). The BLASTn (Basic Local Alignment Search Tool) showed a 99 to 100% similarity with Colletotrichum chrysophillum. The maximum likelihood phylogenetic analysis grouped the isolates in the C. chrysophillum clade, with a high bootstrap value (98%). Based on morphocultural characteristics and the phylogenetic analysis, the isolates associated with M. esculenta anthracnose were identified as C. chrysophillum, with a frequency of 6.67% among Colletotrichum colonies isolated from cassava leaves. The inoculation of three isolates was carried out in three plants, three leaves for each plant, by spraying spore solution with a concentration of 1×106 conidia / ml, without wounding the leaves and placed in a humid chamber at 25 ° C for ten days. Control plants were inoculated with sterile distilled water. From the 2nd day after inoculation, small irregular necrotic lesions appeared that increased in size over time, while control plants remained asymptomatic. Both were pathogenic and the symptoms caused after inoculation were similar to each other and to those observed in the field. In Brazil, anthracnose by C. chrysophillum was reported in cashew (Veloso et al., 2018) and banana trees (Vieira et al., 2017). To our knowledge, this is the first report of cassava anthracnose disease by C. chrysophillum.
The main clinical feature associated with hyperandrogenism in polycystic ovary syndrome (PCOS) in humans is hirsutism, where hair increases its length, pigmentation, and particularly its diameter. ...Currently, it is not known whether PCOS animal models also exhibit changes in the hair. Therefore, the aim of this study was to explore the wool characteristics in sheep prenatally androgenized (PA) with testosterone propionate. After 4 and 13 months of life, wool was collected from the top of the shoulder of both females and males (both androgenized and controls). The offspring sheep were followed for up to 19 months of life to evaluate testosterone and androstenedione serum levels by ultra-high-performance liquid chromatography-tandem mass spectrometry, determine insulin and glucose response to intravenous glucose tolerance test, and address estrus cyclicity during the second breeding season. PA male animals showed a reduction in wool fiber diameter at 4 months of age compared with controls (P = 0.02) but not at 13 months, whereas PA females showed increased hair diameter at 13 months (P = 0.002), with no difference at 4 months. No substantial changes in other hair parameters (length, color, and medullation) were identified. In addition, increased levels of serum testosterone were observed in PA female sheep compared with controls at 12 months (P = 0.03). Our results indicate for the first time, to our knowledge, that changes in wool fiber diameter observed in PA ewes replicate, at the translational level, the increase in hair diameter in hirsute women with PCOS.
Bladder cancer is the fourth most common malignancy in men. It can present along the entire continuum of severity, from mild to well‐differentiated disease to extremely malignant tumors with low ...survival rates. Human RAS genes are the most frequently mutated oncogenes in human cancers, and the critical role of aberrant Ras protein function in carcinogenesis is well established. Therefore, considerable efforts have been devoted to the development of anti‐Ras inhibitors for cancer treatment. This study presents the biphenyl dihydropyrimidinone LaSOM 335 with high activity against T24 bladder cancer cells (IC50 = 10.73 ± 0.53 μM) and selectivity of cytotoxicity for this cancer cell line compared to two non‐cancer cell lines investigated. Furthermore, we also show that this compound reduced vulvar development in the mutant let‐60 gene of Caenorhabditis elegans. Let‐60 is a homolog of the mammalian Ras gene. In addition, we observed that LaSOM 335 inhibits the enzymatic activity of CD73 and decreases CD73 expression. Possibly, this expression decrease is due to downstream EGFR signaling via the Ras–Raf–ERK pathway, that directly regulates CD73 expression via ERK1/2. Evidence suggests that non‐immunomodulating functions of CD73 play an equally important role for cancer cell survival, progression, and migration. Regarding we also notice that LaSOM 335 was safe in the in vivo model of C. elegans. The set of these findings makes this biphenyl dihydropyrimidinone a promising candidate for further investigations in the bladder cancer field.
LaSOM 335 is active against T24 bladder cancer cells, modulates the Ras–Raf–ERK pathway, and decreases CD73 activity.
Physical education (PE) classes in schools are considered relevant to implement interventions, especially focused on physical activity. However, evidence overviews on how PE classes contribute to ...general health (physical, social, affective, and cognitive domains) are still needed. Thus, we summarized evidence synthesis (eg, systematic reviews) that addressed the contribution of PE classes to the health of school-aged children and adolescents.
We performed a scoping review with searches in 8 databases and institutional websites to find systematic reviews or meta-analyses that answered this review's research question. Data charting form included the identification of the study, health outcomes, and PE classes' strategies (policies and environment, curriculum, appropriate instructions, and evaluation). An interactive process was performed to build the evidence summary.
An initial search yielded 2264 titles, and 49 systematic reviews (including 11 with meta-analysis) were included in this review. Most documents reported the main benefits of PE classes on physical domain outcomes (eg, physical activity, cardiorespiratory fitness, body mass index, and fundamental motor skills). However, evidence on the benefits of PE classes in affective (eg, enjoyment, motivation, and autonomy); social (eg, cooperation, problem-solving, and making friends); and cognitive (eg, memory, attention, concentration, and decision making) domains were found. Strategies on PE classes for health benefits were highlighted.
These elements were detailed in the evidence summary, which may be considered to guide researchers, teachers, and practitioners to define research and practice priorities on PE class interventions for health in the school context.
The objective of this study was to analyze the effects of the combination of resistance training (RT) and the hydroethanolic extract (EHE) of Bowdichia virgilioides as markers of oxidative stress ...(OS) in rats with peripheral nerve injury (PNI). Rats were allocated into six groups (n = 10): animals without interventions (C), animals with an exposed nerve but without injury, injured animals, trained and injured animals, injured animals that received EHE, and animals that received a combination of RT and EHE. RT comprised the climbing of stairs. EHE was orally administered (200 mg/kg) for 21 days after PNI induction. RT reduced the amount of lipoperoxidation in plasma (14.11%). EHE reduced lipoperoxidation in the plasma (20.72%) and the brain (41.36). RT associated with the extract simultaneously reduced lipoperoxidation in the plasma (34.23%), muscle (25.13%), and brain (43.98%). There was an increase in total sulhydrilyl levels (a) in the brain (33.33%) via RT; (b) in the brain (44.44%) and muscle (44.51%) using EHE; and (c) in the plasma (54.02%), brain (54.25%), and muscle using the combination of RT + EHE. These results suggest that RT associated with oral EHE results in a decrease in OS.
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