Antimalarial and antioxidant activities of novel artesunate-ellagic acid hybrid compound in vitro and in vivo.

Introduction: Emergence of drug resistant strains of Plasmodium species has necessitated the search for novel antimalarials with unique mechanisms of action. Synthesis of hybrid compounds has been one approach to tackling this challenge. In this study, the synthesis of artesunate-ellagic acid hybrid compound (EA31) from ellagic acid and artesunate and its evaluation for antimalarial and antioxidant activities using in vitro and in vivo models were carried out. Method: EA31 was synthesized from artesunate and ellagic acid. The activities of the hybrid compound against Plasmodium falciparum W2 and P. berghei NK65 were evaluated, and its antioxidant activities were also determined. Results: The results revealed that EA31 was more active against P. falciparum W2 (chloroquine resistant) clone and less cytotoxic to buffalo green monkey kidney cell line compared to artesunate. EA31 was also active against Plasmodium berghei NK65 in vivo. The results revealed inhibition of ß-hematin formation as one of the mechanisms of action of EA31. EA31 also exhibited antioxidant activities. Conclusion: The results revealed that EA31 may exert dual action of killing malaria parasite and mopping the reactive oxygen species that mediate the secondary complications of malaria.

LQFM289: Electrochemical and Computational Studies of a New Trimetozine Analogue for Anxiety Treatment.

This study employs electrochemical and Density Functional Theory (DFT) calculation approaches to investigate the potential of a novel analogue of trimetozine (TMZ) antioxidant profile. The correlation between oxidative stress and psychological disorders indicates that antioxidants may be an effective alternative treatment option. Butylatedhydroxytoluene (BHT) is a synthetic antioxidant widely used in industry. The BHT-TMZ compound derived from molecular hybridization, known as LQFM289, has shown promising results in early trials, and this study aims to elucidate its electrochemical properties to further support its potential as a therapeutic agent. The electrochemical behavior of LQFM289 was investigated using voltammetry and a mechanism for the redox process was proposed based on the compound's behavior. LQFM289 exhibits two distinct oxidation peaks: the first peak, Ep1a ≈ 0.49, corresponds to the oxidation of the phenolic fraction (BHT), and the second peak, Ep2a ≈ 1.2 V (vs. Ag/AgCl/KClsat), denotes the oxidation of the amino group from morpholine. Electroanalysis was used to identify the redox potentials of the compound, providing insight into its reactivity and stability in different environments. A redox mechanism was proposed based on the resulting peak potentials. The DFT calculation elucidates the electronic structure of LQFM289, resembling the precursors of molecular hybridization (BHT and TMZ), which may also dictate the pharmacophoric performance.

Antimicrobial Activity and Molecular Docking Studies of the Biotransformation of Diterpene Acanthoic Acid Using the Fungus Xylaria sp.

Biotransformations are reactions mediated by microorganisms, such as fungi. These bioreactions have high chemo- and stereoselectivity on organic substrates and can be applied in the search for new bioactive compounds. In this study, acanthoic acid (AA) was biotransformed using the fungus Xylaria sp., giving the novel compound 3ß,7ß-dihydroxyacanthoic acid (S1). Both the AA and the product S1 were tested against Gram-positive and Gram-negative bacteria. To identify and validate possible biological targets as enzymes or proteins involved in the activity observed in vitro, we used the molecular docking method. Hydroxylation at the C-3 and C-7 positions of the biotransformation product enhanced its activity against Escherichia coli as well as its binding affinity and interactions with superoxide dismutase 1 (SOD1; PDB ID 4A7G). Based on our results, the SOD1 enzyme was suggested to be a possible target for the antioxidant activity of product S1.

Light effects on Lasiodiplodia theobromae metabolome cultured in vitro.

INTRODUCTION: The present work identified and compared intracellular metabolites and metabolic networks in mycelial cultures of Lasiodiplodia theobromae grown under 12 natural light and 24 hours' dark using a 1 H NMR-based metabolomics approach. MATERIALS AND METHODS: Fungal cultures were grown in potato dextrose media, and metabolites were extracted by sonication with sodium phosphate-buffered saline (pH = 6.0, 10% D2O, 0.1 mM TSP) from mycelium samples collected every week over four weeks. RESULTS: Multivariate analyses revealed that the light exposure group showed a positive correlation within beta-hydroxybutyrate, acetoacetate, acetone, betaine, choline, glycerol, and phosphocholine. On the other hand, phenyl acetate, leucine, isoleucine, valine, and tyrosine were positively correlated with dark conditions. Light favored the oxidative degradation of valine, leucine, and isoleucine, leading to the accumulation of choline, phosphocholine, betaine, and ketone bodies (ketogenesis). Ketogenesis, gluconeogenesis, and the biosynthesis of choline, phosphocholine, and betaine, were considered discriminatory routes for light conditions. The light-sensing pathways were interlinked with fungal development, as verified by the increased production of mycelia biomass without fruiting bodies and stress signaling, as demonstrated by the increased production of pigments.

Comparative genomics uncovers the evolutionary history, demography, and molecular adaptations of South American canids.

The remarkable radiation of South American (SA) canids produced 10 extant species distributed across diverse habitats, including disparate forms such as the short-legged, hypercarnivorous bush dog and the long-legged, largely frugivorous maned wolf. Despite considerable research spanning nearly two centuries, many aspects of their evolutionary history remain unknown. Here, we analyzed 31 whole genomes encompassing all extant SA canid species to assess phylogenetic relationships, interspecific hybridization, historical demography, current genetic diversity, and the molecular bases of adaptations in the bush dog and maned wolf. We found that SA canids originated from a single ancestor that colonized South America 3.9 to 3.5 Mya, followed by diversification east of the Andes and then a single colonization event and radiation of Lycalopex species west of the Andes. We detected extensive historical gene flow between recently diverged lineages and observed distinct patterns of genomic diversity and demographic history in SA canids, likely induced by past climatic cycles compounded by human-induced population declines. Genome-wide scans of selection showed that disparate limb proportions in the bush dog and maned wolf may derive from mutations in genes regulating chondrocyte proliferation and enlargement. Further, frugivory in the maned wolf may have been enabled by variants in genes associated with energy intake from short-chain fatty acids. In contrast, unique genetic variants detected in the bush dog may underlie interdigital webbing and dental adaptations for hypercarnivory. Our analyses shed light on the evolution of a unique carnivoran radiation and how it was shaped by South American topography and climate change.

A positive HPV test with positive p16/Ki-67 double staining in self-sampled vaginal material is an accurate tool to detect women at risk for cervical cancer.

BACKGROUND: The development of efficient strategies for managing high-risk human papillomavirus (HR-HPV)-positive women is a major challenge when human papillomavirus-based primary screening is being performed. The objectives of this study were to evaluate the comparative effectiveness of HR-HPV testing based on self-collection (SC) and HR-HPV testing based on collection by a health professional (HP) and to assess the potential usefulness of HR-HPV testing combined with testing with the biomarkers p16/Ki-67, α-mannosidase, and superoxide dismutase 2 (SOD2). METHODS: This was a cross-sectional study of 232 women admitted for colposcopy because of an abnormal Papanicolaou smear. The collected material underwent liquid-based cytology, HR-HPV detection, and immunocytochemical testing (p16/Ki-67, α-mannosidase, and SOD2). The gold standard was the histopathological result; the positive reference was CIN2+. RESULTS: The overall accuracy of HR-HPV testing was 76.6%; the results for the SC group (78.1%) and the HP group (75.2%) were similar. The positive predictive values (HP, 76.5%; SC, 80.0%), the negative predictive values (HP, 66.7%; SC, 64.3%), the positive likelihood values (HP, 1.35; SC, 1.36), and the negative likelihood values (HP, 0.21; SC, 0.19) were also similar. p16/Ki-67 showed higher sensitivity than the other 2 biomarkers: 78.1% versus 45.8% for α-mannosidase and 44.5% for SOD2. The specificities of the biomarkers were equivalent: 71.4% for p16/Ki-67, 77.8% for α-mannosidase, and 71.2% for SOD2. In the HP group, accuracy also leaned more heavily toward the final score (using α-mannosidase and SOD2) without statistical significance (80.8% vs 77.9%). The contrast with the SC group yielded the same level of accuracy. CONCLUSIONS: SC, when associated with testing with biomarkers, is as accurate as collection by HPs in the detection of women at risk for cervical cancer.

Albinism in Artibeus planirostris (Chiroptera, Phyllostomidae) in the Caatinga biome and updated list of albino bats in Brazil.

Albinism is a genetic disorder that results in a deficiency in melanin production. This type of chromatic alteration may affect several vertebrate species, but is rarely observed in nature. In Brazil, for the bat group, only 15 albino individuals have been registered. Here we present a new case for Artibeus planirostris. A pregnant female of this species with alopecia was captured in the Caatinga biome. A compilation of the distribution of albino bats in Brazil is presented.

Coronavirus Disease 2019 and Human Reproduction: A Changing Perspective.

Since the outbreak of severe acute respiratory coronavirus 2 (SARS-CoV-2), the coronavirus disease 2019 has had a wide range of effects on human health. This paper summarizes the data related to the effects of the SARS-CoV-2 infection on human reproduction. Both the male and female reproductive tract express high levels of receptors and proteins needed for viral cell entry. There is presently no evidence that gametes are affected by the infection. Male fertility may be temporarily reduced due to inflammatory responses following infection. The endometrium is highly susceptible to SARS-CoV-2 cell entry; however, it remains unclear whether this could alter receptivity and embryo implantation. Menstrual cycle changes were reported in women who experienced severe infection; however, they tended to be reversible. For couples undergoing assisted reproduction treatment, the pandemic led to a significant psychological burden, with changes in lifestyle that could directly affect the success of the treatment. Human reproduction societies recommend screening all patients prior to cycle initiation and avoiding treatment of women with severe comorbidities until the pandemic is under control. Finally, for pregnant women, it is expected that the infection is more severe in women in the third trimester and in those with comorbidities. Those who are symptomatic for SARS-CoV-2 are more likely to have increased rates of prematurity and intrapartum fetal distress than those who are asymptomatic. Vertical transmission cannot be completely ruled out, but neonatal infection rates are low. Vaccination appears to be safe and is indicated for use in pregnant and lactating women because the benefits outweigh the risks.

A fertility-oriented method for histological processing of testicular biopsies in men with azoospermia.

The present study was designed to evaluate whether tissue preparation by glutaraldehyde and glycol methacrylate (G/GMA) improves the diagnostic assessment of testicular biopsies from azoospermic men when compared to the standard tissue preparation using Bouin's solution and paraffin. We prospectively included a total of 21 testicular biopsies of sexually mature men aged 29-50 years with infertility and azoospermia. One testicular biopsy fragment from each patient was processed by the G/GMA method, whereas another tissue fragment was contemporarily processed by the conventional Bouin/paraffin (B/P) method. The G/GMA method provided better resolution of cytological details of the seminiferous epithelium, changing the final diagnosis in four cases. The medians of Bergmann's spermatogenesis scores were 0.25 (interquartile range 0.04-0.88) for B/P preparations and 0.79 (interquartile range 0.17-0.96) for G/GMA preparations. Both techniques allowed accurate prediction of sperm recovery from the biopsies (B/P, area under the receiver operating characteristics [ROC] curve 0.88, 95% confidence interval [CI] 0.75-1.00; G/GMA, area under the ROC curve 0.94, 95% CI 0.86-1.00). We conclude that human testicular biopsy preparation with G/GMA improved image resolution under light microscopy and produced more reliable results for the evaluation of spermatogenesis in comparison with B/P, allowing a more precise fertility-oriented diagnosis in azoospermic men.Abbreviations: B/P: Bouin/paraffin; GMA: glycol methacrylate; G/GMA: glutaraldehyde and glycol methacrylate; ICSI: intracytoplasmic sperm injection; OA: obstructive azoospermia; NOA: nonobstructive azoospermia; TESE: testicular sperm extraction.

Effect of photobiomodulation therapy on performance and running economy in runners: A randomized double-blinded placebo-controlled trial.

The objective of this study was to evaluate effects of photobiomodulation therapy (PBMT) on the 3000 m running performance (primary outcome), running economy (RE), metabolic cost and ratings of perceived exertion during running (secondary outcomes). Twenty male endurance athletes performed 4-min treadmill rectangular test at 12 km.h-1 monitored by a gas analyser. After that, PBMT or placebo in each lower limb was applied, followed performed a maximum test of 3000 m. Immediately after 3000 m test, the athletes repeated the treadmill test. Another application of PBMT/placebo was done after the treadmill test, and athletes went back to the laboratory 24 h later to repeat the treadmill test. After a 72 h interval, athletes repeated all procedures with another treatment intervention (PBMT/placebo). Athletes performed the 3000 m running test ~7s faster when treated with PBMT with similar effort score compared placebo condition. The RE remains unchanged immediately post 3000 m running test, nonetheless RE measured post-24 h improved by 5% with PBMT application without changes in metabolic cost. The PBMT pre- and post-conditioning enhanced the 3000 m running performance and improved RE 24 h following the 3000 m test. However, no changes on ratings of perceived exertion and metabolic cost with the application of PBMT.

Kinematic Comparison of the Roundhouse Kick Between Taekwondo, Karate, and Muaythai.

ABSTRACT: Diniz, R, Del Vecchio, FB, Schaun, GZ, Oliveira, HB, Portella, EG, da Silva, ES, Formalioni, A, Campelo, PCC, Peyré-Tartaruga, LA, and Pinto, SS. Kinematic comparison of the roundhouse kick between taekwondo, karate, and muaythai. J Strength Cond Res 35(1): 198-204, 2021-The roundhouse kick (RHK) is frequently executed in taekwondo, karate, and muaythai because of its high technical effectiveness during combat. The purpose of this study was to compare kinematic characteristics during RHK performance between taekwondo, karate, and muaythai athletes. Forty-seven male athletes (25.5 ± 4.7 years, 1.75 ± 0.1 m, and 75.8 ± 11.5 kg) volunteered to participate (taekwondo: 17; karate: 15; and muaythai: 15). Self-selected distance from target, mean and peak fifth metatarsus linear velocity (LV5mean; LV5peak), mean and peak hip (HAVmean; HAVpeak) and knee (KAVmean; KAVpeak) angular velocities, as well as target linear acceleration (TLA) were analyzed with a 3D video motion analysis system. Comparisons between modalities were performed with 1-way analysis of variances and Bonferroni's post hoc test (α = 0.05). Self-selected distance was lower in muaythai compared with taekwondo and karate (p < 0.001). Also, karate had greater LV5mean compared with muaythai (p = 0.001), and muaythai showed higher HAVmean than karate (p = 0.011). In addition, HAVpeak was greater in muaythai than in taekwondo and karate (p < 0.001). No differences were found for KAVmean, KAVpeak, and TLA. Although it is similarly described between modalities, RHK showed distinct kinematic characteristics between taekwondo, karate, and muaythai. Based on these results, coaches and athletes can improve their RHK technique according to the specificities of each combat sport. Specifically, it is suggested that combat strategies should aim to increase the distance from the opponent during combat for muaythai athletes, whereas taekwondo and karate athletes should focus on decreasing it.

Coronavirus disease 2019 and human reproduction: a changing perspective

Since the outbreak of severe acute respiratory coronavirus 2 (SARS-CoV-2), the coronavirus disease 2019 has had a wide range of effects on human health. This paper summarizes the data related to the effects of the SARS-CoV-2 infection on human reproduction. Both the male and female reproductive tract express high levels of receptors and proteins needed for viral cell entry. There is presently no evidence that gametes are affected by the infection. Male fertility may be temporarily reduced due to inflammatory responses following infection. The endometrium is highly susceptible to SARS-CoV-2 cell entry; however, it remains unclear whether this could alter receptivity and embryo implantation. Menstrual cycle changes were reported in women who experienced severe infection; however, they tended to be reversible. For couples undergoing assisted reproduction treatment, the pandemic led to a significant psychological burden, with changes in lifestyle that could directly affect the success of the treatment. Human reproduction societies recommend screening all patients prior to cycle initiation and avoiding treatment of women with severe comorbidities until the pandemic is under control. Finally, for pregnant women, it is expected that the infection is more severe in women in the third trimester and in those with comorbidities. Those who are symptomatic for SARS-CoV-2 are more likely to have increased rates of prematurity and intrapartum fetal distress than those who are asymptomatic. Vertical transmission cannot be completely ruled out, but neonatal infection rates are low. Vaccination appears to be safe and is indicated for use in pregnant and lactating women because the benefits outweigh the risks.

Physiological Predictors of Maximal Incremental Running Performance.

PURPOSE: The aim of this study was to verify whether physiological components [vertical jumps (Squat Jump - SJ and Countermovement Jump - CMJ), eccentric utilization ratio (EUR) of vertical jumps, running economy (RE), metabolic cost (C MET ), first and second ventilatory threshold (VT1 and VT2) maximal oxygen uptake (VO2MAX)] can predict maximal endurance running performance. METHODS: Twenty male runners performed maximal vertical jumps, submaximal running at constant speeds, and maximal incremental running test. Before, we measured anthropometric parameters (body mass and height) and registered the training history and volume. SJ and CMJ tests were evaluated prior to running tests. Initially, the oxygen uptake (VO2) was collected at rest in the orthostatic position for 6 min. Soon after, a 10-min warm-up was performed on the treadmill at 10 km⋅h-1, followed by two 5-min treadmill rectangular tests at 12 and 16 km⋅h-1 monitored by a gas analyzer. After that, the runners performed a maximal incremental test, where the VT1, VT2, and VO2MAX were evaluated, as well as the maximum running speed (vVO2MAX). Thus, RE and C MET were calculated with data obtained during rectangular running tests. Multivariate stepwise regression analyses were conducted to measure the relationship between independent variables (height and power of SJ and CMJ, EUR; RE and C MET 12 and 16 km⋅h-1 ; VT1, VT2, and VO2MAX), as predictors of maximal running performance (vVO2MAX), with significance level at α = 0.05. RESULTS: We found that VO2MAX and RE at 16 km⋅h-1 predict 81% of performance (vVO2MAX) of endurance runners (p < 0.001). CONCLUSION: The main predictors of the maximal incremental running test performance were VO2MAX and RE.

Sprint exercise for subjects with mild-to-moderate Parkinson's disease: Feasibility and biomechanical outputs.

BACKGROUND: High-intensity training, a still unexplored exercise for individuals with Parkinson's disease, is positively related with increased functionality and aerobic profile in healthy individuals. The aim of this work was to evaluate the feasibility, safety, and acceptance of sprint running in individuals with mild-to-moderate Parkinson's. Additionally, we compared sprint biomechanical outputs of force, velocity and power between individuals with Parkinson's disease and healthy. METHODS: Physically trained subjects with Parkinson's, men, (n = 16, 64:9.01 years, stage between 1 and 3 in the Hoehn and Yahr, 16.8:7.1 at Unified Parkinson's disease Rating Scales, and control group (n = 21, 65:9.27 years) performed 20 m sprint sessions. We analyzed the self-reported satisfaction and acceptance using a self-administered questionnaire, and the sprint biomechanics and performance based on high-speed video recordings. FINDINGS: All participants completed the tests with high feasibility, acceptability and satisfaction scores. The sprint maximal force and maximal power outputs were higher in Parkinson's disease. Conversely, control group showed higher mechanical effectiveness values. Interestingly, no difference in velocity capabilities and overall 20-m sprint performance was observed between groups, possibly explained by different mechanical strategies in both groups over the sprint accelerations. Linear regression analyses showed that physical qualities are predictors of mechanical effectiveness, and mechanical variables are important determinants of sprint performance on Parkinson's disease. INTERPRETATION: Sprint is a feasible exercise for people with mild-to-moderate Parkinson's disease. Even though differences in physical qualities and mechanical effectiveness exist between subjects with Parkinson's disease and healthy, there is no overall substantial impact on sprint running performance.

Physical Activity and Incident Depression: A Meta-Analysis of Prospective Cohort Studies.

OBJECTIVE: The authors examined the prospective relationship between physical activity and incident depression and explored potential moderators. METHOD: Prospective cohort studies evaluating incident depression were searched from database inception through Oct. 18, 2017, on PubMed, PsycINFO, Embase, and SPORTDiscus. Demographic and clinical data, data on physical activity and depression assessments, and odds ratios, relative risks, and hazard ratios with 95% confidence intervals were extracted. Random-effects meta-analyses were conducted, and the potential sources of heterogeneity were explored. Methodological quality was assessed using the Newcastle-Ottawa Scale. RESULTS: A total of 49 unique prospective studies (N=266,939; median proportion of males across studies, 47%) were followed up for 1,837,794 person-years. Compared with people with low levels of physical activity, those with high levels had lower odds of developing depression (adjusted odds ratio=0.83, 95% CI=0.79, 0.88; I2=0.00). Furthermore, physical activity had a protective effect against the emergence of depression in youths (adjusted odds ratio=0.90, 95% CI=0.83, 0.98), in adults (adjusted odds ratio=0.78, 95% CI=0.70, 0.87), and in elderly persons (adjusted odds ratio=0.79, 95% CI=0.72, 0.86). Protective effects against depression were found across geographical regions, with adjusted odds ratios ranging from 0.65 to 0.84 in Asia, Europe, North America, and Oceania, and against increased incidence of positive screen for depressive symptoms (adjusted odds ratio=0.84, 95% CI=0.79, 0.89) or major depression diagnosis (adjusted odds ratio=0.86, 95% CI=0.75, 0.98). No moderators were identified. Results were consistent for unadjusted odds ratios and for adjusted and unadjusted relative risks/hazard ratios. Overall study quality was moderate to high (Newcastle-Ottawa Scale score, 6.3). Although significant publication bias was found, adjusting for this did not change the magnitude of the associations. CONCLUSIONS: Available evidence supports the notion that physical activity can confer protection against the emergence of depression regardless of age and geographical region.

Periodontal disease severity in subjects with dementia: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Despite clinical trials and reviews attempt to assess a possible relationship between dementia and periodontal disease, no meta-analysis has been performed and this issue remains undetermined. The aim of this study is to conduct a systematic review and meta-analysis to assess severity of periodontitis in subjects with dementia. METHODS: The search was conducted in Pubmed, Embase/MEDLINE. Two independent reviewers extracted data and assessed the risk bias (Newcastle-Ottawa scale). Meta-analyses were performed using the means of probing depth (PD) and clinical attachment loss (CAL) in patients with or without dementia. The mean difference were analyzed (P ≤ 0.05). RESULTS: Fourteen studies were included in the systematic review. In the qualitative analysis, most studies reported higher prevalence of periodontal disease in dementia patients. The studies had low risk of bias and two meta-analyses were performed for each parameter, including or not a cross-sectional study. The meta-analyses including the cross-sectional study demonstrated significant association between dementia and periodontal disease (mean difference: PD = 1.41; CAL = 1.40, P < 0.05), however, it wasn't confirmed when the cross-sectional study was removed (1.25 mm, P < 0.22) and CAL (1.20 mm, P < 0.22). CONCLUSION: Although the qualitative analysis have suggested worse periodontal conditions in dementia patients, due to different study types and the high heterogeneity among them, the meta-analysis does not support the association between dementia and severity of periodontal disease.