Epithelium-derived 6-nitrodopamine modulates noradrenaline-induced contractions in human seminal vesicles.

AIMS: To evaluate the basal release of 6-nitrodopamine (6-ND) from human isolated seminal vesicles (HISV) and to characterize its action and origin. MAIN METHODS: Left HISV obtained from patients undergoing prostatectomy surgery was suspended in a 3-mL organ bath containing warmed (37 °C) and gassed (95%O2:5%CO2) Krebs-Henseleit's solution (KHS) with ascorbic acid. An aliquot of 2 mL of the supernatant was used to quantify catecholamines by LC-MS/MS. For functional studies, concentration-responses curves to catecholamines were obtained, and pEC50 and Emax values were calculated. Detection of tyrosine hydroxylase and S100 protein were also carried out by both immunohistochemistry and fluorescence in-situ hybridization assays (FISH). KEY FINDINGS: Basal release of 6-ND was higher than the other catecholamines (14.76 ± 14.54, 4.99 ± 6.92, 3.72 ± 4.35 and 5.13 ± 5.76 nM for 6-ND, noradrenaline, adrenaline, and dopamine, respectively). In contrast to the other catecholamines, the basal release of 6-ND was not affected by the sodium current (Nav) channel inhibitor tetrodotoxin (1 µM; 10.4 ± 8.9 and 10.4 ± 7.9 nM, before and after tetrodotoxin, respectively). All the catecholamines produced concentration-dependent HISV contractions (pEC50 4.1 ± 0.2, 4.9 ± 0.3, 5.0 ± 0.3, and 3.9 ± 0.8 for 6-ND, noradrenaline, adrenaline, and dopamine, respectively), but 6-ND was 10-times less potent than noradrenaline and adrenaline. However, preincubation with very low concentration of 6-ND (10-8 M, 30 min) produced significant leftward shifts of the concentration-response curves to noradrenaline. Immunohistochemical and FISH assays identified tyrosine hydroxylase in tissue epithelium of HISV strips. SIGNIFICANCE: Epithelium-derived 6-ND is the major catecholamine released from human isolated seminal vesicles and that modulates smooth muscle contractility by potentiating noradrenaline-induced contractions.

Fosfomycin-Induced Liver Injury: A Case Report.

Fosfomycin is an antibiotic frequently used to treat uncomplicated urinary tract infections. It is normally well-tolerated, but there are some reports of clinically relevant liver injury. We present the case of a 73-year-old female who presented with paucisymptomatic hepatocellular acute liver injury six days after taking fosfomycin. After ruling out viral, ischemic, and autoimmune hepatitis, as well as Wilson disease and biliary disorders, she was diagnosed with drug-induced liver injury (DILI) related to fosfomycin. The patient showed major improvement during the first week and the resolution of liver injury one month after onset. This case report aims to underscore the potential hepatotoxicity of fosfomycin.

Pulmonary and Urologic Sarcoidosis as a Cause of Intermittent Fever of Unknown Origin.

Diagnosing fever of unknown origin (FUO) presents a substantial challenge due to its potential association with various diseases affecting different organs. In 1961, Petersdorf and Beeson initially defined FUO as a condition characterized by a temperature exceeding 38.3 °C on at least three occasions over a minimum three-week period. Despite a week of inpatient investigation, a definitive diagnosis remains unclear.  Sarcoidosis, a granulomatous disease impacting multiple systems, is among the causes of FUO. While the lungs are commonly affected, any organ can be involved, leading to diverse manifestations and clinical courses. Diagnosis relies on clinicopathologic findings and the exclusion of alternative causes of granulomatous disease. The hallmark of sarcoidosis is the development of granulomas in affected organs. Here, we present the case of a 61-year-old man with a history of recurrent spontaneous periurethral abscesses who underwent multiple urological interventions. He developed FUO during hospitalization following treatment for the infectious condition.

Purpura Fulminans as a Rare Manifestation of Invasive Haemophilus influenzae Disease: A Case Report.

Haemophilus influenzae (Hi) is a bacterium usually found in the upper respiratory tract of humans. Though it is recognized as a naturally occurring element in the human bacterial reservoir, Hi infections have the potential to be severe and even fatal, particularly when they result in conditions such as meningitis or epiglottitis. Because of this, Hi invasive infections are considered a reportable disease in Portugal. We report a case of a 58-year-old female, chronically adrenally suppressed on long-term steroids, who developed an invasive Hi type b infection that led to purpura fulminans and multiorgan failure after an acute episode of epiglottitis. According to our review of the literature, only three previous cases of invasive Hi type b disease-causing purpura fulminans have been described.

Gestational diabetes mellitus early prediction by maternal body fat index: A cohort study.

OBJECTIVES: To compare the performance of maternal body fat index (BFI) assessed during the first 20+6 weeks among 138 pregnant women in an ultrasound outpatient clinic as a predictor of gestational diabetes mellitus (GDM) later in pregnancy. METHOD: Maternal visceral and subcutaneous fat was measured with a convex ultrasound probe placed in two locations on the maternal abdominal surface: the first in the mid-sagittal epigastric region, visualising epigastric fat, and the second 2cm above the maternal umbilical scar, visualising periumbilical fat. Ultrasound callipers measured the distance from dermal edge to the linea alba and after from the linea alba to the anterior hepatic surface (epigastric fat). Periumbilical fat was measured from the dermal edge to the linea alba and after from the linea alba to the anterior aortic surface. The BFI formula was [visceral adipose tissue (mm)×subcutaneous adipose tissue (mm)]/maternal height (cm). RESULTS: The best thresholds for predicting GDM outcome for epigastric and periumbilical BFI were 1.2 and 4.8, respectively. Odds ratio, sensitivity and specificity were 5.88 (95% CI 1.86-18.6), 80.9%, 58.0% for the epigastric site and 6.31 (95% CI 1.73-22.94), 84.2%, 54.2% for the periumbilical site. Pre-pregnancy body mass index compatible with adult obesity shows inadequate predictive performance for GDM outcome. Only epigastric BFI above 1.2 maintained statistical significance for GDM in the logistic regression analysis, when compared to periumbilical BFI above 4.8. CONCLUSION: Epigastric BFI above 1.2 during the first half of pregnancy may help identify women at risk of developing GDM later in pregnancy.

Activity of extracts and terpenoids from Tontelea micrantha (Mart. ex Schult.) A.C.Sm. (Celastraceae) against pathogenic bacteria.

The pharmacological properties of plant extracts and phytochemicals, such as flavonoids and terpenoids, remain of great interest. In this work, the effect of extracts, friedelan-3,21-dione, and 3ß-O-D-glucosyl-sitosterol isolated from Tontelea micrantha roots was evaluated against Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumoniae, Klebsiella oxytoca and Escherichia coli. The antibacterial activity was evaluated by the minimum inhibitory and bactericidal concentrations (MIC and MBC, respectively), and the synergistic effect was assessed by the Checkerboard assay. Furthermore, the cytotoxicity of the plant-derived compounds against Vero cells was measured by the 3-(4 5-dimethylthiazol-2-yl)-2 5-diphenyltetrazolium bromide (MTT) method. The biological effects of the isolated compounds were predicted using the PASS online software. The chloroform and hexane extracts of T. micrantha roots showed promising antibacterial effect, with MIC in the range of 4.8-78.0 µg/mL. Further analyses showed that these compounds do not affect the integrity of the membrane. The combination with streptomycin strongly reduced the MIC of this antibiotic and extracts. The extracts were highly toxic to Vero cells, and no cytotoxicity was detected for the two terpenoids isolated from them (i.e. friedelan-3,21-dione and 3ß-O-D-glucosyl-sitosterol; CC50 > 1000 µg/mL). Therefore, extracts obtained from T. micrantha roots significantly inhibited bacterial growth and are considered promising agents against pathogenic bacteria. The cytotoxicity results were very relevant and can be tested in bioassays.

Yellow fever virus infection in human hepatocyte cells triggers an imbalance in redox homeostasis with increased reactive oxygen species production, oxidative stress, and decreased antioxidant enzymes.

Yellow fever (YF) presents a wide spectrum of severity, with clinical manifestations in humans ranging from febrile and self-limited to fatal cases. Although YF is an old disease for which an effective and safe vaccine exists, little is known about the viral- and host-specific mechanisms that contribute to liver pathology. Several studies have demonstrated that oxidative stress triggered by viral infections contributes to pathogenesis. We evaluated whether yellow fever virus (YFV), when infecting human hepatocytes cells, could trigger an imbalance in redox homeostasis, culminating in oxidative stress. YFV infection resulted in a significant increase in reactive oxygen species (ROS) levels from 2 to 4 days post infection (dpi). When measuring oxidative parameters at 4 dpi, YFV infection caused oxidative damage to lipids, proteins, and DNA, evidenced by an increase in lipid peroxidation/8-isoprostane, carbonyl protein, and 8-hydroxy-2'-deoxyguanosine, respectively. Furthermore, there was a significant reduction in the activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), in addition to a reduction in the ratio of reduced to oxidized glutathione (GSH/GSSG), indicating a pro-oxidant environment. However, no changes were observed in the enzymatic activity of the enzyme catalase (CAT) or in the gene expression of SOD isoforms (1/2/3), CAT, or GPx. Therefore, our results show that YFV infection generates an imbalance in redox homeostasis, with the overproduction of ROS and depletion of antioxidant enzymes, which induces oxidative damage to cellular constituents. Moreover, as it has been demonstrated that oxidative stress is a conspicuous event in YFV infection, therapeutic strategies based on antioxidant biopharmaceuticals may be new targets for the treatment of YF.

Exploring the antiviral potential of justicidin B and four glycosylated lignans from Phyllanthus brasiliensis against Zika virus: A promising pharmacological approach.

BACKGROUND: Zika virus (ZIKV) is an emerging arbovirus that in recent years has been associated with cases of severe neurological disorders, such as microcephaly in newborns and Guillain-Barré syndrome in adults. As there is no vaccine or treatment, the search for new therapeutic targets is of great relevance. In this sense, plants are extremely rich sources for the discovery of new bioactive compounds and the species Phyllanthus brasiliensis (native to the Amazon region) remains unexplored. PURPOSE: To investigate the potential antiviral activity of compounds isolated from P. brasiliensis leaves against ZIKV infection. METHODS: In vitro antiviral assays were performed with justicidin B (a lignan) and four glycosylated lignans (tuberculatin, phyllanthostatin A, 5-O-ß-d-glucopyranosyljusticidin B, and cleistanthin B) against ZIKV in Vero cells. MTT colorimetric assay was used to assess cell viability and plaque forming unit assay to quantify viral load. In addition, for justicidin B, tests were performed to investigate the mechanism of action (virucidal, adsorption, internalization, post-infection). RESULTS: The isolated compounds showed potent anti-ZIKV activities and high selectivity indexes. Moreover, justicidin B, tuberculatin, and phyllanthostatin A completely reduced the viral load in at least one of the concentrations evaluated. Among them, justicidin B stood out as the main active, and further investigation revealed that justicidin B exerts its antiviral effect during post-infection stages, resulting in a remarkable 99.9 % reduction in viral load when treatment was initiated 24 h after infection. CONCLUSION: Our findings suggest that justicidin B inhibits endosomal internalization and acidification, effectively interrupting the viral multiplication cycle. Therefore, the findings shed light on the promising potential of isolated compounds isolated from P. brasiliensis, especially justicidin B, which could contribute to the drug development and treatments for Zika virus infections.

Obesity Cut-Off Points Using Prepregnancy Body Mass Index according to Cardiometabolic Conditions in Pregnancy.

Aim: To suggest cut-off points for body mass index (BMI) using gestational hypertension, preeclampsia, and gestational diabetes mellitus (GDM) as cardiometabolic conditions in pregnancy. Methods: In this prospective study, singleton pregnant women from the fetal medicine service of the Brazilian Unified Health System were included. The pregnancy, perinatal, and newborn data were obtained from the clinical medical records. Maternal anthropometry included an assessment of weight and height and the prepregnancy BMI evaluation categorized according to the World Health Organization cut-off points. The area under the curve and confidence interval values from receiver operator curves were generated to identify the optimal cut-off points using prepregnancy BMI with better sensitivity and specificity. Results: Data on 218 pregnancies were analyzed, with 57.9% (n = 124) being classified as overweight/obese, 11% (n = 24) with GDM, 6.9% (n = 15) with preeclampsia, and 11.0% (n = 24) with gestational hypertension. The BMI cut-off points for predicting cardiometabolic conditions were 27.52 kg/m2 (S: 66.7%; E: 63.8%) for women with GDM; 27.40 kg/m2 (S: 73.3%; E: 62.4%; S: 79.2%; E: 64.9%; S: 70.3%; E: 66.3%) for women with preeclampsia, gestational hypertension, and gestational hypertension plus preeclampsia, respectively; and 27.96 kg/m2 (S: 69.6%; E: 65.6%) for women with preeclampsia plus GDM. Conclusion: The findings suggest that the optimal prepregnancy BMI cut-off point is around 27 kg/m2 for pregnant women with maternal cardiometabolic conditions.

Short-Term Effects of Lower-Extremity Heavy Resistance versus High-Impact Plyometric Training on Neuromuscular Functional Performance of Professional Soccer Players.

BACKGROUND: To compare the effects of short-term 8 week heavy-resistance or plyometric training protocols (HRT or PLY) incorporated into regular soccer practice on measures of neuromuscular functional performance in professional soccer players, a single-blind randomized controlled trial was conducted. METHODS: Forty-seven participants aged 22.3 ± 3.52 years were assigned to three groups: HRT (n = 15), PLY (n = 15), and control (CON; n = 17). The HRT group performed 3 sets and 10 repetitions twice a week using 80% of their baseline 1-RM (weeks 1-3), followed by 8 repetitions at 85% 1-RM (weeks 4-6), and 6 repetitions at 90% 1-RM (weeks 7-8) of 6 lower-body strength exercises with a 1 min rest period between sets. The PLY protocol involved a preparatory phase (weeks 1-2), followed by two 3-week progressive periods (weeks 3-5 and weeks 6-8). The plyometric sessions consisted of four jump exercises/drills with progressively increasing number of sets and total number of foot contacts. The rest intervals between repetitions and sets were 15 and 90 s, respectively. Outcome measures included tests assessing 10 and 30 m speed (t10m and t30m), one-repetition maximum half-back squat (1-RM squat), isokinetic peak torques for the quadriceps and hamstring muscles (Qcon and Hcon), countermovement jump (CMJ), and squat jump (SJ). RESULTS: Two-way ANOVA detected main effects of time and group×time interactions for all examined variables, except t30m, 1-RM, and relative 1-RM. Post hoc analyses revealed significant increases in the HRT group (t10m: 6.3%, t30m: 7.1%; absolute 1-RM: 29.6%; relative 1-RM: 30.3%, Qcon: 24.5%; Hcon: 14.4%; CMJ: 5.9%; SJ: 7.2%, all p < 0.001) and the PLY group (t10m: 3.1%; t30m: 4.1%; absolute 1-RM:19.1%; relative 1-RM: 20.3%; Qcon: 12.6%; Hcon: 8.7%; CMJ: 3.3%; SJ: 3.5%, all p < 0.001). HRT was superior compared to PLY in relative 1-RM, Qcon and Hcon (all p < 0.001). In addition, we found knee muscular strength imbalance in 70.5% of participants from the total sample (H/Q ratio < 60%). The HRT and PLY protocols resulted in improved neuromuscular functional performance compared to the regular soccer regime. CONCLUSIONS: This study showed that during the pre-competitive season, additional HRT and PLY drills/exercises as a substitute for standard soccer training as part of a regular 90 min practice twice a week for 8 weeks, can produce acute physical performance-enhancing effects in professional soccer players.

Neuropsychiatric Symptoms are Related to Blood-biomarkers in Major Neurocognitive Disorders.

BACKGROUND: Neuropsychiatric symptoms (NPS) are highly prevalent among individuals with major neurocognitive disorders (MNCD). OBJECTIVE: Here, we characterized blood biomarkers (metabolic, inflammatory, neurotrophic profiles and total antioxidant), body composition, physical fitness and quality of life (QoL) in individuals with MNCD according to NPS. METHODS: The sample comprised 34 older adults (71.4% women; 74.06±6.03 yrs, with MNCD diagnosis) categorized according to 50th percentile [Low (≤12) or High (≥13)] for NPS (Neuropsychiatric Inventory Questionnaire). Sociodemographic, clinical data, body composition, anthropometric, cognitive assessment (ADAS-Cog), physical fitness (Senior Fitness Test), QoL (QoL-Alzheimer's Disease scale) were evaluated, and blood samples were collected for biochemical analysis. RESULTS: Low compared to high NPS group showed higher levels of IL-6, IGF-1and neurotrophic zscore (composite of IGF-1, VEGF-1, BDNF). Additionally, low compared to high NPS group have higher QoL, aerobic fitness and upper body and lower body strength. CONCLUSION: The severity of NPS seems to be related to modified neurotrophic and inflammatory outcomes, lower physical fitness, and poor QoL. Strategies to counteract NPS development may preserve the physical and mental health of individuals with MNCD.

Metabolic mitochondrial alterations prevail in the female rat heart 8 weeks after exercise cessation.

BACKGROUND: The consumption of high-caloric diets strongly contributes to the development of non-communicable diseases (NCDs), including cardiovascular disease, the leading cause of mortality worldwide. Exercise (along with diet intervention) is one of the primary non-pharmacological approaches to promote a healthier lifestyle and counteract the rampant prevalence of NCDs. The present study evaluated the effects of exercise cessation after a short period training on the cardiac metabolic and mitochondrial function of female rats. METHODS: Seven-week-old female Sprague-Dawley rats were fed a control or a high-fat, high-sugar (HFHS) diet and, after 7 weeks, the animals were kept on a sedentary lifestyle or submitted to endurance exercise for 3 weeks (6 days per week, 20-60 min/day). The cardiac samples were analysed 8 weeks after exercise cessation. RESULTS: The consumption of the HFHS diet triggered impaired glucose tolerance, whereas the HFHS diet and physical exercise resulted in different responses in plasma adiponectin and leptin levels. Cardiac mitochondrial respiration efficiency was decreased by the HFHS diet consumption, which led to reduced ATP and increased NAD(P)H mitochondrial levels, which remained prevented by exercise 8 weeks after cessation. Exercise training-induced cardiac adaptations in redox balance, namely increased relative expression of Nrf2 and downstream antioxidant enzymes persist after an eight-week exercise cessation period. CONCLUSIONS: Endurance exercise modulated cardiac redox balance and mitochondrial efficiency in female rats fed a HFHS diet. These findings suggest that exercise may elicit cardiac adaptations crucial for its role as a non-pharmacological intervention for individuals at risk of developing NCDs.

HER2 Status in RAS and BRAF Wild-Type Metastatic Colorectal Cancer: A Portuguese Study.

INTRODUCTION: Colorectal cancer (CRC) is the second-most deadly cancer worldwide. However, there remains a scarcity of precision treatments available for this type of cancer. Amplification or overexpression of human epidermal growth factor receptor 2 (HER2+) is a well-established therapeutic target in gastric and breast cancer. HER2 is positive in approximately 5% of CRC cases and has been implicated in resistance to therapy with anti-epidermal growth factor receptor antibodies. The aim of this study was to evaluate HER2 status in RAS and BRAF wild-type metastatic CRC (mCRC) and its correlation with survival outcomes. MATERIALS AND METHODS: A single-center retrospective analysis of RAS and BRAF wild-type mCRC patients undergoing systemic treatment was conducted from July 2014 to September 2020. Tissue HER2 status was determined by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) and/or chromogenic in situ hybridization (CISH). HER2+ was defined as IHC3 (+) or IHC2 (+) through FISH or CISH (+). RESULTS: Fifty-nine patients were included. The median age of all the included patients was 64 years (33-82). Four patients had HER2+ tumors (7%). Four patients had HER2+ tumors (7%). The majority of HER2+ mCRC cases were males (n=3) and left-sided CRC (n=3). All patients received FOLFIRI plus cetuximab as first-line treatment. At the median follow-up of 24.0 months, patients with HER2-negative mCRC presented with a median overall survival (mOS) of 39.4 months (95% confidence interval (CI) 32.7-46.0) and the four patients with HER2+ mCRC had a mOS of 20.4 months (95% CI; 9.5-31.3; p=0.07). In HER2-negative patients, the median PFS (mPFS) was 11.3 months (95% CI; 9.2-13.4) vsHER2-positive patients with a mPFS of 10.9 months (95% CI; 1.3-20.4; p=0.47). CONCLUSIONS: To our knowledge, this is the first study reporting HER2+ in mCRC patients in a Portuguese population and the HER2+ rate was consistent with previous studies. Our study suggests that HER2+ may potentially be a marker that is able to predict poor prognosis in RAS and BRAF wild-type mCRC.

Untargeted-based metabolomics analysis and in vitro/in silico antiviral activity of extracts from Phyllanthus brasiliensis (Aubl.) Poir.

INTRODUCTION: This study describes the molecular profile and the potential antiviral activity of extracts from Phyllanthus brasiliensis, a plant widely found in the Brazilian Amazon. The research aims to shed light on the potential use of this species as a natural antiviral agent. METHODS: The extracts were analysed using liquid chromatography-mass spectrometry (LC-MS) system, a potent analytical technique to discover drug candidates. In the meantime, in vitro antiviral assays were performed against Mayaro, Oropouche, Chikungunya, and Zika viruses. In addition, the antiviral activity of annotated compounds was predicted by in silico methods. RESULTS: Overall, 44 compounds were annotated in this study. The results revealed that P. brasiliensis has a high content of fatty acids, flavones, flavan-3-ols, and lignans. Furthermore, in vitro assays revealed potent antiviral activity against different arboviruses, especially lignan-rich extracts against Zika virus (ZIKV), as follows: methanolic extract from bark (MEB) [effective concentration for 50% of the cells (EC50 ) = 0.80 µg/mL, selectivity index (SI) = 377.59], methanolic extract from the leaf (MEL) (EC50 = 0.84 µg/mL, SI = 297.62), and hydroalcoholic extract from the leaf (HEL) (EC50 = 1.36 µg/mL, SI = 735.29). These results were supported by interesting in silico prediction, where tuberculatin (a lignan) showed a high antiviral activity score. CONCLUSIONS: Phyllanthus brasiliensis extracts contain metabolites that could be a new kick-off point for the discovery of candidates for antiviral drug development, with lignans becoming a promising trend for further virology research.

Bioactivity of Macronutrients from Chlorella in Physical Exercise.

Chlorella is a marine microalga rich in proteins and containing all the essential amino acids. Chlorella also contains fiber and other polysaccharides, as well as polyunsaturated fatty acids such as linoleic acid and alpha-linolenic acid. The proportion of the different macronutrients in Chlorella can be modulated by altering the conditions in which it is cultured. The bioactivities of these macronutrients make Chlorella a good candidate food to include in regular diets or as the basis of dietary supplements in exercise-related nutrition both for recreational exercisers and professional athletes. This paper reviews current knowledge of the effects of the macronutrients in Chlorella on physical exercise, specifically their impact on performance and recovery. In general, consuming Chlorella improves both anaerobic and aerobic exercise performance as well as physical stamina and reduces fatigue. These effects seem to be related to the antioxidant, anti-inflammatory, and metabolic activity of all its macronutrients, while each component of Chlorella contributes its bioactivity via a specific action. Chlorella is an excellent dietary source of high-quality protein in the context of physical exercise, as dietary proteins increase satiety, activation of the anabolic mTOR (mammalian Target of Rapamycin) pathway in skeletal muscle, and the thermic effects of meals. Chlorella proteins also increase intramuscular free amino acid levels and enhance the ability of the muscles to utilize them during exercise. Fiber from Chlorella increases the diversity of the gut microbiota, which helps control body weight and maintain intestinal barrier integrity, and the production of short-chain fatty acids (SCFAs), which improve physical performance. Polyunsaturated fatty acids (PUFAs) from Chlorella contribute to endothelial protection and modulate the fluidity and rigidity of cell membranes, which may improve performance. Ultimately, in contrast to several other nutritional sources, the use of Chlorella to provide high-quality protein, dietary fiber, and bioactive fatty acids may also significantly contribute to a sustainable world through the fixation of carbon dioxide and a reduction of the amount of land used to produce animal feed.

Systemic and Pulmonary Inflammation/Oxidative Damage: Implications of General and Respiratory Muscle Training in Chronic Spinal-Cord-Injured Patients.

Chronic spinal cord injury affects several respiratory-function-related parameters, such as a decrease in respiratory volumes associated with weakness and a tendency to fibrosis of the perithoracic muscles, a predominance of vagal over sympathetic action inducing airway obstructions, and a difficulty in mobilizing secretions. Altogether, these changes result in both restrictive and obstructive patterns. Moreover, low pulmonary ventilation and reduced cardiovascular system functionality (low venous return and right stroke volume) will hinder adequate alveolar recruitment and low O2 diffusion, leading to a drop in peak physical performance. In addition to the functional effects described above, systemic and localized effects on this organ chronically increase oxidative damage and tissue inflammation. This narrative review describes both the deleterious effects of chronic spinal cord injury on the functional effects of the respiratory system as well as the role of oxidative damage/inflammation in this clinical context. In addition, the evidence for the effect of general and respiratory muscular training on the skeletal muscle as a possible preventive and treatment strategy for both functional effects and underlying tissue mechanisms is summarized.

Dose-response effect of a recreational team handball-based exercise programme on cardiometabolic health and physical fitness in inactive middle-aged-to-elderly males - a randomised controlled trial.

This study aimed at examining the dose-response of a recreational team handball (TH) exercise-based programme on cardiometabolic health and physical fitness in inactive middle-aged-to-elderly males without TH experience. Fifty-four inactive middle-aged-to-elderly men (67.5 ± 4.2 years; stature 168.8 ± 6.2 cm; body mass 78.4 ± 10.7 kg; fat mass 27.1 ± 5.3%; BMI 27.4 ± 2.9 kg/m2; VO2peak 27.3 ± 4.8 mL/min/kg) were randomised into three intervention groups performing 1 (TH1, n = 13), 2 (TH2, n = 15), or 3 (TH3, n = 12) 60-min weekly recreational TH-based training sessions, for 16 weeks, and a control group (CG, n = 14). A time x group interaction was observed for VO2peak, aerobic performance, fasting plasma insulin and body and fat mass (p ≤ 0.043) with TH3 showing the greatest overall effects. Post-intervention differences were observed in aerobic performance (TH3>CG, TH1 and TH2; TH2>CG), body mass (TH3>CG and TH1), fat mass (TH3>CG), VO2peak (TH3>CG) and plasma insulin (TH3>CG) (p ≤ 0.040). In conclusion, recreational TH performed for 60-min thrice and twice per week results in improved aerobic performance for middle-aged-to-elderly men. Moreover, it was observed that three weekly sessions were more effective in providing overall cardiometabolic benefits compared to training with a lower weekly frequency. ClinicalTrials.gov ID: NCT05295511.Trial registration: ClinicalTrials.gov identifier: NCT05295511.Highlights: We observed high intensities and fun levels during recreational TH, organised as formal and small-sided games, for middle-aged-to-elderly men during a 16-week period, independently of the number of weekly training sessions.Marked positive effects on aerobic performance and cardiometabolic health were observed in the intervention group that performed 3 weekly sessions.The study results indicate that recreational TH training with low frequency and volume results in some beneficial effects on cardiometabolic fitness and health for middle-aged-to-elderly men, but future studies with more participants or longer intervention periods are warranted to explore this possibility.

Cytotoxicity, structural, conformational, and techno-functional properties of α-lactalbumin nanostructured aggregates.

Protein nanostructures can be used in food applications to improve the techno-functional properties of a food formulation. This study aims to find the best conditions for the production and conformational change of α-lactalbumin nanostructured aggregates. The criteria to determine the best operating conditions to produce α-lactalbumin nanostructured aggregates were intensification of foaming and emulsification, techno-functional proprieties, cytotoxic, and antibacterial activity of nanostructures compared with native α-lactalbumin. Conformational alterations occurred in the α-helix and sheet-ß protein structures. The size obtained by dynamic light scattering was 163.84 nm with a polydispersity index of 0.29. The nano protein improved the techno-functional property compared to the native protein. Additionally, nanostructures had no cytotoxic effect and were innocuous to bacterial activity. Thus, this study presents the best conditions to produce α-lactalbumin nanostructured aggregates with improved properties that allow new food industry applications.

Oropouche virus infection induces ROS production and oxidative stress in liver and spleen of mice.

Oropouche virus (OROV) is the aetiological agent of Oropouche fever, the symptoms of which are common to most arboviruses, such as fever, headache, malaise, nausea and vomiting. More than half a million people have been infected with OROV since its isolation in 1955. Although Oropouche fever is classified as a neglected and emerging disease, to date, there are no antiviral drugs or vaccines available against the infection and little is known about its pathogenicity. Therefore, it is essential to elucidate the possible mechanisms involved in its pathogenesis. Since oxidative stress plays a pivotal role in the progression of various viral diseases, in this study, redox homeostasis in the target organs of OROV infection was evaluated using an animal model. Infected BALB/c mice exhibited reduced weight gain, splenomegaly, leukopenia, thrombocytopenia, anaemia, development of anti-OROV neutralizing antibodies, increased liver transaminases, and serum levels of pro-inflammatory cytokines tumour necrosis factor (TNF-α) and interferon-γ (IFN-γ). The OROV genome and infectious particles were detected in the liver and spleen of infected animals, with liver inflammation and an increase in the number and total area of lymphoid nodules in the spleen. In relation to redox homeostasis in the liver and spleen, infection led to an increase in reactive oxygen species (ROS) levels, increased oxidative stress biomarkers malondialdehyde (MDA) and carbonyl protein, and decreased activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Taken together, these results help elucidate some important aspects of OROV infection that may contribute to the pathogenesis of Oropouche.

Virucidal antiviral activity of Maytenus quadrangulata extract against Mayaro virus: Evidence for the presence of catechins.

ETHNOPHARMACOLOGICAL RELEVANCE: Mayaro virus (MAYV) is an arbovirus endemic to the Amazon region, which comprises the states of the North and Midwest region of Brazil and encompasses the largest tropical forest in the world, the Amazon Forest. The confirmation of its potential transmission by Aedes aegypti and recent cases in Brazil, mainly in large centers in the northern region, led to the classification of Mayaro fever as an emerging disease. Traditional medicine is commonly used to treat various diseases, mainly by local riverside populations. Some species of the genus Maytenus, which have similar morphologies, are popularly used to treat infections and inflammations. In this context, our research group has studied and confirmed the antiviral activity of several plant-derived compounds. However, several species of this same genus have not been studied and therefore deserve attention. AIM OF THE STUDY: This study aimed to demonstrate the effects of ethyl acetate extracts of leaves (LAE) and branches (TAE) of Maytenus quadrangulata against MAYV. MATERIALS AND METHODS: Mammalian cells (Vero cells) were used to evaluate the cytotoxicity of the extracts. After cell infection by MAYV and the treatment with the extracts, we evaluated the selectivity index (SI), the virucidal effect, viral adsorption and internalization, and the effect on viral gene expression. The antiviral action was confirmed by quantifying the viral genome using RT-qPCR and by analyzing the effect on virus yield in infected cells. The treatment was performed based on the effective concentration protective for 50% of the infected cells (EC50). RESULTS: The leaves (LAE; EC50 12.0 µg/mL) and branches (TAE; EC50 101.0 µg/mL) extracts showed significative selectivity against the virus, with SI values of 79.21 and 9.91, respectively, which were considered safe. Phytochemical analysis revealed that the antiviral action was associated with the presence of catechins, mainly in LAE. This extract was chosen for the subsequent studies since it reduced the viral cytopathic effect and virus production, even at high viral loads [MOI (multiplicity of infection) 1 and 5]. The effects of LAE resulted in a marked reduction in viral gene expression. The viral title was drastically reduced when LAE was added to the virus before infection or during replication stages, reducing virus production up to 5-log units compared to infected and untreated cells. CONCLUSION: Through kinetic replication, MAYV was not detected in Vero cells treated with LAE throughout the viral cycle. The virucidal effect of LAE inactivates the viral particle and can intercept the virus at the end of the cycle when it gains the extracellular environment. Therefore, LAE is a promising source of antiviral agents.