Does yoga improve sexual function? A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Yoga practice can increase blood flow in the genital area, increase muscular strength, and improve body perception, which is related to sexual function. This study aimed to summarize the available evidence about the effects of yoga on sexual function in adults. METHODS: Systematic searches of five databases were conducted from inception to April 28, with the last update on September 28, 2023. Randomized clinical trials (RCTs) that compared yoga with nonintervention control groups on sexual function in adults. Risk of bias and certainty of evidence were assessed by the Cochrane risk of bias tool 2, and the GRADE approach, respectively. Summary effect size measures were calculated using a random-effects model estimation and are reported as standardized mean differences and 95% confidence intervals. Reporting followed the PRISMA guidelines. RESULTS: Ten RCTs that comprised 730 adults (range mean age, 26.64-68.2 years; 680 [93.2 %] women) were included. For the primary outcome, yoga intervention was associated with a significant small improvement in sexual function (-0.31; -0.47 to -0.15, p = 0.0002), with some concerns about risk of bias in nine RCTs (90%) and low-certainty evidence. Subgroup analyses revealed that yoga interventions performed by women (-0.36; -0.52 to -0.21, p < 0.00001), healthy individuals (-0.38; -0.59 to -0.16, p = 0.0006), or middle-aged individuals (-0.44; -0.63 to -0.25, p < 00001) significantly improved sexual function compared with control groups. CONCLUSION: Yoga was associated with a small improvement in sexual function compared with nonintervention control groups in adults. However, high-quality, larger RCTs are required to draw more definitive conclusions.

Immunotherapy Combining Mimotopes Selected by Phage Display Plus Amphotericin B Is Effective for Treatment Against Visceral Leishmaniasis.

The treatment for visceral leishmaniasis (VL) causes toxicity in patients, entails high cost and/or leads to the emergence of resistant strains. No human vaccine exists, and diagnosis presents problems related to the sensitivity or specificity of the tests. Here, we tested two phage clones, B1 and D11, which were shown to be protective against Leishmania infantum infection in a murine model as immunotherapeutics to treat mice infected with this parasite species. The phages were used alone or with amphotericin B (AmpB), while other mice received saline, AmpB, a wild-type phage (WTP) or WTP/AmpB. Results showed that the B1/AmpB and D11/AmpB combinations induced polarised Th1-type cellular and humoral responses, which were primed by high levels of parasite-specific IFN-γ, IL-12, TNF-α, nitrite and IgG2a antibodies, which reflected in significant reductions in the parasite load in distinct organs of the animals when analyses were performed 1 and 30 days after the treatments. Reduced organic toxicity was also found in these animals, as compared with the controls. In conclusion, preliminary data suggest the potential of the B1/AmpB and D11/AmpB combinations as immunotherapeutics against L. infantum infection.

Dopaminergic Modulation and Computational ADMET Insights for the Antidepressant-like Effect of N-(3-(Phenylselanyl)prop-2-yn-1-yl)benzamide.

The compound N-(3-(phenylselanyl)prop-2-yn-1-yl)benzamide (SePB), which combines a selenium atom and a benzamide nucleus in an organic structure, has demonstrated a fast antidepressant-like effect in mice. This action is influenced by the serotonergic system and represents a promising development in the search for novel antidepressant drugs to treat major depressive disorder (MDD), which often resists conventional treatments. This study aimed to further explore the mechanism underlying the antidepressant-like effect of SePB by investigating the involvement of the dopaminergic and noradrenergic systems in the tail suspension test (TST) in mice and evaluating its pharmacokinetic profile in silico. Preadministration of the dopaminergic antagonists haloperidol (0.05 mg/kg, intraperitoneally (i.p.)), a nonselective antagonist of dopamine (DA) receptors, SCH23390 (0.01 mg/kg, subcutaneously (s.c.)), a D1 receptor antagonist, and sulpiride (50 mg/kg, i.p.), a D2/3 receptor antagonist, before SePB (10 mg/kg, intragastrically (i.g.)) prevented the anti-immobility effect of SePB in the TST, demonstrating that these receptors are involved in the antidepressant-like effect of SePB. Administration of the noradrenergic antagonists prazosin (1 mg/kg, i.p.), an α1-adrenergic antagonist, yohimbine (1 mg/kg, i.p.), an α2-adrenergic antagonist, and propranolol (2 mg/kg, i.p.), a ß-adrenergic antagonist, did not block the antidepressant-like effect of SePB on TST, indicating that noradrenergic receptors are not involved in this effect. Additionally, the coadministration of SePB and bupropion (a noradrenaline/dopamine reuptake inhibitor) at subeffective doses (0.1 and 3 mg/kg, respectively) produced antidepressant-like effects. SePB also demonstrated good oral bioavailability and low toxicity in computational absorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses. These findings suggest that SePB has potential as a new antidepressant drug candidate with a particular focus on the dopaminergic system.

N-(3-((3-(trifluoromethyl)phenyl)selanyl)prop-2-yn-1-yl) benzamide induces antidepressant-like effect in mice: involvement of the serotonergic system.

RATIONALE: Major Depressive Disorder (MDD) significantly impairs the quality of life for those affected. While the exact causes of MDD are not fully understood, the deficit of monoamines, especially serotonin and noradrenaline, is widely accepted. Resistance to long-term treatments and adverse effects are often observed, highlighting the need for new pharmacological therapies. Synthetic organic compounds containing selenium have exhibited pharmacological properties, including potential antidepressant effects. OBJECTIVE: To evaluate the antidepressant-like effect of N-(3-((3-(trifluoromethyl)phenyl)selenyl)prop-2-yn-1-yl) benzamide (CF3SePB) in mice and the involvement of the serotonergic and noradrenergic systems. METHODS: Male Swiss mice were treated with CF3SePB (1-50 mg/kg, i.g.) and 30 min later the forced swimming test (FST) or tail suspension test (TST) was performed. To investigate the involvement of the serotonergic and noradrenergic systems in the antidepressant-like effect of CF3SePB, mice were pre-treated with p-CPA (a 5-HT depletor, 100 mg/kg, i.p.) or the receptor antagonists WAY100635 (0.1 mg/kg, s.c., a 5-HT1A receptor antagonist), ketanserin (1 mg/kg, i.p., a 5-HT2A/2C receptor antagonist), ondansetron (1 mg/kg, i.p., a 5-HT3 receptor antagonist), GR110838 (0.1 mg/kg, i.p., a 5-HT4 receptor antagonist), prazosin (1 mg/kg, i.p., an α1-adrenergic receptor antagonist), yohimbine (1 mg/kg, i.p., an α2-adrenergic receptor antagonist) and propranolol (2 mg/kg, i.p., a non-selective beta-adrenergic receptor antagonist) at specific times before CF3SePB (50 mg/kg, i.g.), and after 30 min of CF3SePB administration the FST was performed. RESULTS: CF3SePB showed an antidepressant-like effect in both FST and TST and this effect was related to the modulation of the serotonergic system, specially the 5-HT1A and 5-HT3 receptors. None of the noradrenergic antagonists prevented the antidepressant-like effect of CF3SePB. The compound exhibited a low potential for inducing acute toxicity in adult female Swiss mice. CONCLUSION: This study pointed a new compound with antidepressant-like effect, and it could be considered for the development of new antidepressants.

1-(Phenylselanyl)-2-(p-tolyl)indolizine: A selenoindolizine with potential antidepressant-like activity in mice mediated by the modulation of dopaminergic and noradrenergic systems.

1-(Phenylselanyl)-2-(p-tolyl)indolizine (MeSeI) is a selenoindolizine with an antidepressant-like effect in mice by regulation of the serotonergic system. This study investigated the involvement of dopaminergic and noradrenergic systems in the antidepressant-like action of MeSeI. For this purpose, Swiss male mice were pretreated with different antagonists, after 15 min, the MeSeI was administrated by intragastric (i.g.) via; after 30 min, the mouse behavior was assessed in the forced swimming test (FST). The action of MeSeI on the activity of monoamine oxidase (MAO) was determined. The pretreatment of mice with haloperidol (0.05 mg/kg, intraperitoneally, i.p.; non-selective dopamine receptor antagonist), sulpiride (50 mg/kg, i.p.; D2 receptor antagonist), yohimbine (1 mg/kg, i.p.; α2 receptor antagonist), and propranolol (2 mg/kg, i.p.; non-selective ß receptor antagonist), inhibited the anti-immobility action of MeSeI (50 mg/kg, i.g.) in the FST. This blocking effect was not observed when SCH23390 (0.01 mg/kg, i.p.; D1 receptor antagonist), and prazosin (1 mg/kg, i.p.; α1 receptor antagonist) were administered. The coadministration of subeffective doses of bupropion (3 mg/kg. i.g.; dopamine and noradrenaline reuptake inhibitor) and MeSeI (0.5 mg/kg. i.g.) reduced the immobility time in the FST. Furthermore, MeSeI inhibited MAO-A and B activities in vitro and ex vivo tests. These results suggest that MeSeI exerts its antidepressant-like effect via regulation of the D2, α2, and ß1 receptors and the inhibition of MAO-A and B activities. Molecular docking investigations corroborated these results. This study provides comprehensive insights into the antidepressant-like mechanism of MeSeI in mice, suggesting its potential as a novel antidepressant candidate.

In Vitro Bactericidal Activity of Biogenic Copper Oxide Nanoparticles for Neisseria gonorrhoeae with Enhanced Compatibility for Human Cells.

Resistance to antibiotics and antimicrobial compounds is a significant problem for human and animal health globally. The development and introduction of new antimicrobial compounds are urgently needed, and copper oxide nanoparticles (CuO NPs) have found widespread application across various sectors including biomedicine, pharmacy, catalysis, cosmetics, and many others. What makes them particularly attractive is the possibility of their synthesis through biogenic routes. In this study, we synthesized biogenic green tea (GT, Camellia sinensis)-derived CuO NPs (GT CuO NPs) and examined their biophysical properties, in vitro toxicity for mammalian cells in culture, and then tested them against Neisseria gonorrhoeae, an exemplar Gram-negative bacterium from the World Health Organization's Priority Pathogen List. We compared our synthesized GT CuOP NPs with commercial CuO NPs (Com CuO NPs). Com CuO NPs were significantly more cytotoxic to mammalian cells (IC50 of 7.32 µg/mL) than GT CuO NPs (IC50 of 106.1 µg/mL). GT CuO NPs showed no significant increase in bax, bcl2, il6, and il1ß mRNA expression from mammalian cells, whereas there were notable rises after treatment with Com CuO NPs. GT-CuO NPs required concentrations of 0.625 and 3.125 µg/mL to kill 50 and 100% of bacteria, respectively, whereas Com-CuO NPs needed concentrations of 15.625 and 30 µg/mL to kill 50 and 100% of bacteria, and the antibiotic ceftriaxone killed 50 and 100% with 3.125 and 30 µg/mL. Gonococci could be killed within 30 min of exposure to GT CuO NPs and the NPs could kill up to 107 within 1 h. In summary, this is the first report to our knowledge that describes the bioactivity of biogenic CuO NPs against N. gonorrhoeae. Our data suggest that biogenic nanoparticle synthesis has significant advantages over traditional chemical routes of synthesis and highlights the potential of GT-CuO NPs in addressing the challenges posed by multidrug-resistant Neisseria gonorrhoeae infections.

Bacteria associated with the in hospite Symbiodiniaceae's phycosphere.

Symbiotic interactions between Symbiodiniaceae and bacteria are still poorly explored, especially those in hospite. Here, we adapted a technique that allows for the enrichment of intact and metabolically active in hospite Symbiodiniaceae cells (ihSC) and their associated bacteria from the tissue of the model coral Pocillopora damicornis, using a discontinuous gradient of solution of isotonic Percoll (SIP). The ihSC were concentrated in the 50% SIP fraction, as determined by microscopy. The presence of bacteria associated with ihSC was confirmed by fluorescence in situ hybridization, while microbiome analysis indicated that bacteria of the families Halieaceae, Flavobacteriaceae, and Alcanivoraceae are significantly associated with ihSC. Extracellular vesicles that could be exuding molecules were detected on the symbiosome membranes. Our technique and data contribute to elucidate ihSC-bacteria interactions.

Exploring the antioxidant potential of chalcogen-indolizines throughout in vitro assays.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are highly reactive molecules produced naturally by the body and by external factors. When these species are generated in excessive amounts, they can lead to oxidative stress, which in turn can cause cellular and tissue damage. This damage is known to contribute to the aging process and is associated with age-related conditions, including cardiovascular and neurodegenerative diseases. In recent years, there has been an increased interest in the development of compounds with antioxidant potential to assist in the treatment of disorders related to oxidative stress. In this way, compounds containing sulfur (S) and/or selenium (Se) have been considered promising due to the relevant role of these elements in the biosynthesis of antioxidant enzymes and essential proteins with physiological functions. In this context, studies involving heterocyclic nuclei have significantly increased, notably highlighting the indolizine nucleus, given that compounds containing this nucleus have been demonstrating considerable pharmacological properties. Thus, the objective of this research was to evaluate the in vitro antioxidant activity of eight S- and Se-derivatives containing indolizine nucleus and different substituents. The in vitro assays 1,1-diphenyl-2-picryl-hydrazil (DPPH) scavenger activity, ferric ion (Fe3+) reducing antioxidant power (FRAP), thiobarbituric acid reactive species (TBARS), and protein carbonylation (PC) were used to access the antioxidant profile of the compounds. Our findings demonstrated that all the compounds showed FRAP activity and reduced the levels of TBARS and PC in mouse brains homogenates. Some compounds were also capable of acting as DPPH scavengers. In conclusion, the present study demonstrated that eight novel organochalcogen compounds exhibit antioxidant activity.

Validation of NUTRIFICO Mnemonic as a Nutritional Approach and Breaking Dismal News in Palliative Care / Validação do Mnemônico NUTRIFICO como Abordagem Nutricional e Comunicação de Notícias Difíceis em Cuidados Paliativos / Validación del Mneumónico NUTRIFICO como Enfoque Nutricional y Comunicación de Noticias Difíciles en Cuidados Paliativos

A assistência nutricional em cuidados paliativos possui papel preventivo e visa assegurar as necessidades nutricionais do paciente na tentativa de auxiliar o controle dos sintomas, manter a hidratação satisfatória, ressignificar a alimentação, reduzir a ansiedade, retardar o desenvolvimento da caquexia, preservar o peso e a composição nutricional. Objetivo: Desenvolver e validar o mnemônico NUTRIFICO como abordagem de assistência nutricional e comunicação de notícias difíceis em cuidados paliativos. Método: Pesquisa de desenvolvimento e validação de conteúdo que utilizou a técnica Delphi com a aplicação do delineamento misto com abordagens qualitativas e quantitativas para a coleta e análise dos dados. Os participantes, nutricionistas com atuação em cuidados paliativos e/ou formação na área, foram recrutados por amostragem do tipo bola de neve. O percentual de concordância mínimo definido para validação foi de 80% pela escala Likert de cinco pontos. Resultados: Quarenta participantes, incluindo oito "sementes", foram convidados a participar do estudo. Destes, 16 assinaram o Termo de Consentimento Livre e Esclarecido (TCLE). A análise de conteúdo seguiu duas rodadas Delphi e foi obtida uma taxa de concordância superior a 80% entre os participantes para todos os componentes. A versão final do mnemônico NUTRIFICO resultou em dois princípios-chave, oito componentes e 12 recomendações. Conclusão: O mnemônico NUTRIFICO foi considerado válido quanto ao conteúdo e, portanto, pertinente à aplicação na abordagem nutricional e comunicação de notícias difíceis em cuidados paliativos.

Nutritional assistance in palliative care has a preventive role and seeks to ensure the patient's nutritional needs in an attempt to help to control the symptoms, maintain satisfactory hydration, reframe food, reduce anxiety, delay the development of cachexia, preserve weight and nutritional composition. Objective: To develop and validate the NUTRIFICO mnemonic as an approach to nutritional assistance and communication of dismal news in palliative care. Method: Research development and validation of content utilizing the Delphi technique with the application of a mixed design with qualitative and quantitative approaches for data collection and analysis. The participants, nutritionists with experience in palliative care and/or training in the area, were recruited by sampling using the snowball method. The minimum agreement percentage defined for validation was 80% on the five-point Likert scale. Results: Forty participants were invited to participate in the study, including eight "seeds" and 16 signed the Informed Consent Form (ICF). The content analysis followed two Delphi rounds, an agreement rate greater than 80% was obtained among participants for all the components. The final version of the NUTRIFICO mnemonic presented two key principles, eight components and twelve recommendations. Conclusion: The mnemonic NUTRIFICO was validated in terms of content and relevant for the application in the nutritional approach and communication of dismal news in palliative care

DHA-rich fish oil plays a protective role against experimental cerebral malaria by controlling inflammatory and mechanical events from infection.

Every year, thousands of children, particularly those under 5 years old, die because of cerebral malaria (CM). Following conventional treatment, approximately 25% of surviving individuals have lifelong severe neurocognitive sequelae. Therefore, improved conventional therapies or effective alternative therapies that prevent the severe infection are crucial. Omega-3 (Ω-3) polyunsaturated fatty acids (PUFAs) are known to have antioxidative and anti-inflammatory effects and protect against diverse neurological disorders, including Alzheimer's and Parkinson's diseases. However, little is known regarding the effects of Ω-3 PUFAs against parasitic infections. In this study, C57BL/6 mice received supplemental treatment of a fish oil rich in the Ω-3 PUFA, docosahexaenoic acid (DHA), which was started 15 days prior to infection with Plasmodium berghei ANKA and was maintained until the end of the study. Animals treated with the highest doses of DHA, 3.0 and 6.0 g/kg body weight, had 60 and 80% chance of survival, respectively, while all nontreated mice died by the 7th day postinfection due to CM. Furthermore, the parasite load during the critical period for CM development (5th to 11th day postinfection) was controlled in treated mice. However, after this period all animals developed high levels of parasitemia until the 20th day of infection. DHA treatment also effectively reduced blood-brain barrier (BBB) damage and brain edema and completely prevented brain hemorrhage and vascular occlusion. A strong anti-inflammatory profile was observed in the brains of DHA-treated mice, as well as, an increased number of neutrophil and reduced number of CD8+ T leukocytes in the spleen. Thus, this is the first study to demonstrate that the prophylactic use of DHA-rich fish oil exerts protective effects against experimental CM, reducing the mechanical and immunological events caused by the P. berghei ANKA infection.

Pharmacological and computational analysis of the involvement of the 5-HT4 receptor in the antidepressant-like effect of N-(3-(phenylselanyl)prop-2-yn-1-yl)benzamide in mice.

The serotonin type 4 receptor (5-HT4R)shows promise as a target for treating major depressive disorder (MDD). Studies have demonstrated that 5-HT4R agonists have a faster antidepressant-like effect compared to conventional medications. Developing drugs that modulate this receptor could lead to faster and more effective MDD treatments. The compound N-(3-(phenylselanyl)prop-2-yn-1-yl)benzamide (SePB) induces an antidepressant-like effect in mice. The present study explored if the 5-HT4R mediates SePB's antidepressant effect. For this, male Swiss mice were treated with GR113808 (0.1 mg/kg, intraperitoneally - i.p.), a 5-HT4R antagonist, and SePB (10 mg/kg, intragastrically - i.g), and then subjected to the tail-suspension test (TST) and open-field test (OFT). In silico tests were conducted to analyze SePB's binding affinity to the 5-HT4R and identify participating amino acid residues. The administration of GR113808 blocked the antidepressant-like effect of SePB in the TST without changing locomotor activity in the OFT. Moreover, SePB exhibited a high binding affinity between the 5-HT4R (-7.9 kcal/mol) and the amino acid residues Leu298, Asp100, Thr97, Arg96, Glu80, Leu81, Cys184, Val185, and Phe186 seem to be important for this interaction. The involvement of the 5-HT4R in the antidepressant-like effect of SePB suggests potential for novel therapies in MDD.

Synthesis of 1,2,3-Triazole-Containing Methoxylated Cinnamides and Their Antileishmanial Activity against the Leishmania braziliensis Species.

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.

Antidepressant-like Effect of 1-(2-(4-(4-Ethylphenyl)-1H-1,2,3-triazol-1-yl)phenyl)ethan-1-one in Mice: Evidence of the Contribution of the Serotonergic System.

Major depressive disorder (MDD) is a psychiatric disorder that affects a large portion of the population, with dysregulation of the serotonergic system, which is deeply involved in both the pathophysiology of MDD and mechanism of action of many antidepressants. Current pharmacological therapies do not meet the neurobiological needs of all depressed individuals, making the development of new antidepressants necessary. In recent decades, compounds containing triazoles have become promising due to their range of biological activities, including antidepressant activity. In this study, we evaluated the antidepressant-like effect of a hybrid containing triazole and acetophenone, 1-(2-(4-(4-ethylphenyl)-1H-1,2,3-triazol-1-yl)phenyl)ethan-1-one (ETAP) (0.5-5 mg/kg), in the forced swimming test (FST) and tail suspension test (TST) in mice, as well as the involvement of the serotonergic system in this effect. Our findings demonstrated that ETAP exhibited an antidepressant-like effect from the dose of 1 mg/kg and that this effect is modulated by 5-HT2A/2C and 5-HT4 receptors. We also demonstrated that this effect may be related to inhibition of monoamine oxidase A activity in the hippocampus. Additionally, we evaluated the in silico pharmacokinetic profile of ETAP, which predicted its penetration into the central nervous system. ETAP exhibited a low potential for toxicity at a high dose, making this molecule interesting for the development of a new therapeutic strategy for MDD.

Acute effects of high-intensity resistance training on central blood pressure parameters of elderly hypertensive women: a crossover clinical trial.

OBJECTIVE: Assess the acute effects of a high-intensity resistance training session on central blood pressure (CBP) parameters of elderly hypertensive women. METHODS: Forty physically active hypertensive women were included in resistance training and control protocols. Resistance training exercises were bench press, leg press and lat pull-down. The resistance training protocol consisted of three sets of 10 repetitions to volitional failure with 90 s of rest between sets. No exercise was performed in the control protocol. CBP parameters were measured in four moments: before (PRE), immediately after (T0), 30 min (T30) and 60 min (T60) following both protocols. RESULTS: Resistance training significantly increased central SBP (cSBP) 107.4 ±â€Š16.3 vs. 117.5 ±â€Š16.7), augmentation index ((24.9 ±â€Š12.7 vs. 33.1 ±â€Š12.0), pulse wave velocity (PWV 9.7 ±â€Š1.0 vs. 10.3 ±â€Š1.1), peripheral pulse pressure (pPP 48.5 ±â€Š11.7 vs. 58.9 ±â€Š13.1), central pulse pressure (cPP 38.3 ±â€Š11.6 vs. 46.5 ±â€Š13.1) and amplified pulse pressure (ampPP 10.2 ±â€Š4.2 vs. 12.4 ±â€Š5.6) immediately after exercises. The comparison between groups showed higher values of cSBP (117.5 ±â€Š16.7 vs. 106.3 ±â€Š14.6), augmentation index (20.9 ±â€Š11.0 vs. 33.1 ±â€Š12.0), pPP (46.6 ±â€Š11.0 vs. 58.9 ±â€Š13.1) and cPP (36 ±â€Š10.2 vs. 46.5 ±â€Š13.1) at T0. After 30 min, all variables returned to the baseline values. CONCLUSION: High-intensity resistance training session increased CBP parameters immediately after exercises, but those changes were not sustained after 30 min.

Involvement of the serotonergic system in the antidepressant-like effect of 1-(phenylselanyl)-2-(p-tolyl)indolizine in mice.

RATIONALE: Depression is a mental disorder that affects approximately 280 million people worldwide. In the search for new treatments for mood disorders, compounds containing selenium and indolizine derivatives show promising results. OBJECTIVES AND METHODS: To evaluate the antidepressant-like effect of 1-(phenylselanyl)-2-(p-tolyl)indolizine (MeSeI) (0.5-50 mg/kg, intragastric-i.g.) on the tail suspension test (TST) and the forced swim test (FST) in adult male Swiss mice and to elucidate the role of the serotonergic system in this effect through pharmacological and in silico approaches, as well to evaluate acute oral toxicity at a high dose (300 mg/kg). RESULTS: MeSeI administered 30 min before the FST and the TST reduced immobility time at doses from 1 mg/kg and at 50 mg/kg and increased the latency time for the first episode of immobility, demonstrating an antidepressant-like effect. In the open field test (OFT), MeSeI did not change the locomotor activity. The antidepressant-like effect of MeSeI (50 mg/kg, i.g.) was prevented by the pre-treatment with p-chlorophenylalanine (p-CPA), a selective tryptophan hydroxylase inhibitor (100 mg/kg, intraperitoneally-i.p. for 4 days), with ketanserin, a 5-HT2A/2C receptor antagonist (1 mg/kg, i.p.), and with GR113808, a 5-HT4 receptor antagonist (0.1 mg/kg, i.p.), but not with WAY100635, a selective 5-HT1A receptor antagonist (0.1 mg/kg, subcutaneous-s.c.) and ondansetron, a 5-HT3 receptor antagonist (1 mg/kg, i.p.). MeSeI showed a binding affinity with 5-HT2A, 5 -HT2C, and 5-HT4 receptors by molecular docking. MeSeI (300 mg/kg, i.g.) demonstrated low potential to cause acute toxicity in adult female Swiss mice. CONCLUSION: In summary, MeSeI exhibits an antidepressant-like effect mediated by the serotonergic system and could be considered for the development of new treatment strategies for depression.

Ultrastructural changes induced by açaí (Euterpe oleracea Mart) in MCF-7 breast cancer cell line.

Açaí (Euterpe oleracea Mart) is an Amazon plant with many biological properties. Previous report of this group evidenced autophagy induction after treatment with açaí seed extract in MCF-7 breast cancer cell lines by acridine orange assay. The aim of this study was to evaluate the ultrastructural changes induced by açaí seed extract in MCF-7 breast cancer cell lines. First, MCF- 7 breast cancer cell line viability was evaluated by MTT assay. Acridine orange assay showed increase in the acidic compartments, suggesting autophagolysosome formation. These cells were treated with 25 µg/ml for 24 h and evaluated by transmission electron microscopy (MET). This analysis showed that açaí seed extract induced autophagy, confirmed by autophagolysosome formation. Furthermore, açaí seed extract increased the number of mitochondria, suggesting the enrollment of reactive oxygen species in autophagy.

HIIE Protocols Promote Better Acute Effects on Blood Glucose and Pressure Control in People with Type 2 Diabetes than Continuous Exercise.

This study compared the acute effects of a session of different high-intensity interval exercise (HIIE) protocols and a session of moderate-intensity continuous exercise (MICE) on blood glucose, blood pressure (BP), and heart rate (HR) in people with Type 2 Diabetes Mellitus (DM2). The trial included 44 participants (age: 55.91 ± 1.25 years; BMI: 28.95 ± 0.67 kg/m2; Hb1Ac: 9.1 ± 2.3%; 76 mmol/mol) randomized into three exercise protocols based on the velocity at which maximum oxygen consumption was obtained (vVO2 max): long HIIE (2 min at 100% vV̇o2peak + 2 min of passive rest); short HIIE (30 s at 100% vV̇o2peak + 30 s of passive rest); or MICE (14 min at 70% vV̇o2peak) on a treadmill. Capillary blood glucose, BP, and HR measurements were taken at rest, during peak exercise, immediately after the end of exercise, and 10 min after exercise. Long and short HIIE protocols reduced capillary blood glucose by 32.14 mg/dL and 31.40 mg/dL, respectively, and reduced systolic BP by 12.43 mmHg and 8.73 mmHg, respectively. No significant changes were observed for MICE. HIIE was found to promote more acute effects than MICE on glycemia and BP in people with DM2.

High-Intensity Interval Training Improves Cardiac Autonomic Function in Patients with Type 2 Diabetes: A Randomized Controlled Trial.

Different exercise models have been used in patients with type 2 diabetes mellitus (T2D), like moderate intensity continuous training (MICT) and high intensity interval training (HIIT); however, their effects on autonomic modulation are unknown. The present study aimed to compare the effects of different exercise modes on autonomic modulation in patients with T2D. In total, 44 adults with >5 years of T2D diagnosis were recruited and stratified into three groups: HIIT-30:30 (n = 15, age 59.13 ± 5.57 years) that performed 20 repetitions of 30 s at 100% of VO2peak with passive recovery, HIIT-2:2 (n = 14, age 61.20 ± 2.88) that performed 5 repetitions of 2 min at 100% of VO2peak with passive recovery, and MICT (n = 15, age 58.50 ± 5.26) that performed 14 min of continuous exercise at 70% of VO2peak. All participants underwent anamnesis and evaluation of cardiorespiratory fitness and cardiac autonomic modulation. All protocols were equated by total distance and were performed two times per week for 8 weeks. Group × time interactions were observed for resting heart rate (HRrest) [F(2.82) = 3.641; p = 0.031] and SDNN [F(2.82) = 3.462; p = 0.036]. Only the HIIT-30:30 group significantly reduced SDNN (p = 0.002 and 0.025, respectively). HRrest reduced more in the HIIT-30:30 group compared with the MICT group (p = 0.038). Group × time interactions were also observed for offTAU [F(2.82) = 3.146; p = 0.048] and offTMR [F(2.82) = 4.424; p = 0.015]. The MICT group presented increased values of offTAU compared with the HIIT-30:30 and HIIT-2:2 groups (p = 0.001 and 0.013, respectively), representing a slower HR response after eight weeks of intervention. HIIT, specially HIIT-30:30, represents a promising measure for improving autonomic modulation in patients with T2D.

Inhalation of dimethyl fumarate-encapsulated solid lipid nanoparticles attenuate clinical signs of experimental autoimmune encephalomyelitis and pulmonary inflammatory dysfunction in mice.

RATIONALE: The FDA-approved Dimethyl Fumarate (DMF) as an oral drug for Multiple Sclerosis (MS) treatment based on its immunomodulatory activities. However, it also caused severe adverse effects mainly related to the gastrointestinal system. OBJECTIVE: Investigated the potential effects of solid lipid nanoparticles (SLNs) containing DMF, administered by inhalation on the clinical signs, central nervous system (CNS) inflammatory response, and lung function changes in mice with experimental autoimmune encephalomyelitis (EAE). MATERIALS AND METHODS: EAE was induced using MOG35-55 peptide in female C57BL/6J mice and the mice were treated via inhalation with DMF-encapsulated SLN (CTRL/SLN/DMF and EAE/SLN/DMF), empty SLN (CTRL/SLN and EAE/SLN), or saline solution (CTRL/saline and EAE/saline), every 72 h during 21 days. RESULTS: After 21 days post-induction, EAE mice treated with DMF-loaded SLN, when compared with EAE/saline and EAE/SLN, showed decreased clinical score and weight loss, reduction in brain and spinal cord injury and inflammation, also related to the increased influx of Foxp3+ cells into the spinal cord and lung tissues. Moreover, our data revealed that EAE mice showed signs of respiratory disease, marked by increased vascular permeability, leukocyte influx, production of TNF-α and IL-17, perivascular and peribronchial inflammation, with pulmonary mechanical dysfunction associated with loss of respiratory volumes and elasticity, which DMF-encapsulated reverted in SLN nebulization. CONCLUSION: Our study suggests that inhalation of DMF-encapsulated SLN is an effective therapeutic protocol that reduces not only the CNS inflammatory process and disability progression, characteristic of EAE disease, but also protects mice from lung inflammation and pulmonary dysfunction.

High Fasting Glycemia Predicts Impairment of Cardiac Autonomic Control in Adults With Type 2 Diabetes: A Case-Control Study.

Introduction: Type 2 diabetes (T2D) is characterized by a metabolic disorder that elevates blood glucose concentration. Chronic hyperglycemia has been associated with several complications in patients with T2D, one of which is cardiac autonomic dysfunction that can be assessed from heart rate variability (HRV) and heart rate recovery (HRR) response, both associated with many aspects of health and fitness, including severe cardiovascular outcomes. Objective: To evaluate the effects of T2D on cardiac autonomic modulation by means of HRV and HRR measurements. Materials and Methods: This study has an observational with case-control characteristic and involved ninety-three middle-aged adults stratified into two groups (control group - CG, n = 34; diabetes group - DG, n = 59). After signing the free and informed consent form, the patients were submitted to the evaluation protocols, performed biochemical tests to confirm the diagnosis of T2D, collection of R-R intervals for HRV analysis and cardiopulmonary effort test to quantify HRR. Results: At rest, the DG showed a reduction in global HRV (SDNN= 19.31 ± 11.72 vs CG 43.09 ± 12.74, p < 0.0001), lower parasympathetic modulation (RMSSD= 20.49 ± 14.68 vs 52.41 ± 19.50, PNN50 = 4.76 ± 10.53 vs 31.24 ± 19.24, 2VD%= 19.97 ± 10.30 vs 28.81 ± 9.77, p < 0.0001 for both indices) and higher HRrest when compared to CG. After interruption of physical exercise, a slowed heart rate response was observed in the DG when compared to the CG. Finally, a simple linear regression showed that fasting glycemia was able to predict cardiac autonomic involvement in volunteers with T2D. Conclusion: Patients with T2D presented lower parasympathetic modulation at rest and slowed HRR after physical exercise, which may be associated with higher cardiovascular risks. The findings show the glycemic profile as an important predictor of impaired cardiac autonomic modulation.