Search

Male and female rats were treated daily for 13 weeks with an ethanol extract of Cissampelos sympodialis leaves (9, 45 and 225 mg[sol ]kg). The food consumption, body weight and behavioural effects in the open-field test were evaluated by weekly monitoring. The results showed that the extract chronic treatment in female rats (45 and 225 mg[sol ]kg) reduced significantly the food intake and the body weight, and produced several alterations in the open-field test. These findings indicate that repeated oral administration of the extract may produce a sex-dependent difference in anoretic and behavioural effects. [ABSTRACT FROM AUTHOR]

The acute treatment of mice with an ethanolic extract from the seed pod of Dioclea grandiflora (EDgP) at doses of 75, 150 and 300 mg/kg by intraperitoneal administration produced a significant antinociceptive effect as displayed by the acetic acid-induced writhing test and the formalin test. The antinociception was observed through the first (neurogenic pain) and second (inflammatory pain) phases in the formalin test. The hot plate test did not show an increase in the antinociceptive latency whereas the motor performance was affected by the administration at 300 mg/kg at the beginning (30 minutes) of the observation period but not at later periods (60 and 120 minutes). These results suggest that EDgP has a central antinociceptive action and a possible anti-inflammatory activity in mice. [ABSTRACT FROM AUTHOR]

Nitrogen (N) availability plays a crucial role in plant development. However, studies indicate that the pathosystem of pathogenic fungi, such as Bipolaris maydis , which causes Southern Corn Leaf Blight (SCLB) in popcorn, interacts with N availability. Therefore, this study seeks to select popcorn inbred lines (ILs), considering contrasting environments regarding N availability (low N-LN and optimal N-ON). For this, 90 ILs from 16 populations from tropical and temperate climates from South America were evaluated in five experiments using a randomized complete block design (three replications), with four common controls. From the tests, the level of severity of the ILs to SCLB was evaluated. Three trials showed greater severity in ON, one trial had higher severity in LN, and one trial did not show significant differences. However, the genotype x nitrogen level (GxN) interaction was always present. Of the 90 ILs, 73 showed resistance in both N levels, three only in LN, and four only in ON, while 10 were susceptible in both environments. On average, the lines were more susceptible in ON, and the observed GxN interactions indicate that there is a distinct behavior of the genotypes regarding the response to N in the soil, which reinforces the importance of selection in contrasting environments.

This study aimed to develop, assess, and test an Objective Structured Clinical Examination (OSCE) to evaluate nurses' competency in planning and managing infusion therapy. The study adopted a methodological approach with a quantitative design and was conducted from December 2020 to August 2021 at a university hospital in São Paulo, Brazil. Data collection occurred in 3 stages: development of scenarios and assessment checklists, evaluation of expert consensus, and testing scenarios with the target audience. Data analysis involved calculating the Modified Kappa coefficient. The OSCE comprised 8 clinical stations, designed based on the theoretical framework of the Vessel Health and Preservation model and the Infusion Therapy Standards of Practice, which delineate evidence-based procedures for vascular access and infusion therapy. During expert assessment and examination testing, all evaluated items demonstrated coefficient values ≥0.74. Thus, the study successfully developed evidence-based OSCE for infusion therapy, showing strong expert consensus. Testing with nurses yielded positive outcomes, affirming the effectiveness of the educational practice's design and structure., Competing Interests: Conflict of Interest:The authors report no conflicts of interest., (Copyright © 2025 Infusion Nurses Society.)

Background/Objectives: Degradation by physical and chemical agents affects the properties of essential oils; therefore, this study aimed to protect the volatile compounds present in essential oils through biopolymer encapsulation. Methods: The Achyrocline satureioides (Lam) DC. essential oil was obtained by steam distillation at 2.5 bar. The nano-sized physical coating of the active oil core resulted in an optimal polymer/oil ratio of 1:3 and particle diameter of 178 nm. The particle morphology was evaluated using scanning electron microscopy and transmission electron microscopy. The inclusion of the essential oil in the polymer was confirmed using thermogravimetric analysis. Results: The pH of the formulation remained stable for 90 days, and controlled release and encapsulation efficiencies were evaluated. Formulations were evaluated using the perfumery radar technique, which indicated a predominantly woody profile. The diffusion of fragrant compounds in the air was assessed over time and mathematically modeled. Conclusions: The produced nanostructures were efficient for the controlled release of volatile compounds from the essential oil of Achyrocline satureioides .

The objective of this study was to evaluate the genetic diversity among traditional common bean accessions through morphological descriptors and molecular markers. Sixty-seven common bean accessions from the Germplasm bank of the Instituto Federal of Espírito Santo-Campus de Alegre were evaluated. For this, 25 specific morphological descriptors were used, namely 12 quantitative and 13 qualitative ones. A diversity analysis based on morphological descriptors was carried out using the Gower algorithm. For molecular characterization, 23 ISSR primers were used to estimate dissimilarity using the Jaccard Index. Based on the dendrograms obtained by the UPGMA method, for morphological and molecular characterization, high genetic variability was observed between the common bean genotypes studied, evidenced by cophenetic correlation values in the order of 0.99, indicating an accurate representation of the dissimilarity matrix by the UPGMA clustering. In the morphological characterization, high phenotypic diversity was observed between the accessions, with grains of different shapes, colors, and sizes, and the accessions were grouped into nine distinct groups. Molecular characterization was efficient in separating the genotypes in the Andean and Mesoamerican groups, with the 23 ISSR primers studied generating an average of 6.35 polymorphic bands. The work identified divergent accessions that can serve different market niches, which can be indicated as parents to form breeding programs in order to obtain progenies with high genetic variability.

Epilepsy, a chronic neurological disorder characterized by recurrent unprovoked seizures, presents a substantial challenge in approximately one-third of cases exhibiting resistance to conventional pharmacological treatments. This study investigated the effect of 4-allyl-2,6-dimethoxyphenol, a phenolic compound derived from various natural sources, in different models of induced seizures and its impact on animal electroencephalographic (EEG) recordings. Adult male Swiss albino mice were pre-treated (i.p.) with a dose curve of 4-allyl-2,6-dimethoxyphenol (50, 100, or 200 mg/kg), its vehicle (Tween), or standard antiepileptic drug (Diazepam; or Phenytoin). Subsequently, the mice were subjected to different seizure-inducing models - pentylenetetrazole (PTZ), 3-mercaptopropionic acid (3-MPA), pilocarpine (PILO), or maximal electroshock seizure (MES). EEG analysis was performed on other animals surgically implanted with electrodes to evaluate brain activity. Significant results revealed that animals treated with 4-allyl-2,6-dimethoxyphenol exhibited increased latency to the first myoclonic jerk in the PTZ and PILO models; prolonged latency to the first tonic-clonic seizure in the PTZ, 3-MPA, and PILO models; reduced total duration of tonic-clonic seizures in the PTZ and PILO models; decreased intensity of convulsive seizures in the PTZ and 3-MPA models; and diminished mortality in the 3-MPA, PILO, and MES models. EEG analysis indicated an increase in the percentage of total power attributed to beta waves following 4-allyl-2,6-dimethoxyphenol administration. Notably, the substance protected from behavioral and electrographic seizures in the PTZ model, preventing increases in the average amplitude of recording signals while also inducing an increase in the participation of theta and gamma waves. These findings suggest promising outcomes for the tested phenolic compound across diverse pre-clinical seizure models, highlighting the need for further comprehensive studies to elucidate its underlying mechanisms and validate its clinical relevance in epilepsy management., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest, financial or personal, that could have influenced the findings presented in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This is a nonclinical, controlled, and triple-blind study to investigate the effects of codeine-associated geraniol on the modulation of orofacial nociception and its potential central nervous system depressing effect in an animal model. The orofacial antinociceptive activity of geraniol in combination with codeine was assessed through the following tests: (i) formalin-induced pain, (ii) glutamate-induced pain, and (iii) capsaicin-induced pain. Six animals were equally distributed into six groups and received the following treatments, given intraperitoneally (i.p.) 30 minutes before the experiments: a) geraniol/codeine 50/30 mg/kg; b) geraniol/codeine 50/15 mg/kg; c) geraniol/codeine 50/7.5 mg/kg; d) geraniol 50 mg/kg; e) codeine 30 mg/kg (positive control); or f) 0.9% sodium chloride (negative control). We performed pain behavior analysis after the injection of formalin (20 µL, 20%), glutamate (20 µL, 25 µM), and capsaicin (20 µL, 2.5 µg) into the paranasal region. Rubbing time of the paranasal region by the hind or front paw was used as a parameter. In the neurogenic phase of the formalin test, the geraniol/codeine at 50/7.5 mg/kg was able to promote the maximum antinociceptive effect, reducing nociception by 71.9% (p < 0.0001). In the inflammatory phase of the formalin test, geraniol/codeine at 50/30 mg/kg significantly reduced orofacial nociception (p < 0.005). In the glutamate test, geraniol/codeine at 50/30 mg/kg reduced the rubbing time by 54.2% and reduced nociception in the capsaicin test by 66.7% (p < 0.005). Geraniol alone or in combination does not promote nonspecific depressing effects on the central nervous system. Based on our findings, we suggest the possible synergy between geraniol and codeine in the modulation of orofacial pain.

Tetrahydrolinalool (THL) is an acyclic monoterpene alcohol, produced during linalol metabolism and also a constituent of essential oils. As described in the literature, many monoterpenes present anticonvulsant properties, and thus we became interested in evaluating the anticonvulsant activity of Tetrahydrolinalool using in mice model as well as in silico approaches. Our results demonstrated that THL increased latency to seizure onset and also reduced the mortality, in picrotoxin induced seizure tests. The results may be related to GABAergic regulation, which was also suggested in seizure testing induced by 3-mercapto-propionic acid. In the strychnine-induced seizure testing, none of the groups pretreated with THL modulated the parameters indicative of anticonvulsant effect. The electrophysiological results revealed that THL treatment reduces seizures induced by pentylenetetrazole. The in silico molecular docking studies showed that the interaction between THL and a GABAA receptor model formed a stable complex, in comparison to the crystaligraphic structure of diazepam, a structurally related ligand. In conclusion, all the evidences showed that THL presents effective anticonvulsant activity related to the GABAergic pathway, being a candidate for treatment of epileptic syndromes., (© 2024 Wiley-VCH GmbH.)

Pterocaulon polystachyum is a species of pharmacological interest for providing volatile and non-volatile extracts with antifungal and amebicidal properties. The biological activities of non-volatile extracts may be related to the presence of coumarins, a promising group of secondary metabolites. In the present study, leaves and inflorescences previously used for the extraction of essential oils instead of being disposed of were subjected to extraction with supercritical CO 2 after pretreatment with microwaves. An experimental design was followed to seek the best extraction condition with the objective function being the maximum total extract. Pressure and temperature were statistically significant factors, and the optimal extraction condition was 240 bar, 60 °C, and pretreatment at 30 °C. The applied mathematical models showed good adherence to the experimental data. The extracts obtained by supercritical CO 2 were analyzed and the presence of coumarins was confirmed. The extract investigated for cytotoxicity against bladder tumor cells (T24) exhibited significant reduction in cell viability at concentrations between 6 and 12 μg/mL. The introduction of green technology, supercritical extraction, in the exploration of P. polystachyum as a source of coumarins represents a paradigm shift with regard to previous studies carried out with this species, which used organic solvents. Furthermore, the concept of circular bioeconomy was applied, i.e., the raw material used was the residue of a steam-distillation process. Therefore, the approach used here is in line with the sustainable exploitation of native plants to obtain extracts rich in coumarins with cytotoxic potential against cancer cells.

Rationale: Recently, we demonstrated that the activation of the nociceptin/orphanin FQ (N/OFQ) receptor (NOP) signaling facilitates depressive-like behaviors. Additionally, literature findings support the ability of the N/OFQ-NOP system to modulate the hypothalamic-pituitary-adrenal (HPA) axis., Objectives: Considering that dysfunctional HPA axis is strictly related to stress-induced psychopathologies, we aimed to study the role of the HPA axis in the pro-depressant effects of NOP agonists., Methods: Mice were treated prior to stress with the NOP agonist Ro 65-6570, and immobility time in the forced swimming task and corticosterone levels were measured. Additionally, the role of endogenous glucocorticoids and CRF was investigated using the glucocorticoid receptor antagonist mifepristone and the CRF 1 antagonist antalarmin in the mediation of the effects of Ro 65-6570., Results: The NOP agonist in a dose-dependent manner further increased the immobility of mice in the second swimming session compared to vehicle. By contrast, under the same conditions, the administration of the NOP antagonist SB-612111 before stress reduced immobility, while the antidepressant nortriptyline was inactive. Concerning in-serum corticosterone in mice treated with vehicle, nortriptyline, or SB-612111, a significant decrease was observed after re-exposition to stress, but no differences were detected in Ro 65-6570-treated mice. Administration of mifepristone or antalarmin blocked the Ro 65-6570-induced increase in the immobility time in the second swimming session., Conclusions: Present findings suggest that NOP agonists increase vulnerability to depression by hyperactivating the HPA axis and then increasing stress circulating hormones and CRF 1 receptor signaling., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We investigated whether mood and lifestyle-related indicators of physical health are differentially expressed according to self-reported levels of depressive symptoms among young adults with a current episode of major depression. In a cross-sectional study, we recruited 94 young adults (females = 67, 71.3%; males = 27, 28.7%; aged 18-35 years) with a current episode of major depression. We assessed their mood with the Profile of Mood States (POMS), and Beck Anxiety Inventory-(BAI), sleep with the Pittsburgh Sleep Quality Index (PSQI), physical activity with the Simple Physical Activity Questionnaire (SIMPAQ), and their cardiorespiratory fitness. Participants' depression levels were classified as follows using established cut-points: (a) Mild Depressive Symptoms (MIDS, BDI-II 14-19 points, n = 17), (b) Moderate Depressive Symptoms (MODS, BDI-II 20-28 points, n = 37) or (c) Severe Depressive Symptoms (SEDS, BDI-II 29-63 points, n = 40). As expected, we found that young adults with SEDS, when compared to those with MODS and MIDS, showed higher depressive mood on the POMS, and they exhibited greater anxiety symptoms, lower reported 'vigor' on physical activity measures, worse sleep quality as expressed by their global score sleep; daytime dysfunction; and sleep disturbance, and they showed lower cardiorespiratory fitness. Those with moderate depressive symptoms only differed from those with mild symptoms with respect to hostility, fatigue and mood disturbance. Although there was a gradient whereby worse mental and physical health indicators were more closely related to the SEDS depression categorization, while healthier indicators were associated with the MIDS category, some parameters were not different between the MDD severity groups, particularly when comparing MIDS and MODS. Clinicians treating patients with MDD should consider these factors when designing lifestyle-based interventions., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Pain is characterized by the unpleasant sensory and emotional sensation associated with actual or potential tissue damage, whereas nociception refers to the mechanism by which noxious stimuli are transmitted from the periphery to the CNS. The main drugs used to treat pain are nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics, which have side effects that limit their use. Therefore, in the search for new drugs with potential antinociceptive effects, essential oils have been studied, whose constituents (monoterpenes) are emerging as a new therapeutic possibility. Among them, linalool and its metabolites stand out. The present study aims to investigate the antinociceptive potential of linalool and its metabolites through a screening using an in silico approach. Molecular docking was used to evaluate possible interactions with important targets involved in antinociceptive activity, such as α 2 -adrenergic, GABAergic, muscarinic, opioid, adenosinergic, transient potential, and glutamatergic receptors. The compounds in the investigated series obtained negative energies for all enzymes, representing satisfactory interactions with the targets and highlighting the multi-target potential of the L4 metabolite. Linalool and its metabolites have a high likelihood of modulatory activity against the targets involved in nociception and are potential candidates for future drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Brain tumors have high morbidity and mortality rates, accounting for 1.4% of all cancers. Gliomas are the most common primary brain tumors in adults. Currently, several therapeutic approaches are used; however, they are associated with side effects that affect patients'quality of life. Therefore, further studies are needed to develop novel therapeutic protocols with a more favorable side effect profile. In this context, cannabinoid compounds may serve as potential alternatives., Objective: This study aimed to review the key enzymatic targets involved in glioma pathophysiology and evaluate the potential interaction of these targets with four cannabinoid derivatives through molecular docking simulations., Methods: Molecular docking simulations were performed using four cannabinoid compounds and six molecular targets associated with glioma pathophysiology., Results: Encouraging interactions between the selected enzymes and glioma-related targets were observed, suggesting their potential activity through these pathways. In particular, cannabigerol showed promising interactions with epidermal growth factor receptors and phosphatidylinositol 3- kinase, while Δ-9-tetrahydrocannabinol showed remarkable interactions with telomerase reverse transcriptase., Conclusion: The evaluated compounds exhibited favorable interactions with the analyzed enzymatic targets, thus representing potential candidates for further in vitro and in vivo studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Ethanol (EtOH) exposure during late pregnancy leads to enduring impairments in learning and memory that may stem from damage to components of the posterior limbic memory system, including the retrosplenial cortex (RSC) and anterior thalamic nuclei (ATN). In rodents, binge-like EtOH exposure during the first week of life (equivalent to the third trimester of human pregnancy) triggers apoptosis in these brain regions. We hypothesized that this effect induces long-lasting alterations in the function of RSC-projecting ATN neurons. To test this hypothesis, vesicular GABA transporter-Venus mice (expressing fluorescently tagged GABAergic interneurons) were subjected to binge-like EtOH vapor exposure on postnatal day (P) 7. This paradigm activated caspase 3 in the anterodorsal (AD), anteroventral (AV), and reticular thalamic nuclei at P7 but did not reduce neuronal density in these areas at P60-70. At P40-60, we injected red retrobeads into the RSC and performed patch-clamp slice electrophysiological recordings from retrogradely labeled neurons in the AD and AV nuclei 3-4 days later. We found significant effects of treatment on instantaneous action potential (AP) frequency and AP overshoot, as well as sex × treatment interactions for AP threshold and overshoot in AD neurons. A sex × treatment interaction was detected for AP number in AV neurons. EtOH exposure also reduced the frequency and amplitude of spontaneous excitatory postsynaptic currents and increased the charge transfer of spontaneous inhibitory postsynaptic currents. These results highlight a novel cellular mechanism that could contribute to the lasting learning and memory deficits associated with developmental EtOH exposure., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Major depressive disorder is a severe mood disorder characterized by different emotions and feelings. This study investigated the antidepressant activity of the phenylpropanoid methyleugenol (ME) in adult female mice exposed to a stress model induced by dexamethasone. The animals were randomly divided into groups containing eight animals and were pre-administered with dexamethasone (64 μg/kg subcutaneously). After 165 and 180 min, they were treated with ME (25, 50 and 100 mg/kg intraperitoneally) or imipramine (10 mg/kg intraperitoneally) after 45 min and 30 min, respectively; they were then submitted to tests which were filmed. The videos were analyzed blindly. In the tail suspension test, ME (50 mg/kg) increased latency and reduced immobility time. In the splash test, ME (50 mg/kg) decreased grooming latency and increased grooming time. In the open field, there was no statistical difference for the ME groups regarding the number of crosses, and ME (50 mg/kg) increased the number of rearing and time spent in the center. Regarding in silico studies, ME interacted with dopaminergic D1 and α1 adrenergic pathway receptors and with tryptophan hydroxylase inhibitor. In the in vivo evaluation of the pathways of action, the antidepressant potential of ME (50 mg/kg) was reversed by SCH23390 (4 mg/kg intraperitoneally) dopaminergic D1 receptor, Prazosin (1 mg/kg intraperitoneally) α1 adrenergic receptor, and PCPA (4 mg/kg intraperitoneally) tryptophan hydroxylase inhibitor. Our findings indicate that ME did not alter with the locomotor activity of the animals and shows antidepressant activity in female mice with the participation of the D1, α1 and serotonergic systems.

Purpose: This study aimed to analyze the effects of training load on stress tolerance (ST) and secretory immunoglobulin A (SIgA) in male and female high-intensity functional fitness (HIFF) athletes during two different 10 and consecutive weekly training volume loads [higher (week 1) and lower volume (week 2)]. Methods: 14 athletes [7 males: 29.3 (±5.8) years; 86.3 (±8.2) kg and 176.8 (±3.8) cm and 7 females: 32.7 (±4.4) years; 60.0 (±6.7) kg and 162.5 (±5.9) cm] participated. The ST, assessed by Daily Analysis of Life Demand in Athletes questionnaire (DALDA) and Saliva sampling were performed in four time-points (pre (T1) and post (T2) week 1; pre (T3) and post (T4) week 2). Results: Female athletes showed a decrease in ST (symptoms of stress) from 15 T1 to T3 [F (3,36) = 7.184, p ˂ 0.001, ηp 2 = 0.374], without difference in male athletes ( p > .05). There is a significant difference of SIgA concentration [F (3.36) = 3.551; p = .024; ηp 2 = 0.228], with a significant decrease in female athletes group in T2 compared to T1 ( p = .013) and T4 ( p = .023). In addition, the different training volume loads did not impact mucosal immunity in male athletes ( p > .05). Conclusion: The current findings suggest that higher HIFF volume results in decreased ST and SIgA concentration in female 20 athletes and a subsequent decrease in training volume loads contributed to restoring these variables.

Due to the complex nature of pain and the participation of physical, cognitive, psychological and behavioral aspects, pain management has several approaches. The use of medicinal plants in developing countries is quite expressive. Seeking new options for the treatment of emerging or debilitating diseases. Therefore, the present study seeks to elucidate the effects of the monoterpene, citronellal, differentiating its activity by isomers (R)-(+) and (S)-(-) citronellal. The study used several methods to evaluate the effects of citronellal isomers on motor coordination, nociceptive response, and the involvement of opioid, glutamatergic, and transient receptor pathways. The methods included rota-rod, hot-plate, and formalin tests, as well as the use of specific inhibitors and agonists. Data were analyzed using inferential statistics with a 95% confidence level. Both isomers did not significantly affect the motor coordination of the studied animals. The isomer (S)-(-) citronellal showed better results in relation to its structural counterpart, managing to have an antinociceptive effect in the formalin and hot plate tests with a lower concentration (100 mg/kg) and presenting fewer side effects, however, the this study was not able to elucidate the mechanism of action of this isomer despite having activity in studies with substances that act on specific targets such as glutamate and capsaicin, its activity was not reversed with the use of antagonists for pathways related to nociception. While the (R)-(+) citronellal isomer, despite showing total activity only at a concentration of 150 mg/kg, was able to determine its mechanism of action related to the opioid pathway by reversing its activity by the antagonist naloxone, being this is a pathway already correlated with nociception control treatments, however, it is also related to some unwanted side effects. In this way, new studies are sought to elucidate the mechanism related to the isomer (S)-(-) citronellal and a possibility of use in other areas related to the treatment of pain or inflammation.

This bibliometric analysis aims to analyze the global scientific production of COVID-19 and vaccines. First, a search for scientific articles was performed using the advanced query in the Web of Science™ database, more precisely in its core collection, on 18 February 2023. Data from 7754 articles were analyzed using the Bibliometrix R package and the Biblioshiny application. The evaluated articles were published mainly in 2022 (60%). The scientific journals that published the most about COVID-19 and vaccines were "Vaccines", "Vaccine" and "Human Vaccines & Immunotherapeutics". The University of Oxford was the most productive institution, with the authors of the articles mainly originating from the United States, China and the United Kingdom. The United States, despite having carried out the most significant number of collaborations, published mainly with local researchers. The 15 most cited articles and the KeyWords Plus™ evidenced the focus of the published articles on the safety and efficacy of vaccines against COVID-19, as well as on the evaluation of vaccine acceptance, more specifically on vaccine hesitancy. Research funding came primarily from US government agencies.

Alzheimer's and Parkinson's are neurodegenerative disorders that affect a great number of people around the world, seriously compromising the quality of life of individuals, due to motor and cognitive damage. In these diseases, pharmacological treatment is used only to alleviate symptoms. This emphasizes the need to discover alternative molecules for use in prevention. Using Molecular Docking, this review aimed to evaluate the anti-Alzheimer's and anti-Parkinson's activity of linalool and citronellal, as well as their derivatives. Before performing Molecular Docking simulations, the compounds' pharmacokinetic characteristics were evaluated. For Molecular Docking, 7 chemical compounds derived from citronellal, and 10 compounds derived from linalool, and molecular targets involved in Alzheimer's and Parkinson's pathophysiology were selected. According to the Lipinski rules, the compounds under study presented good oral absorption and bioavailability. For toxicity, some tissue irritability was observed. For Parkinson-related targets, the citronellal and linalool derived compounds revealed excellent energetic affinity for α-Synuclein, Adenosine Receptors, Monoamine Oxidase (MAO), and Dopamine D 1 receptor proteins. For Alzheimer disease targets, only linalool and its derivatives presented promise against BACE enzyme activity. The compounds studied presented high probability of modulatory activity against the disease targets under study, and are potential candidates for future drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: The understanding of biological responses to psychedelics with antidepressant potential is imperative. Here we report how a set of acute parameters, namely emotional (depressive symptoms), cognitive (psychedelic experience), and physiological (salivary cortisol), recorded during an ayahuasca dosing session, modulated serum brain-derived neurotrophic factor (BDNF), serum cortisol (SC), serum interleukin 6 (IL-6), plasma C-reactive protein (CRP), and salivary cortisol awakening response (CAR)., Methods: Results were analyzed 2 days after the psychedelic intervention (ayahuasca) versus placebo in both patients with treatment-resistant depression and healthy volunteers. These measures were assessed as part of a randomized double-blinded, placebo-controlled trial ( n = 72)., Results: Results revealed that larger reductions of depressive symptoms during the dosing session significantly moderated higher levels of SC in patients. Whereas lesser changes in salivary cortisol levels during the ayahuasca intervention were related to higher BDNF levels in patients with a larger clinical response in the reduction in depressive symptoms. No moderator was found for patient's CAR, IL-6, and CRP responses to ayahuasca and for all biomarker responses to ayahuasca in healthy controls and in the placebo group., Discussion: In summary, some specific emotional and physiological parameters during experimental ayahuasca session were revealed as critical moderators of the improvement of major depression biomarkers, mainly BDNF and SC two days after ayahuasca intake. These findings contribute to paving the way for future studies investigating the biological antidepressant response to psychedelic therapy., Competing Interests: JS and DP were directors of a not-for-profit Medicinal Psychedelics Research Institute. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sousa, de Oliveira Tavares, de Menezes Galvão, de Almeida, Palhano-Fontes, Lobão-Soares, de Morais Freire, Nunes, Maia-de-Oliveira, Perkins, Sarris, de Araujo and Galvão-Coelho.)

Background: This study aimed to compare the stress tolerance, competitive anxiety, heart rate variability and salivary cortisol before and during successive futsal competitive matches (3 matches in 4 days) in young male futsal players., Methods: 10 young male futsal players (16.9 ± 0.7 age; 71.0 ± 5.1 kg; 174.9 ± 4.3 cm) were monitored during one training session and across a competitive period with 3 successive matches. External load was determined by the PlayerLoad method, while session rating of perceived exertion was used to calculate the internal training and competitive load. The stress tolerance was examined using Daily Analysis of Life Demand in Athletes questionnaire and the Competitive State Anxiety Inventory was used to analyze the competitive anxiety. The Time and frequency monitoring parameters were used to analyze the vagal cardiac autonomic marker. sC was analyzed using enzyme-linked immunosorbent assay., Results: A generalized estimating equation showed a significant difference for PlayerLoad from M1 to TS, M2 and M3, from M2 to M3 (p < 0.05), and for session rating of perceived exertion from M1 to Ts and M3 (p < 0.05). A difference for sources [χ 2 (3)  = 1.481, p = 0.68] or symptoms [χ 2 (3)  = 3.893, p = 0.27] was not found. There was no significant difference in any of the competitive anxiety [cognitive anxiety (F (1.644; 14.799)  = 4.6, p = 0.73, ŋ 2 p = 0.28), somatic anxiety (F (2,09; 18,85)  = 26.07 p = 0.057; ŋ 2 p  = 0.27) or self-confidence (F (2.07; 18.85)  = 15.875 p = 0.152; ŋ 2 p  = 0.18)] domains. The HRV parameters (time domain and frequency) and Salivary Cortisol (sC) (χ 2 (3)  = 4.320 p = 0.229) did not significantly change during the successive matches., Conclusion: The competitive scenario in which the players were evaluated did not significantly modify the stress tolerance, or the athletes' state of anxiety, which in turn was not able to promote changes in the cardiac vagal modulation or in the sC levels before the matches., (© 2022. The Author(s).)

Acridine derivatives have been found with anticancer and antinociceptive activities. Herein, we aimed to evaluate the toxicological, antitumor, and antinociceptive actions of N'-(6-chloro-2-methoxyacridin-9-yl)-2-cyanoacetohydrazide (ACS-AZ), a 9-aminoacridine derivative with antimalarial activity. The toxicity was assessed by acute toxicity and micronucleus tests in mice. The in vivo antitumor effect of ACS-AZ (12.5, 25, or 50 mg/kg, intraperitoneally, i.p.) was determined using the Ehrlich tumor model, and toxicity. The antinociceptive efficacy of the compound (50 mg/kg, i.p.) was investigated using formalin and hot plate assays in mice. The role of the opioid system was also investigated. In the acute toxicity test, the LD 50 (lethal dose 50%) value was 500 mg/kg (i.p.), and no detectable genotoxic effect was observed. After a 7-day treatment, ACS-AZ significantly ( p < 0.05) reduced tumor cell viability and peritumoral microvessels density, suggesting antiangiogenic action. In addition, ACS-AZ reduced ( p < 0.05) IL-1β and CCL-2 levels, which may be related to the antiangiogenic effect, while increasing ( p < 0.05) TNF-α and IL-4 levels, which are related to its direct cytotoxicity. ACS-AZ also decreased ( p < 0.05) oxidative stress and nitric oxide (NO) levels, both of which are crucial mediators in cancer known for their angiogenic action. Moreover, weak toxicological effects were recorded after a 7-day treatment (biochemical, hematological, and histological parameters). Concerning antinociceptive activity, ACS-AZ was effective on hotplate and formalin (early and late phases) tests ( p < 0.05), characteristic of analgesic agents with central action. Through pretreatment with the non-selective (naloxone) and μ1-selective (naloxonazine) opioid antagonists, we observed that the antinociceptive effect of ACS-AZ is mediated mainly by μ1-opioid receptors ( p < 0.05). In conclusion, ACS-AZ has low toxicity and antitumoral activity related to cytotoxic and antiangiogenic actions that involve the modulation of reactive oxygen species, NO, and cytokine levels, in addition to antinociceptive properties involving the opioid system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mangueira, de Sousa, Batista, de Abrantes, Moura, Ferreira, de Almeida, Braga, Leite, Medeiros, Cavalcanti, Moura, Silvestre, Batista and Sobral.)

Episodic-like memory (ELM) consists in the capacity of nonhuman animals to remember 'where' and 'when' a specific episode occurred ('what'). Previous studies have showed that Wistar rats can form an ELM, but not after a 24 h retention delay. On the other hand, it has been demonstrated that caffeine can improve episodic memory consolidation in humans. Therefore, we verified whether acute post-sample caffeine administration could improve ELM consolidation in Wistar rats, as well if it could be related to neurochemical changes in the prefrontal cortex and hippocampus - regions related to episodic-like memory processing. 46 Male Wistar Rats, approximately 3 months-old, were divided into four groups as follows: untreated (n = 11), saline (n = 11), caffeine 10 mg ∕kg i.p (n = 12); caffeine 15 mg∕kgi.p (n = 12) and tested in WWWhen/ELM task. The animals treated with caffeine in different dosages (10 mg/kg and 15 mg/kg) discriminated temporally and spatially the objects, respectively. These groups also showed a dopamine renewal rate in the hippocampus, suggesting that there was an increase in the turnover compared with the groups with no caffeine administration. We can conclude that caffeine leads to an improvement in the consolidation of the temporal ('what-when') and spatial ('what-where') aspects of episodic-like memory., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This study evaluated the orofacial antinociceptive effect of (S)-(-)-perillyl alcohol (PA) associated with codeine (C) and investigated the possible molecular anchorage mechanisms of PA. Mice (n = 5 per group) were treated with PA alone and associated with codeine and assigned to the following groups: 75.0 mg/kg PA; 75.0 mg/kg PA + C 30 mg/kg; PA 37.5 mg/kg + C 15.0 mg/kg; C 30.0 mg/kg; and control. Nociception was induced by formalin, capsaicin, and glutamate, and was quantified based on the duration (in seconds) of face grooming. The possible mechanisms of action were evaluated by molecular docking study. In the formalin test, PA75/C30 presented an effect in the neurogenic (p < 0.0001) and inflammatory (p < 0.005) phases. Mice treated with PA75 (p < 0.0001) and PA75/C30 (p < 0.0005) showed a reduced nociceptive behavior in the capsaicin test. Glutamate-induced nociception also was blocked by PA75 (p < 0.0005) and C30 (p < 0.0005). The molecular anchorage analysis indicated high negative binding energy values for the evaluated receptors, especially glutamate receptors (AMPA -79.57 Kcal/mol, mGLUR6 -71.25, and NMDA -66.33 Kcal/mol). PA associated with codeine showed orofacial antinociceptive activity, with theoretical evidence of interaction with glutamate receptors.

Abstract: Mortatti, AL, Oliveira, RSCd, Pinto, JCBdL, Galvão-Coelho, NL, Almeida, RN, Aoki, MS, and Moreira, A. A congested match schedule alters internal match load and affects salivary immunoglobulin A concentration in youth soccer players. J Strength Cond Res 36(6): 1655-1659, 2022-The aim of this study was to analyze the effects of a congested match schedule (CMS) undertaken after a tapering week, on internal match load (IML) and salivary immunoglobulin A (SIgA) concentration in 12 youth soccer players (16.6 ± 0.5 years; 175 ± 8 cm; 65 ± 8 kg) who performed 4 official matches within a 4-day period. Internal match load was determined using the session-rating of perceived exertion method and the competitive strain (CS) and monotony index (MI) were also determined. Saliva sampling was conducted, before the last training day of a tapering week (training) preceding the CMS, 60 minutes before the first match (match-1), and 22 hours after match 4 (postmatch 4). Salivary immunoglobulin A was analyzed by ELISA. The results of the analysis of variance with repeated measures showed a significant difference for IML across the matches (p < 0.001). A significant reduction in SIgA was observed from prematch 1 to postmatch 4 (p = 0.019). Regarding the change in SIgA (ΔSIgA), 58.3% of the players presented values equal/higher than the minimal detectable change. A large within-individual correlation was observed between ΔSIgA and MI and CS (r = 0.71 and r = 0.72: p < 0.01, respectively). The current findings suggest that youth players participating in a CMS may present a decrease in mucosal immunity function. In addition, data suggest that the MI and CS may be used as valuable markers for monitoring competition load during CMS in youth soccer players., (Copyright © 2020 National Strength and Conditioning Association.)

Epilepsy is a chronic neurological disorder affecting 1-2% of world population, and one-third of patients are refractory to pharmacological treatment. This fact has stimulated research for new antiepileptic drugs and natural products have been an important source. trans -Anethole (TAN) is a phenylpropanoid, component of some essential oils, extracted from plants, and its effects have been little studied. Therefore, this study is aimed at investigating the TAN effect in classic seizure models and evaluate the electroencephalographic (EEG) profile of animals treated with this substance. For this, Swiss male mice ( Mus musculus ) were used, and the lethal dose was evaluated and subsequently submitted to the test maximal electroshock (MES), the pentylenetetrazole- (PTZ) induced seizure test, and the EEG profile. Initially, the LD50 for TAN was estimated in 1000 mg/kg (i.p.) dose and there was no sign of acute toxicity or death. In the MES test, TAN 300, i.p. (12.00 ± 2.9 s) and 400 mg/kg, i.p. (9.00 ± 4.4 s) doses was able to decrease tonic seizures duration induced by electric discharge (0.5 mA, 150 pulses/s, for 0.5 s). In the PTZ test (75 mg/kg, i.p.), TAN 400 mg/kg, i.p. increased the latency to myoclonic jerks (80.0 (56.0-134.0)), the latency totonic-clonic seizures (900.0 (861.0-900.0) and decrease seizure duration (0.0 (0.0-10.0)). No deaths were found in this groups compared to vehicle. EEG analysis showed an amplitude decrease of waves (ratio of baseline) in TAN 300 (1.82 ± 0.23) and 400 mg/kg (1.06 ± 0.16) groups. In this way, TAN at 400 mg/kg was able to inhibit and/or attenuate seizures by increasing the time for the onset of spasms and convulsions, as reducing the duration of seizures. The EEG profile corroborate with this results showing a reduction in the amplitude of waves compared to the PTZ group. Thus, TAN showed an anticonvulsant effect in all experimental models performed, behavioral and electroencephalographic., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022 Erika da Guedes et al.)

A widely disseminated native species from Australia, Acacia mearnsii , which is mainly cultivated in Brazil and South Africa, represents a rich source of natural tannins used in the tanning process. Many flowers of the Acacia species are used as sources of compounds of interest for the cosmetic industry, such as phenolic compounds. In this study, supercritical fluid extraction was used to obtain non-volatile compounds from A. mearnsii flowers for the first time. The extract showed antimicrobial activity and the presence of p -anisic acid, a substance with industrial and pharmaceutical applications. The fractionation of the extract was performed using a chromatographic column and the fraction containing p -anisic acid presented better minimum inhibitory concentration (MIC) results than the crude extract. Thus, the extraction process was optimized to maximize the p -anisic acid extraction. The response surface methodology and the Box-Behnken design was used to evaluate the pressure, temperature, the cosolvent, and the influence of the particle size on the extraction process. After the optimization process, the p -anisic acid yield was 2.51% w / w and the extraction curve was plotted as a function of time. The simulation of the extraction process was performed using the three models available in the literature., Competing Interests: The authors declare no conflicts of interest.

Background: Nosodes are homeopathic preparations (HPs) obtained from tissues or substances associated with the targeted disease or from culture of the pathogenic agent. Nosodes are thought to modulate host resistance, easing symptoms or promoting cure. A few studies have been published about control of plant-parasitic nematodes with HPs, but none with nosodes. Conceptually, nosodes prepared from nematode infective stages might interact with the plant's pathogen-recognition system and initiate or modulate plant resistance to nematodes., Objective: Our goal was to investigate whether nosodes prepared from second-stage juveniles (J 2 ) of Meloidogyne enterolobii can affect the moderate resistance already existing in the lettuce cultivar 'Elisa'., Methods: Nosodes at the Hahnemannian concentrations (cH) 6, 18, 30 and 42 were applied on lettuce plants through irrigation, with a constant daily dosage. The nosode treatment started at the seedling stage, before nematode inoculation with 3,000 eggs + J 2 per plant. A series of absolute and relative controls, and 10 replicates per treatment, were employed. At harvest, variables related to plant growth and nematode reproduction were assessed., Results: The nosode at 6, 18, and 30cH reduced ( p <0.05) the nematode reproduction factor and root density. The nosode effect was cH-dependent since nematode reproduction was favored by treatment with 42cH. The nosode also affected ( p <0.05) lettuce roots, which presented higher or lower fresh weight and volume depending on the cH applied and the condition-parasitized or not., Conclusion: Nosodes obtained from Meloidogyne J 2 may affect plant parasitism by nematodes, possibly by interfering with plant resistance. The nature-positive or negative-and intensity of the nosode effect depends on the cH applied to the plants. Further studies are necessary to identify which cH values are more effective in reducing nematode reproduction without causing negative side effects on plant growth., Competing Interests: None declared., (Faculty of Homeopathy. This article is published by Thieme.)

The study aim was to analyze the effects of successive matches on the internal match load, stress tolerance, salivary cortisol concentration and countermovement vertical jump height in twelve youth soccer players (16.6 ± 0.5 yr; 175 ± 8 cm; 65 ± 8 kg) who performed four official matches within a four day-period with a 24-h recovery interval between the matches. The internal match load, monotony index and competitive strain, as well as stress tolerance were examined. Saliva samples were collected and countermovement vertical jump height was assessed 60 min pre and 30 min post each match; delta of salivary cortisol and countermovement vertical jump height for each match were analyzed. Salivary cortisol was analyzed using an enzyme-linked immunosorbent assay. The results of ANOVA with repeated measures showed no differences between matches for the internal match load (p > 0.05). The scores of the monotony index and competitive strain were 4.3 (±2.3) and 8104 (±6795) arbitrary units, respectively. There was no difference for stress tolerance between matches (p > 0.05). Delta values of salivary cortisol were not different among the assessed matches (F (3,33) = 1.397, p = 0.351, η 2 : 0.09); however, delta of countermovement vertical jump height decreased from match 1 to match 4 (F (3,33) = 8.64, p < 0.001, η 2 : 0.44). The current findings suggest that participating in four successive matches, with 24-h of recovery in between, may not lead to changes in stress tolerance and salivary cortisol of youth players, but it may induce a decrease in players' jumping performance after the fourth match., (© 2021 Julio Cesar Barbosa de Lima Pinto, Romerito Sóstenes Canuto de Oliveira, Nicole Leite Galvão-Coelho, Raissa Nóbrega de Almeida, Alexandre Moreira, Arnaldo Luis Mortatti, published by Sciendo.)

Background: Molecular biomarkers are promising tools to be routinely used in clinical psychiatry. Among psychiatric diseases, major depression disorder (MDD) has gotten attention due to its growing prevalence and morbidity., Methods: We tested some peripheral molecular parameters such as serum mature Brain-Derived Neurotrophic Factor (mBDNF), plasma C-Reactive Protein (CRP), serum cortisol (SC), and the salivary Cortisol Awakening Response (CAR), as well as the Pittsburgh sleep quality inventory (PSQI), as part of a multibiomarker panel for potential use in MDD diagnosis and evaluation of disease's chronicity using regression models, and ROC curve., Results: For diagnosis model, two groups were analyzed: patients in the first episode of major depression (MD: n = 30) and a healthy control (CG: n = 32). None of those diagnosis models tested had greater power than Hamilton Depression Rating Scale-6. For MDD chronicity, a group of patients with treatment-resistant major depression (TRD: n = 28) was tested across the MD group. The best chronicity model (p < 0.05) that discriminated between MD and TRD included four parameters, namely PSQI, CAR, SC, and mBDNF (AUC ROC = 0.99), with 96% of sensitivity and 93% of specificity., Conclusion: These results indicate that changes in specific biomarkers (CAR, SC, mBDNF and PSQI) have potential on the evaluation of MDD chronicity, but not for its diagnosis. Therefore, these findings can contribute for further studies aiming the development of a stronger model to be commercially available and used in psychiatry clinical practice., Competing Interests: The authors have declared that no competing interests exist.

The comprehension of the pathophysiology of the major depressive disorder (MDD) is essential to the strengthening of precision psychiatry. In order to determine the relationship between the pathophysiology of the MDD and its clinical progression, analyzed by severity of the depressive symptoms and sleep quality, we conducted a study assessing different peripheral molecular biomarkers, including the levels of plasma C-reactive protein (CRP), serum mature brain-derived neurotrophic factor (mBDNF), serum cortisol (SC), and salivary cortisol awakening response (CAR), of patients with MDD ( n = 58) and a control group of healthy volunteers ( n = 62). Patients with the first episode of MDD ( n = 30) had significantly higher levels of CAR and SC than controls ( n = 32) and similar levels of mBDNF of controls. Patients with treatment-resistant depression (TRD, n = 28) presented significantly lower levels of SC and CAR, and higher levels of mBDNF and CRP than controls ( n = 30). An increased severity of depressive symptoms and worse sleep quality were correlated with levels low of SC and CAR, and with high levels of mBDNF. These results point out a strong relationship between the stages clinical of MDD and changes in a range of relevant biological markers. This can assist in the development of precision psychiatry and future research on the biological tests for depression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 de Menezes Galvão, Almeida, de Sousa, Leocadio-Miguel, Palhano-Fontes, de Araujo, Lobão-Soares, Maia-de-Oliveira, Nunes, Hallak, Schuch, Sarris and Galvão-Coelho.)

Rheumatoid arthritis, arthrosis and gout, among other chronic inflammatory diseases are public health problems and represent major therapeutic challenges. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed clinical treatments, despite their severe side effects and their exclusive action in improving symptoms, without effectively promoting the cure. However, recent advances in the fields of pharmacology, medicinal chemistry, and chemoinformatics have provided valuable information and opportunities for development of new anti-inflammatory drug candidates. For drug design and discovery, thiophene derivatives are privileged structures. Thiophene-based compounds, like the commercial drugs Tinoridine and Tiaprofenic acid, are known for their anti-inflammatory properties. The present review provides an update on the role of thiophene-based derivatives in inflammation. Studies on mechanisms of action, interactions with receptors (especially against cyclooxygenase (COX) and lipoxygenase (LOX)), and structure-activity relationships are also presented and discussed. The results demonstrate the importance of thiophene-based compounds as privileged structures for the design and discovery of novel anti-inflammatory agents. The studies reveal important structural characteristics. The presence of carboxylic acids, esters, amines, and amides, as well as methyl and methoxy groups, has been frequently described, and highlights the importance of these groups for anti-inflammatory activity and biological target recognition, especially for inhibition of COX and LOX enzymes.

Hydroxycitronellal (HC) is a monoterpene present in essential oils of aromatic plants of different species, obtained from semisynthesis of citronellal, and is widely used as a fragrance in cosmetics. The objective of this work was to evaluate the possible anxiolytic-like activity of HC and its possible mechanism of action using in vivo and in silico methodologies. Swiss male mice ( Mus musculus ) were treated with HC (12.5, 25, and 50 mg/kg, i.p.) and subjected to the rota rod, elevated plus maze, and open field tests. No significant impairments were observed in the rota rod tests for the motor activity of the animals treated with HC at 12.5, 25, and 50 mg/kg, i.p., indicating no myo-relaxing or sedative effects. In the elevated plus maze, HC (in the three doses) induced significant increases in the percentage of entries (respectively, 34.8%, 33.8%, and 38.6%) and in the length of stay (respectively, 49.9%, 56.1%, and 57.0%) in the open arms of the EPM, as well as the number of crossings in the open field tests. The mechanism of action of the compound's anxiolytic-like activity can be attributed to the involvement of GABA A receptors, and this interaction was observed in in vivo and in silico studies. For HC, the results suggest anxiolytic-like effects, possibly via modulation of the GABAergic system. The use of natural products to treat anxiety can become an alternative to existing synthetic products., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Jéssica C. Andrade et al.)

Objective: This study aims to correlate new experimental data relevant to the description of the combined evaporation/permeation process of a perfume applied onto the skin., Methods: The vapour pressure data were measured by thermogravimetric analysis (TG-DTA). The Antoine constants and the Clarke and Glew parameters were determined for the same set of fragrance molecules to describe its low vapour pressures at new temperature ranges. The permeability coefficient of a set of 14 fragrance molecules in ethanolic solution was determined by Franz diffusion cell experiments, using porcine skin. The samples were analysed by gas chromatography with a flame ionization detector (GC/FID) and high-performance liquid chromatography with UV visible detector (HPLC/UV). A QSAR model was proposed to correlate the experimental data., Results: The Antoine constants were determined and presented low standard deviations. The Clarke and Glew physically significant parameters were obtained along with its statistical analysis. The fitting is good since the magnitude order is in accordance with the literature, associated with the low correlation between the estimated parameters and low standard deviations. The presented correlation, based on a mixture using only ethanol as solvent, showed better results than previous QSAR models with a standard relative deviation ( σ r ) of 0.190, a standard error (SE) of 0.397 and a determination coefficient (R 2 ) of 0.7786., Conclusion: The dataset is still small compared to larger and more general QSAR models; however, it is much more specific as to the type of solvent and class of materials studied. This work represents an advance for the modelling of the perfume diffusion process since it specifies important properties that until then had been treated in a more general way., (© 2021 Society of Cosmetic Scientists and the Société Française de Cosmétologie.)

The use of more than one control technique can maximize the reduction of the damages caused by the fungus Asperisporium caricae causal agent of the black spot in the papaya crop. The objective of this work was to evaluate the sensitivity of the fungi Hansfordia pulvinata and Acremonium spp. to alternative products with potential for use in the control of the black-spotted ptarmigan. Three isolates of Acremonium spp. (A-598, A-602 and A-617) and an isolate of H. pulvinata (H-611) were grown in BDA medium containing Agro-Mos®, Bion®, Ecolife®, Hortifospk®, Matriz G®, Vitaphol® separately. The Amistar 500WG ® fungicide was used as a positive control and pure BDA as a negative control. The toxicity of the tested products was determined based on the values of the biological index, derived from the means of mycelial growth, sporulation and germination of conidia, in each experimental unit. In this way it was possible to select the products classified as compatible for all isolates, and to test them in vivo. In the greenhouse, only the isolates and isolates with selected products, were applied in papaya plants with foliar symptoms of black-spotted. The incidence of leaves with hyperparasites and the percentage of black-painted lesions colonized by the tested isolates were evaluated. Thus, the H-611 isolate proved to be compatible with most of the alternative products tested, except with Hortifos®. Bion® and Matrix® products were compatible with all tested isolates and could be used in conjunction with Acremonium spp. and H. pulvinata to control the papaya black spot, since these products did not present toxicity on the hyperparasitic fungi.

Background: Natural products, such as phenylpropanoids, which are found in essential oils derived from aromatic plants, have been explored during non-clinical psychopharmacology studies, to discover new molecules with relevant pharmacological activities in the central nervous system, especially antidepressant and anxiolytic activities. Major depressive disorder is a highly debilitating psychiatric disorder and is considered to be a disabling public health problem, worldwide, as a primary factor associated with suicide. Current clinically administered antidepressants have late-onset therapeutic actions, are associated with several side effects, and clinical studies have reported that some patients do not respond well to treatment or reach complete remission., Objective: To review important new targets for antidepressant activity and to select phenylpropanoids with antidepressant activity, using Molegro Virtual Docker and Ossis Data Warris, and to verify substances with more promising antidepressant activity., Results and Conclusion: An in silico molecular modeling study, based on homology, was conducted to determine the three-dimensional structure of the 5-hydroxytryptamine 2A receptor (5- HT2AR), then molecular docking studies were performed and the predisposition for cytotoxicity risk among identified molecules was examined. A model for 5-HT2AR homology, with satisfactory results, was obtained indicating the good stereochemical quality of the model. The phenylpropanoid 4-allyl-2,6-dimethoxyphenol showed the lowest binding energy for 5-HT2AR, with results relevant to the L-arginine/nitric oxide (NO)/cGMP pathway, and showed no toxicity within the parameters of mutagenicity, carcinogenicity, reproductive system toxicity, and skin-tissue irritability, when evaluated in silico; therefore, this molecule can be considered promising for the investigation of antidepressant activity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Treatment of pain and fever remains an important challenge for modern medicine. Non-steroidal anti-inflammatory drugs (NSAIDs) are the pharmacological options most often used, but their frequent use exposes the patient to serious side effects and dangerous drug interactions. In this context, thiophene derivatives are promising therapeutic alternatives. In this study, we evaluated the in vivo and in silico antinociceptive and antipyretic properties of RMD86 , a thiophene derivative. At 100 mg/kg, RMD86 induced no significant changes in the motor coordination of mice in the Rotarod test. At 25, 50, and 100 mg/kg RMD86 significantly reduced the number of abdominal contortions induced by acetic acid (antinociceptive activity) in mice when compared to the control. In the formalin test, for the first phase, there was a reduction in licking times at doses of 50 and 100 mg/kg. In the second phase, reduction occurred at all doses. In the hot plate test, RMD86 (at 100 mg/kg) increased latency time in the first 30 min. For antipyretic activity, RMD86, when compared to the reference drug acetaminophen (250 mg/kg), significantly reduced pyrexia at 30, 60, and 120 min, at dosages of 25, 50 and 100 mg/kg. Molecular docking studies revealed that RMD86 presents a greater number of interactions and lower energy values than both the co-crystallized ligand and the reference drug (meloxicam) against COX-1 and COX-2 isoenzymes. The results give evidence of the analgesic and antipyretic properties like NSAIDs suggesting its potential for pain therapy., Competing Interests: The authors declare no conflict of interest., (© 2020 Published by Elsevier Ltd.)

Background: Ayahuasca is a traditional Amazon brew and its potential antidepressant properties have recently been explored in scientific settings. We conducted a double-blind placebo-controlled trial of ayahuasca with treatment-resistant depression patients ( n = 28) and healthy controls ( n = 45)., Aims: We are evaluating the blood inflammatory biomarkers: C-reactive protein and interleukin 6, as a potential consequence of ayahuasca intake and their correlation with serum cortisol and brain-derived neurotrophic factor levels. Blood samples were collected at pre-treatment and 48 hours after substance ingestion to assess the concentration of inflammatory biomarkers, together with administration of the Montgomery-Åsberg Depression Rating Scale., Results: At pre-treatment, patients showed higher C-reactive protein levels than healthy controls and a significant negative correlation between C-reactive protein and serum cortisol levels was revealed ( rho = -0.40, n = 14). C-reactive protein in those patients was not correlated with Montgomery-Åsberg Depression Rating Scale scores. We observed a significant reduction of C-reactive protein levels across time in both patients and controls treated with ayahuasca, but not with placebo. Patients treated with ayahuasca showed a significant correlation ( rho = + 0.57) between larger reductions of C-reactive protein and lower depressive symptoms at 48 hours after substance ingestion (Montgomery-Åsberg Depression Rating Scale). No significant result with respect to interleukin 6 and brain-derived neurotrophic factor was found. Furthermore, these biomarkers did not predict the antidepressant response or remission rates observed., Conclusions: These findings enhance the understanding of the biological mechanisms behind the observed antidepressant effects of ayahuasca and encourage further clinical trials in adults with depression.

Introduction: Pain is considered an unpleasant sensory and emotional experience, being considered as one of the most important causes of human suffering. Computational chemistry associated with bioinformatics has stood out in the process of developing new drugs, through natural products, to manage this condition., Objective: To analyze, through literature data, recent molecular coupling studies on the antinociceptive activity of essential oils and monoterpenes., Data Source: Systematic search of the literature considering the years of publications between 2005 and December 2019, in the electronic databases PubMed and Science Direct ., Eligibility Criteria: Were considered as criteria of 1) Biological activity: non-clinical effects of an OE and/or monoterpenes on antinociceptive activity based on animal models and in silico analysis, 2) studies with plant material: chemically characterized essential oils and/or their constituents isolated, 3) clinical and non-clinical studies with in silico analysis to assess antinociceptive activity, 4) articles published in English. Exclusion criteria were literature review, report or case series, meta-analysis, theses, dissertations, and book chapter., Results: Of 16,006 articles, 16 articles fulfilled all the criteria. All selected studies were non-clinical. The most prominent plant families used were Asteraceae, Euphorbiaceae, Verbenaceae, Lamiaceae, and Lauraceae. Among the phytochemicals studied were α-Terpineol, 3-(5-substituted-1,3,4-oxadiazol-2-yl)-N'-[2-oxo-1,2-dihydro-3H-indol-3-ylidene] propane hydrazide, β-cyclodextrin complexed with citronellal, (-)-α-bisabolol, β-cyclodextrin complexed with farnesol, and p-Cymene. The softwares used for docking studies were Molegro Virtual Docker, Sybyl ® X, Vlife MDS, AutoDock Vina, Hex Protein Docking, and AutoDock 4.2 in PyRx 0.9. The molecular targets/complexes used were Nitric Oxide Synthase, COX-2, GluR2-S1S2, TRPV1, β-CD complex, CaV 1 , CaV 2.1 , CaV 2.2 , and CaV 2.3 , 5-HT receptor, delta receptor, kappa receptor, and MU (μ) receptor, alpha adrenergic, opioid, and serotonergic receptors, muscarinic receptors and GABA A opioid and serotonin receptors, 5-HT 3 and M 2 receptors. Many of the covered studies used molecular coupling to investigate the mechanism of action of various compounds, as well as molecular dynamics to investigate the stability of protein-ligand complexes., Conclusions: The studies revealed that through the advancement of more robust computational techniques that complement the experimental studies, they may allow some notes on the identification of a new candidate molecule for therapeutic use., (Copyright © 2020 Assis, Aragão Neto, da Fonsêca, de Andrade, Braga, Badr, Maia, Castro, Scotti, Scotti and de Almeida.)

Sleep disturbance is a symptom consistently found in major depression and is associated with a longer course of illness, reduced response to treatment, increased risk of relapse and recurrence. Chronic insomnia has been associated with changes in cortisol and serum brain-derived neurotrophic factor (BDNF) levels, which in turn are also changed in major depression. Here, we evaluated the relationship between sleep quality, salivary cortisol awakening response (CAR), and serum BDNF levels in patients with sleep disturbance and treatment-resistant major depression ( n = 18), and in a control group of healthy subjects with good ( n = 21) and poor ( n = 18) sleep quality. We observed that the patients had the lowest CAR and sleep duration of all three groups and a higher latency to sleep than the healthy volunteers with a good sleep profile. Besides, low CAR was correlated with more severe depressive symptoms and worse sleep quality. There was no difference in serum BDNF levels between groups with distinct sleep quality. Taken together, our results showed a relationship between changes in CAR and in sleep quality in patients with treatment-resistant depression, which were correlated with the severity of disease, suggesting that cortisol could be a physiological link between sleep disturbance and major depression., (Copyright © 2020 Santiago, Galvão, de Almeida, Mota-Rolim, Palhano-Fontes, Maia-de-Oliveira, de Araújo, Lobão-Soares and Galvão-Coelho.)

Purpose: To analyze the concept of adverse reaction to medications and to develop the new nursing diagnosis Risk for Adverse Reactions to Medications., Methods: Concept analysis using Walker and Avant's eight step method., Findings: Thirty-three articles indexed in four databases were included. The components of the new nursing diagnosis were determined, including possible nursing outcomes and interventions., Conclusions: The concept analysis supported the development of the new nursing diagnosis Risk for Adverse Reactions to Medications, which may help nurses to evaluate and identify patients susceptible to adverse reactions., Implications for Nursing Practice: The establishment of this nursing diagnosis will provide nurses an opportunity to implement interventions to anticipate and effectively intervene with patients at risk for this condition., (© 2019 NANDA International, Inc.)

We aimed to evaluate the orofacial antinociceptive effect of geraniol in mice and its molecular anchorage mechanism. Seven mice per group (probabilistic sample) were treated with geraniol (12.5, 25 and 50 mg/kg, i.p.), morphine (6 mg/kg, i.p.) and vehicle (saline + Tween 80 at 0.2%, i.p.) 30 minutes prior to the beginning of the experiment. Injecting glutamate (25 μM), capsaicin (2.5 μg) and formalin (2%) into the right upper lip (perinasal) of the mouse induced nociception. Behavioral analysis of the animals considered the friction time (in seconds) of the mentioned region using hind or front paws by a researcher blinded to the treatment groups. The statistical analysis was performed blindly, considering α = 5%. The results showed that in the glutamate and capsaicin tests, concentrations of 25 mg/kg and 50 mg/kg presented antinociceptive activity (p < 0.005, power> 80%). In the formalin test, geraniol was able to reduce nociception at a concentration of 50 mg/kg (p < 0.005, power> 80%). In the molecular anchorage study, high values of binding between the evaluated substance and receptors of glutamate were observed (metabotropic glutamate receptor, -87.8501 Kcal/mol; N-methyl-D-aspartate, -86.4451 Kcal/mol; α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, -85.6755 Kcal/mol). Geraniol presented orofacial antinociceptive activity, probably by interacting with glutamate-related receptors.

Depression is a health problem that compromises the quality of life of the world's population. It has different levels of severity and a symptomatic profile that affects social life and performance in work activities, as well as a high number of deaths in certain age groups. In the search for new therapeutic options for the treatment of this behavioral disorder, the present review describes studies on antidepressant activity of cinnamic acids, which are natural products found in medicinal plants and foods. The description of the animal models used and the mechanisms of action of these compounds are discussed.

Epilepsy is a most disabling neurological disorder affecting all age groups. Among the various mechanisms that may result in epilepsy, neuronal hyperexcitability and oxidative injury produced by an excessive formation of free radicals may play a role in the development of this pathology. Therefore, new treatment approaches are needed to address resistant conditions that do not respond fully to current antiepileptic drugs. This paper reviews studies on the anticonvulsant activities of essential oils and their chemical constituents. Data from studies published from January 2011 to December 2018 was selected from the PubMed database for examination. The bioactivity of 19 essential oils and 16 constituents is described. Apiaceae and Lamiaceae were the most promising botanical families due to the largest number of reports about plant species from these families that produce anticonvulsant essential oils. Among the evaluated compounds, β-caryophyllene, borneol, eugenol and nerolidol were the constituents that presented antioxidant properties related to anticonvulsant action. These data show the potential of these natural products as health promoting agents and use against various types of seizure disorders. Their properties on oxidative stress may contribute to the control of this neurological condition. However, further studies on the toxicological profile and mechanism of action of essential oils are needed.