Ecotoxicological evaluation of an aqueous phytoextract of Melia azedarach L.

Melia azedarach L. is a Meliaceae that has shown important insecticidal activities. However, few researchers have extensively studied the toxicology of aqueous extracts of M. azedarach (MAE). Therefore, the main objective of this study was to characterize the phyto-eco-toxicological profile of MAE. First, a botanical and phytochemical characterization of MAE was performed using a histological, and metabolomic multi-analytical approach. Second, the toxicological effects on pollinating insects (Apis mellifera ligustica) and soil collembola (Folsomia candida) were evaluated. In addition, acute toxicity was evaluated in zebrafish (Danio rerio) to assess effects on aquatic fauna, and toxicity was determined in human neuroblastoma (SH-SY5Y) and fibroblast (FB-21) cell models. Finally, phytotoxic effects on germination of Cucumis sativus L., Brassica rapa L. and Sorghum vulgare L. were considered. Metabolomic analyses revealed the presence of not only limonoids but also numerous alkaloids, flavonoids and terpenoids in MAE. Histological analyses allowed us to better localize the areas of leaf deposition of the identified secondary metabolites. Regarding the ecotoxicological data, no significant toxicity was observed in bees and collembola at all doses tested. In contrast, severe cardiac abnormalities were observed in zebrafish embryos at concentrations as low as 25 µg/mL. In addition, MAE showed toxicity at 1.6 µg/mL and 6.25 µg/mL in FB-21 and SH-SY5Y cells, respectively. Finally, MAE inhibited seed germination with inhibitory concentrations starting from 5.50 µg/mL in B. rapa, 20 µg/mL in S. vulgare, and 31 µg/mL in C. sativus. Although M. azedarach extracts are considered valuable natural insecticides, their ecological impact cannot be underestimated. Even the use of an environmentally friendly solvent (an aqueous solution), for the first time, is not without side effects. Therefore, the data collected in this study show the importance of evaluating the dosages, modes of administration and production methods of M. azedarach phytoextracts in agricultural settings.

Exploring the Anti-Inflammatory and Antioxidant Potential, Metabolite Composition and Inorganic Profile of Cistus monspeliensis L. Aerial Parts and Roots.

This work focuses on Cistus monspeliensis L. aerial parts (AP) and roots (R) extracts, investigating the anti-inflammatory and antioxidant potential of the two organs in comparison. At dosages between 1.56 and 6.25 µg/mL, both extracts showed a protective effect against LPS inflammatory stimulus on a macrophage cell line (RAW 264.7). Interestingly, only R was able to significantly reduce both IL-1ß and IL-6 mRNA gene expression in the presence of LPS. Moreover, the treatment of a neuroblastoma cell line (SH-SY5Y) with AP and R at 6.25 µg/mL increased the cell survival rate by nearly 20% after H2O2 insult. However, only R promoted mitochondria survival, exhibited a significantly higher production of ATP and a higher activity of the enzyme catalase than the control. Both AP and R had similar primary metabolites; in particular, they both contained 1-O-methyl-epi-inositol. Labdane and methoxylated flavonoids were the most characteristic compounds of AP, while R contained mainly catechins, gallic acid, and pyrogallol derivatives. Considering the importance of elemental composition in plants, the inorganic profile of AP and R was also investigated and compared. No potentially toxic elements, such as Pb, were detected in any sample.

Cannabis Sativa Oil Promotes Social Interaction and Ultrasonic Communication by Acting on Oxytocin Pathway.

Objective: Cannabis sativa is the most used recreational drug worldwide. In recent years, there has been a growing interest in the potential therapeutic benefits of medicinal cannabis to treat a variety of psychiatric and neurological conditions. In particular, cannabidiol (CBD), a nonpsychoactive cannabis constituent, has been investigated for its potential prosocial effects on behavior, although the molecular mechanisms underlying this effect are still largely unknown. The aim of this study was to investigate the effect of a C. sativa oil CBD rich (CS oil) on social interaction and ultrasonic communication in mice. Study Design: Twenty-seven adult male mice (B6; 129P F2) were treated daily with vehicle or CS oil for 2 weeks. At Day 14, mice were tested for behavior (social interaction test and ultrasonic communication). Forty minutes before the behavioral tests, mice were exposed to intranasal treatment with vehicle or the oxytocin receptor antagonist, L-371,257. After behavioral tests, VH- and CS oil-treated mice were sacrificed, RNA was extracted from the hypothalamus and used for quantitative Real Time-PCR experiments. Results: We found that a 2-week treatment with the CS oil on mice exerted a prosocial effect associated with an increase in ultrasonic vocalizations. These effects were inhibited by pretreating mice with an oxytocin receptor antagonist. In addition, at the molecular level, we found that CS oil treatment caused a significant increase in oxytocin and a decrease in oxytocin receptor expression levels in the brain hypothalamus. Conclusion: Our results suggest that CS oil promotes social behavior by acting on oxytocin pathway.

Exploring ultrasonic communication in mice treated with Cannabis sativa oil: Audio data processing and correlation study with different behaviours.

Studying ultrasonic vocalizations (USVs) plays a crucial role in understanding animal communication, particularly in the field of ethology and neuropharmacology. Communication is associated with social behaviour; so, USVs study is a valid assay in behavioural readout and monitoring in this context. This paper delved into an investigation of ultrasonic communication in mice treated with Cannabis sativa oil (CS mice), which has been demonstrated having a prosocial effect on behaviour of mice, versus control mice (vehicle-treated, VH mice). To conduct this study, we created a dataset by recording audio-video files and annotating the duration of time that test mice spent engaging in social activities, along with categorizing the types of emitted USVs. The analysis encompassed the frequency of individual sounds as well as more complex sequences of consecutive syllables (patterns). The primary goal was to examine the extent and nature of diversity in ultrasonic communication patterns emitted by these two groups of mice. As a result, we observed statistically significant differences for each considered pattern length between the two groups of mice. Additionally, the study extended its research by considering specific behaviours, aiming to ascertain whether dissimilarities in ultrasonic communication between CS and VH mice are more pronounced or subtle within distinct behavioural contexts. Our findings suggest that while there is variation in USV communication between the two groups of mice, the degree of this diversity may vary depending on the specific behaviour being observed.

Ion channel dysfunction and fibrosis in atrial fibrillation: Two sides of the same coin.

BACKGROUND: Atrial fibrillation (AF) is a common heart rhythm disorder that is associated with an increased risk of stroke and heart failure (HF). Initially, an association between AF and ion channel dysfunction was identified, classifying the pathology as a predominantly electrical disease. More recently it has been recognized that fibrosis and structural atrial remodeling play a driving role in the development of this arrhythmia also in these cases. PURPOSE: Understanding the role of fibrosis in genetic determined AF could be important to better comprise the pathophysiology of this arrhythmia and to refine its management also in nongenetic forms. In this review we analyze genetic and epigenetic mechanisms responsible for AF and their link with atrial fibrosis, then we will consider analogies with the pathophysiological mechanism in nongenetic AF, and discuss consequent therapeutic options.

Social isolation consequences: lessons from COVID-19 pandemic in a context of dynamic lock-down in Chile.

BACKGROUND: Chile did not adopt general and unified lockdowns for the whole nation but organized itself with dynamic and sometimes irregular lockdowns. These dynamics and consequences of social isolation could be generalized to other contexts of isolation such as those affecting minorities such as immigrants, prisoners, refugees. METHODS: In this study, we investigated the physical and mental health symptoms associated with lifestyle changes due to lockdown among university students in Chile. We examined psychopathological variations in relation to mental health problems in a healthy young population. Our goal was to develop interventions to address these new psychosocial problems in potentially comparable post-pandemic contexts. From May 10th 2021 to June 2th 2021, 420 University students took part in an anonymous survey asking for information on habits and symptoms that emerged during the lockdown in response to the COVID-19 pandemic. Three health outcomes were assessed: digestive disorders; headache; fear of COVID-19. Covariates including conditions and lifestyle during the pandemic, SARS-CoV-2 infections in the family, financial situation and productivity were considered in the analysis. RESULTS: Participants experienced headache and fear of COVID-19 quite frequently during the lockdown period. More than half of the sample also experienced social isolation. Female gender, sleep quality, memory difficulties, and a change in eating habits resulted associated with an increased risk of health outcomes such as headaches and digestive disorders. CONCLUSIONS: The results of this study fit within an original pandemic context: The results of this study can help identify needs and promote solutions applicable to different contexts. Future interventions should focus on the promotion and implementation of healthy habits focused on sleep hygiene, psychoeducation on the use of mobile devices and gender medicine with the support of healthcare organizations and University.