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Piplartine, also known as piperlongumine, is a natural and biologically active amide alkaloid found in various Piper species within the Piperaceae family. It possesses numerous beneficial properties that can be leveraged in the development of nanotechnological and pharmaceutical products. However, information on the effects of piplartine on mammalian embryonic development is scarce. This study aims to assess the general toxicity and teratogenic potential of piplartine during the embryonic development of mice. Pregnant mice received daily treatments of 25, 50, or 100 mg/kg of piplartine via gavage from the sixth day of gestation (implantation) to the eighteenth. On the eighteenth day, the mice were euthanized, and whole organs, blood samples (for hematological and biochemical analyses), and bone marrow cells (for DNA fragmentation and cell cycle assays) were collected. The uterus was examined for implantation sites and embryo resorptions. Additionally, fetuses were collected to assess for fetal anomalies. Piplartine did not result in maternal or embryo-fetal toxicity, induce fetal anomalies, cause hematological and biochemical alterations, or lead to DNA fragmentation. The oral administration of piplartine is safe and does not exhibit toxicity or teratogenic effects in mice. This finding opens avenues for the development of piplartine-based biotechnological products for therapeutic interventions in disease treatment.

Cajuína is a processed drink derived from cashew and is widely consumed in the northeast region of Brazil. This study evaluated the effect of a cajuína-based hydroelectrolytic drink on the aerobic performance and hydration status of recreational runners. Seventeen males (31.9 ± 1.6 years, 51.0 ± 1.4 ml/kg/min) performed three time-to-exhaustion running sessions on a treadmill at 70% VO2max, ingesting cajuína hydroelectrolytic drink (CJ), high carbohydrate commercial hydroelectrolytic drink (CH) and mineral water (W) every 15 min during the running test. The participants ran 80.3 ± 8.4 min in CJ, 70.3 ± 6.8 min in CH and 71.8 ± 6.9 min in W, with no statistical difference between procedures. Nevertheless, an effect size of η2 = 0.10 (moderate) was observed. No statistical difference was observed in the concentrations of sodium, potassium, and osmolality in both serum and urine between the three conditions. However, the effect size was moderate (urine sodium) and high (serum sodium, potassium, and osmolality). Urine specific gravity, sweating rate and heart rate were not significantly different between drinks. The cajuína-based hydroelectrolytic drink promotes similar effects compared to commercial hydroelectrolytic drink and water, considering specific urine gravity, heart rate, sweating, and time to exhaustion in recreational runners.

Ready-to-eat (RTE) and ready-to-heat (RTH) dishes are food items that help save time, physical energy, and mental effort in all food-related activities. Convenience of use, variability of supply, and adaptability to different consumption occasions have led to an increase of acceptance among consumers through the years. Specialized databases can help in this context, where food composition databases can provide information and data to create sustainable nutritional models by reducing the now growing number of chronic diseases. This paper aims at developing a database of LanguaLTM and FoodEx2 codes of 50 food preparations and ready-to-eat dishes designed for consumption outside the home. LanguaLTM, as well as FoodEx2, are classification and description systems for indexing, in the sense of a systematic description, of foods based on a hierarchical model (parent–child relationship), thus facilitating the international exchange of data on food composition, consumption, assessing chronic and/or acute exposure to a certain agent, and not least the assessment of nutrient intake. The database, here presented, consists of the codes of fifty ready-to-eat products present on the market in Italy, obtained by using the two mostly commonly used and widely recognized coding systems: LanguaLTM and FoodEx2. This database represents a tool and a guideline for other compilers and users to apply coding systems to ready-to-eat products. Moreover, it can be represented a resource for several applications, such as nutritional cards, nutritional facts, food labels, or booklet and brochures for promotion of food products, to be used at health and food nutrition interface, useful for consumers, dieticians, and food producers.

Opioids such as morphine are the first choice in acute and chronic pain treatment. However, they lead to addiction. Several studies have searched (i) to find a molecule that can replace morphine use or (ii) to reduce its adverse effects. This work aimed to evaluate whether (–)-Borneol [(–)-BOR], a bicyclic monoterpene, in doses of 25, 50, and 100 mg/kg (i.p.), has an antiaddictive effect on morphine (5 mg/kg, i.p.) and reduces its withdrawal symptoms precipitated by naloxone (8 mg/kg, i.p.) in Swiss mice. Furthermore, the (–)-BOR genotoxic potential was also investigated by the comet assay. The antiaddictive effect of (–)-BOR was evaluated by the conditioned preference place (CPP). The CPP was induced by morphine administration during the conditioning phase. The effects of (–)-BOR on the rewarding characteristics of morphine were tested in mice with the administration of (–)-BOR, naloxone, or vehicle (NaCl 0.9%), 30 min before morphine. This work also investigated the (–)-BOR effect on morphine withdrawal symptoms precipitated by naloxone. Morphine withdrawal symptoms were induced by administering morphine twice daily for 5 days, precipitated by naloxone administration on the sixth day. The effect of (–)-BOR on reducing morphine withdrawal symptoms was evaluated in mice that received (–)-BOR before daily morphine administration. Finally, the comet assay was performed to assess the DNA damage degree caused by the (–)-BOR (100 mg/kg, i.p.) administration. The comet assay was performed on peripheral blood taken from the tail of each animal. Cyclophosphamide (50 mg/kg, i.p.) was used to induce DNA damage. After starting the protocol, analyses were performed for 4 h (acute effect) and 24 h (repair effect). The (–)-BOR (100 mg/kg, i.p.) significantly attenuated (*** p < 0.001) the acquisition of morphine-induced CPP and reduced only the jumping behavior in the morphine withdrawal model. The best-studied dose was 100 mg/kg, being evaluated, then, in the comet assay. (–)-BOR at 100 mg/kg did not show the genotoxic effect when compared with the cyclophosphamide group (CYCLO, 50 mg/kg, i.p.) after 4 h or 24 h, a period that corresponded to the repair time of DNA fragmentation. The study showed that (–)-BOR attenuated the acquisition of CPP by morphine and made opioid withdrawal milder. In the comet assay, although (–)-BOR caused DNA damage, this damage was significantly less than the damage by CYCLO, at either 4 h or 24 h after the treatments.

Chronic cigarette smoking is associated with regional metabolite abnormalities in choline-containing compounds, creatine-containing compounds, glutamate, and N-acetylaspartate. The effects of cigarette smoking on anterior frontal cortical gamma-aminobutyric acid (GABA) concentration are unknown. This study compared chronic smokers (n = 33) and nonsmokers (n = 31) on anterior cingulate cortex (ACC) and right dorsolateral prefrontal cortex (DLPFC) GABA+ (the sum of GABA and coedited macromolecules) concentrations and associations of GABA+ levels in these regions with seven neurocognitive domains of functioning, decision making, and impulsivity measures. Smokers had significantly lower right DLPFC GABA+ concentration than nonsmokers, but groups were equivalent on ACC GABA+ level. Across groups, greater number of days since end of menstrual cycle was related to higher GABA+ level in the ACC but not right DLPFC GABA+ concentration. In exploratory correlation analyses, higher ACC and right DLPFC GABA+ levels were associated with faster processing speed and better auditory-verbal memory, respectively, in the combined group of smokers and nonsmokers; in smokers only, higher ACC GABA+ was related to better decision making and auditory-verbal learning. This study contributes additional novel data on the adverse effects of chronic cigarette smoking on the adult human brain and demonstrated ACC and DLPFC GABA+ concentrations were associated with neurocognition and decision making/impulsivity in active cigarette smokers. Longitudinal studies on the effects of smoking cessation on regional brain GABA levels, with a greater number of female participants, are required to determine if the observed metabolite abnormalities are persistent or normalize with smoking cessation.

Abstract Background The purpose of this study was to evaluate the overall diet quality effects, mainly on antioxidant nutritional status and some cytokines related to the cellular immune response as well as oxidative stress in a healthy Italian population group. Methods An observational study was conducted on 131 healthy free-living subjects. Dietary intake was assessed by dietary diary. Standardised procedures were used to make anthropometric measurements. On blood samples (serum, plasma and whole blood) were evaluated: antioxidant status by vitamin A, vitamin E, carotenoids, vitamin C, uric acid, SH groups, SOD and GPx activities; lipid blood profile by total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides; total antioxidant capacity by FRAP and TRAP; the immune status by TNF-α, and IL-10 cytokines; the levels of malondialdehyde in the erythrocytes as marker of lipid peroxidation. Results The daily macronutrients intake (g/day) have shown a high lipids consumption and significant differences between the sexes with regard to daily micronutrients intake. On total sample mean Mediterranean Diet Score (MDS) was 4.5 ± 1.6 and no significant differences between the sexes were present. A greater adherence to a Mediterranean dietary pattern increases the circulating plasma levels of carotenoids (lutein plus zeaxanthin, cryptoxanthin, α and β-carotene), vitamin A and vitamin E. The levels of endogenous antioxidants were also improved. We observed higher levels in anti-inflammatory effect cytokines (IL-10) in subjects with MDS ≥ 6, by contrast, subjects with MDS ≤ 3 show higher levels in sense of proinflammatory (TNF α P < 0.05). Lower levels of MDA were associated with MDS > 4. Our data suggest a protective role of vitamin A against chronic inflammatory conditions especially in subjects with the highest adherence to the Mediterranean-type dietary pattern. Conclusions Mediterranean dietary pattern is associated with significant amelioration of multiple risk factors, including a better cardiovascular risk profile, reduced oxidative stress and modulation of inflammation.

Background: Heart failure (HF) remains a prevalent syndrome with significant morbidity and mortality. Optimal drug and device therapies are crucial to reduce the risk of death or HF admission. Yet, less symptomatic patients with good functional capacity are often perceived as having a low risk of adverse events and their attending physicians may suffer from prescription inertia or refrain from performing therapy optimization. Maximum or peak oxygen consumption (pVO2) assessed during cardiopulmonary exercise testing (CPET) is often used as a prognosis indicator and surrogate marker for functional capacity. Our goal was to assess clinical outcomes in a seemingly low risk HF population in Weber class A (pVO2>20 mL/kg/min) with reduced left ventricular ejection fraction (LVEF). Methods: Single-center retrospective observational study enrolling consecutive HF patients with LVEF20 mL/kg/min were included. The primary endpoint was a composite of all-cause death or HF hospitalizations at two years after CPET. We also assessed the rates of N-terminal pro b-type natriuretic peptide (NT-proBNP) elevations at baseline. Results: Seventy-two patients were included (mean age of 53 ± 10 years; 86% male; 90% NYHA I-II; median LVEF 32%; median pVO2 24 mL/kg/min). At baseline, 93% had an NT-proBNP level >125 pg/mL (median NT-proBNP 388 [201–684] pg/mL). Overall, seven patients (10%) met the primary endpoint: three died (4%) and five (7%) had at least one HF admission. Among those who died, only one patient had an HF admission during follow up. Conclusion: In a clinically stable HFrEF population with good functional capacity, persistent neurohormonal activation was present in the majority, and one in ten patients died or had a HF admission at two years’ follow-up. These findings support the urgent need to motivate clinicians to pursue optimal drug uptitration even in less symptomatic patients. Resumo: Introdução: A insuficiência cardíaca (IC) com fração de ejeção reduzida é uma síndrome prevalente com morbimortalidade significativa. O aprimoramento da terapêutica é crucial para reduzir o risco de morte ou admissão por IC. No entanto, doentes paucissintomáticos com boa capacidade funcional são frequentemente considerados como tendo um baixo risco de eventos adversos, não são, por isso, alvo de aprimoramento terapêutico. O consumo máximo de oxigénio (pVO2), avaliado durante provas de esforço cardiorrespiratórias (PECR), é utilizado como um marcador prognóstico e da capacidade funcional do doente. O nosso objetivo foi avaliar o número e tipo de eventos clínicos numa população de IC com aparente baixo risco em classe Weber A (pVO2 > 20 mL/kg/min) e fração de ejeção ventricular esquerda (FEVE) reduzida. Métodos: Estudo observacional, retrospetivo, unicêntrico, incluindo doentes consecutivos com IC com FEVE 20 mL/kg/min foram incluídos. O endpoint primário foi um composto de morte por todas as causas ou hospitalização por IC nos dois anos após a PECR. Também avaliámos a percentagem de doentes com elevação basal de NT-proBNP. Resultados: Foram incluídos 72 doentes (idade 53 ± 10 anos; 86% homens; 90% classe NYHA I-II; FEVE média 32%; pVO2 mediana 24 mL/kg/min), 93% apresentavamm um nível de NT-proBNP >125 pg/mL (NT-proBNP mediano 388 [201-684] pg/mL). Globalmente, sete doentes (10%) atingiram o endpoint primário: três por óbito (4%) e cinco (7%) tiveram pelo menos uma hospitalização por IC. Entre os doentes que faleceram, apenas um teve uma hospitalização por IC, pelo que contabilizado pelo primeiro evento (hospitalização). Conclusão: Numa população clinicamente estável de doentes com ICFEr e boa capacidade funcional, a maioria apresentou ativação neuro-hormonal persistente e um em cada dez atingiu o endpoint primário (óbito ou internamento por IC) durante um follow-up de dois anos após a PECR. Esses achados fortalecem a necessidade urgente de promover a prescrição otimizada de terapêuticas modificadoras de doença.

We previously reported that at 1-and-4 weeks of sobriety, those who relapsed after treatment demonstrated significantly smaller total frontal cortical volume than individuals who maintained abstinence for at least 12 months post treatment. The segmentation method employed did not permit examination of frontal subregions that serve as nodes of the executive, salience and emotional regulation networks; structural abnormalities in these circuits are associated with relapse in those seeking treatment for alcohol use disorders (AUD). The primary goal of this study was to determine if frontal cortical subregion volume recovery during early abstinence is associated with long-term abstinence from alcohol. We compared bilateral components of the dorsal prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex and insula volumes, at 1 and 4 weeks of abstinence, between individuals who resumed drinking within 12 months of treatment (Relapsers) those who showed sustained abstinence over 12 months following treatment (Abstainers) and healthy Controls. At 1 and 4 weeks of sobriety, Relapsers demonstrated significantly smaller volumes than Controls in 15 of 20 regions of interest, while Abstainers only had smaller volumes than Controls in 5 of 20 regions. In Relapsers, increasing volumes over 1 month in multiple frontal subregions and the insula were associated with longer duration of abstinence after treatment. The persistent bilateral frontal and insula volume deficits in Relapsers over 4 weeks from last alcohol use may have implications for neurostimulation methods targeting anterior frontal/insula regions, and represent an endophenotype that differentiates those who respond more favorably to available psychosocial and pharmacological interventions.

Since ancient times, medicinal plants have been a universal source of biologically active substances with high potential for the treatment of various diseases and disorders. For centuries, traditional communities have often relied on medicinal plants to treat health problems. Therefore, accurate information is required and knowledge about traditional medicinal plants requires evaluation, and great attention should be given to the possible integration of these plants as therapeutic agents or as complements to conventional pharmacological therapies in the healthcare system. Recently, Griffonia simplicifolia (DC.) Baill., initially used as a holistic remedy, has attracted attention from many researchers and consumers because of its multiple health-promoting effects. This growing interest prompted us to give an updated review of the botanical, geographical, historical, and therapeutic potentials of Griffonia simplicifolia (DC.) Baill. in terms of its in vitro and in vivo health effects, nutritional uses, and possible applications in line with biodiversity and sustainability concepts. This paper also presents a quantitative research analysis of the published studies related to this plant that are available in the literature. To retrieve the publications related to this plant, a bibliographic search was carried out using the Scopus database. The bibliometric data were extracted and processed using VOSviewer software (v.1.6.16, 2020). Technological possible applications in terms of patents request presented was also performed. A total of 1386 publications, from the year 1970 to the year 2021, were obtained by the literature search, and these had been collectively cited 38,805 times. The large amount of literature data available documents the interest in this plant’s use as a tool for integrating traditional holistic healing approach, e.g., using plants, herbs, and holistic remedies, into the healthcare system as supporting tools and/or therapeutic agents, which is a current worldwide challenge.

In recent years, EVs have emerged as promising vehicles for coding and non-coding RNAs (ncRNAs), which have demonstrated remarkable potential as biomarkers for various diseases, including chronic liver diseases (CLDs). EVs are small, membrane-bound particles released by cells, carrying an arsenal of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and other ncRNA species, such as piRNAs, circRNAs, and tsRNAs. These ncRNAs act as key regulators of gene expression, splicing, and translation, providing a comprehensive molecular snapshot of the cells of origin. The non-invasive nature of EV sampling, typically via blood or serum collection, makes them highly attractive candidates for clinical biomarker applications. Moreover, EV-encapsulated ncRNAs offer unique advantages over traditional cell-free ncRNAs due to their enhanced stability within the EVs, hence allowing for their detection in circulation for extended periods and enabling more sensitive and reliable biomarker measurements. Numerous studies have investigated the potential of EV-enclosed ncRNAs as biomarkers for CLD. MiRNAs, in particular, have gained significant attention due to their ability to rapidly respond to changes in cellular stress and inflammation, hallmarks of CLD pathogenesis. Elevated levels of specific miRNAs have been consistently associated with various CLD subtypes, including metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), and chronic hepatitis B and C. LncRNAs have also emerged as promising biomarkers for CLD. These transcripts are involved in a wide range of cellular processes, including liver regeneration, fibrosis, and cancer progression. Studies have shown that lncRNA expression profiles can distinguish between different CLD subtypes, providing valuable insights into disease progression and therapeutic response. Promising EV-enclosed ncRNA biomarkers for CLD included miR-122 (elevated levels of miR-122 are associated with MASLD progression and liver fibrosis), miR-21 (increased expression of miR-21 is linked to liver inflammation and fibrosis in CLD patients), miR-192 (elevated levels of miR-192 are associated with more advanced stages of CLD, including cirrhosis and HCC), LncRNA HOTAIR (increased HOTAIR expression is associated with MASLD progression and MASH development), and LncRNA H19 (dysregulation of H19 expression is linked to liver fibrosis and HCC progression). In the present review, we focus on the EV-enclosed ncRNAs as promising tools for the diagnosis and monitoring of CLD of various etiologies.

This study aims to evaluate the hepatoprotective, hypolipidemic and aortic morphometric effects of fish oil rich in omega-3 in hypercholesterolemic BALB/c mice. This is an experimental model that included 16 male BALB/c mice (Mus musculus) divided into three groups (G1 (standard commercial chow and 0.9% saline solution), G2 (hypercholesterolemic diet and 0.9% saline solution) and G3 (hypercholesterolemic diet and fish oil)) for 8 weeks. There was no significant difference in the treatment with omega-3-rich fish oil in the lipid profile (p > 0.05). In the histological analysis, group G2 detected the presence of hepatitis and liver tissue necrosis, but this was not observed in group G3. As for the morphometry in the light area of the vessel, the G1 group had a higher score (2.62 ± 0.36 mm2) when compared to G2 (2.10 ± 0.16 mm2) and G3 (2.26 ± 0.25 mm2) (p < 0.05). The vessel wall thickness did not differ between the groups (p > 0.05). It is concluded that supplementation with fish oil rich in omega-3 carried out in this study may have a protective effect on liver tissue, but it has not yet improved the lipid and morphometric profile. Despite this research being preliminary, it is a relevant study with future prospects for improving the doses of EPA and DHA in order to better elucidate the benefits of fish oil in models of dyslipidemia.