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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.

Aim: Cardiovascular disease (CVD) are among the main causes of death worldwide and dyslipidemias account for one of the risk factors for these diseases. Habitual apple consumption appears to be inversely associated with reduced cardiovascular risk. Then, this systematic review aims to investigate the effect of chronic apple consumption on the lipid profile of adults with dyslipidemia. Methods: A systematic search was performed in electronic databases, including PubMed, Embase, Web of Science and Scopus, without restriction of year of publication. Inclusion criteria were randomized clinical trials in humans that investigated the effect of chronic consumption of whole fresh or dried apple, for a period longer than two weeks of intervention on the lipid profile. Results: Based on the methodology used and following the pre-established search strategies, 4,468 articles were found. After applying the inclusion and exclusion criteria, five articles were selected for qualitative evaluation, covering 522 adult participants of both sexes. Three randomized controlled trials included in this review demonstrated that there was a decrease in plasma total cholesterol (TC), triglyceride and low-density lipoprotein cholesterol (LDL-c) concentrations, in addition to an increase in high-density lipoprotein cholesterol (HDL-c) concentration. Two other studies found different results. Low risk of bias was identified in three studies. Conclusions: The analysis of the studies indicates that the consumption of fresh and/or dried apples with the peel has a beneficial effect on the lipid profile of adults, with a decrease in TC and LDL-c. These effects may be related to polyphenols and soluble fibers, among other functional compounds present in this fruit.

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.

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.

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.

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.

AimsMagnetic resonance imaging (MRI) studies report widespread cortical thinning in individuals with alcohol use disorder (AUD), but did not consider potential effects of pro-atherogenic conditions such as hypertension, type 2 diabetes mellitus, hepatitis C seropositivity and hyperlipidemia on cortical thickness. The conditions are associated with regional cortical thinning in those without AUD. We predicted that individuals with concurrent AUD and pro-atherogenic conditions demonstrate the greatest regional cortical thinning in areas most vulnerable to decreased perfusion.MethodsTreatment-seeking individuals with AUD (n = 126) and healthy controls (CON; n = 49) completed a 1.5 T MRI study. Regional cortical thickness was quantitated via FreeSurfer. Individuals with AUD and pro-atherogenic conditions (Atherogenic+), AUD without pro-atherogenic conditions (Atherogenic-) and CON were compared on regional cortical thickness.ResultsIndividuals with AUD showed significant bilateral cortical thinning compared to CON, but Atherogenic+ demonstrated the most widespread and greatest magnitude of regional thinning, while Atherogenic- had reduced thickness primarily in anterior frontal and posterior parietal lobes. Atherogenic+ also showed a thinner cortex than Atherogenic- in lateral orbitofrontal and dorso/dorsolateral frontal cortex, mesial and lateral temporal and inferior parietal regions.ConclusionsOur results demonstrate significant bilateral cortical thinning in individuals with AUD relative to CON, but the distribution and magnitude were influenced by comorbid pro-atherogenic conditions. The magnitude of cortical thinning in Atherogenic+ strongly corresponded to cortical watershed areas susceptible to decreased perfusion, which may result in morphometric abnormalities. The findings indicate that pro-atherogenic conditions may contribute to cortical thinning in those seeking treatment for AUD.

Cigarette smoking is associated with neurocognitive dysfunction in various populations, including those seeking treatment for an alcohol use disorder (AUD). This study compared the rate and extent of recovery on measures of processing speed, executive functions, general intelligence, visuospatial skills and working memory in treatment-seeking alcohol dependent individuals (ALC) who were never-smokers (nvsALC), former-smoker (fsALC), and active smokers (asALC), over approximately 8 months of abstinence from alcohol. Methods: ALC participants were evaluated at approximately 1 month of abstinence (AP1; n = 132) and reassessed after 8 months of sobriety (AP2; n = 54). Never-smoking controls (CON; n = 33) completed a baseline and follow-up (n = 19) assessment approximately 9 months later. Domains evaluated were executive functions, general intelligence, processing speed, visuospatial skills and working memory; a domain composite was formed from the arithmetic average of the foregoing domains. nvsALC showed greater improvement than fsALC, asALC and CON on most domains over the AP1-AP2 interval. fsALC demonstrated greater recovery than asALC on all domains except visuospatial skills; fsALC also showed greater improvements than CON on general intelligence, working memory and domain composite. asALC did not show significant improvement on any domain over the AP1-AP2 interval. At 8 months of abstinence, asALC were inferior to CON and nvsALC on multiple domains, fsALC performed worse than nvsALC on several domains, but nvsALC were not different from CON on any domain. Our results provide robust evidence that smoking status influenced the rate and extent of neurocognitive recovery between 1 and 8 months of abstinence in this ALC cohort. Chronic smoking in AUD likely contributes to the considerable heterogeneity observed in neurocognitive recovery during extended abstinence. The findings provide additional strong support for the benefits of smoking cessation and the increasing clinical movement to offer smoking cessation resources concurrent with treatment for AUD.

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.

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.