Gilberto Alves

Background/Objectives: Acorn flour has attracted attention as a potential starch-based excipient, yet comprehensive data on its powder properties and compaction behaviour remain limited. This study aimed to characterise the physicochemical properties and tableting performance of raw acorn (Quercus spp.) flour and to critically assess its viability for direct compression. Methods: Native flour was characterised for particle size distribution, moisture content, bulk and tapped densities, and flowability. Tablets of pure flour and binary mixtures containing 10% w/w paracetamol were compressed at 10 kN. Tablet quality was evaluated in terms of hardness, friability, disintegration time, and dissolution profile. Results: The flour exhibited particle size distributions of d10 = 13 µm, d50 = 54 µm, and d90 = 413 µm, with a loss on drying of 5.67% w/w. Flow properties, however, were unfavourable: Carr’s index of 35.9% and Hausner ratio of 1.56 classify the material as having very poor flowability, effectively precluding direct compression without modification. Pure flour compacts achieved moderate hardness (60–70 N at 10 kN) but failed friability testing, with values exceeding the pharmacopoeial limit of 1%. Conclusions: Overall, raw acorn flour displays cohesive behaviour under compression but suffers from inadequate flow properties and insufficient tablet mechanical strength. These findings indicate that substantial formulation or processing interventions are required before acorn flour can be considered a viable excipient for direct compression applications.

Cancer remains a public health concern with high rates of incidence and mortality, despite the significant advances achieved in recent decades. Therefore, this study aimed to develop novel hybrid molecules with potential anticancer properties. To this end, a steroid nucleus, specifically pregnenolone or dehydroepiandrosterone (DHEA), was covalently linked to a (thio)barbiturate scaffold. The hybrid molecules showed relevant antiproliferative activity against breast (MCF‐7) and prostate (PC‐3) cancer cells (IC ₅₀ = 8.73–38.53 and 4.08–36.01 µM, respectively), with selectivity indices of up to 2.79. The most promising compounds 4b (pregnenolone–barbiturate hybrid) and 7f (DHEA–thiobarbiturate hybrid) induced cell cycle arrest in the G0/G1 phase of breast cancer cells, with the DHEA–thiobarbiturate hybrid demonstrating a 6.6‐ and a 2.0‐fold increase in apoptotic cells compared with untreated cells and cells treated with the anticancer drug 5‐fluourouracil, respectively. Interestingly, a docking study suggested that these new hybrids may exhibit significant affinity for CYP17 and 5α‐reductase enzymes. Preliminary pharmacokinetic investigation of the most promising hybrids suggested low intestinal absorption, which may be improved through appropriate formulation strategies. Overall, these findings indicate that these novel hybrid compounds, incorporating both (thio)barbiturates and steroid nuclei, represent a promising strategy for the development of anticancer drug candidates.

Medicinal plants are gaining attention as natural alternatives to chemical additives in poultry production. This study evaluated the antioxidant and anticoccidial activities of both aqueous (AQ) and hydromethanolic (HM) extracts of Mentha aquatica (ME), Rosmarinus officinalis (RO), and Thymus algeriensis (TH). In vitro assays were conducted against Eimeria oocysts, while in vivo trials involved 450 Cobb 500 broiler chicks randomly distributed into nine groups, including untreated and infected controls, more specifically, a group treated with Toltrazuril, and six groups treated with plant extracts at two concentrations (15 and 25 mL/L in drinking water). Administration began on day 7, and all animals except uninfected controls were inoculated orally with 10,000 sporulated Eimeria oocysts on day 10. Growth performance, feed efficiency, oocyst output, lesion scores, and histopathological changes were assessed until day 32. HM extracts showed higher antioxidant activity, particularly ME-HM. RO-HM, which demonstrated the strongest in vitro anticoccidial effect. The in vivo results revealed that TH-AQ and RO-AQ significantly improved body weight, feed conversion efficiency, and intestinal integrity. Anticoccidial indices (ACI) confirmed their efficacy, with values exceeding 180 for TH and RO, indicating excellent anticoccidial activity comparable to that of Toltrazuril. These findings support the potential of these phytogenic extracts as practical natural tools in poultry health management.

Background: Potentially inappropriate medications (PIMs) and potential prescription omissions (PPOs) have been widely explored, but few studies focused on patients aged 75 years and over. This study was planned to explore the demographic and clinical characteristics of the older patients admitted to Units for Integrated Continuous Care, and to assess the prevalence and potential predictors of PIMs and PPOs. Methods: An observational, retrospective, and multicenter study was performed on 135 patients aged 75 years or older (i.e., 75–84 years and ≥85 years). PIMs and PPOs were investigated by applying the Screening Tool of Older People’s Prescriptions (STOPP) and Screening Tool to Alert to Right Treatment (START) criteria. Results: The oldest-old patients (≥85 years) were less likely to come from a hospital, had fewer daily medications and a lower number of oral doses, but they presented a higher Charlson Comorbidity Index, were more dependent on activities of daily living, and were less obese than those aged 75–84 years. Results showed a high prevalence of PIMs and PPOs in both age groups. The more common PIMs and PPOs were the same in both age groups. The oldest-old patients who suffered falls were more likely to have a prescription omission of vitamin D supplements. The PIM index was not significantly different between age groups but was higher in the oldest-old group. Conclusions: Patients with a higher number of prescriptions had a higher risk of PIMs. Regarding PPOs, male gender and fall risk were predictors in the youngest group, while the number of comorbidities was significantly associated with PPOs in the oldest group. This study supports the usefulness of the STOPP/START criteria to identify PIMs and PPOs in these patients, but more research is required to determine the potential adverse outcomes of PIMs and PPOs and their clinical and economic consequences.

The cultivation and processing of fruits generate a wide range of by-products (e.g., pulp, seeds, pomace, leaves, and stems), which are often underutilized despite being rich sources of phenolic compounds with well-documented bioactive properties. The bioactive potential of these compounds has attracted significant interest from both the pharmaceutical and food sectors, offering opportunities for their use in functional foods, dietary supplements, natural medicines, and additives. Among these, phenolic acids have shown promising potential in modulating risk factors associated with metabolic syndrome (MetS), a condition encompassing hypertension, dyslipidemia, hyperglycemia, and abdominal obesity, and contributing significantly to cardiovascular disease. Given the global burden of MetS and the need for novel preventive strategies, numerous studies have investigated the bioactivity of phenolic acids derived from fruit by-products. In this review, we critically examine recent studies regarding the phenolic acid composition of fruit-derived by-products and their biological activity in relation to MetS-related risk factors. This work aims to synthesize current findings, highlight prevailing research trends, and identify existing gaps in the literature to inform future research and promote the sustainable use of fruit by-products in the prevention and management of MetS.

IntroductionAlthough there are numerous options for epilepsy treatment, its effective control continues unsatisfactory. Thus, search for alternative therapeutic options to improve the efficacy/safety binomial of drugs becomes very attractive to investigate. In this context, intranasal administration of antiseizure drugs formulated on state-of-the-art nanosystems can be a promising strategy.Areas coveredThis work gives a comprehensive overview of different intranasal nanosystems for antiseizure drug administration developed and evaluated on preclinical studies over the last 10 years and published in 'PubMed' and 'Web of Science' databases. Additionally, it highlights their pharmaceutical critical quality attributes and in vivo pharmacological outputs that might infer possible results when transposing to clinical trials.Expert OpinionResearch into optimized nanosystems encapsulating antiseizure drugs to enhance direct nose-to-brain delivery has increased over the last years. Particularly, the interest in formulating first- and second-generation antiseizure drugs in nanoparticles is here highlighted, having demonstrated its in vivo safety and improvement on pharmacokinetic and efficacy outputs. Still, none of them were brought to clinical trials. Thus, considering the existing barriers between preclinical and clinical trials, if supported by robust and targeted quality by design approaches, intranasal drug delivery can be presented as a valid and superior alternative for epilepsy treatment.

Water mint (Mentha aquatica) is used in many formulations worldwide as a functional food and natural remedy to treat gastrointestinal disorders, lung diseases, and certain mental disorders such as epilepsy and depression. This study assessed the bioactivity of its infusion extract (INF) and hydroethanolic extract (HE) to highlight its health benefits. These extracts were analyzed for their chemical composition by HPLC-DAD-ESI-MSn, their antioxidant and antidiabetic properties, and their capacities to protect human erythrocytes against induced hemoglobin oxidation and lipid peroxidation. The effect on normal human dermal fibroblast (NHDF) cells and on the N27 rat dopaminergic neuron cell line was also assessed. The chromatographic analysis identified 57 compounds belonging to hydroxycinnamic acids, flavanones, flavone, and isoflavonoids. In respect to the biological potential, the Mentha aquatica extracts revealed a notable capacity for 2,2-diphenyl-1-picrylhydrazyl, nitric oxide, and superoxide radicals, as well as for the inhibition of α-glucosidase action and the protection of human erythrocytes against oxidative damage. Quantification revealed noteworthy phenolic content in both extracts. Additionally, the extracts demonstrated less cytotoxic effects regarding the NHDF and N27 cell lines. Overall, Mentha aquatica presents promising antioxidant activity and a spectrum of potential biological activities, underscoring its significance as a novel antioxidant candidate for applications in animal nutrition, human medicine, and natural product research in the pharmaceutical and nutraceutical industries.

Plant-derived phenolic compounds are recognized to provide several health benefits for humans, including anticancer, anti-inflammatory, and antioxidant proprieties. Their bioavailability in the human body has a significant impact on these outcomes. Their bioaccessibility and bioavailability are highly dependent on the structure and manner in which phenolics enter into the organism, through a complex food matrix, for instance, or as pure isolates. Furthermore, the bioaccessibility of phenolic compounds in the body is greatly impacted by interactions with a broad range of other macromolecules (such as proteins, lipids, dietary fibers, and polysaccharides) in food or during digestion. Encapsulation is a process that can improve bioaccessibility and bioavailability by guaranteeing coating of the active ingredients, controlled release, and targeted distribution to specific parts of the digestive system. However, this field has not yet received enough attention, due to the complex mechanisms through which phenolics act in the body. This review attempts to shed light on the results of research that has been performed on the potential and therapeutic benefits of encapsulated polyphenols in both health and disease.

Oral administration of medicines has been the most common route for drug delivery as it is cost-effective and is convenient for patients