Gedunin is an important limonoid present in several genera of the Meliaceae family, mainly in seeds. Several biological activities have been attributed to gedunin, including antibacterial, insecticidal, antimalarial, antiallergic, anti-inflammatory, anticancer, and neuroprotective effects. The discovery of gedunin as a heat shock protein (Hsp) inhibitor represented a very important landmark for its application as a biological therapeutic agent. The current study is a critical literature review based on the several biological activities so far described for gedunin, its therapeutic effect on some human diseases, and future directions of research for this natural compound.

The Neem tree, Azadirachta indica A. Juss., is known for its large spectrum of compounds with biological and pharmacological interest. These include, among others, activities that are anticancer, antibacterial, antiviral, and anti-inflammatory. Some neem compounds are also used as insecticides, herbicides, and/or antifeedants. The safety of these compounds is not always taken into consideration and few in vivo toxicity studies have been performed. The current study is a literature review of the latest in vivo toxicity of A. indica. It is divided in two major sections—aquatic animals toxicity and mammalian toxicity—each related to neem’s application as a pesticide or a potential new therapeutic drug, respectively.

From 53 samples of human faeces containing Giardia lamblia cysts, 18 isolates were successfully excysted in vitro, and cultivated axenically in TYI-S-33 modified medium. The in vitro effects of metronidazole and albendazole on these isolates were evaluated by the trophozoite adherence inhibition method. The IC₅₀ was between 2.4 and 11.5 µM for metronidazole and 0.027 and 0.192 µM for albendazole. These IC₅₀ values were similar to those found for the ATCC 30888 and 30957 reference isolates. All isolates were susceptible to the antiparasitic drugs tested. These results suggest that resistance of G. lamblia to metronidazole and albendazole does not seem to be a significant problem in our population.

There is an increase in the popularity of craft beer, which is produced by small, independent, and traditional breweries. Since craft beer popularity is rising in Portugal this research focused on assessing physicochemical parameters, total phenolic content (TPC) and the antioxidant capacity of Portuguese craft beers and raw materials used in beer production. In this experimental study, 19 beer samples were analyzed. Parameters such as pH, Total Acidity, Reducing Sugar Content and TPC were evaluated. For the determination of antioxidant activity, DPPH scavenging activity and metal chelating activity (MCA) were analyzed in all samples. Craft beers demonstrated a high phenolic content (ranging from 343.78 mg GAE/L to 2172.49 mg GAE/L), significantly different from industrial beers. Craft beers demonstrated a higher inhibition of DPPH radicals and higher MCA than the raw materials. DPPH inhibition ranged from 36.5% to 96.0% for malt and 64.7% to 79.6% in hops samples. MCA also varied between the different samples, with results of 12.0% to 24.8% in malt samples and 3.8% to 23.5% in hops. Raw materials can potentially influence the antioxidant activity of the resulting beer. Positive correlations between TPC and physicochemical properties can be useful to help consumers choose beers with added value for health.

This study aimed to investigate the influence of genetic variants in neuroplasticity-related genes on antidepressant treatment phenotypes. The BDNF-TrkB signaling pathway, as well as the downstream kinases Akt and ERK and the mTOR pathway, have been implicated in depression and neuroplasticity. However, clinicians still struggle with the unpredictability of antidepressant responses in depressed patients. We genotyped 26 polymorphisms in BDNF, NTRK2, NGFR, CREB1, GSK3B, AKT, MAPK1, MTOR, PTEN, ARC, and SYN1 in 80 patients with major depressive disorder treated according to the Texas Medical Algorithm for 27 months at Hospital Magalhães Lemos, Porto, Portugal. Our results showed that BDNF rs6265, PTEN rs12569998, and SYN1 rs1142636 SNP were associated with treatment-resistant depression (TRD). Additionally, MAPK1 rs6928 and GSK3B rs6438552 gene polymorphisms were associated with relapse. Moreover, we found a link between the rs6928 MAPK1 polymorphism and time to relapse. These findings suggest that the BDNF, PTEN, and SYN1 genes may play a role in the development of TRD, while MAPK1 and GSK3B may be associated with relapse. GO analysis revealed enrichment in synaptic and trans-synaptic transmission pathways and glutamate receptor activity with TRD-associated genes. Genetic variants in these genes could potentially be incorporated into predictive models of antidepressant response.

Introduction: While biosimilar medicines can contribute to the sustainability of healthcare systems, their utilization rate varies across European countries. This study aims to identify and systematize policy measures and instruments used in European countries to increase biosimilar market share.Methods: A systematic review was conducted according to PRISMA 2020 recommendations. Medline-PubMed, Web of Science and ScienceDirect databases were searched using inclusion criteria that required full articles published in English between January 2006 and November 2023. Reviews, letters, reports, editorials and comments or opinion articles were excluded from this study.Results: Of the 1,137 articles, only 13 met the eligibility criteria for analysis, which covered a total of 28 European countries. Pricing regulation measures were found in 27 of these countries with tendering, price-linkage and internal reference price being the most used. Tendering was used by 27 countries to procure biosimilars in inpatient setting. Prescribing guidelines and recommendations were the widely used instrument. Some European countries adopted physician incentives, quotas, and prescription by international non-proprietary name.Conclusion: Automatic substitution was not commonly recommended or applied. Interchangeability and switching will become increasingly relevant issues. It is important that the positive results from some countries serve as an example for the future of these medicines in the European market.Systematic review registration: https://inplasy.com/, Identifier INPLASY2023120032.