Chitosan Nanoparticles for Enhanced Immune Response and Delivery of Multi-Epitope Vaccines in a BALB/c Mouse Model.

: is the leading cause of chronic gastritis, peptic ulcer, gastric adenocarcinoma, and mucosal-associated lymphoma. Due to the emerging problems with antibiotic treatment against in clinical practice, vaccination has gained more interest. Oral immunization is considered a promising approach for preventing initial colonization of this bacterium in the gastrointestinal tract, establishing a first line of defense at gastric mucosal surfaces.

Proteostasis Decline and Redox Imbalance in Age-Related Diseases: The Therapeutic Potential of NRF2.

Nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of cellular homeostasis, overseeing the expression of a wide array of genes involved in cytoprotective processes such as antioxidant and proteostasis control, mitochondrial function, inflammation, and the metabolism of lipids and glucose. The accumulation of misfolded proteins triggers the release, stabilization, and nuclear translocation of NRF2, which in turn enhances the expression of critical components of both the proteasomal and lysosomal degradation pathways. This process facilitates the clearance of toxic protein aggregates, thereby actively maintaining cellular proteostasis.

Nitroaromatic-based triazene prodrugs to target the hypoxic microenvironment in glioblastoma.

Hypoxia is a hallmark of the glioblastoma multiforme microenvironment and represents a promising therapeutic target for cancer treatment. Herein, we report nitroaromatic-based triazene prodrugs designed for selective activation by tumoral endogenous reductases and release of the cytotoxic methyldiazonium ion a self-immolative mechanism. While compounds bearing a 2-nitrofuran bioreductive group were more efficiently activated by nitroreductases, 4-nitrobenzyl prodrugs 1b, 1d and 1e elicited a more pronounced cytotoxic effect against LN-229 and U-87 MG glioblastoma cell lines under hypoxic conditions when compared to temozolomide (TMZ), the golden standard for glioblastoma treatment.

Combining in vitro, in vivo, and in silico approaches to evaluate the effect of serotonergic-based topical therapies on mild to moderate psoriasis.

Psoriasis, a chronic inflammatory skin disease, poses a significant burden on patients' quality of life and healthcare systems. While mild-to-moderate cases are treated topically, usually combined with phototherapy, severe cases require systemic treatment with immunosuppressants, retinoids or biologics. However, all available treatments have drawbacks in terms of efficiency and side effects.

Phytochemical Characterization and Biological Activity of Two Species from Guinea-Bissau.

The dried leaves of A.Rich. and Planch.

Dissemination of arr-2 and arr-3 is associated with class 1 integrons in Klebsiella pneumoniae clinical isolates from Portugal.

\nKlebsiella pneumoniae is a common pathogen of healthcare-associated infections expressing a plethora of antimicrobial resistance loci, including ADP-ribosyltransferase coding genes (arr), able to mediate rifampicin resistance. The latter has activity against a broad range of microorganisms by inhibiting DNA-dependent RNA polymerases. This study aims to characterise the arr distribution and genetic context in 138 clinical isolates of K.

Genetic Diversity and Antiretroviral Resistance in HIV-1-Infected Patients Newly Diagnosed in Cabo Verde.

The high genetic variability of HIV-1 and the emergence of transmitted drug resistance (TDR) can impact treatment efficacy. In this study, we investigated the prevalent HIV-1 genotypes and drug-resistance-associated mutations in drug-naïve HIV-1 individuals in Cabo Verde. The study, conducted between 2018 and 2019, included drug-naïve HIV-1 individuals from the São Vicente, Boa Vista, Fogo, and Santiago islands.

HIV-1 Antiretroviral Drug Resistance in Mozambique: A Systematic Review and Meta-Analysis.

This systematic review assessed the prevalence of transmitted and acquired HIV drug resistance (HIVDR) and the associated risk factors in Mozambique. A search of the PubMed, Cochrane, B-On, and Scopus databases up to December 2023 was conducted and included 11 studies with 1118 HIV-1 pol sequences. Drug resistance mutations (DRMs) to NNRTIs were found in 13% of the drug-naive individuals and 31% of those on ART, while NRTI resistance occurred in 5% and 10%, respectively.

Unveiling the Potential of C Factor Applied to Pilot Bioavailability/Bioequivalence Studies-A Case Study with Pazopanib Drug Products.

When companies are uncertain about the potential of a new formulation to be bioequivalent to a Reference product, it is common practice to carry out downsized pilot studies as a gatekeeping in vivo strategy to decide whether to move forward or not with a full-size pivotal study. However, due to the small study size, these studies are inarguably more sensitive to variability. To address and mitigate the uncertainty of the conclusions of pilot studies concerning the maximum observed concentration (C), the factor was proposed as an alternative approach to the average bioequivalence statistical methodology.

Liposomal Formulation of an Organogold Complex Enhancing Its Activity as Antimelanoma Agent-In Vitro and In Vivo Studies.

The therapeutic management of melanoma, the most aggressive form of skin cancer, remains challenging. In the search for more effective therapeutic options, metal-based complexes are being investigated for their anticancer properties. Cisplatin was the first clinically approved platinum-based drug and, based on its success, other metals (e.

Assessing Protein Content and Dimer Formation in the Bevacizumab Reference Product and Biosimilar Versions Marketed in Spain.

Background: The manufacture of biologics is a complex, controlled, and reproducible process that results in a product that meets specifications. This should be based on data from batches used to demonstrate manufacturing consistency. Ten batches of originator product (Avastin) were analyzed over a 10-year period.

Copper and Antimicrobial Residues in the Liver and Kidney-Antimicrobial Resistance and Cu Tolerance Unrelated in from Piglets' Faeces.

Antimicrobials, widely used in livestock, have induced the emergence of antimicrobial-resistant bacteria, prompting farmers to explore alternatives like copper. This study aims to determine antimicrobial residues and Cu concentrations in the liver and kidney of piglets and to investigate the correlation between Cu and antimicrobial use and the resistance to Cu and antimicrobials of isolated from piglets' faeces. Antimicrobial residues were quantified by UHPLC-ToF-MS; Cu was quantified using FAAS; microbiological methods were used for isolation, CuSO minimal inhibitory concentration (MIC), and antimicrobial susceptibility; and to detect genes, Real-Time PCR was used.

Design, Synthesis, and Biological Evaluation of Novel Urea-Containing Carnosic Acid Derivatives with Anticancer Activity.

A series of novel carnosic acid derivatives incorporating urea moieties at the C-20 position was synthesized and evaluated for their antiproliferative activity against the HCT116 colorectal cancer cell line. Most derivatives demonstrated enhanced antiproliferative activity compared to that of carnosic acid . The most promising derivatives were tested in other colorectal cancer cell lines (SW480, SW620, and Caco-2), melanoma (A375), and pancreatic cancer (MiaPaca-2).

Patterns of outpatient proton‒pump inhibitors use among older adults in a duplicative health system: comparing public and private prescribing.

Background: Proton-pump-inhibitors (PPIs) are overprescribed, posing challenges to patients and healthcare systems. In Portugal, the public National Health Service (NHS) provides universal coverage and reimburses medication regardless of prescription origin, i.e.

Fostering consensus for the implementation of a clinical pharmacy specialization: a nominal group technique approach with pharmacy stakeholders.

Objectives: To explore the need for a specialization in clinical pharmacy and the model to be adopted, as perceived by Portuguese stakeholders.

Methods: A nominal group technique through two online meetings addressed four questions: pros and cons of specialization models used internationally; preferred model for Portugal; and success factors for implementation.

Key Findings: All nine stakeholders recognized the need to train pharmacists in clinical pharmacy and agreed specialization is essential, through a model including strong clinical undergraduate education, supplemented with postgraduate training.

Microglia and Immune cells interactions in multiple sclerosis cognitive impairment: a postmortem study.

Multiple Sclerosis (MS), a neuroinflammatory disease of the central nervous system, is one of the commonest causes of non-traumatic disability among young adults. Impaired cognition arises as an impactful symptom affecting more than 50% of the patients and with substantial impact on social, economic, and individual wellbeing. Despite the lack of therapeutic strategies, many efforts have been made to understand the mechanisms behind cognitive impairment in MS patients.

Diagnostic performance of biopsy-based methods for determination of Helicobacter pylori infection in dyspeptic Mozambican patients.

Background: Helicobacter pylori (H. pylori) is a Gram-negative bacterium capable of colonizing the human stomach, which can lead to various gastrointestinal conditions. Several invasive and non-invasive methods exist for diagnosing H.

4-Oxo-β-lactams as Covalent Inhibitors of the Mitochondrial Intramembrane Protease PARL.

Rhomboid proteases play a variety of physiological roles, but rhomboid protease inhibitors have been mostly developed for the model rhomboid GlpG. In this work, we screened different electrophilic scaffolds against the human mitochondrial rhomboid PARL and found 4-oxo-β-lactams as submicromolar inhibitors. Multifaceted computations suggest explanations for the activity at the molecular scale and provide models of covalently bound complexes.

Exploring the Biological Activity of Phytocannabinoid Formulations for Skin Health Care: A Special Focus on Molecular Pathways.

Recent advancements have highlighted the potential of cannabis and its phytocannabinoids (pCBs) in skin health applications. These compounds, through their interaction with the endocannabinoid system (ECS), show promise for skin health products. Their ability to regulate inflammation, oxidative stress and cell proliferation makes them useful in addressing skin problems such as inflammation, scarring, healing, acne and aging, positioning them as valuable tools for innovative skincare solutions.

Two-in-one nanoparticle platform induces a strong therapeutic effect of targeted therapies in P-selectin-expressing cancers.

Combined therapies in cancer treatment aim to enhance antitumor activity. However, delivering multiple small molecules imposes challenges, as different drugs have distinct pharmacokinetic profiles and tumor penetration abilities, affecting their therapeutic efficacy. To circumvent this, poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-based nanoparticles were developed as a platform for the codelivery of synergistic drug ratios, improving therapeutic efficacy by increasing the percentage of injected dose reaching the tumor.

Uncovering layer by layer the risk of nanoplastics to the environment and human health.

Nanoplastics (NPs), defined as plastic particles with dimensions less than 100 nm, have emerged as a persistent environmental contaminant with potential risk to both environment and human health. Nanoplastics might translocate across biological barriers and accumulate in vital organs, leading to inflammatory responses, oxidative stress, and genotoxicity, already reported in several organisms. Disruptions to cellular functions, hormonal balance, and immune responses were also linked to NPs exposure in assays.

Selective Lipophilization of Natural Phenolic Alcohols Induced by Choline Chloride-Based Natural Deep Eutectic Solvents.

In this scientific work, a novel and green method for selective lipophilization of EVOO's bioactive phenolic alcohols (PAs), namely, tyrosol, hydroxytyrosol, and its metabolite homovanillyl alcohol as fatty acid esters, is elucidated. The PAs have been employed as hydrogen bond donors in the formation of natural deep eutectic solvents (NADES) with choline chloride (ChCl). The fast and cheap esterification method by formation of choline chloride-based deep eutectic solvents promotes the derivatization of PAs with various fatty acids as acylating agents in the absence of organic solvents and catalysts.

Oranges, potatoes and phytonutrients; why are they good for human health.

Dietary chemoprevention has emerged as a cost-effective approach to control most prevalent chronic diseases including cancer. Changes in dietary patterns and lifestyle, such as increasing the consumption of fruits and vegetables and more balanced intakes of meat and plant foods, are a practical and effective strategy for reducing the incidence of chronic diseases. Phytonutrients (or phytochemicals) are found in eatable fruits and vegetables that, daily ingested, may exhibit a potential for modulating human metabolism in a manner favourable for the prevention of chronic and degenerative diseases.