Isoquinolinequinone N-oxides with diverging mechanisms of action induce collateral sensitivity against multidrug resistant cancer cells.

Multidrug resistance (MDR) is a major challenge in cancer research. Collateral sensitizers, compounds that exploit the enhanced defense mechanisms of MDR cells as weaknesses, are a proposed strategy to overcome MDR. Our previous work reported the synthesis of two novel Isoquinolinequinone (IQQ) N-oxides that induce collateral sensitivity in MDR ABCB1-overexpressing non-small cell lung cancer (NSCLC) and colorectal cancer cells.

A Comparison of Active Pharmacovigilance Strategies Used to Monitor Adverse Events to Antiviral Agents: A Systematic Review.

Introduction: The safety of antiviral agents in real-world clinical settings is crucial, as pre-marketing studies often do not capture all adverse events (AE). Active pharmacovigilance strategies are essential for detecting and characterising these AE comprehensively.

Objective: The aim of this study was to identify and characterise active pharmacovigilance strategies used in real-world clinical settings for patients under systemic antiviral agents, focusing on the frequency of AE and the clinical data sources used.

Discovery of Potent Isoquinolinequinone -Oxides to Overcome Cancer Multidrug Resistance.

Multidrug resistance (MDR) of human tumors has resulted in an immediate need to develop appropriate new drugs. This work outlines the development of 20 potent IQQ -oxide derivatives in two isomeric families, both exhibiting nanomolar GI against human tumor cell lines. Preliminary NCI-60 tumor screening sees the C(6) isomers achieve a mean GI > 2 times lower than the corresponding C(7) isomers.

A comprehensive analysis of digital health-focused Living Labs: innovative approaches to dementia.

The increasing prevalence of dementia demands innovative solutions; however, existing technological products often lack tailored support for individuals living with this condition. The Living Lab approach, as a collaborative innovation method, holds promise in addressing this issue by actively involving end-users in the design and development of solutions adapted to their needs. Despite this potential, the approach still faces challenges due to its lack of recognition as a research methodology and its absence of tailored guidelines, particularly in dementia care, prompting inquiries into its effectiveness.

The interplay between climate change and ageing: A systematic review of health indicators.

Climate change and rapid population ageing pose challenges for communities and public policies. This systematic review aims to gather data from studies that present health indicators establishing the connection between climate change and the physical and mental health of the older population (≥ 65 years), who experience a heightened vulnerability to the impacts of climate change when compared to other age cohorts. This review was conducted according to the PICO strategy and following Cochrane and PRISMA guidelines.

Unveiling the future: precision pharmacovigilance in the era of personalized medicine.

In the era of personalized medicine, pharmacovigilance faces new challenges and opportunities, demanding a shift from traditional approaches. This article delves into the evolving landscape of drug safety monitoring in the context of personalized treatments. We aim to provide a succinct reflection on the intersection of tailored therapeutic strategies and vigilant pharmacovigilance practices.

Assessing medication use patterns by clinical outcomes severity among inpatients with COVID-19: A retrospective drug utilization study.

Purpose: This study assessed medication patterns for inpatients at a central hospital in Portugal and explored their relationships with clinical outcomes in COVID-19 cases.

Methods: A retrospective study analyzed inpatient medication data, coded using the Anatomical Therapeutic Chemical classification system, from electronic patient records. It investigated the association between medications and clinical severity outcomes such as ICU admissions, respiratory/circulatory support needs, and hospital discharge status, including mortality (identified by ICD-10-CM/PCS codes).

A systematic review on experimental studies about patient adherence to treatment.

A better understanding of patients' adherence to treatment is a prerequisite to maximize the benefit of healthcare provision for patients, reduce treatment costs, and is a key factor in a variety of subsequent health outcomes. We aim to understand the state of the art of scientific evidence about which factors influence patients' adherence to treatment. A systematic literature review was conducted using PRISMA guidelines in five separate electronic databases of scientific publications: PubMed, PsycINFO (ProQuest), Cochrane library (Ovid), Google Scholar, and Web of Science.

Novel family of [RuCp(N,N)(P)] compounds with simultaneous anticancer and antibacterial activity: Biological evaluation and solution chemistry studies.

A family of ten novel ruthenium(II)-cyclopentadienyl organometallics of general formula [Ru(η-CH)(N,N)(PPh(CHCOOR)][CFSO] (1-10) in which (N,N) = 4,4'-R'-2,2'-bipyridyl (R = -H or -CHCHOH; R' = -H, -CH, -OCH, -CHOH, and -CH-biotin) was prepared from [Ru(η-CH)(PPh(CHCOOH))Cl]. All compounds were fully characterized by means of several spectroscopic and analytical techniques, and the molecular structures of [Ru(η-CH)(PPh(CHCOOH))Cl], 1, 3 and 4 have been additionally studied by single-crystal X-ray diffraction. The anticancer activity of all compounds was evaluated in sensitive and multidrug-resistant counterpart cell lines from human colorectal cancer (Colo 205 and Colo 320) and non-small cell lung cancer NSCLC (A549, NCI-H460 versus NCI-H460/R) as well.

Rats prefer condensed milk to strawberry jam - a new possibility for voluntary oral drug administration.

Voluntary oral drug administration using sweet substances promotes rodents' therapeutic compliance while reducing stress induced by forced drug administration. We aimed to test whether rats would willingly eat strawberry jam or condensed milk from a syringe, and which one they would prefer. Our results show that rats prefer condensed milk, demonstrating its potential as a vehicle for the voluntary oral administration of drugs in experimental protocols.

Changing the paradigm in health and care services: modern value chains using open innovation for the creation of new digital health solutions.

Digital Health is a subject of extensive discourse when considering its current and future significance. This significance arises from a convergence of various factors, including the escalating capabilities and cost-effectiveness of computing and communication technology, coupled with the mounting demands and challenges faced by healthcare systems. The integration of health and technology, when studied collectively with the purpose of addressing tangible real-world issues, holds the potential to generate substantial outcomes that greatly influence the provision of clinical and social care, thereby enhancing the overall well-being of both individuals and populations.

The role of Extracellular Vesicles in glycolytic and lipid metabolic reprogramming of cancer cells: Consequences for drug resistance.

In order to adapt to a higher proliferative rate and an increased demand for energy sources, cancer cells rewire their metabolic pathways, a process currently recognized as a hallmark of cancer. Even though the metabolism of glucose is perhaps the most discussed metabolic shift in cancer, lipid metabolic alterations have been recently recognized as relevant players in the growth and proliferation of cancer cells. Importantly, some of these metabolic alterations are reported to induce a drug resistant phenotype in cancer cells.

Fibroblasts in pancreatic cancer: molecular and clinical perspectives.

Pancreatic stellate cells (PSCs) and cancer-associated fibroblasts (CAFs) are highly abundant cells in the pancreatic tumor microenvironment (TME) that modulate desmoplasia. The formation of a dense stroma leads to immunosuppression and therapy resistance that are major causes of treatment failure in pancreatic ductal adenocarcinoma (PDAC). Recent evidence suggests that several subpopulations of CAFs in the TME can interconvert, explaining the dual roles (antitumorigenic and protumorigenic) of CAFs in PDAC and the contradictory results of CAF-targeted therapies in clinical trials.

ACE and ACE2 catalytic activity in the fecal content along the gut.

Background: Angiotensin-converting enzyme (ACE) and ACE2 are two major enzymes of the renin-angiotensin-aldosterone system (RAAS), which control the formation/degradation of angiotensin (Ang) II and Ang1-7, regulating their opposite effects. We aimed at evaluating the catalytic activity of ACE and ACE2 in the intestinal content and corresponding intestinal tissue along the gut of Wistar Han rats.

Methods: Portions of the ileum, cecum, proximal colon, and distal colon, and the corresponding intestinal content were collected from Wistar Han rats.

The role of extracellular vesicles in the transfer of drug resistance competences to cancer cells.

Drug resistance remains a major hurdle to successful cancer treatment, being accountable for approximately 90% of cancer-related deaths. In the past years, increasing attention has been given to the role of extracellular vesicles (EVs) in the horizontal transfer of drug resistance in cancer. Indeed, many studies have described the dissemination of therapy resistance traits mediated by EVs, which may be transferred from drug resistant tumor cells to their drug sensitive counterparts.

Analysis of risk factors for canine mast cell tumors based on the Kiupel and Patnaik grading system among dogs with skin tumors.

Background: Skin tumors are the most frequently diagnosed lesions, of which 7%-21% are mast cell tumors (MCTs). There is a great effort to identify factors that can influence the prospective course of MCTs. Although, the histological grade is considering an important predictor helping to determine the malignancy and metastatic potential of MCTs.

3D Cell Culture Models as Recapitulators of the Tumor Microenvironment for the Screening of Anti-Cancer Drugs.

Today, innovative three-dimensional (3D) cell culture models have been proposed as viable and biomimetic alternatives for initial drug screening, allowing the improvement of the efficiency of drug development. These models are gaining popularity, given their ability to reproduce key aspects of the tumor microenvironment, concerning the 3D tumor architecture as well as the interactions of tumor cells with the extracellular matrix and surrounding non-tumor cells. The development of accurate 3D models may become beneficial to decrease the use of laboratory animals in scientific research, in accordance with the European Union's regulation on the 3R rule (Replacement, Reduction, Refinement).

Impact of cancer metabolism on therapy resistance - Clinical implications.

Despite an increasing arsenal of anticancer therapies, many patients continue to have poor outcomes due to the therapeutic failures and tumor relapses. Indeed, the clinical efficacy of anticancer therapies is markedly limited by intrinsic and/or acquired resistance mechanisms that can occur in any tumor type and with any treatment. Thus, there is an urgent clinical need to implement fundamental changes in the tumor treatment paradigm by the development of new experimental strategies that can help to predict the occurrence of clinical drug resistance and to identify alternative therapeutic options.

Different Ability of Multidrug-Resistant and -Sensitive Counterpart Cells to Release and Capture Extracellular Vesicles.

Cancer multidrug resistance (MDR) is one of the main challenges for cancer treatment efficacy. MDR is a phenomenon by which tumor cells become resistant to several unrelated drugs. Some studies have previously described the important role of extracellular vesicles (EVs) in the dissemination of a MDR phenotype.

The Role of Anthocyanins, Deoxyanthocyanins and Pyranoanthocyanins on the Modulation of Tyrosinase Activity: An In Vitro and In Silico Approach.

Tyrosinase is the central enzyme involved in the highly complex process of melanin formation, catalyzing the rate-limiting steps of this biosynthetic pathway. Due to such a preponderant role, it has become a major target in the treatment of undesired skin pigmentation conditions and also in the prevention of enzymatic food browning. Numerous phenolic-based structures from natural sources have been pointed out as potential tyrosinase inhibitors, including anthocyanins.