Search Results (6)

The extracellular matrix (ECM) is the common denominator of more than 50 chronic diseases. Some of these chronic pathologies lead to enhanced tissue formation and deposition, whereas others are associated with increased tissue degradation, and some exhibit a combination of both, leading to severe tissue alterations. To develop effective therapies for diseases affecting the lung, liver, kidney, skin, intestine, musculoskeletal system, heart, and solid tumors, we need to modulate the ECM’s composition to restore its organization and function. Across diverse organ diseases, there are common denominators and distinguishing factors in this fibroinflammatory axis, which may be used to foster new insights into drug development across disease indications. The 2nd Extracellular Matrix Pharmacology Congress took place in Copenhagen, Denmark, from 17 to 19 June 2024 and was hosted by the International Society of Extracellular Matrix Pharmacology. The event was attended by 450 participants from 35 countries, among whom were prominent scientists who brought together state-of-the-art research on organ diseases and asked important questions to facilitate drug development. We highlight key aspects of the ECM in the liver, kidney, skin, intestine, musculoskeletal system, lungs, and solid tumors to advance our understanding of the ECM and its central targets in drug development. We also highlight key advances in the tools and technology that enable this drug development, thereby supporting the ECM. Full article

Chronic pain is a common consequence of breast cancer (BC) and its treatments. Pain neuroscience education (PNE) is a non-pharmacological intervention that adopts a biopsychosocial approach and has already been proven to be effective for different chronic pain syndromes. The present review aims to critically assess clinical trials comparing the efficacy of PNE to traditional biomedical education (BME) in reducing BC-related pain and improving quality of life. We conducted a literature search in scientific databases, including all studies regarding PNE use specifically for BC-related pain. Ongoing randomized controlled and observational studies were identified from ClinicalTrials.gov and congress proceedings. A total of eight clinical trials met the review criteria. The participants were all administered physical therapy and assigned to receive either BME or PNE interventions. Among the completed clinical studies, one reported no statistically relevant differences between the two groups, whereas the other showed lower levels of pain-related indexes in the PNE population compared to the BME one. While the current literature is inconclusive regarding the effectiveness of PNE for managing BC pain, we strongly support the need for further trials, as PNE could empower BC patients in both prevention of and coping with pain, offering the advantage of having no side effects. Full article

The unintended modulation of nuclear receptor (NR) activity by drugs can lead to toxicities amongst the endocrine, gastrointestinal, hepatic cardiovascular, and central nervous systems. While secondary pharmacology screening assays include NRs, safety risks due to unintended interactions of small molecule drugs with NRs remain poorly understood. To identify potential nonclinical and clinical safety effects resulting from functional interactions with 44 of the 48 human-expressed NRs, we conducted a systematic narrative review of the scientific literature, tissue expression data, and used curated databases (OFF-X™) (Off-X, Clarivate) to organize reported toxicities linked to the functional modulation of NRs in a tabular and machine-readable format. The top five NRs associated with the highest number of safety alerts from peer-reviewed journals, regulatory agency communications, congresses/conferences, clinical trial registries, and company communications were the Glucocorticoid Receptor (GR, 18,328), Androgen Receptor (AR, 18,219), Estrogen Receptor (ER, 12,028), Retinoic acid receptors (RAR, 10,450), and Pregnane X receptor (PXR, 8044). Toxicities associated with NR modulation include hepatotoxicity, cardiotoxicity, endocrine disruption, carcinogenicity, metabolic disorders, and neurotoxicity. These toxicities often arise from the dysregulation of receptors like Peroxisome proliferator-activated receptors (PPARα, PPARγ), the ER, PXR, AR, and GR. This dysregulation leads to various health issues, including liver enlargement, hepatocellular carcinoma, heart-related problems, hormonal imbalances, tumor growth, metabolic syndromes, and brain function impairment. Gene expression analysis using heatmaps for human and rat tissues complemented the functional modulation of NRs associated with the reported toxicities. Interestingly, certain NRs showed ubiquitous expression in tissues not previously linked to toxicities, suggesting the potential utilization of organ-specific NR interactions for therapeutic purposes. Full article

Cirrhotic cardiomyopathy (CCM), cardiac dysfunction in end-stage liver disease in the absence of prior heart disease, is an important clinical entity that contributes significantly to morbidity and mortality. The original definition for CCM, established in 2005 at the World Congress of Gastroenterology (WCG), was based upon known echocardiographic parameters to identify subclinical cardiac dysfunction in the absence of overt structural abnormalities. Subsequent advances in cardiovascular imaging and in particular myocardial deformation imaging have rendered the WCG criteria outdated. A number of investigations have explored other factors relevant to CCM, including serum markers, electrocardiography, and magnetic resonance imaging. CCM characteristics include a hyperdynamic circulatory state, impaired contractility, altered diastolic relaxation, and electrophysiological abnormalities, particularly QT interval prolongation. It is now known that cardiac dysfunction worsens with the progression of cirrhosis. Treatment for CCM has traditionally been limited to supportive efforts, but new pharmacological studies appear promising. Left ventricular diastolic dysfunction in CCM can be improved by targeted heart rate reduction. Ivabradine combined with carvedilol improves left ventricular diastolic dysfunction through targeted heart rate reduction, and this regimen can improve survival in patients with cirrhosis. Orthotopic liver transplantation also appears to improve CCM. Here, we canvass diagnostic challenges associated with CCM, introduce cardiac physiology principles and the application of echocardiographic techniques, and discuss the evidence behind therapeutic interventions in CCM. Full article

This Issue collates the abstracts presented at the 25th Biennial International Congress on Thrombosis held on 23–26 May 2018. Prevention and treatment of thromboembolic events is a main issue in medicine that involves all the components of the health care system. Recently, a strong boost in this field came from the introduction of new antithrombotic agents whose use is expanding with the need for more information obtained by real-life studies. Thus, ICT 2018 was an important venue to compare clinical experiences and learn new advances in basic and pharmacological sciences. Full article

The 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017) was arranged within the celebration of the 65th Anniversary of the Faculty of Pharmacy at Comenius University in Bratislava, Slovakia from 5–8 September 2017 to get together specialists in medicinal chemistry, organic synthesis, pharmaceutical analysis, screening of bioactive compounds, pharmacology and drug formulations; promote the exchange of scientific results, methods and ideas; and encourage cooperation between researchers from all over the world. The topic of the conference, “Drug Synthesis and Analysis,” meant that the symposium welcomed all pharmacists and/or researchers (chemists, analysts, biologists) and students interested in scientific work dealing with investigations of biologically active compounds as potential drugs. The authors of this manuscript were plenary speakers and other participants of the symposium and members of their research teams. The following summary highlights the major points/topics of the meeting. Full article