Cancer patients, especially long cancer survivors, are exposed to several cardio-metabolic diseases, including diabetes, heart failure, and atherosclerosis, which increase their risk of cardiovascular mortality. Therapy with glucagon-like peptide 1 (GLP1) receptor agonists demonstrated several beneficial cardiovascular effects, including atherosclerosis and heart failure prevention. Cardiovascular outcome trials (CVOTs) suggest that GLP-1 RA could exert cardiorenal benefits and systemic anti-inflammatory effects in patients with type-2 diabetes through the activation of cAMP and PI3K/AkT pathways and the inhibition of NLRP-3 and MyD88.
View Article and Find Full Text PDFLimited data are available about the coastal ecology of the Calabria region, in the southern Italy. As well, data about the levels of biodiversity and the structure of food webs in these environments are totally missing. However, considering the wide range of physical and ecological conditions distinguishing these ecosystems, a remarkable spread of biodiversity is expected.
View Article and Find Full Text PDFIn the last decades, pharmaceuticals have emerged as a new class of environmental contaminants. Antihypertensives, including angiotensin-converting enzyme (ACE) inhibitors, are of special concern due to their increased consumption over the past years. However, the available data on their putative effects on the health of aquatic animals, as well as the possible interaction with biological systems are still poorly understood.
View Article and Find Full Text PDFBackground: Anthracycline-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in patients with cancer. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) exert multiple cardiometabolic benefits in patients with/without type 2 diabetes, chronic kidney disease, and heart failure with reduced and preserved ejection fraction. We hypothesized that the SGLT2i dapagliflozin administered before and during doxorubicin (DOXO) therapy could prevent cardiac dysfunction and reduce pro-inflammatory pathways in preclinical models.
View Article and Find Full Text PDFAnthracycline-induced cardiomyopathies and sarcopenia are frequently seen in cancer patients, affecting their overall survival and quality of life; therefore, new cardioprotective and anti-sarcopenic strategies are needed. Vericiguat is a new oral guanylate cyclase activator that reduces heart failure hospitalizations or cardiovascular death. This study highlighted the potential cardioprotective and anti-sarcopenic properties of vericiguat during anthracycline therapy.
View Article and Find Full Text PDFCreated and published in a printed volume in 1611, the emblem chosen by the literary Academy of the Umoristi is intriguing at multiple levels. At a time when the water cycle was still unknown, the image engaged the thorny question of how the evaporation of salty seawater, condensed into clouds, could subsequently pour down as sweet rain. Additionally, the Lucretian motto "Redit agmine dulci" audaciously evoked the philosophy of atoms.
View Article and Find Full Text PDFBackground: Immune checkpoint blockade in monotherapy or combinatorial regimens with chemotherapy or radiotherapy have become an integral part of oncology in recent years. Monoclonal antibodies against CTLA-4 or PD-1 or PDL-1 are the most studied ICIs in randomized clinical trials, however, more recently, an anti-LAG3 (Lymphocyte activation gene-3) antibody, Relatlimab, has been approved by FDA in combination with Nivolumab for metastatic melanoma therapy. Moreover, Atezolizumab is actually under study in association with Ipilimumab for therapy of metastatic lung cancer.
View Article and Find Full Text PDFBackground: The regenerating zebrafish fin skeleton is comprised of multiple bony fin rays, each made of alternating bony segments and fin ray joints. This pattern is regulated by the gap junction protein Connexin43 (Cx43), which provides instructional cues to skeletal precursor cells (SPCs). Elevated Cx43 favors osteoblast differentiation and disfavors joint forming cell differentiation.
View Article and Find Full Text PDFCohesins are ATPase complexes that play central roles in cellular processes such as chromosome division, DNA repair, and gene expression. Cohesinopathies arise from mutations in cohesin proteins or cohesin complex regulators and encompass a family of related developmental disorders that present with a range of severe birth defects, affect many different physiological systems, and often lead to embryonic fatality. Treatments for cohesinopathies are limited, in large part due to the lack of understanding of cohesin biology.
View Article and Find Full Text PDFCancer patients treated with immune checkpoint inhibitors (ICIs) are exposed to a high risk of atherosclerosis and cardiometabolic diseases due to systemic inflammatory conditions and immune-related atheroma destabilization. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key protein involved in metabolism of low-density lipoprotein (LDL) cholesterol. PCSK9 blocking agents are clinically available and involve monoclonal antibodies, and SiRNA reduces LDL levels in high-risk patients and atherosclerotic cardiovascular disease events in multiple patient cohorts.
View Article and Find Full Text PDFCornelia de Lange syndrome (CdLS) and Roberts syndrome (RBS) are severe developmental maladies that arise from mutation of cohesin (including , CdLS) and (RBS). Though ESCO2 activates cohesin, CdLS and RBS etiologies are currently considered non-synonymous and for which pharmacological treatments are unavailable. Here, we identify a unifying mechanism that integrates these genetic maladies to pharmacologically-induced teratogenicity via thalidomide.
View Article and Find Full Text PDFCytokines in cardiac tissue plays a key role in progression of cardiometabolic diseases and cardiotoxicity induced by several anticancer drugs. Interleukin-1β is one on the most studied regulator of cancer progression, survival and resistance to anticancer treatments. Recent findings indicate that interleukin1-β exacerbates myocardial damages in cancer patients treated with chemotherapies and immune check-point inhibitors.
View Article and Find Full Text PDFChanges to allometry, or the relative proportions of organs and tissues within organisms, is a common means for adaptive character change in evolution. However, little is understood about how relative size is specified during development and shaped during evolution. Here, through a phylogenomic analysis of genome-wide variation in 35 species of flying fishes and relatives, we identify genetic signatures in both coding and regulatory regions underlying the convergent evolution of increased paired fin size and aerial gliding behaviors.
View Article and Find Full Text PDFGap junctions mediate direct cell-to-cell communication by forming channels that physically couple cells, thereby linking their cytoplasm, permitting the exchange of molecules, ions, and electrical impulses. Gap junctions are assembled from connexin (Cx) proteins, with connexin 43 (Cx43) being the most ubiquitously expressed and best studied. While the molecular events that dictate the Cx43 life cycle have largely been characterized, the unusually short half-life of Cxs of only 1-5 h, resulting in constant endocytosis and biosynthetic replacement of gap junction channels, has remained puzzling.
View Article and Find Full Text PDFRenal cell carcinoma (RCC) represents the main renal tumors and are highly metastatic. Sunitinib, a recently-approved, multi-targeted Tyrosine Kinases Inhibitor (TKi), prolongs survival in patients with metastatic renal cell carcinoma and gastrointestinal stromal tumors, however a dose related cardiotoxicity was well described. Polydatin (3,4',5-trihydroxystilbene-3-β-d-glucoside) is a monocrystalline compound isolated from Polygonum cuspidatum with consolidated anti-oxidant and anti-inflammatory properties, however no studies investigated on its putative cardioprotective and chemosensitizing properties during incubation with sunitinib.
View Article and Find Full Text PDFThe World Cancer Research Fund and American Institute for Cancer Research (WCRF/AICR) advise cancer survivors to follow their lifestyle recommendations for cancer prevention. Recent research indicates that a proper diet could exerts beneficial metabolic and immune effects in humans through the involvement of several, not yet properly known, metabolic pathways. Here, we argue that following WCRF/AICR recommendations could be a strategy to prevent cardiovascular outcomes [fulminant myocarditis, heart failure, venous thromboembolism (VTE)] and acute respiratory distress syndrome (ARDS) in patients during follow-up post COVID-19 infection.
View Article and Find Full Text PDFThe coronavirus disease-2019 (COVID-19) is a highly transmissible viral illness caused by SARS-CoV-2, which has been defined by the World Health Organization as a pandemic, considering its remarkable transmission speed worldwide. SARS-CoV-2 interacts with angiotensin-converting enzyme 2 and TMPRSS2, which is a serine protease both expressed in lungs, the gastro-intestinal tract, and cardiac myocytes. Patients with COVID-19 experienced adverse cardiac events (hypertension, venous thromboembolism, arrhythmia, myocardial injury, fulminant myocarditis), and patients with previous cardiovascular disease have a higher risk of death.
View Article and Find Full Text PDFAlthough meningococcal disease has a low incidence in Italy, it is a public health concern owing to its high lethality rate and high frequency of transitory and/or permanent sequelae among survivors. The highest incidence rates are recorded in infants, children and adolescents, and most of the cases are due to B. In Italy, anti-meningococcal B (anti-MenB) vaccination is free for infants but, despite the considerable disease burden in adolescents, no national recommendation to vaccinate in this age-group is currently available.
View Article and Find Full Text PDFBackground: Several strategies based on immune checkpoint inhibitors (ICIs) have been developed for cancer therapy, opening to advantages in cancer outcomes. However, several ICI-induced side effects have emerged in these patients, especially a rare but clinically significant cardiotoxicity with high rate of mortality. We studied the cytotoxic and pro-inflammatory properties of Ipilimumab and Nivolumab, the underlying pathways and cytokine storm involved.
View Article and Find Full Text PDFThe gap junction protein Connexin 43 (Cx43) contributes to cell fate decisions that determine the location of fin ray joints during regeneration. Here, we provide insights into how Cx43, expressed medially, influences changes in gene expression in lateral skeletal precursor cells. Using the Gap27 peptide inhibitor specific to Cx43, we show that Cx43-gap junctional intercellular communication (GJIC) influences Cx43-dependent skeletal phenotypes, including segment length.
View Article and Find Full Text PDFThe burden of diarrheal diseases is very high, accounting for 1.7 to 5 billion cases per year worldwide. Typhoid fever (TF) and cholera are potentially life-threatening infectious diseases, and are mainly transmitted through the consumption of food, drink or water that have been contaminated by the feces or urine of subjects excreting the pathogen.
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