Molecular pathogenetic mechanisms and new therapeutic perspectives in anthracycline-induced cardiomyopathy

Anthracyclines are among the most powerful drugs for the treatment of oncologic diseases both in childhood and in adulthood. Nevertheless, their major antineoplastic efficacy can be seriously impaired by collateral toxic cardiac effects causing cardiomyopathy with chronic heart failure that is refractory to conventional medical therapy

Actualities on molecular pathogenesis and repairing processes of cerebral damage in perinatal hypoxic-ischemic encephalopathy

Hypoxic-ischemic encephalopathy (HIE) is the most important cause of cerebral damage and long-term neurological sequelae in the perinatal period both in term and preterm infant

Liver injury, SARS-COV-2 infection and COVID-19: What physicians should really know?

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19), which in males, especially in advanced age, can sometimes evolve into acute respiratory distress syndrome. In addition, mild to moderate alterations in liver function tests (LFTs) have been reported in the worst affected patients. Our review aims to analyse data on the incidence and prognostic value of LFT alterations, the underlying mechanisms and the management of pre-existing liver disease in COVID-19 affected patients

Sub-Toxic Human Amylin Fragment Concentrations Promote the Survival and Proliferation of SH-SY5Y Cells via the Release of VEGF and HspB5 from Endothelial RBE4 Cells

This work is licensed under a Creative Commons Attribution 4.0 International License.Human amylin is a 37-residue peptide hormone (hA1-37) secreted by β-cells of the pancreas and, along with insulin, is directly associated with type 2 diabetes mellitus (T2DM). Amyloid deposits within the islets of the pancreas represent a hallmark of T2DM. Additionally, amylin aggregates have been found in blood vessels and/or brain of patients with Alzheimer’s disease, alone or co-deposited with β-amyloid. The purpose of this study was to investigate the neuroprotective potential of human amylin in the context of endothelial-neuronal “cross-talk”. We initially performed dose-response experiments to examine cellular toxicity (quantified by the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] MTT assay) of different hA17–29 concentrations in endothelial cells (RBE4). In the culture medium of these cells, we also measured heat shock protein B5 (HspB5) levels by ELISA, finding that even a sub-toxic concentration of hA17–29 (3 µM) produced an increase of HspB5. Using a cell medium of untreated and RBE4 challenged for 48 h with a sub-toxic concentration of hA17–29, we determined the potential beneficial effect of their addition to the medium of neuroblastoma SH-SY5Y cells. These cells were subsequently incubated for 48 h with a toxic concentration of hA17–29 (20 µM). We found a complete inhibition of hA17–29 toxicity, potentially related to the presence in the conditioned medium not only of HspB5, but also of vascular endothelial growth factor (VEGF). Pre-treating SH-SY5Y cells with the anti-Flk1 antibody, blocking the VEGF receptor 2 (VEGFR2), significantly decreased the protective effects of the conditioned RBE4 medium. These data, obtained by indirectly measuring VEGF activity, were strongly corroborated by the direct measurement of VEGF levels in conditioned RBE4 media as detected by ELISA. Altogether, these findings highlighted a novel role of sub-toxic concentrations of human amylin in promoting the secretion of proteic factors by endothelial cells (HspB5 and VEGF) that support the survival and proliferation of neuron-like cells.National Science Foundation (CHE-1411993)NIH COBRE P20GM103638American Heart Association-Midwest Affiliate Postdoctoral Research Fellowship (NFP0075515)Neuropsychopharmacology Research Program 2017 (RC-06-05

Pentraxin-3 in late-preterm newborns with hypoxic respiratory failure.

The aim of this study was: echocardiographical assessment of cardiac alterations in late-preterm newborns with hypoxic respiratory failure (HRF), and, study serum pentraxin-3 (PTX-3) in relation to the severity of respiratory impairment and to some echocardiographic parameters (i.e. ejection fraction (EF), stroke volume (SV) and cardiac output (CO). We enrolled in this study 40 newborn infants whose 22 (group I) with moderate HRF and 18 (group II) with severe HRF. In group I the mean values of EF, SV and CO were significantly higher than in the group II. Our results showed a significant increase of PTX-3 in group II patients at 24h of life when compared to group I. Taking patients all together (n=40), we found a significant (R=-73) reverse correlation between EF and serum values of PTX-3. PTX-3 in our patients with HRF is affected by the severity of the hypoxic insult and correlate with the cardio-vascular impairment

Inhibition of Larval Development of Marine Copepods Acartia tonsa by Neonocotinoids

Neonicotinoids (NEOs) are neurotoxic pesticides widely used in agriculture due to their high effectiveness against pest insects. Despite their widespread use, very little is known about their toxicity towards marine organisms, including sensitive and ecologically relevant taxa such as copepods. Thus, we investigated the toxicity of five widely used NEOs, including acetamiprid (ACE), clothianidin (CLO), imidacloprid (IMI), thiacloprid (THI), and thiamethoxam (TMX), to assess their ability to inhibit the larval development of the copepod Acartia tonsa. The more toxic NEOs were ACE (EC50 = 0.73 μg L−1), TMX (EC50 = 1.71 μg L−1) and CLO (EC50 = 1.90 μg L−1), while the less toxic compound was IMI (EC50 = 8.84 μg L−1). Early life-stage mortality was unaffected by NEOs at all of the tested concentrations. The calculated toxicity data indicated that significant effects due to ACE (EC20 = 0.12 μg L−1), THI (EC20 = 0.88 μg L−1) and TMX (EC20 = 0.18 μg L−1) are observed at concentrations lower than established chronic aquatic life benchmarks reported by USEPA for freshwater invertebrates. Nevertheless, since environmental concentrations of NEOs are generally lower than the threshold concentrations we calculated for A. tonsa, the effects may be currently of concern only in estuaries receiving wastewater discharges or experiencing intense runoff from agricultur

Ethanol-mediated stress promotes autophagic survival and aggressiveness of colon cancer cells via activation of Nrf2/HO-1 pathway

Epidemiological studies suggest that chronic alcohol consumption is a lifestyle risk factor strongly associated with colorectal cancer development and progression. The aim of the present study was to examine the effect of ethanol (EtOH) on survival and progression of three different colon cancer cell lines (HCT116, HT29, and Caco-2). Our data showed that EtOH induces oxidative and endoplasmic reticulum (ER) stress, as demonstrated by reactive oxygen species (ROS) and ER stress markers Grp78, ATF6, PERK and, CHOP increase. Moreover, EtOH triggers an autophagic response which is accompanied by the upregulation of beclin, LC3-II, ATG7, and p62 proteins. The addition of the antioxidant N-acetylcysteine significantly prevents autophagy, suggesting that autophagy is triggered by oxidative stress as a prosurvival response. EtOH treatment also upregulates the antioxidant enzymes SOD, catalase, and heme oxygenase (HO-1) and promotes the nuclear translocation of both Nrf2 and HO-1. Interestingly, EtOH also upregulates the levels of matrix metalloproteases (MMP2 and MMP9) and VEGF. Nrf2 silencing or preventing HO-1 nuclear translocation by the protease inhibitor E64d abrogates the EtOH-induced increase in the antioxidant enzyme levels as well as the migration markers. Taken together, our results suggest that EtOH mediates both the activation of Nrf2 and HO-1 to sustain colon cancer cell survival, thus leading to the acquisition of a more aggressive phenotype

Impacts of exhaust gas cleaning systems (EGCS) discharge waters on planktonic biological indicators

Exhaust Gas Cleaning Systems (EGCS), operating in open-loop mode, continuously release acidic effluents (scrubber waters) to marine waters. Furthermore, scrubber waters contain high concentrations of metals, polycyclic aromatic hydrocarbons (PAHs), and alkylated PAHs, potentially affecting the plankton in the receiving waters. Toxicity tests evidenced significant impairments in planktonic indicators after acute, early-life stage, and long-term exposures to scrubber water produced by a vessel operating with high sulphur fuel. Acute effects on bacterial bioluminescence (Aliivibrio fischeri), algal growth (Phaeodactylum tricornutum, Dunaliella tertiolecta), and copepod survival (Acartia tonsa) were evident at 10 % and 20 % scrubber water, while larval development in mussels (Mytilus galloprovincialis) showed a 50 % reduction at ∼5 % scrubber water. Conversely, larval development and reproductive success of A. tonsa were severely affected at scrubber water concentrations ≤1.1 %, indicating the risk of severe impacts on copepod populations which in turn may result in impairment of the whole food web