Search results for "M1"
showing 10 items of 837 documents
Oxidative Stress, Neuroinflammation and Mitochondria in the Pathophysiology of Amyotrophic Lateral Sclerosis
2020
Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron (MN) disease. Its primary cause remains elusive, although a combination of different causal factors cannot be ruled out. There is no cure, and prognosis is poor. Most patients with ALS die due to disease-related complications, such as respiratory failure, within three years of diagnosis. While the underlying mechanisms are unclear, different cell types (microglia, astrocytes, macrophages and T cell subsets) appear to play key roles in the pathophysiology of the disease. Neuroinflammation and oxidative stress pave the way leading to neurodegeneration and MN death. ALS-associated mitochondrial dysfunction occurs at different le…
Resveratrol in Autism Spectrum Disorders: Behavioral and Molecular Effects
2020
Resveratrol (RSV) is a polyphenolic stillbenoid with significant anti-oxidative and anti-inflammatory properties recently tested in animal models of several neurological diseases. Altered immune alteration and oxidative stress have also been found in patients with autism spectrum disorders (ASD), and these alterations could add to the pathophysiology associated with ASD. We reviewed the current evidence about the effects of RSV administration in animal models and in patients with ASD. RSV administration improves the core-symptoms (social impairment and stereotyped activity) in animal models and it also displays beneficial effects in other behavioral abnormalities such as hyperactivity, anxi…
Blocking oestradiol synthesis pathways with potent and selective coumarin derivatives
2018
A comprehensive set of 3-phenylcoumarin analogues with polar substituents was synthesised for blocking oestradiol synthesis by 17-b-hydroxysteroid dehydrogenase 1 (HSD1) in the latter part of the sulphatase pathway. Five analogues produced 62% HSD1 inhibition at 5 mM and, furthermore, three of them produced 68% inhibition at 1 mM. A docking-based structure-activity relationship analysis was done to determine the molecular basis of the inhibition and the cross-reactivity of the analogues was tested against oestrogen receptor, aromatase, cytochrome P450 1A2, and monoamine oxidases. Most of the analogues are only modestly active with 17-b-hydroxysteroid dehydrogenase 2 – a requirement for lowe…
Liraglutide Ameliorates Erectile Dysfunction via Regulating Oxidative Stress, the RhoA/ROCK Pathway and Autophagy in Diabetes Mellitus
2020
Background Erectile dysfunction (ED) occurs more frequently and causes a worse response to the first-line therapies in diabetics compared with nondiabetic men. Corpus cavernosum vascular dysfunction plays a pivotal role in the occurrence of diabetes mellitus ED (DMED). The aim of this study was to investigate the protective effects of glucagon-like peptide-1 (GLP-1) analog liraglutide on ED and explore the underlying mechanisms in vivo and in vitro. Methods Type 1 diabetes was induced in rats by streptozotocin, and the apomorphine test was for screening the DMED model in diabetic rats. Then they were randomly treated with subcutaneous injections of liraglutide (0.3 mg/kg/12 h) for 4 weeks. …
Mitochondrial Dysfunction, Oxidative Stress and Neuroinflammation in Neurodegeneration with Brain Iron Accumulation (NBIA)
2020
The syndromes of neurodegeneration with brain iron accumulation (NBIA) encompass a group of invalidating and progressive rare diseases that share the abnormal accumulation of iron in the basal ganglia. The onset of NBIA disorders ranges from infancy to adulthood. Main clinical signs are related to extrapyramidal features (dystonia, parkinsonism and choreoathetosis), and neuropsychiatric abnormalities. Ten NBIA forms are widely accepted to be caused by mutations in the genes PANK2, PLA2G6, WDR45, C19ORF12, FA2H, ATP13A2, COASY, FTL1, CP, and DCAF17. Nonetheless, many patients remain without a conclusive genetic diagnosis, which shows that there must be additional as yet undiscovered NBIA gen…
Lycopene and Vascular Health
2018
Lycopene is a lipophilic, unsaturated carotenoid, found in red-colored fruits and vegetables, including tomatoes, watermelon, papaya, red grapefruits, and guava. The present work provides an up to date overview of mechanisms linking lycopene in the human diet and vascular changes, considering epidemiological data, clinical studies, and experimental data. Lycopene may improve vascular function and contributes to the primary and secondary prevention of cardiovascular disorders. The main activity profile of lycopene includes antiatherosclerotic, antioxidant, anti-inflammatory, antihypertensive, antiplatelet, anti-apoptotic, and protective endothelial effects, the ability to improve the metabol…
The role of Ca(2+) in cell death caused by oxidative glutamate toxicity and ferroptosis
2018
Ca(2+) ions play a fundamental role in cell death mediated by oxidative glutamate toxicity or oxytosis, a form of programmed cell death similar and possibly identical to other forms of cell death like ferroptosis. Ca(2+) influx from the extracellular space occurs late in a cascade characterized by depletion of the intracellular antioxidant glutathione, increases in cytosolic reactive oxygen species and mitochondrial dysfunction. Here, we aim to compare oxidative glutamate toxicity with ferroptosis, address the signaling pathways that culminate in Ca(2+) influx and cell death and discuss the proteins that mediate this. Recent evidence hints toward a role of the machinery responsible for stor…
An Ethanolic Extract of Ampelopsis Radix Exerts Anti-colorectal Cancer Effects and Potently Inhibits STAT3 Signaling In Vitro
2017
Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide. Signal transducer and activator of transcription 3 (STAT3) signaling is constantly activated in CRC, and has been proposed as a pathogenic factor and a therapeutic target of CRC. Ampelopsis Radix (AR), a traditional Chinese medicinal herb, possesses low toxicity and has long been used clinically for the treatment of cancers including CRC. Some constituents of AR have been reported to exert anticancer properties by targeting STAT3. However, the anti-CRC mode and mechanism of action of AR have not been fully elucidated. Here, we investigated the involvement of STAT3 signaling in the anti-CRC effect…
Cytoprotective Effects of Dinitrosyl Iron Complexes on Viability of Human Fibroblasts and Cardiomyocytes
2019
Nitric oxide (NO) is an important signaling molecule that plays a key role in maintaining vascular homeostasis. Dinitrosyl iron complexes (DNICs) generating NO are widely used to treat cardiovascular diseases. However, the involvement of DNICs in the metabolic processes of the cell, their protective properties in doxorubicin-induced toxicity remain to be clarified. Here, we found that novel class of mononuclear DNICs with functional sulfur-containing ligands enhanced the cell viability of human lung fibroblasts and rat cardiomyocytes. Moreover, DNICs demonstrated remarkable protection against doxorubicin-induced toxicity in fibroblasts and in rat cardiomyocytes (H9c2 cells). Data revealed t…
Proton Pump Inhibitors Display Antitumor Effects in Barrett's Adenocarcinoma Cells
2016
Recent evidence has reported that proton pump inhibitors (PPIs) can exert antineoplastic effects through the disruption of pH homeostasis by inhibiting vacuolar ATPase (H+-VATPase), a proton pump overexpressed in several tumor cells, but this aspect has not been deeply investigated in EAC yet. In the present study, the expression of H+-VATPase was assessed through the metaplasia-dysplasia-adenocarcinoma sequence in Barrett’s esophagus (BE) and the antineoplastic effects of PPIs and cellular mechanisms involved were evaluated in vitro. H+-VATPase expression was assessed by immunohistochemistry in paraffined-embedded samples or by immunofluorescence in cultured BE and EAC cell lines. Cells we…