Background
Oxidative stress is strongly associated with aging and age-related diseases and plays a crucial role in endothelial dysfunction development.
Aim
To better understand the molecular ...mechanisms of aging and stress response in humans, we examined changes to young and older human endothelial cells over time (72, 96 and 120 h), before and after H
2
O
2
-induced stress.
Methods
We measured the expression of the deacetylase Sirtuin 1 (Sirt1) and its transcriptional target Forkhead box O3a (Foxo3a); TBARS, a well-known marker of overall oxidative stress, and catalase activity as index of antioxidation. Moreover, we quantified levels of cellular senescence by senescence-associated β galactosidase (SA-βgal) assay.
Results
Under oxidative stress induction older cells showed a progressive decrease of Sirt1 and Foxo3a expression, persistently high TBARS levels with high, but ineffective Cat activity to counteract such levels. In addition cellular senescence drastically increased in older cells compared with Young cells both in presence and in the absence of oxidative stress.
Discussion
By following the cell behavior during the time course, we can hypothesize that while in young cells an oxidative stress induction stimulated an adequate response through activation of molecular factor crucial to counteract oxidative stress, the older cells are not able to adequately adapt themselves to external stress stimuli.
Conclusions
During their life, endothelial cells impair the ability to defend themselves from oxidative stress stimuli. This dysfunction involves the pathway of Sirt1 a critical regulator of oxidative stress response and cellular lifespan, underlining its crucial role in endothelial homeostasis control during aging and age-associated diseases.
Ficus rubiginosa plant extract showed antimicrobial activity, but no evidence concerning its antiviral properties was reported. The antiviral activity of the methanolic extract (MeOH) and its ...n-hexane (H) and ethyl acetate (EA) fractions against Herpes simplex virus-1 (HSV-1), Human coronavirus (HCoV) -229E, and Poliovirus-1 (PV-1) was investigated in the different phases of viral infection in the VERO CCL-81 cell line. To confirm the antiviral efficacy, a qPCR was conducted. The recorded cytotoxic concentration 50% was 513.1, 298.6, and 56.45 µg/mL for MeOH, H, and EA, respectively, assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay after 72 h of treatment. The Ficus rubiginosa leaf extract inhibited the replication of HSV-1 in the early stages of infection, showing a complete inhibition up to 0.62, 0.31, and 1.25 µg/mL. Against HCoV-229E, a total inhibition up to 1.25 µg/mL for MeOH and H as well as 5 µg/mL for EA was observed. Otherwise, no activity was recorded against PV-1. The leaf extract could act directly on the viral envelope, destructuring the lipid membrane and/or directly blocking the enriched proteins on the viral surface. The verified gene inhibition suggested that the treatments with M, H, and EA impaired HSV-1 and HCoV-229E replication, with a greater antiviral efficiency against HSV-1 compared to HCoV-229E, possibly due to a greater affinity of Ficus rubiginosa towards membrane glycoproteins and/or the different lipid envelopes.
With the aim of investigating the relationship between the fast fluctuations of proteins and their allosteric behavior, we perform molecular dynamics simulations of two model PDZ domains with ...differential allosteric responses. We focus on protein dynamics in the THz regime (0.1–3 THz) as opposed to lower frequencies. By characterizing the dynamic modulation of the protein backbone induced by ligand binding in terms of single residue and pairwise distance fluctuations, we identify a response nucleus modulated by the ligand that is visible only at THz frequencies. The residues of this nucleus undergo a significant stiffening and an increase in mutual coordination upon binding. Additionally, we find that the dynamic modulation is significantly more intense for the side chains, where it is also redistributed to distal regions not immediately in contact with the ligand allowing us to better define the response nucleus at THz frequencies. The overlap between the known allosterically responding residues of the investigated PDZ domains and the modulated region highlighted here suggests that fast THz dynamics could play a role in allosteric mechanisms.
G protein-coupled receptors (GPCRs) are the most important regulators of cardiac function and are commonly targeted for medical therapeutics. Formyl-Peptide Receptors (FPRs) are members of the GPCR ...superfamily and play an emerging role in cardiovascular pathologies. FPRs can modulate oxidative stress through nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent reactive oxygen species (ROS) production whose dysregulation has been observed in different cardiovascular diseases. Therefore, many studies are focused on identifying molecular mechanisms of the regulation of ROS production. FPR1, FPR2 and FPR3 belong to the FPRs family and their stimulation triggers phosphorylation of intracellular signaling molecules and nonsignaling proteins that are required for NADPH oxidase activation. Some FPR agonists trigger inflammatory processes, while other ligands activate proresolving or anti-inflammatory pathways, depending on the nature of the ligands. In general, bacterial and mitochondrial formylated peptides activate a proinflammatory cell response through FPR1, while Annexin A1 and Lipoxin A4 are anti-inflammatory FPR2 ligands. FPR2 can also trigger a proinflammatory pathway and the switch between FPR2-mediated pro- and anti-inflammatory cell responses depends on conformational changes of the receptor upon ligand binding. Here we describe the detrimental or beneficial effects of the main FPR agonists and their potential role as new therapeutic and diagnostic targets in the progression of cardiovascular diseases.
Crenotherapy is recognized as being effective in patients with osteoarthritis of the spine, but to date there is no indication if it is effective for patients who are overweight or obese. The aim of ...this study is to evaluate the efficacy of sulphurous crenotherapy on pain and disability in overweight/obese subjects affected by chronic low back pain from spine osteoarthritis. Forty-three patients (63 ± 8.8 years) affected by chronic low back pain from lumbar spine osteoarthritis were enrolled in this study. Subjects were treated with 2 weeks of sulphurous creno-treatments. Subjective pain was measured by a numerical rating scale score (NRS), and functional mobility of the lumbar spine was measured using the Oswestry Disability Index (ODI) before and after crenotherapy. Both crenotherapy groups (normal weight: A1; overweight/obese: A2) experienced significantly improved NRS and ODI scores (A1: p < 0.001 and p = 0.001; A2: p = 0.001 and p = 0.001). At end of the treatment, significant improvements were observed as a result of the crenotherapy in overweight/obese subjects in terms of pain reduction measured with NRS (p = 0.03) and in terms of function mobility of the lumbar spine measured with ODI (p = 0.006). This study highlights the beneficial effect of sulphurous crenotherapy on the painful symptomatology and disability in both normal weight and overweight/obese patients suffering from chronic low back pain associated with lumbar spine osteoarthritis.
Exercise training (ET) is a natural activator of silent mating type information regulation 2 homolog 1 (SIRT1), a stress-sensor able to increase the endogenous antioxidant system. SIRT1 activators ...include polyphenols and vitamins, the antioxidant properties of which are well-known. Antioxidant supplements are used to improve athletic performance. However, they might blunt ET-related benefits. Middle-distance runners (MDR) taking (MDR-S) or not taking antioxidant supplements (MDR-NoS) were compared with each other and with sedentary subjects (CTR) to evaluate the ET effects on SIRT1 levels and oxidative stress, and to investigate whether an exogenous source of antioxidants could interfere with such effects. Thirty-two MDR and 14 CTR were enrolled. MDR-S took 240 mg vitamin C and 15 mg vitamin E together with mineral salts. SIRT1 mRNA and activity were measured in PBMCs. Total oxidative status (TOS) and total antioxidant capacity (TEAC) were determined in plasma. MDR showed higher levels of SIRT1 mRNA (p = 0.0387) and activity (p = 0.0055) than did CTR. MDR-NoS also showed higher levels than did MDR-S without reaching statistical significance. SIRT1 activity was higher (p = 0.0012) in MDR-NoS (1909 ± 626) than in MDR-S (1276 ± 474). TOS did not differ among the groups, while MDR showed higher TEAC levels than did CTR (2866 ± 581 vs. 2082 ± 560, p = 0.0001) as did MDR-S (2784 ± 643) and MDR-NoS (2919 ± 551) (MDR-S vs. CTR, p = 0.0007 and MDR-NoS vs. CTR, p = 0.003). TEAC (β = 0.4488356, 95% CI 0.2074645 0.6902067; p < 0.0001) and the MDR-NoS group (β = 744.6433, 95% CI 169.9954 1319.291; p= 0.012) predicted SIRT1 activity levels. Antioxidant supplementation seems to hinder the role of ET as a natural activator of SIRT1.
The objective of this study was to determine the effects of aging and exercise training on SIRT1 activity and to identify a pathway linking SIRT1 to antioxidant response and cell cycle regulation in ...rats. SIRT1 is a NAD(+)-dependent deacetylase involved in the oxidative stress response and aging. The effects of aging and of moderate and prolonged exercise training in rats are unknown. We measured SIRT1 activity in heart and adipose tissue of young (6 months old), sedentary old (24 months), and trained old (24 months) rats using an assay kit. Peroxidative damage was determined by measuring levels of thiobarbituric reactive substances (TBARS) and the protein-aldehyde adduct 4-hydroxynonenal (4-HNE). MnSOD, catalase, and FOXO3a levels were evaluated by Western blot, and GADD45a, cyclin D(2), and FOXO3a mRNA by RT-PCR. Aging significantly reduced SIRT1 activity in heart, but not in adipose tissue, increased TBARS and 4-HNE and decreased Mn-SOD and catalase expression in both heart and adipose tissue. Aging did not affect FOXO3a protein expression in the heart or FOXO3a mRNA in adipose tissue. Exercise training significantly increased FOXO3a protein in the heart and FOXO3a mRNA in adipose tissue of aged rats. It also significantly increased Mn-SOD and catalase levels in both heart and adipose tissue. The exercise-induced increase in SIRT1 activity in the heart caused a decrease in cyclin D(2) and an increase in GADD45a mRNA expression. There was a similar decrease in cyclin D(2), and no changes in GADD45a mRNA expression in adipose tissue. We concluded that exercise training, which significantly increases SIRT1 activity, could counteract age-related systems impairment.
Oxidative stress, a condition induced by an excessive amount of free radicals, such as reactive oxygen species (ROS), shows several gender-related differences in basal cellular redox state and ...antioxidant responses. Crenotherapy with sulfureous mineral water can improve the cellular redox state. In this retrospective observational study, gender-related differences in the efficacy of sulfureous crenotherapy in decreasing oxidant species were investigated. Seventy-eight patients, stratified by sex, with osteoarthritis or degenerative joint disease and Vulgar psoriasis who have received a cycle of sulfureous mud-bath therapy + sulfureous hydropinotherapy were enrolled. Plasma concentration of oxidant species and clinical outcomes were measured at baseline and at the end of treatment. After 2 weeks of sulfureous crenotherapy, a significant amelioration of clinical outcomes and a significant reduction of oxidant species were observed in both sexes, more marked in females than in males (p = 0.0001 and p = 0.04, respectively). For patients with high oxidant species at baseline, females showed a greater reduction in itching compared to males (−95% vs. −50%), while men had a higher amelioration in pain and morning stiffness (−45% vs. −32%, and −50% vs. −37%, respectively). In conclusion, sulfureous crenotherapy can be a valuable strategy to improve cellular redox state in both sexes.
The presentation will illustrate how to realize, in a transparent tank, a stable refractive index gradient by using sucrose solutions and a gelling agent. The apparatus will be used in a classroom ...for hand-on experiments on the refraction of light and on related topics, with particular emphasis on atmospheric effects such as mirages and Fata Morgana. Besides, in the preparation of this activity thermodynamical concepts, such as solubility, phase transitions and thermal stability are also involved. The ingredients and tools used in the preparation are easily available in household stores and do not present any risk of serious injuries. The potential applications of a refractive index gradient for optical fibres will be illustrated as well.
The prevention or early treatment of pathological scars is the most appropriate therapeutic approach. Gels and patches containing onion extract and allantoin are safe and effective in patients with ...scars of various origins and severity. However, no controlled studies have evaluated the effects of the patch formulation in women after Cesarean delivery. This study aimed to investigate the effects of a patch containing Allium cepa and allantoin on Cesarean section (C-section) scars.
This is an observational study. Women were consecutively recruited at the University Hospital of Salerno and subdivided into two groups considering the number of C-section. Group A included subjects without and group B with a history of C-section. Scars assessment was made using digital photographs and the Patient and Observer Scar Assessment Scale (POSAS). After 4 weeks, the C-section of the women who had applied a patch containing Allium cepa and allantoin and those of women who had not used any products (controls) were re-evaluated as at baseline. The Observers independently performed the scars assessment at baseline and after 4 weeks. Data are expressed as the difference of the POSAS scores after 4 weeks minus the POSAS scores at baseline. The statistical significance was established at a p value <0.05.
Ninety-three subjects completed the study (47 in group A and 46 in group B). Women who had used a patch showed an improvement in total score by observer scale when compared with controls (p = 0.013). By the patient scale, no significant changes from baseline were found in group A and group B. Group B with patch showed changes in scars' pigmentation (p = 0.015), relief (p = 0.039), and pliability (p = 0.046) in comparison of controls. Digital photographs confirmed such improvements in women who had already undergone previous C-section, while no significant changes from baseline were found in women without a history of C-section.
Intense treatment of just 4 weeks with a patch containing Alium Cepa extract and allantoin was able to improve pigmentation, relief, and pliability of C-section scars in women with a history of C-section.
ClinicalTrials.gov, identifier NCT04046783.
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