Strategies to Counteract Oxidative Stress and Inflammation in Chronic-Degenerative Diseases 2.0

: Oxidative stress and inflammation are recognized as pivotal contributors and common features of several chronic degenerative diseases, including cancer, metabolic syndrome, type 2 diabetes, cardiovascular diseases and neurodegenerative disorders, affecting a high percentage of the population [...]

Natural Compounds as a Strategy to Optimize " In Vitro" Expansion of Stem Cells

The efficient use of stem cells for transplantation is often limited by the relatively low number of stem cells collected. The ex vivo expansion of human stem cells for clinical use is a potentially valuable approach to increase stem cell number. Currently, most of the procedures used to expand stem cells are carried out using a 21% oxygen concentration, which is about 4- to 10-fold greater than the concentration characteristic of their natural niches. Hyperoxia might cause oxidative stress with a deleterious effect on the physiology of cultured stem cells. In this review, we investigate and critically examine the available information on the ability of natural compounds to counteract hyperoxia-induced damage in different types of stem cells ex vivo. In particular, we focused on proliferation and stemness maintenance in an attempt to draw up useful indications to define new culture media with a promoting activity on cell expansion in vitro

Combination of Epigallocatechin Gallate and Sulforaphane Counteracts In Vitro Oxidative Stress and Delays Stemness Loss of Amniotic Fluid Stem Cells

Amniotic fluid stem cells (AFSCs) are characterized in vivo by a unique niche guarantying their homeostatic role in the body. Maintaining the functionality of stem cells ex vivo for clinical applications requires a continuous improvement of cell culture conditions. Cellular redox status plays an important role in stem cell biology as long as reactive oxygen species (ROS) concentration is finely regulated and their adverse effects are excluded. The aim of this study was to investigate the protective effect of two antioxidants, sulforaphane (SF) and epigallocatechin gallate (EGCG), against in vitro oxidative stress due to hyperoxia and freeze-thawing cycles in AFSCs. Human AFSCs were isolated and characterized from healthy subjects. Assays of metabolic function and antioxidant activity were performed to investigate the effect of SF and EGCG cotreatment on AFSCs. Real-time PCR was used to investigate the effect of the cotreatment on pluripotency, senescence, osteogenic and adipogenic markers, and antioxidant enzymes. Alkaline phosphatase assays and Alizarin Red staining were used to confirm osteogenic differentiation. The cotreatment with SF and EGCG was effective in reducing ROS production, increasing GSH levels, and enhancing the endogenous antioxidant defences through the upregulation of glutathione reductase, NAD(P)H:quinone oxidoreductase-1, and thioredoxin reductase. Intriguingly, the cotreatment sustained the stemness state by upregulating pluripotency markers such as OCT4 and NANOG. Moreover, the cotreatment influenced senescence-associated gene markers in respect to untreated cells. The cotreatment upregulated osteogenic gene markers and promoted osteogenic differentiation in vitro. SF and EGCG can be used in combination in AFSC culture as a strategy to preserve stem cell functionality

Sulforaphane Modulates AQP8-Linked Redox Signalling in Leukemia Cells

Sulforaphane, a biologically active isothiocyanate compound extracted from cruciferous vegetables, has been shown to exert cytotoxic effects on many human cancer cells, including leukemia. However, the exact molecular mechanisms behind the action of sulforaphane in hematological malignancies are still unclear. Like other cancer cells, leukemia cells produce high level of reactive oxygen species; in particular, hydrogen peroxide derived from Nox family is involved in various redox signal transduction pathways, promoting cell proliferation and survival. Recent evidence show that many tumour cell types express elevated level of aquaporin isoforms, and we previously demonstrated that aquaporin-8 acts as H2O2 transport facilitator across the plasma membrane of B1647 cells, a model of acute myeloid human leukemia. Thus, the control of AQP8-mediated H2O2 transport could be a novel strategy to regulate cell signalling and survival. To this purpose, we evaluated whether sulforaphane could somehow affect aquaporin-8-mediated H2O2 transport and/or Nox-mediated H2O2 production in B1647 cell line. Results indicated that sulforaphane inhibited both aquaporin-8 and Nox2 expression, thus decreasing B1647 cells viability. Moreover, the data obtained by coimmunoprecipitation technique demonstrated that these two proteins are linked to each other; thus, sulforaphane has an important role in modulating the downstream events triggered by the axis Nox2-aquaporin-8. Cell treatment with sulforaphane also reduced the expression of peroxiredoxin-1, which is increased in almost all acute myeloid leukemia subtypes. Interestingly, sulforaphane concentrations able to trigger these effects are achievable by dietary intake of cruciferous vegetables, confirming the importance of the beneficial effect of a diet rich in bioactive compounds

d-mannose treatment neither affects uropathogenic Escherichia coli properties nor induces stable FimH modifications

Abstract: Urinary tract infections (UTIs) are mainly caused by uropathogenic Escherichia coli (UPEC). Acute and recurrent UTIs are commonly treated with antibiotics, the efficacy of which is limited by the emergence of antibiotic resistant strains. The natural sugar d-mannose is considered as an alternative to antibiotics due to its ability to mask the bacterial adhesin FimH, thereby preventing its binding to urothelial cells. Despite its extensive use, the possibility that d-mannose exerts “antibiotic-like” activity by altering bacterial growth and metabolism or selecting FimH variants has not been investigated yet. To this aim, main bacterial features of the prototype UPEC strain CFT073 treated with d-mannose were analyzed by standard microbiological methods. FimH functionality was analyzed by yeast agglutination and human bladder cell adhesion assays. Our results indicate that high d-mannose concentrations have no effect on bacterial growth and do not interfere with the activity of different antibiotics. d-mannose ranked as the least preferred carbon source to support bacterial metabolism and growth, in comparison with d-glucose, d-fructose, and l-arabinose. Since small glucose amounts are physiologically detectable in urine, we can conclude that the presence of d-mannose is irrelevant for bacterial metabolism. Moreover, d-mannose removal after long-term exposure did not alter FimH’s capacity to bind to mannosylated proteins. Overall, our data indicate that d-mannose is a good alternative in the prevention and treatment of UPEC-related UTIs

Protective Effect of Wheat Derived Non-specific lipid-transfer Protein 2 on Vascular Endothelium Inflammation

The important functions of the endothelium and the relationship between cardiovascular risk factors and endothelial dysfunction suggest the primary role of this tissue as a target for dietary strategies aimed at the prevention from related diseases. Cereals are key component of a healthy and balanced diet, and the presence of non-specific lipid-transfer protein 2 (nsLTP2) in wheat represents an added value to contribute to maintain the functionality of the vascular endothelium and consequently of the cardiovascular system. Indeed, nsLTP2 downregulates the expression of the main cell adhesion molecules induced by a pro-inflammatory cytokine and, meanwhile, upregulates heme oxigenase-1, exerting a cytoprotective/anti-inflammatory activity. Therefore, nsLTP2 might represent a food-derived tool to protect the vascular system against several pathological condition

Identification of Anti-Neuroinflammatory Bioactive Compounds in Essential Oils and Aqueous Distillation Residues Obtained from Commercial Varieties of Cannabis sativa L

Neuroinflammation, which is mainly triggered by microglia, is a key contributor to multiple neurodegenerative diseases. Natural products, and in particular Cannabis sativa L., due to its richness in phytochemical components, represent ideal candidates to counteract neuroinflammation. We previously characterized different C. sativa commercial varieties which showed significantly different chemical profiles. On these bases, the aim of this study was to evaluate essential oils and aqueous distillation residues from the inflorescences of three different hemp varieties for their anti-neuroinflammatory activity in BV-2 microglial cells. Cells were pretreated with aqueous residues or essential oils and then activated with LPS. Unlike essential oils, aqueous residues showed negligible effects in terms of anti-inflammatory activity. Among the essential oils, the one obtained from 'Gorilla Glue' was the most effective in inhibiting pro-inflammatory mediators and in upregulating anti-inflammatory ones through the modulation of the p38 MAPK/NF-kappa B pathway. Moreover, the sesquiterpenes (E)-caryophyllene, alpha-humulene, and caryophyllene oxide were identified as the main contributors to the essential oils' anti-inflammatory activity. To our knowledge, the anti-neuroinflammatory activity of alpha-humulene has not been previously described. In conclusion, our work shows that C. sativa essential oils characterized by high levels of sesquiterpenes can be promising candidates in the prevention/counteraction of neuroinflammation

transperineal laser ablation (TPLA) with ultrasound/MRI fusion guidance in the treatment of localized radiotherapy-resistant prostate cancer

objective: the objective of this study was to assess the technical feasibility, safety, and efficacy of transperineal laser ablation (TPLA) guided by ultrasound/magnetic resonance (MR) fusion as a salvage treatment for refractory focal prostate cancer. methods: a total of five patients who had undergone radiation therapy (RT) for prostate carcinoma and biochemical recurrence, confirmed by both prostate-specific antigen (PSA) levels and MRI (3T mpMRI), were enrolled in this study. focal ablation was performed using a 1064 nm diode laser. Post-ablation follow-up was conducted for a duration of 18 months, which included regular PSA sampling, 3T mpMRI, and ultrasound/MR fusion-guided biopsies systematic and targeted at the site of the focal treatment. results: the focal ablation procedure was carried out in an outpatient setting regimen with optimal clinical and biochemical outcomes. no recurrence was detected throughout the follow-up period. conclusion: TPLA focal treatment effectively manages local recurrences of RT refractory prostate cancer without side-effects or complications. preservation of quality of life and functional outcomes, along with a >70% reduction in PSA, were achieved. advances in knowledge: our study investigated TPLA as a salvage treatment for low-risk recurrent prostate cancer after RT, demonstrating its tolerability, feasibility, and effectiveness

CT Images in Follicular Lymphoma: Changes after Treatment Are Predictive of Cardiac Toxicity in Patients Treated with Anthracycline-Based or R-B Regimens

The aim of this study is to evaluate changes in epicardial adipose tissue (EAT) and cardiac extracellular volume (ECV) in patients with follicular lymphoma (FL) treated with R-CHOP-like regimens or R-bendamustine. We included 80 patients with FL between the ages of 60 and 80 and, using computed tomography (CT) performed at onset and at the end of treatment, we assessed changes in EAT by measuring tissue density at the level of the cardiac apex, anterior interventricular sulcus and posterior interventricular sulcus of the heart. EAT is known to be associated with metabolic syndrome, increased calcium in the coronary arteries and therefore increased risk of coronary artery disease. We also evaluated changes in ECV, which can be used as an early imaging marker of cardiac fibrosis and thus myocardial damage. The R-CHOP-like regimen was associated with lower EAT values (p < 0.001), indicative of a less active metabolism and more adipose tissue, and an increase in ECV (p < 0.001). Furthermore, in patients treated with anthracyclines and steroids (R-CHOP-like) there is a greater decrease in ejection fraction (EF p < 0.001) than in the R-B group. EAT and ECV may represent early biomarkers of cardiological damage, and this may be considered, to our knowledge, the first study investigating radiological and cardiological parameters in patients with FL

Role of Neutrophil-to-Lymphocyte Ratio (NLR) in Patients with Mycosis Fungoides

background: the neutrophil/lymphocyte ratio (NLR) at baseline has been demonstrated to correlate with higher stages of disease and to be a prognostic factor in numerous cancers. however, its function as a prognostic factor for mycosis fungoides (MF) has not been yet clarified. objective: our work aimed to assess the association of the NLR with different stages of MF and to outline whether higher values of this marker are related to a more aggressive MF.methods: we retrospectively calculated the NLRs in 302 MF patients at the moment of diagnosis. the NLR was obtained using the complete blood count values.results: the median NLR among patients with early stage disease (low-grade IA-IB-IIA) was 1.88, while the median NLR for patients with high-grade MF (IIB-IIIA-IIIB) was 2.64. statistical analysis showed positive associations of advanced MF stages with NLRs higher than 2.3. conclusions: our analysis demonstrates that the NLR represents a cheap and easily available parameter functioning as a marker for advanced MF. this might guide physicians in recognizing patients with advanced stages of disease requiring a strict follow-up or an early treatment