Heme oxygenase-1 in central nervous system malignancies

Central nervous system tumors are the most common pediatric solid tumors and account for 20%-25% of all childhood malignancies. Several lines of evidence suggest that brain tumors show altered redox homeostasis that triggers the activation of various survival pathways, leading to disease progression and chemoresistance. Among these pathways, heme oxygenase-1 (HO-1) plays an important role. HO-1 catalyzes the enzymatic degradation of heme with the simultaneous release of carbon monoxide (CO), ferrous iron (Fe2+), and biliverdin. The biological effects of HO-1 in tumor cells have been shown to be cell-specific since, in some tumors, its upregulation promotes cell cycle arrest and cellular death, whereas, in other neoplasms, it is associated with tumor survival and progression. This review focuses on the role of HO-1 in central nervous system malignancies and the possibility of exploiting such a target to improve the outcome of well-established therapeutic regimens. Finally, several studies show that HO-1 overexpression is involved in the development and resistance of brain tumors to chemotherapy and radiotherapy, suggesting the use of HO-1 as an innovative therapeutic target to overcome drug resistance. The following keywords were used to search the literature related to this topic: nuclear factor erythroid 2 p45-related factor 2, heme oxygenase, neuroblastoma, medulloblastoma, meningioma, astrocytoma, oligodendroglioma, glioblastoma multiforme, and gliomas

Effectiveness of a Sustainable Training Program Combining Supervised Outdoor Exercise with Telecoaching on Physical Performance in Elderly People

The decrease in functional abilities can negatively influence quality of life and autonomy in elderly people, and physical exercise plays a crucial role regardless of the type. Among the latter, also due to the COVID-19 pandemic, outdoor exercise and telecoaching are settings that have been widely implemented. Hence, the aim of this study was to investigate the effectiveness of a sustainable training program combining supervised outdoor exercise with telecoaching on physical performance in elderly people. A total of 60 participants were recruited and divided into two groups: a trained group (TG) and an untrained group (UG), based on their participation in an 8-week sustainable training program consisted of five sessions/week, which included two sessions/week of supervised outdoor exercise and three sessions/week of telecoaching. Participants were evaluated before and at the end of the training program using the handgrip test, Timed Up and Go (TUG) test, short physical performance battery (SPPB), and Tinetti scale. In the TG, we found a significant improvement in the following tests: right handgrip (p < 0.001); left handgrip (p < 0.001); TUG (p < 0.001); SPPB (p = 0.01); and Tinetti scale (p = 0.006). A detailed analysis of the SPPB and Tinetti scale showed the lack of significant changes in walking ability: gait speed (p > 0.05) and walking parameters in the Tinetti scale (p > 0.05). Based on our results, we suggest that a sustainable training program combining supervised outdoor exercise with telecoaching could be effective in the elderly population for improving balance capacity and strength

Plasma heme oxygenase-1 is decreased in peripheral artery disease patients

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Caffeic Acid Phenethyl Ester Regulates PPAR’s Levels in Stem Cells-Derived Adipocytes

Hypertrophic obesity inhibits activation of peroxisome proliferators-activated receptor gamma (PPARγ), considered the key mediator of the fully differentiated and insulin sensitive adipocyte phenotype. We examined the effects of Caffeic Acid Phenethyl Ester (Cape), isolated from propolis, a honeybee hive product, on Adipose Stem Cells (ASCs) differentiation to the adipocyte lineage. Finally we tested the effects of Cape on insulin-resistant adipocytes. Quantification of Oil Red O-stained cells showed that lipid droplets decreased following Cape treatment as well as radical oxygen species formation. Additionally, exposure of ASC to high glucose levels decreased adiponectin and increased proinflammatory cytokines mRNA levels, which were reversed by Cape-mediated increase of insulin sensitivity. Cape treatment resulted in decreased triglycerides synthesis and increased beta-oxidation. Exposure of ASCs to Lipopolysaccharide (LPS) induced a reduction of PPARγ, an increase of IL-6 levels associated with a well-known stimulation of lipolysis; Cape partially attenuated the LPS-mediated effects. These observations reveal the main role of PPARγ in the adipocyte function and during ASC differentiation. As there is now substantial interest in functional food and nutraceutical products, the observed therapeutic value of Cape in insulin-resistance related diseases should be taken into consideration

SPARC expression in CML is associated to imatinib treatment and to inhibition of leukemia cell proliferation

BACKGROUND: SPARC is a matricellular glycoprotein with growth-inhibitory and antiangiogenic activity in some cell types. The study of this protein in hematopoietic malignancies led to conflicting reports about its role as a tumor suppressor or promoter, depending on its different functions in the tumor microenvironment. In this study we investigated the variations in SPARC production by peripheral blood cells from chronic myeloid leukemia (CML) patients at diagnosis and after treatment and we identified the subpopulation of cells that are the prevalent source of SPARC. METHODS: We evaluated SPARC expression using real-time PCR and western blotting. SPARC serum levels were detected by ELISA assay. Finally we analyzed the interaction between exogenous SPARC and imatinib (IM), in vitro, using ATP-lite and cell cycle analysis. RESULTS: Our study shows that the CML cells of patients at diagnosis have a low mRNA and protein expression of SPARC. Low serum levels of this protein are also recorded in CML patients at diagnosis. However, after IM treatment we observed an increase of SPARC mRNA, protein, and serum level in the peripheral blood of these patients that had already started at 3 months and was maintained for at least the 18 months of observation. This SPARC increase was predominantly due to monocyte production. In addition, exogenous SPARC protein reduced the growth of K562 cell line and synergized in vitro with IM by inhibiting cell cycle progression from G1 to S phase. CONCLUSION: Our results suggest that low endogenous SPARC expression is a constant feature of BCR/ABL positive cells and that IM treatment induces SPARC overproduction by normal cells. This exogenous SPARC may inhibit CML cell proliferation and may synergize with IM activity against CML

Telecoaching as a new training method for elderly people: a systematic review

BackgroundThe numerous restrictive measures implemented during the recent COVID-19 pandemic have reduced the levels of physical activity (PA) carried out by elderly people and telecoaching (TC) could be a training method to maintain the recommended levels of PA. In fact, TC uses information and digital communications technologies, such as computers and mobile devices, to access training services remotely. Thus, this study aimed to systematically review the scientific literature to verify the application, efficacy, and safety of TC training programs.MethodsPubMed, Scopus, and Web of Sciences databases were used for this review, and randomized controlled trials analyzing TC training programs for elderly people were included. Only articles written in English and published in the last decade were considered.Results3 articles were included in the qualitative synthesis including 194 elderly people. The sample size ranged from 12 to 117 and the TC training program from 8 to 12 weeks. The TC training programs were applied to elderly people with metabolic diseases and respiratory diseases. TC training program was effective in elderly people with metabolic diseases while the benefits for respiratory diseases have yet to be clarified.ConclusionTC seems to be a safe, effective, and injury-free training method, despite its limited application in elderly population. Future studies should better investigate this training method in elderly people in order to evaluate the effectiveness in a wider range of diseases

Role of Adrenomedullin in LPS-mediated lung injury

Acute Respiratory Distress Syndrome is a life-threatening disease characterized by diffuse lung injury that leads to respiratory failure and death. Among various endogenous protective peptides, adrenomedullin (AM) has been demonstrated to play a major role. The aim of our study was to assess the significance of AM in the complex pathophysiological cascade underlying lipopolysaccharide (LPS) mediated inflammatory response. In the first set of our experiments we showed that LPS induced a significant increase in the activation of the mitogen-activated protein kinase (MAPK) transduction signals in epithelial respiratory cells. In particular, our results showed a time and dose dependent activation of ERK and JNK pathways. No significant changes were observed for p38MAPK phosphorylation. Luminex analysis further confirmed the significant increase of IL-6 release along with a significant increase of MCP-1 , VEGF and IL-8. Pre-treatment of cells with AM (0.5 and 1 ng/ml) showed that AM was able to prevent JNK and ERK phosphorylation. Such effect turned into a significant reduction of IL-6 and TNF- gene transcription and induction of heme oxygenase-1 (Hsp32). Taken all together our data suggest that AM may play a major role in reducing LPS mediated inflammatory response by reducing the activation of MAPK signal transduction pathway

Are (poly)phenols contained in 100% fruit juices mediating their effects on cardiometabolic risk factors? A meta-regression analysis

BackgroundThe consumption of 100% fruit juices has not been associated with substantial detrimental outcomes in population studies and may even contribute to improving the cardiometabolic profile if included in a healthy balanced diet. The main contributors to such potential beneficial effects include vitamins, minerals, and likely the (poly)phenol content. This study aimed to investigate whether the (poly)phenols contained in 100% fruit juices may mediate their effects on cardiometabolic risk factors based on published randomized controlled trials (RCT).MethodsA systematic search in PubMed/MEDLINE and Embase, updated till the end of October 2022, was carried out to identify RCT providing quantitative data on (poly)phenol content in 100% fruit juices and used as an intervention to improve cardiometabolic parameters such as blood lipids, glucose, and blood pressure. Meta-regression analysis was performed to calculate the effect of the intervention [expressed as standardized mean difference and 95% confidence intervals (CI)] using the (poly)phenol content as moderator.ResultsA total of 39 articles on RCT investigating the effects of 100% fruit juices on cardiometabolic risk factors reporting data on total (poly)phenol and anthocyanin content were included in the analysis. Total (poly)phenol content was substantially unrelated to any outcome investigated. In contrast, each 100 mg per day increase in anthocyanins was related to 1.53 mg/dL decrease in total cholesterol (95% CI, −2.83, −0.22, p = 0.022) and 1.94 mg/dL decrease in LDL cholesterol (95% CI, −3.46, −0.42, p = 0.012). No other potential mediating effects of anthocyanins on blood triglycerides, glucose, systolic and diastolic pressure were found, while a lowering effect on HDL cholesterol after excluding one outlier study was observed.DiscussionIn conclusion, the present study showed that anthocyanins may mediate the potential beneficial effects of some 100% fruit juices on some blood lipids. Increasing the content of anthocyanins through specific fruit varieties or plant breeding could enhance the health benefits of 100% fruit juices

Liraglutide Reduces Oxidative Stress And Restores Heme Oxygenase-1 and Ghrelin Levels in Patients with Type 2 Diabetes: A Prospective Pilot Study

Context: Liraglutide is a glucagon-like peptide-1 analog and glucose-lowering agent whose effects on cardiovascular risk markers have not been fully elucidated. Objective: We evaluated the effect of liraglutide on markers of oxidative stress, heme oxygenase-1 (HO-1), and plasma ghrelin levels in patients with type-2 diabetes mellitus (T2DM). Design and Setting: A prospective pilot study of 2 months duration has been performed at the Unit of Diabetes and Cardiovascular Prevention at University of Palermo, Italy. Patients and Intervention(s): Twenty subjects with T2DM (10 men and 10 women; meanage: 57 +/- 13 y) were treated with liraglutide sc (0.6 mg/d for 2 wk, followed by 1.2 mg/d) in addition to metformin (1500 mg/d orally) for 2 months. Patients with liver disorders or renal failure were excluded. Main Outcome Measure(s): Plasma ghrelin concentrations, oxidative stress markers, and heat-shock proteins, including HO-1 were assessed. Results: The addition of liraglutide resulted in a significant decrease in glycated hemoglobin (HbA1c) (8.5 +/- 0.4 vs 7.5 +/- 0.4%, P LT .0001). In addition, plasma ghrelin and glutathione concentrations increased (8.2 +/- 4.1 vs 13.6 +/- 7.3 pg/ml, P = .0007 and 0.36 +/- 0.06 vs 0.44 +/- 0.07 nmol/ml, P = .0002, respectively), whereas serum lipid hydroperoxides and HO-1 decreased (0.11 +/- 0.05 vs 0.04 +/- 0.07 pg/ml, P = .0487 and 7.7 +/- 7.7 vs 3.6 +/- 1.8 pg/ml, P = .0445, respectively). These changes were not correlated with changes in fasting glycemia or HbA1c. Conclusions: In a 2-months prospective pilot study, the addition of liraglutide to metformin resulted in improvement in oxidative stress as well as plasma ghrelin and HO-1 concentrations in patients with T2DM. These findings seemed to be independent of the known effects of liraglutide on glucose metabolism