Regulation of redox signaling in HIF-1-dependent tumor angiogenesis

Angiogenesis is the process of blood vessel growth. The angiogenic switch consists of new blood vessel formation that, in carcinogenesis, can lead to the transition from a harmless cluster of dormant cells to a large tumorigenic mass with metastatic potential. Hypoxia, that is, the scarcity of oxygen, is a hallmark of solid tumors to which they adapt by activating hypoxia-inducible factor-1 (HIF-1), a transcription factor triggering de novo angiogenesis. HIF-1 and the angiogenic molecules that are expressed upon its activation are modulated by redox status. Modulations of the redox environment can influence the angiogenesis signaling at different levels, thereby impinging on the angiogenic switch. This review provides a molecular overview of the redox-sensitive steps in angiogenic signaling, the main molecular players involved, and their crosstalk with the unfolded protein response. New classes of inhibitors of these modulators which might act as antiangiogenic drugs in cancer are also discussed

Pharmacokinetic properties of radiolabeled mutant Interleukin-2v:a PET imaging study

Interleukin-2 (IL2) is a cytokine that can stimulate cytotoxic immune cells to attack infected and malignant cells. Unfortunately, IL2 can also cause serious immune-related toxicity. Recently, a mutant of IL2 (IL2v) with abolished CD25 binding, increased plasma half-life and less toxicity was engineered. Unlike wild-type IL2 (wt-IL2), mutant IL2v does not bind to the α-subunit (CD25) of the high affinity IL2αβγ receptor, but only to its β and γ subunit. Here, we investigated the biological properties of IL2v and compared with the wt-IL2 using fluorine-18 and PET. [18F]FB-IL2v binds specifically to IL2 receptors (IL2R) on activated human peripheral blood monocytes (hPBMCs) and is cleared mainly by the kidneys (Balb/c mice). [18F]FB-IL2v PET studies in SCID mice injected with hPBMCs revealed high uptake in the implant (0.85 ± 0.15 SUV), which was significantly reduced after pretreatment with wt-IL2 or mutant IL2v (SUV 0.26 ± 0.1 and 0.46 ± 0.1,p< 0.01). Compartment modeling and Logan graphical analysis in wistar rats inoculated with hPBMCs indicated that the binding of [18F]FB-IL2v to IL2R was reversible. The volume of distribution (VT) and the non-displaceable binding potential (BPnd) of mutant [18F]FB-IL2v in the implant were approximately 3 times lower than those of wild-type [18F]FB-IL2 (p< 0.01). Pretreatment with wt-IL2 significantly reduced the VTand BPnd of mutant [18F]FB-IL2v in the implant (p< 0.001). This demonstrates that wild-type [18F]FB-IL2 binds stronger to IL2R and has faster kinetics than [18F]FB-IL2v, which makes it less suitable as a therapeutic drug. [18F]FB-IL2v, on the other hand, seems to have better properties for use as a therapeutic drug

COVID-19 Pandemic as Risk Factors for Excessive Weight Gain in Pediatrics: The Role of Changes in Nutrition Behavior. A Narrative Review

During the coronavirus disease 2019 (COVID-19) pandemic, social isolation, semi-lockdown, and “stay at home” orders were imposed upon the population in the interest of infection control. This dramatically changes the daily routine of children and adolescents, with a large impact on lifestyle and wellbeing. Children with obesity have been shown to be at a higher risk of negative lifestyle changes and weight gain during lockdown. Obesity and COVID-19 negatively affect children and adolescents’ wellbeing, with adverse effects on psychophysical health, due in large part to food choices, snacking between meals, and comfort eating. Moreover, a markable decrease in physical activity levels and an increase in sedentary behavior is associated with weight gain, especially in children with excessive weight. In addition, obesity is the most common comorbidity in severe cases of COVID-19, suggesting that immune dysregulation, metabolic unbalance, inadequate nutritional status, and dysbiosis are key factors in the complex mechanistic and clinical interplay between obesity and COVID-19. This narrative review aims to describe the most up-to-date evidence on the clinical characteristics of COVID-19 in children and adolescents, focusing on the role of excessive weight and weight gain in pediatrics. The COVID-19 pandemic has taught us that nutrition education interventions, access to healthy food, as well as family nutrition counselling should be covered by pediatric services to prevent obesity, which worsens disease outcomes related to COVID-19 infection

Unhealthy lifestyle and oxidative damage in childhood obesity.

PURPOSE: Oxidized LDL cholesterol (oxLDL) has been considered as a sensor of oxidative stress (OS) in childhood obesity. We integrated and related our oxLDL existing results previously assessed in overweight/obese children to lifestyle variables to investigate OS-related lifestyle variables. METHODS: 178 Caucasian children/adolescents have been evaluated and according to BMI percentiles have been classified as normal weight (BMI < 75th); overweight (BMI 75-97th) and obese (BMI > 97th). Serum oxLDL levels have been measured. The dietary habits and physical activity have been also assessed. RESULTS: No differences between normal weight and overweight/obese children were detected according to the total score of dietary habits section. Normal weight subjects reported a higher total physical activity score (p = 0.001) compared to overweight/ obese children. No correlation between oxLDL and total dietary habits and physical activity scores was noted. Increased oxLDL in subjects drinking < 1 L/day of water (p = 0.022) and in daily consumers of chocolate drinks at breakfast (p = 0.029) was observed, while a decreased oxLDL was reported in subjects consuming a breakfast based mainly on fruits (p = 0.004). Moreover, "high-fat diet" and "always eating a dessert at the end of the meal" were correlated with increased oxLDL with a trend towards significance. As regards physical activity, no correlations were observed. CONCLUSIONS: Diet and physical activity may not have an immediate impact on OS response in children with or without obesity. Unhealthy lifestyle, including increased fat, simple sugar intake, poor water intake, emerged as external exposome predictors of OS, that may be monitored to improve health status

Nutritional status and metabolic profile in neurologically impaired pediatric surgical patients

Malnutrition is reported in pediatric neuromotor disability and impacts the child's health. We described the nutritional and metabolic status in neurologically impaired (NI) children undergoing surgery

Pediatric Obesity-Related Asthma: The Role of Nutrition and Nutrients in Prevention and Treatment

Childhood obesity rates have dramatically risen in numerous countries worldwide. Obesity is likely a factor in increased asthma risk, which is already one of the most widespread chronic respiratory pathologies. The pathogenic mechanism of asthma risk has still not yet been fully elucidated. Moreover, the role of obesity-related inflammation and pulmonary overreaction to environmental triggers, which ultimately result in asthma-like symptoms, and the importance of dietary characteristics is well recognized. Diet is an important adjustable element in the asthma development. Food-specific composition of the diet, in particular fat, sugar, and low-quality nutrients, is likely to promote the chronic inflammatory state seen in asthmatic patients with obesity. An unbalanced diet or supplementation as a way to control asthma more efficiently has been described. A personalized dietary intervention may improve respiratory symptoms and signs and therapeutic response. In this narrative review, we presented and discussed more recent literature on asthma associated with obesity among children, focusing on the risk of asthma among children with obesity, asthma as a result of obesity focusing on the role of adipose tissue as a mediator of systemic and local airway inflammation implicated in asthma regulation, and the impact of nutrition and nutrients in the development and treatment of asthma. Appropriate early nutritional intervention could possibly be critical in preventing and managing asthma associated with obesity among children

The Effect of Removable Orthodontic Appliances on Oral Microbiota: A Systematic Review

Background (1): Removable orthodontic appliances may favor plaque accumulation and oral microbe colonization. This might be associated with intraoral adverse effects on enamel or periodontal tissues. The proposed systematic review was carried out to evaluate qualitatively and quantitatively the microbiological changes occurring during orthodontic therapy with removable orthodontic appliances. Methods (2): PubMed, Cochrane Library, Embase, Web of Science, Scopus, Ovid Medline, and Dentistry and Oral Sciences Source were searched. The research included every article published up to January 2020. The Preferred Reporting Items for Reporting Systematic reviews and Meta Analyses (PRISMA) protocol and the “Swedish Council on Technology Assessment in Health Care Criteria for Grading Assessed Studies” (SBU) method were adopted to conduct this systematic review. Results (3): The current study has a moderate evidence, demonstrating that removable appliances do influence the oral microbiota. Significant alterations occur just 15 days after the beginning of therapy, independently from the type of appliance. Furthermore, the levels of oral pathogens decrease significantly or even returned to pre-treatment levels several months later the therapy end. Conclusions (4): This review suggests that orthodontic treatment with removable appliances induces changes to oral microflora, but these alterations might not be permanent

Lipogenic signalling modulates prostate cancer cell adhesion and migration via modification of Rho GTPases

Fatty acid synthase (FASN) is commonly overexpressed in prostate cancer and associated with tumour progression. FASN is responsible for de novo synthesis of the fatty acid palmitate; the building block for protein palmitoylation. Recent work has suggested that alongside its established role in promoting cell proliferation FASN may also promote invasion. We now find depletion of FASN expression increases prostate cancer cell adhesiveness, impairs HGF-mediated cell migration and reduces 3D invasion. These changes in motility suggest that FASN can mediate actin cytoskeletal remodelling; a process known to be downstream of Rho family GTPases. Here, we demonstrate that modulation of FASN expression specifically impacts on the palmitoylation of the atypical GTPase RhoU. Impaired RhoU activity in FASN depleted cells leads to reduced adhesion turnover downstream of paxillin serine phosphorylation, which is rescued by addition of exogenous palmitate. Moreover, canonical Cdc42 expression is dependent on the palmitoylation status of RhoU. Thus we uncover a novel relationship between FASN, RhoU and Cdc42 that directly influences cell migration potential. These results provide compelling evidence that FASN activity directly promotes cell migration and supports FASN as a potential therapeutic target in metastatic prostate cancer