ADULT DOMINANT POLYCYSTIC KIDNEY DISEASE: A PROTOTYPICAL DISEASE FOR PHARMANUTRITION INTERVENTIONS

Adult Dominant Polycystic Kidney Disease (ADPKD) is an inherited disease, associated with the development of liquid-filled cysts in the kidneys and other organs, causing renal failure. Most patients with ADPKD have mutations in either PKD1 or PKD2 genes, which encode for the two components of ion channels located in cilia and endoplasmic reticulum. These mutations cause an increase in intracellular cAMP and activate mTOR, the AMPK pathway and Jak/Stat-dependent gene transcription ultimately leading to enhanced cell proliferation and survival in cyst epithelium and to fluid release in cyst cavities. The aim of the present review is to discuss the main literature evidence suggesting that these pathologically activated transduction pathways can be targeted with an integrated pharmacological and nutritional, pharmanutrition, strategy

Annurca apple polyphenol extract selectively kills MDA-MB-231 cells through ROS generation, sustained JNK activation and cell growth and survival inhibition

Polyphenols represent the most studied class of nutraceuticals that can be therapeutics for a large spectrum of diseases, including cancer. In this study, we investigated for the first time the antitumor activities of polyphenol extract from Annurca apple (APE) in MDA-MB-231 triple negative breast cancer cells, and we explored the underlying mechanisms. APE selectively inhibited MDA-MB-231 cell viability and caused G2/M phase arrest associated with p27 and phospho-cdc25C upregulation and with p21 downregulation. APE promoted reactive oxygen species (ROS) generation in MDA-MB-231 cells while it acted as antioxidant in non-tumorigenic MCF10A cells. We demonstrated that ROS generation represented the primary step of APE antitumor activity as pretreatment with antioxidant N-acetylcysteine (NAC) prevented APE-induced G2/M phase arrest, apoptosis, and autophagy. APE downregulated Dusp-1 and induced a significant increase in JNK/c-Jun phosphorylation that were both prevented by NAC. Moreover, downregulation of JNK by its specific inhibitor SP600125 significantly diminished the anticancer activity of APE indicating that ROS generation and sustained JNK activation represented the main underlying mechanism of APE-induced cell death. APE also inhibited AKT activation and downregulated several oncoproteins, such as NF-kB, c-myc, and beta-catenin. In light of these results, APE may be an attractive candidate for drug development against triple negative breast cancer

SARS-CoV-2 vaccination modelling for safe surgery to save lives : data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population.Peer reviewe

Annurca apple polyphenol extract selectively kills MDA-MB-231 cells through ROS generation, sustained JNK activation and cell growth and survival inhibition

Polyphenols represent the most studied class of nutraceuticals that can be therapeutics for a large spectrum of diseases, including cancer. In this study, we investigated for the first time the antitumor activities of polyphenol extract from Annurca apple (APE) in MDA-MB-231 triple negative breast cancer cells, and we explored the underlying mechanisms. APE selectively inhibited MDA-MB-231 cell viability and caused G2/M phase arrest associated with p27 and phospho-cdc25C upregulation and with p21 downregulation. APE promoted reactive oxygen species (ROS) generation in MDA-MB-231 cells while it acted as antioxidant in non-tumorigenic MCF10A cells. We demonstrated that ROS generation represented the primary step of APE antitumor activity as pretreatment with antioxidant N-acetylcysteine (NAC) prevented APE-induced G2/M phase arrest, apoptosis, and autophagy. APE downregulated Dusp-1 and induced a significant increase in JNK/c-Jun phosphorylation that were both prevented by NAC. Moreover, downregulation of JNK by its specific inhibitor SP600125 significantly diminished the anticancer activity of APE indicating that ROS generation and sustained JNK activation represented the main underlying mechanism of APE-induced cell death. APE also inhibited AKT activation and downregulated several oncoproteins, such as NF-kB, c-myc, and β-catenin. In light of these results, APE may be an attractive candidate for drug development against triple negative breast cance

Effects of Dietary Intervention on Nutritional Status in Elderly Individuals with Chronic Kidney Disease

The prevalence of chronic kidney disease (CKD) is rising, especially in elderly individuals. The overlap between CKD and aging is associated with body composition modification, metabolic abnormalities, and malnutrition. Renal care guidelines suggest treating CKD patient with a low-protein diet according to the renal disease stage. On the other hand, geriatric care guidelines underline the need for a higher protein intake to prevent malnutrition. The challenge remains of how to reconcile a low dietary protein intake with insuring a favorable nutritional status in geriatric CKD populations. Therefore, this study aims to evaluate the effect of a low-protein adequate energy intake (LPAE) diet on nutritional risk and nutritional status among elderly CKD (stage 3–5) patients and then to assess its impact on CKD metabolic abnormalities. To this purpose, 42 subjects [age ≥ 65, CKD stage 3–5 in conservative therapy, and Geriatric Nutritional Risk Index (GNRI) ≥ 98] were recruited and the LPAE diet was prescribed. At baseline and after 6 months of the LPAE diet, the following data were collected: age, sex, biochemical parameters, anthropometric measurements, body composition, and the GNRI. According to their dietary compliance, the subjects were divided into groups: compliant and non-compliant. For the compliant group, the results obtained show no increased malnutrition risk incidence but, rather, an improvement in body composition and metabolic parameters, suggesting that the LPAE diet can provide a safe tool in geriatric CKD patients

Dietary Polyphenols, Microbiome, and Multiple Sclerosis: From Molecular Anti-Inflammatory and Neuroprotective Mechanisms to Clinical Evidence

Multiple sclerosis (MS) is a multifactorial, immune-mediated disease caused by complex gene-environment interactions. Dietary factors modulating the inflammatory status through the control of the metabolic and inflammatory pathways and the composition of commensal gut microbiota, are among the main environmental factors involved in the pathogenesis of MS. There is no etiological therapy for MS and the drugs currently used, often accompanied by major side effects, are represented by immunomodulatory substances capable of modifying the course of the disease. For this reason, nowadays, more attention is paid to alternative therapies with natural substances with anti-inflammatory and antioxidant effects, as adjuvants of classical therapies. Among natural substances with beneficial effects on human health, polyphenols are assuming an increasing interest due to their powerful antioxidant, anti-inflammatory, and neuroprotective effects. Beneficial properties of polyphenols on the CNS are achieved through direct effects depending on their ability to cross the blood-brain barrier and indirect effects exerted in part via interaction with the microbiota. The aim of this review is to examine the literature about the molecular mechanism underlying the protective effects of polyphenols in MS achieved by experiments conducted in vitro and in animal models of the disease. Significant data have been accumulated for resveratrol, curcumin, luteolin, quercetin, and hydroxytyrosol, and therefore we will focus on the results obtained with these polyphenols. Clinical evidence for the use of polyphenols as adjuvant therapy in MS is restricted to a smaller number of substances, mainly curcumin and epigallocatechin gallate. In the last part of the review, a clinical trial studying the effects of these polyphenols in MS patients will also be revised

The Synergic Effect of a Nutraceutical Supplementation Associated to a Mediterranean Hypocaloric Diet in a Population of Overweight/Obese Adults with NAFLD

Overweight/obesity is often associated with a non-alcoholic fatty liver disease (NAFLD). The study aim was to investigate the effects of a nutraceutical supplementation associated to a Mediterranean-hypocaloric-diet (MHD) on ultrasound-liver-steatosis (ULS) grade improvement in overweight/obese patients with NAFLD. A total of 68 subjects (BMI ≥ 25 kg/m2) with NAFLD were recruited, randomized into 2 groups and treated for 3 months: the Nutraceutical group was treated with MHD plus nutraceutical supplementation (Vitamin E, L-glutathione, silymarin and hepato-active compounds); the Control-group only with a MHD. Anthropometric measurements, body composition, biochemical parameters and Hepatic steatosis index (HSI) were evaluated at baseline and after 3 months; patients with HSI >36 underwent a liver ultrasound to determine liver steatosis grade (3 severe, 2 moderate, 1 mild). In all patients, a significant improvement in nutritional and biochemical parameters was observed after treatment. After treatment, the nutraceutical group showed a significant improvement in hepatic steatosis, either according to ULS-grade (11.1% and 5.6% of patients with mild and moderate liver steatosis, respectively, showed a complete NAFLD regression; 33.3% and 22.2% of patients with moderate and severe liver steatosis, respectively showed a regression to mild liver steatosis), or according to HSI (49.3 ± 10.1 vs. 43.3 ± 9.0, p = 0.01), suggesting that a healthy diet is still the best choice, although the use of specific supplements can enhance the efficacy of dietary intervention in overweight/obese patients with NAFLD