New Regenerative and Anti-Aging Medicine Approach Based on Single-Stranded Alpha-1 Collagen for Neo-Collagenesis Induction: Clinical and Instrumental Experience of a New Injective Polycomponent Formulation for Dermal Regeneration.

This study explores the efficacy of a novel polycomponent formulation (KARISMA Rh Collagen® FACE, Taumedika Srl, Rome, Italy), containing 200 mg/mL of non-crosslinked high-molecular-weight hyaluronic acid (HMW-HA), 200 µg/mL of a human recombinant polypeptide of collagen-1 alpha chain, and 40 mg/mL of carboxymethyl cellulose (CMC) as a regenerative medicine for skin regeneration and rejuvenation. This formulation combines non-crosslinked high-molecular-weight hyaluronic acid, human recombinant polypeptide of collagen-1 alpha chain, and carboxymethyl cellulose to stimulate collagen type I production and enhance skin hydration. This study involved 100 subjects with varying skin conditions, divided into three groups based on skin aging, smoking history, and facial scarring, to evaluate the product's effectiveness in skin regeneration and aesthetic improvement. The methodology included two injections of Karisma (2 mL for each injection) one month apart, with evaluations conducted using FACE-Q questionnaires, the SGAIS Questionnaire, and Antera 3D skin scanner measurements at baseline, 30 days, and 60 days post-treatment. The results demonstrated a significant reduction in skin roughness and an improvement in skin quality across all the groups, with no correlation between the outcomes and the patient's age. The subjective assessments also indicated high satisfaction with the treatment's aesthetic results. The analyzed data allow us to conclude that the single-stranded collagen with hyaluronic acid and carboxymethyl-cellulose formulation is able to stimulate the skin's regenerative response, yielding significant results both in vitro and, through our study, also in vivo. This new polycomponent formulation effectively stimulates skin regeneration, improving skin quality and texture, with significant aesthetic benefits perceived by patients, and a low incidence of adverse events, marking a promising advancement in regenerative medicine.

MiRNAs Expression Modulates Osteogenesis in Response to Exercise and Nutrition.

In recent years, many articles have been published describing the impact of physical activity and diet on bone health. This review has aimed to figure out the possible epigenetic mechanisms that influence bone metabolism. Many studies highlighted the effects of macro and micronutrients combined with exercise on the regulation of gene expression through miRs. The present review will describe how physical activity and nutrition can prevent abnormal epigenetic regulation that otherwise could lead to bone-metabolism-related diseases, the most significant of which is osteoporosis. Nowadays, it is known that this effect can be carried out not only by endogenously produced miRs, but also through those intakes through the diet. Indeed, they have also been found in the transcriptome of animals and plants, and it is possible to hypothesise an interaction between miRNAs produced by different kingdoms and epigenetic influences on human gene expression. In particular, the key to the activation pathways triggered by diet and physical activity appears to be the activation of Runt-related transcription factor 2 (RUNX2), the expression of which is regulated by several miRs. Among the main miRs involved are exercise-induced miR21 and 21-5p, and food-induced miR 221-3p and 222-3p.

The Role of Consumption of Molybdenum Biofortified Crops in Bone Homeostasis and Healthy Aging.

Osteoporosis is a chronic disease and public health issue in aging populations. Inadequate intake of micronutrients increases the risk of bone loss during an adult's lifespan and therefore of osteoporosis. The aim of the study was to analyze the effects of consumption of biofortified crops with the micronutrient molybdenum (Mo) on bone remodeling and metabolism in a population of adults and seniors. The trial enrolled 42 senior and 42 adult people randomly divided into three groups that consumed lettuce biofortified with molybdenum (Mo-biofortified group) or without biofortification (control group) or molybdenum in a tablet (Mo-tablet group) for 12 days. We chose an experimental period of 12 days because the bone remodeling marker levels are influenced in the short term. Therefore, a period of 12 days allows us to determine if there are changes in the indicators. Blood samples, obtained at time zero and at the end of the study, were compared within the groups adults and seniors for the markers of bone resorption, C-terminal telopeptide (CTX) and bone formation osteocalcin, along with the markers of bone metabolism, parathyroid hormone (PTH), calcitonin, albumin-adjusted calcium, vitamin D, phosphate and potassium. Consumption of a Mo tablet did not affect bone metabolism in the study. Consumption of Mo-biofortified lettuce significantly reduced levels of CTX and PTH and increased vitamin D in adults and seniors while levels of osteocalcin, calcitonin, calcium, potassium and phosphate were not affected. The study opens up new considerations about the role of nutrition and supplementation in the prevention of chronic diseases in middle-aged and older adults. Consumption of Mo-biofortified lettuce positively impacts bone metabolism in middle-aged and older adults through reduced bone resorption and improved bone metabolism while supplementation of Mo tablets did not affect bone remodeling or metabolism. Therefore, Mo-biofortified lettuce may be used as a nutrition intervention to improve bone homeostasis and prevent the occurrence of osteoporosis in the elderly.

Boosting plant food polyphenol concentration by saline eustress as supplement strategies for the prevention of metabolic syndrome: an example of randomized interventional trial in the adult population.

Introduction: Phenolic compounds in lettuce can increase by the application of positive stress (eustress) such as moderate saline stress. Phenolic compounds possess antioxidant capacity that is a key factor in the detoxification of excess reactive oxygen species. A double-blinded randomized interventional and placebo- controlled study design was carried out to compare the effect of daily dietary eustress lettuce ingestion in hepatic, lipid, bone, glucose, and iron metabolism. Methods: Forty-two healthy volunteers, 19 female and 23 male participants, were divided into two groups. Participants were randomized into a polyphenol-enriched treatment (PET) arm or control arm. Each arm consumed 100 g/day of control or eustress (polyphenols enriched treatment = PET) lettuce for 12 days. Primary study outcomes were serological analysis for assessing hepatic, lipid, bone, iron, and glucose markers at baseline and after 12 days. Secondary outcomes assessed body composition. Results: Salinity stress reduced plant yield but increased caffeic acid (+467%), chlorogenic acid (+320%), quercetin (+538%), and rutin (+1,095%) concentrations. The intake of PET lettuce reduced PTH, low-density lipoprotein (LDL), cholesterol, alanine transaminase (ALT), and aspartate transaminase (AST) enzyme levels and increased vitamin D and phosphate levels, while iron and glucose metabolism were unaffected. Discussion: Supplementation with eustress lettuce by increasing polyphenols concentration ameliorates hepatic, lipid, and bone homeostasis. Body composition was not affected. Clinical trial registration: https://classic.clinicaltrials.gov/ct2/show/NCT06002672, identifier: NCT06002672.

Dare to jump: The effect of the new high impact activity SuperJump on bone remodeling. A new tool to maintain fitness during COVID-19 home confinement.

SuperJump is a high impact activity performed on an elastic trampoline that mixes aerobic and anaerobic exercises already proposed as home-based activity for preventing a sedentary lifestyle. We determined in a randomized controlled trial whether 20 weeks of SuperJump activity would promote bone formation and reduce resorption in eumenorrheic women. Twenty-four women were randomized to a non-exercise group (control group) or an exercise group that performed SuperJump activity three times a week for 20 weeks. Blood samples were collected in both groups at baseline and at the end of the 20 weeks and compared within and between the groups for C-terminal telopeptide (CTX), a marker of bone resorption, osteocalcin, a marker of bone formation, and the markers of bone metabolism parathyroid hormone (PTH), calcitonin, albumin-adjusted calcium (Aa calcium), vitamin D, phosphate and potassium. After 20 weeks of SuperJump activity, levels of CTX were significantly reduced while levels of osteocalcin were increased. PTH, calcium and potassium were involved in the mechanism of action because PTH was reduced while calcium and potassium were increased. Calcitonin, vitamin D and phosphate levels did not change. These data suggest that SuperJump activity is able to reduce bone resorption and improve bone formation by acting on essential regulators of bone metabolism. They also suggest that SuperJump training may be used as a valuable intervention to prevent the occurrence of osteoporosis in aging because it improves bone homeostasis in favor of bone formation and could counteract a sedentary lifestyle, such as during COVID-19 home confinement, which could itself contribute to the variation of bone metabolism. Trial registration: Clinicaltrials.gov NCT04942691 -retrospectively registered.

From Small Peptides to Large Proteins against Alzheimer'sDisease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder in the elderly. The two cardinal neuropathological hallmarks of AD are the senile plaques, which are extracellular deposits mainly constituted by beta-amyloids, and neurofibrillary tangles formed by abnormally phosphorylated Tau (p-Tau) located in the cytoplasm of neurons. Although the research has made relevant progress in the management of the disease, the treatment is still lacking. Only symptomatic medications exist for the disease, and, in the meantime, laboratories worldwide are investigating disease-modifying treatments for AD. In the present review, results centered on the use of peptides of different sizes involved in AD are presented.

Effects of a Resistance Training Protocol on Physical Performance, Body Composition, Bone Metabolism, and Systemic Homeostasis in Patients Diagnosed with Parkinson's Disease: A Pilot Study.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor impairments and it is correlated with loss of bone mineral density. This study aimed to analyze the effects of resistance training on bone metabolism, systemic homeostasis, body composition, and physical performance in people with PD. Thirteen subjects (age 64.83 ± 5.70) with PD diagnosis were recruited. Participants performed neuromuscular tests, body composition assessment, and blood sample analysis at baseline, and after an 11 weeks-training period. Each training session lasted 90 min, three times a week. The participants had significant improvements in the timed up and go (p < 0.01), sit to stand (p < 0.01), dominant peg-board (p < 0.05), dominant foot-reaction time (p < 0.01), and functional reach tests (p < 0.05). They showed better pressure foot distributions in the left forefoot (p < 0.05) and hindfoot (p < 0.05) and increased cervical right lateral bending angle (p < 0.05). The protocol affects bone metabolism markers osteocalcin (p < 0.05), calcium (p < 0.01), PTH (p < 0.01), the C-terminal telopeptide (CTX) (p < 0.01), and vitamin D (p < 0.05). Eleven weeks of resistance training improved manual dexterity, static and dynamic balance, reaction time, cervical ROM, and reduced bone loss in people with PD.

A New Potential Dietary Approach to Supply Micronutrients to Physically Active People through Consumption of Biofortified Vegetables.

Micronutrients are required in many reactions involved in physical activity and exercise. Most physically active people do not meet the body's needs in terms of micronutrients through diet. The novelty of the present manuscript is the use of an innovative dietary approach to supply micronutrients to physically active people through biofortified food. Therefore, the key point of this study was to verify whether supplementation with biofortified vegetables-and specifically molybdenum (Mo)-enriched lettuce-in healthy volunteers affects essential regulators of body homeostasis and, specifically, hematological parameters, iron and lipid metabolism, and hepatic function. Twenty-four healthy volunteers were allocated in a double-blinded manner to either a control group that consumed lettuce, or the intervention group, which consumed Mo-enriched lettuce, for 12 days. Blood samples were collected at baseline (T0) and after 12 days (T1). We found that supplementation with Mo-enriched lettuce did not affect hematological parameters, liver function, or lipid metabolism, but significantly improved iron homeostasis by increasing non-binding hemoglobin iron by about 37% and transferrin saturation by about 42%, while proteins of iron metabolism (e.g., transferrin, ferritin, ceruloplasmin) were not affected. The serum molybdenum concentration increased by about 42%. In conclusion, this study shows that consumption of Mo-biofortified lettuce ameliorates iron homeostasis in healthy subjects, and suggests that it could be used as a new nutritional supplementation strategy to avoid iron deficiency in physically active people.

Stand-Alone or Combinatorial Effects of Grafting and Microbial and Non-Microbial Derived Compounds on Vigour, Yield and Nutritive and Functional Quality of Greenhouse Eggplant.

The current research investigated the effects of endophytic fungi such as Trichoderma atroviride (Ta) or Ascophyllum nodosum seaweed extract (An) and their combination on growth, yield, nutritive and functional features, and mineral profile of 'Birgah' F1 eggplant either ungrafted, self-grafted or grafted onto the Solanum torvum rootstock. Eggplant exposed to An or An+Ta had a significant increase in root collar diameter 50 days after transplanting (RCD50), total yield (TY), marketable yield (MY), ascorbic acid (AA) content, Mg, Cu, and Zn concentration, and a reduction in glycoalkaloids (GLY) compared with the control. Furthermore, grafted plants had a higher TY, MY, number of marketable fruits (NMF), RCD50, AA, Cu, and Zn and a lower SSC, GLY, and Mg than the ungrafted plants. The combination of grafting and An+Ta significantly improved mean weight of marketable fruits (MF), plant height 50 days after transplanting (PH50), number of leaves 50 days after transplanting (NL50), fruit dry matter (FDM), chlorogenic acid (ClA), proteins, and K and Fe concentration. This combination also produced fruits of high premium quality as evidenced by the higher AA and ClA concentration, the lower GLY concentration, and an overall improved mineral profile.

Biofortification: Effect of Iodine Fortified Food in the Healthy Population, Double-Arm Nutritional Study.

It is estimated that one-third of the world's population lives in areas where iodine (I) is scarce and its deficiency is responsible for many related disorders, such as goiter, reproductive failure, hearing loss, growth impairment, congenital I deficiency syndrome, and numerous kinds of brain injury. Mineral deficiencies can be overcome via dietary diversification and mineral supplementation. An alternative or even complementary way is represented by the intake of biofortified foods, which can tackle this lack of micronutrients. In this short-term double-arm nutritional intervention study, a cohort of ten people was supplemented with curly endive leaf biofortified with I and ten people with curly endive without biofortification (Intervention Study on Iodine Biofortification Vegetables (Nutri-I-Food - Full-Text View - ClinicalTrials.gov). The effects on whole-body homeostasis and specifically on I, glucose, lipid, and hepatic, iron metabolism was investigated. Blood samples were obtained at baseline and after 12 days of supplementation with curly endive and compared with controls. Hematochemical and urinary parameters were analyzed at baseline and after 12 days. The results showed that short-term I curly endive intervention did not affect the whole body homeostasis in healthy people and revealed an increase in I concentration in urine samples and an increase in vitamin D, calcium, and potassium concentration in blood samples only in the biofortified cohort respect to controls. This study suggests that short-term consumption of I curly endive crops is safe and could positively impact body health.

Impact on Glucose Homeostasis: Is Food Biofortified with Molybdenum a Workable Solution? A Two-Arm Study.

Diabetes is expected to increase up to 700 million people worldwide with type 2 diabetes being the most frequent. The use of nutritional interventions is one of the most natural approaches for managing the disease. Minerals are of paramount importance in order to preserve and obtain good health and among them molybdenum is an essential component. There are no studies about the consumption of biofortified food with molybdenum on glucose homeostasis but recent studies in humans suggest that molybdenum could exert hypoglycemic effects. The present study aims to assess if consumption of lettuce biofortified with molybdenum influences glucose homeostasis and whether the effects would be due to changes in gastrointestinal hormone levels and specifically Peptide YY (PYY), Glucagon-Like Peptide 1 (GLP-1), Glucagon-Like Peptide 2 (GLP-2), and Gastric Inhibitory Polypeptide (GIP). A cohort of 24 people was supplemented with biofortified lettuce for 12 days. Blood and urine samples were obtained at baseline (T0) and after 12 days (T2) of supplementation. Blood was analyzed for glucose, insulin, insulin resistance, ß-cell function, and insulin sensitivity, PYY, GLP-1, GLP-2 and GIP. Urine samples were tested for molybdenum concentration. The results showed that consumption of lettuce biofortified with molybdenum for 12 days did not affect beta cell function but significantly reduced fasting glucose, insulin, insulin resistance and increased insulin sensitivity in healthy people. Consumption of biofortified lettuce did not show any modification in urine concentration of molybdenum among the groups. These data suggest that consumption of lettuce biofortified with molybdenum improves glucose homeostasis and PYY and GIP are involved in the action mechanism.

Is the Secret in the Gut? SuperJump Activity Improves Bone Remodeling and Glucose Homeostasis by GLP-1 and GIP Peptides in Eumenorrheic Women.

We showed that twenty weeks of SuperJump activity, an innovative workout training performed on an elastic minitrampoline, reduced bone resorption and increased bone formation in eumenorrheic women acting on the key points of the regulation of bone metabolism. The present study analyzed whether the gastrointestinal hormones are involved in the mechanism of action and if it has an impact on glucose homeostasis. The control group was composed of twelve women, similar to the exercise group that performed SuperJump activity for twenty weeks. The analysis was performed on blood samples and investigated GLP-1, GIP, GLP-2, PYY, ghrelin, glucose, insulin, insulin resistance, ß-cell function, and insulin sensitivity. The results showed that the activity contributes to raising the GLP-1and GIP levels, and not on GLP-2, PYY, and ghrelin, which did not change. Moreover, SuperJump activity significantly reduced fasting insulin, glucose, insulin resistance, and increased insulin sensitivity but did not affect beta cell function. These data suggest that GLP-1, and GIP are involved in the mechanism of action that improves bone and glucose homeostasis following 20 weeks of SuperJump activity in eumenorrheic women.

The Impact of Diet and Physical Activity on Bone Health in Children and Adolescents.

There is growing recognition of the role of diet and physical activity in modulating bone mineral density, bone mineral content, and remodeling, which in turn can impact bone health later in life. Adequate nutrient composition could influence bone health and help to maximize peak bone mass. Therefore, children's nutrition may have lifelong consequences. Also, physical activity, adequate in volume or intensity, may have positive consequences on bone mineral content and density and may preserve bone loss in adulthood. Most of the literature that exists for children, about diet and physical activity on bone health, has been translated from studies conducted in adults. Thus, there are still many unanswered questions about what type of diet and physical activity may positively influence skeletal development. This review focuses on bone requirements in terms of nutrients and physical activity in childhood and adolescence to promote bone health. It explores the contemporary scientific literature that analyzes the impact of diet together with the typology and timing of physical activity that could be more appropriate depending on whether they are children and adolescents to assure an optimal skeleton formation. A description of the role of parathyroid hormone (PTH) and gut hormones (gastric inhibitory peptide (GIP), glucagon-like peptide (GLP)-1, and GLP-2) as potential candidates in this interaction to promote bone health is also presented.

Analysis of Body Perception, Preworkout Meal Habits and Bone Resorption in Child Gymnasts.

The beneficial effects of physical activity on body image perception and bone are debated among artistic gymnasts. Gymnasts seem to be at greater risk of developing body dissatisfaction, eating disorders and osteoporosis due to inadequate nutrition and attention to the appearance of the body. The objective of this work was to investigate the association between the artistic gymnast and a more favorable body image compared to their sedentary peers and if a preworkout high-carbohydrate meal (HCM; 300 kcal, 88% carbohydrates, 9% protein, 3% fat) or high-protein meal (HPM; 300 kcal, 55% carbohydrates, 31% protein, 13% fat) is able to attenuate bone resorption in young rhythmic gymnasts. Twenty-eight preadolescent female gymnasts were examined. Self-esteem tests were used to analyze body image perception. Preworkout eating habits were examined by short food frequency questions (FFQ) validated for children. The biomarker of the bone resorption C-terminal telopeptide region of collagen type 1 (CTX) was measured in the urine (fasting, postmeal and postworkout). Gymnasts reported higher satisfaction with their body appearance compared to sedentary peers. Of the gymnasts, 30% did not have a preworkout meal regularly, and the timing of the consumption was variable. Bone resorption was decreased by the HCM, consumed 90 min before the training, with respect to the HPM. The study suggests that playing artistic gymnastics is associated with a positive body self-perception in a child. The variability in preworkout meal frequency and timing need attention to prevent inadequate eating habits in light of the ability of the HCM to reduce acute bone resorption.

Pistachio Consumption Alleviates Inflammation and Improves Gut Microbiota Composition in Mice Fed a High-Fat Diet.

High-fat diet (HFD) induces inflammation and microbial dysbiosis, which are components of the metabolic syndrome. Nutritional strategies can be a valid tool to prevent metabolic and inflammatory diseases. The aim of the present study was to evaluate if the chronic intake of pistachio prevents obesity-associated inflammation and dysbiosis in HFD-fed mice. Three groups of male mice (four weeks old; n = 8 per group) were fed for 16 weeks with a standard diet (STD), HFD, or HFD supplemented with pistachios (HFD-P; 180 g/kg of HFD). Serum, hepatic and adipose tissue inflammation markers were analyzed in HFD-P animals and compared to HFD and STD groups. Measures of inflammation, obesity, and intestinal integrity were assessed. Fecal samples were collected for gut microbiota analysis. Serum TNF-α and IL-1ß levels were significantly reduced in HFD-P compared to HFD. Number and area of adipocytes, crown-like structure density, IL-1ß, TNF-α, F4-80, and CCL-2 mRNA expression levels were significantly reduced in HFD-P subcutaneous and visceral adipose tissues, compared to HFD. A significant reduction in the number of inflammatory foci and IL-1ß and CCL-2 gene expression was observed in the liver of HFD-P mice compared with HFD. Firmicutes/Bacteroidetes ratio was reduced in HFD-P mice in comparison to the HFD group. A pistachio diet significantly increased abundance of healthy bacteria genera such as Parabacteroides, Dorea, Allobaculum, Turicibacter, Lactobacillus, and Anaeroplasma, and greatly reduced bacteria associated with inflammation, such as Oscillospira, Desulfovibrio, Coprobacillus, and Bilophila. The intestinal conductance was lower in HFD-P mice than in the HFD mice, suggesting an improvement in the gut barrier function. The results of the present study showed that regular pistachio consumption improved inflammation in obese mice. The positive effects could be related to positive modulation of the microbiota composition.

Increased Body Weight and Fat Mass After Subchronic GIP Receptor Antagonist, but Not GLP-2 Receptor Antagonist, Administration in Rats.

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are hormones secreted from the enteroendocrine cells after a meal. They exert their actions through activation of G protein-coupled receptors (R), the GIPR and GLP-2R, respectively. Both have been reported to influence metabolism. The purpose of the study was to investigate the role of the hormones in the regulation of lipid and bone homeostasis by subchronic treatment with novel GIPR and GLP-2R antagonists. Rats were injected once daily with vehicle, GIPR, or GLP-2R antagonists for 3 weeks. Body weight, food intake, body composition, plasma lipoprotein lipase (LPL), adipokines, triglycerides and the marker of bone resorption carboxy-terminal collagen crosslinks (CTX), were examined. In rats, subchronic treatment with GIPR antagonist, rat GIP (3-30)NH2, did not modify food intake and bone resorption, but significantly increased body weight, body fat mass, triglycerides, LPL, and leptin levels compared with vehicle treated rats. Subchronic (Pro3)GIP (a partial GIPR agonist), GLP-2(11-33), and GLP-2(3-33) (GLP-2R antagonists) treatment did not affect any parameter. The present results would be consistent with a role for GIP, but not GLP-2, in the maintenance of lipid homeostasis in rats, while neither GIPR nor GLP-2R antagonism appeared to influence bone resorption in rats.

Health benefits of pistachios consumption.

The health benefits of nuts, mainly in relation to the improvement of dysmetabolic conditions such as obesity, type 2 diabetes mellitus and the related cardiovascular diseases, have been widely demonstrated. Compared to other nuts, pistachios have a lower fat and caloric content, and contain the highest levels of unsaturated fatty acids, potassium, γ-tocopherol, phytosterols and xanthophyll carotenoids, all substances that are well known for their antioxidant and anti-inflammatory actions. This variety of nutrients contributes to the growing body of evidence that the consumption of pistachios improves health, leading to a greater potential of healthy antioxidant and anti-inflammatory activity, glycemic control, and endothelial function. The present review examines the nutrients and phytochemicals present in pistachios as well as the potential health benefits of including pistachios in a diet.

Glucagon-like peptide-2 reduces the obesity-associated inflammation in the brain.

Growing evidence suggests a link between obesity and neurodegeneration. The purpose of the present study was to explore the neuroprotective potential of glucagon-like peptide-2 (GLP-2) in the brain of high fat diet (HFD)-fed mice. Markers of inflammation and oxidative stress were analysed in the brains of obese mice chronically treated with [Gly2]-GLP-2 (teduglutide), the stable analogue of the GLP-2, and they were compared to age-matched untreated obese and lean animals. Neurodegeneration was examined by TUNEL assay. HFD feeding increased the expression of pro-inflammatory mediators (NF-kB, IL-8, TNF-α, IL-1ß and IL-6), glial fibrillary acidic protein (GFAP), index of gliosis and neurodegeneration, stress marker proteins (p-ERK, Hsp60 and i-NOS), amyloid-ß precursor protein (APP). [Gly2]-GLP-2 treatment significantly attenuated the HFD-induced increased expression of the various markers, as well as the higher levels of reactive oxygen species found in brains of untreated-HFD mice. Immunofluorescence confirmed that the increase of GFAP or APP in the brain cortex of HFD mice were less prominent in the [Gly2]-GLP-2 treated group. TUNEL-positive cell number in brain sections of [Gly2]-GLP-2-treated HFD-fed mice was significantly lesser in comparison with untreated-HFD animals and similar to STD fed mice. In conclusion, the results of the present study suggest that GLP-2 stable analogue improves the obesity-associated neuroinflammation and the central stress conditions, it reduces the neuronal apoptotic death, providing evidence for a neuroprotective role of the peptide.

Rescuing the CFTR protein function: Introducing 1,3,4-oxadiazoles as translational readthrough inducing drugs.

Nonsense mutations in the CFTR gene prematurely terminate translation of the CFTR mRNA leading to the production of a truncated protein that lacks normal function causing a more severe form of the cystic fibrosis (CF) disease. About 10% of patients affected by CF show a nonsense mutation. A potential treatment of this alteration is to promote translational readthrough of premature termination codons (PTCs) by Translational Readthrough Inducing Drugs (TRIDs) such as PTC124. In this context we aimed to compare the activity of PTC124 with analogues differing in the heteroatoms position in the central heterocyclic core. By a validated protocol consisting of computational screening, synthesis and biological tests we identified a new small molecule (NV2445) with 1,3,4-oxadiazole core showing a high readthrough activity. Moreover, we evaluated the CFTR functionality after NV2445 treatment in CF model systems and in cells expressing a nonsense-CFTR-mRNA. Finally, we studied the supramolecular interactions between TRIDs and CFTR-mRNA to assess the biological target/mechanism and compared the predicted ADME properties of NV2445 and PTC124.