Early postnatal administration of an AAV9 gene therapy is safe and efficacious in CLN3 disease.

CLN3 disease, caused by biallelic mutations in the gene, is a rare pediatric neurodegenerative disease that has no cure or disease modifying treatment. The development of effective treatments has been hindered by a lack of etiological knowledge, but gene replacement has emerged as a promising therapeutic platform for such disorders. Here, we utilize a mouse model of CLN3 disease to test the safety and efficacy of a cerebrospinal fluid-delivered AAV9 gene therapy with a study design optimized for translatability.

Influence of iron supplementation on fatigue, mood states and sweating profiles of healthy non-anemic athletes during a training exercise: A double-blind, randomized, placebo-controlled, parallel-group study.

Iron is specifically important to athletes, and attention has grown to the association between sports performance and iron regulation in the daily diets of athletes. The study presents new insights into stress, mood states, fatigue, and sweating behavior among the non-anemic athletes with sweating exercise habits who consumed a routine low dose (3.6 mg/day) of iron supplementation.

Structural Investigation of Hesperetin-7--Glucoside Inclusion Complex with β-Cyclodextrin: A Spectroscopic Assessment.

Flavonoids are biologically active natural products of great interest for their potential applications in functional foods and pharmaceuticals. A hesperetin-7--glucoside inclusion complex with β-cyclodextrin (HEPT7G/βCD; SunActive HCD) was formulated via the controlled enzymatic hydrolysis of hesperidin with enzyme. The conversion rate was nearly 98%, estimated using high-performance liquid chromatography analysis.

Genotoxicity and mutagenicity evaluation of isoquercitrin-γ-cyclodextrin molecular inclusion complex using Ames test and a combined micronucleus and comet assay in rats.

Flavonoids such as quercetin and its glucosides, especially isoquercitrin are well known as anti-inflammatory, anti-allergic, and anti-carcinogenic, etc. The safety of isoquercitrin formulations needs to be established prior to their use in functional food applications. The mutagenicity and genotoxicity of the IQC-γCD inclusion complex were assessed with three standard assays of the bacterial reverse mutation assay (Ames test) and using a combined in-vivo micronucleus and comet assay under the Organisation for Economic Co-operation and Development (OECD) guidelines.

Green Tea Catechin Association with Ultraviolet Radiation-Induced Erythema: A Systematic Review and Meta-Analysis.

Catechins are a part of the chemical family of flavonoids, a naturally occurring antioxidant, and a secondary metabolite in certain plants. Green tea catechins are well recognized for their essential anti-inflammatory, photo-protective, antioxidant, and chemo-preventive functions. Ultraviolet radiation is a principal cause of damage to the skin.

13-Weeks subchronic toxicity of isoquercitrin-γ-cyclodextrin (IQC-γCD) molecular inclusion complex in Sprague-Dawley rats.

Flavonoids such as quercetin and its glycoside Isoquercitrin and are abundantly present in the diet and have various pharmacological effects. However, limited data about its potential toxicity is available. In this study, we aim to evaluate the subchronic toxicity of the isoquercitrin-γ-cyclodextrin (IQC-γCD) molecular inclusion complex (SunActive® QCD/EN) in Sprague-Dawley (SD) rats.

AAV9 Gene Therapy Increases Lifespan and Treats Pathological and Behavioral Abnormalities in a Mouse Model of CLN8-Batten Disease.

CLN8 disease is a rare form of neuronal ceroid lipofuscinosis caused by biallelic mutations in the CLN8 gene, which encodes a transmembrane endoplasmic reticulum protein involved in trafficking of lysosomal enzymes. CLN8 disease patients present with myoclonus, tonic-clonic seizures, and progressive declines in cognitive and motor function, with many cases resulting in premature death early in life. There are currently no treatments that can cure the disease or substantially slow disease progression.

A multimodal approach to identify clinically relevant biomarkers to comprehensively monitor disease progression in a mouse model of pediatric neurodegenerative disease.

While research has accelerated the development of new treatments for pediatric neurodegenerative disorders, the ability to demonstrate the long-term efficacy of these therapies has been hindered by the lack of convincing, noninvasive methods for tracking disease progression both in animal models and in human clinical trials. Here, we unveil a new translational platform for tracking disease progression in an animal model of a pediatric neurodegenerative disorder, CLN6-Batten disease. Instead of looking at a handful of parameters or a single "needle in a haystack", we embrace the idea that disease progression, in mice and patients alike, is a diverse phenomenon best characterized by a combination of relevant biomarkers.

Clinical evaluation of Emblica Officinalis Gatertn (Amla) in healthy human subjects: Health benefits and safety results from a randomized, double-blind, crossover placebo-controlled study.

The preventive efficacies and safety of (Amla), a most important and extensively studied plant in the traditional Indian Ayurvedic system of medicine, are presented. Eligible healthy adult subjects (n = 15) were randomized to receive either amla or placebo (500 mg per day) during an 18-week study. The efficacy parameters evaluated were the vascular function, blood hematology, oxidative and inflammatory biomarkers, glucose and lipid profiles, urinalysis, and liver hepatotoxicity.

Enhanced mTOR complex 1 signaling attenuates diabetic cardiac injury in OVE26 mice.

The protein kinase mechanistic target of rapamycin (mTOR) performs diverse cellular functions through 2 distinct multiprotein complexes, mTOR complex (mTORC)1 and 2. Numerous studies using rapamycin, an mTORC1 inhibitor, have implicated a role for mTORC1 in several types of heart disease. People with diabetes are more susceptible to heart failure.

Gene Therapy Corrects Brain and Behavioral Pathologies in CLN6-Batten Disease.

CLN6-Batten disease, a form of neuronal ceroid lipofuscinosis is a rare lysosomal storage disorder presenting with gradual declines in motor, visual, and cognitive abilities and early death by 12-15 years of age. We developed a self-complementary adeno-associated virus serotype 9 (scAAV9) vector expressing the human CLN6 gene under the control of a chicken β-actin (CB) hybrid promoter. Intrathecal delivery of scAAV9.

Searching for novel biomarkers using a mouse model of CLN3-Batten disease.

CLN3-Batten disease is a rare, autosomal recessive disorder involving seizures, visual, motor and cognitive decline, and premature death. The Cln3Δex7/8 mouse model recapitulates several phenotypic characteristics of the most common 1.02kb disease-associated deletion.

Short-Term Administration of Mycophenolate Is Well-Tolerated in CLN3 Disease (Juvenile Neuronal Ceroid Lipofuscinosis).

Mycophenolate, an immunosuppressant, is commonly used off-label for autoimmune neurological conditions. In CLN3 disease, a neurodegenerative disorder of childhood, preclinical and clinical data suggest secondary autoimmunity and inflammation throughout the central nervous system are key components of pathogenesis. We tested the short-term tolerability of mycophenolate in individuals with CLN3 disease, in preparation for possible long-term efficacy trials of this drug.

High Protein Pasta is Not More Satiating than High Fiber Pasta at a Lunch Meal, Nor Does it Decrease Mid-Afternoon Snacking in Healthy Men and Women.

This study compared satiety after high protein pasta (16 g protein, 6 g fiber), high fiber pasta (11 g protein, 8 g fiber) or control pasta (11 g protein, 6 g fiber) in a randomized, placebo-controlled, double-blind crossover trial. Participants were 36 healthy and men and women from the University of Minnesota campus. Fasted men and women ate calorie controlled, but macronutrient different pastas at 12:00 pm along with 500 mL of water.

Estimation and interpretation of fermentation in the gut: coupling results from a 24 h batch in vitro system with fecal measurements from a human intervention feeding study using fructo-oligosaccharides, inulin, gum acacia, and pea fiber.

Gut bacteria ferment fiber at different rates to primarily short chain fatty acids (SCFA) and gas while proteins are metabolized to SCFA, branched chain fatty acids (BCFA), gas, and undesirable metabolites. Large volumes of gas produced in vivo may contribute to bloating and flatulence in an individual. The objectives of this trial were to (1) compare the in vitro fermentation profiles of fructo-oligosaccharides (FOS), inulin, gum acacia, and pea fiber alone or blended using a 24 h batch model and (2) relate these findings to a human study that fed enteral formula fortified with fiber blend (FB) or no fiber (FF).

Diminished autophagy limits cardiac injury in mouse models of type 1 diabetes.

Cardiac autophagy is inhibited in type 1 diabetes. However, it remains unknown if the reduced autophagy contributes to the pathogenesis of diabetic cardiomyopathy. We addressed this question using mouse models with gain- and loss-of-autophagy.

Fermentation profiles of wheat dextrin, inulin and partially hydrolyzed guar gum using an in vitro digestion pretreatment and in vitro batch fermentation system model.

This study investigated the fermentation and microbiota profiles of three fibers, wheat dextrin (WD), partially hydrolyzed guar gum (PHGG), and inulin, since little is known about the effects of WD and PHGG on gut microbiota. A treatment of salivary amylase, pepsin, and pancreatin was used to better physiologic digestion. Fibers (0.

Polydextrose and soluble corn fiber increase five-day fecal wet weight in healthy men and women.

Dietary fiber has well-established beneficial effects on laxation. Many fibers have been developed with positive sensory properties and 2 such fibers are polydextrose (PDX) and soluble corn fiber (SCF), which can be added to many commercially produced products. We conducted a randomized, double-blind, placebo-controlled, crossover study comparing the laxative effects of PDX and SCF at a dose of 20 g/d with a low fiber control (LFC) eaten daily as a muffin and cereal in 36 healthy men and women.

Resveratrol attenuates doxorubicin-induced cardiomyocyte death via inhibition of p70 S6 kinase 1-mediated autophagy.

Resveratrol is a plant-derived polyphenol that can attenuate the cardiotoxic effects of doxorubicin (DOX), a powerful antibiotic widely used in cancer chemotherapy. However, the underlying protective mechanisms of resveratrol remain elusive. Here, we show that resveratrol inhibited DOX-induced autophagy and cardiomyocyte death, and autophagy suppression is an important mechanism that mediates the ability of resveratrol to protect against DOX cardiotoxicity.

Caloric restriction mimetic 2-deoxyglucose antagonizes doxorubicin-induced cardiomyocyte death by multiple mechanisms.

Caloric restriction (CR) is a dietary intervention known to enhance cardiovascular health. The glucose analog 2-deoxy-D-glucose (2-DG) mimics CR effects in several animal models. However, whether 2-DG is beneficial to the heart remains obscure.

The use of a wireless motility device (SmartPill®) for the measurement of gastrointestinal transit time after a dietary fibre intervention.

Historically, measurement of gastrointestinal transit time has required collection and X-raying of faecal samples for up to 7 d after swallowing radio-opaque markers; a tedious, labour-intensive technique for both subjects and investigators. Recently, a wireless motility capsule (SmartPill®), which uses gut pH, pressure and temperature to measure transit time, has been developed. This device, however, has not been validated with dietary interventions.

Wheat dextrin, psyllium, and inulin produce distinct fermentation patterns, gas volumes, and short-chain fatty acid profiles in vitro.

Dietary fiber fermentation decreases luminal pH by the production of short-chain fatty acids (SCFAs). Additional proposed physiological benefits of fiber fermentation include decreased growth of pathogenic bacteria, increased mineral absorption, and serving as an energy source for the colon epithelium. This study examined three common fiber supplements--wheat dextrin (WD) (Benefiber, Novartis Consumer Health Inc.

Evaluation of the effect of four fibers on laxation, gastrointestinal tolerance and serum markers in healthy humans.

Background: Average dietary fiber intake in the United States is roughly half of the recommended amount. As new dietary fiber products are introduced to increase fiber intake, it is critical to evaluate the physiological effects of such fibers.

Aims: This study examined the effect of 4 fibers derived from maize or tapioca on fecal chemistry, gastrointestinal (GI) symptoms and serum markers of chronic disease.

Transcription factor GATA4 inhibits doxorubicin-induced autophagy and cardiomyocyte death.

Doxorubicin (DOX) is a potent anti-tumor drug known to cause heart failure. The transcription factor GATA4 antagonizes DOX-induced cardiotoxicity. However, the protective mechanism remains obscure.

Fructooligosaccharides exhibit more rapid fermentation than long-chain inulin in an in vitro fermentation system.

This study investigated how chain length affects fermentation properties of fructooligosaccharides (FOSs) and inulin (IN). Chain lengths of FOSs and IN vary from an average degree of polymerization (DP) of 3 to greater than 20. Three samples classified as FOSs (samples A, B, and C) and 3 samples classified as IN (samples D, E, and F) were fermented via an in vitro batch method with human fecal inoculum as the source of microbes.