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Generation of reactive oxygen species in the anterior eye segment. Synergistic codrugs of N-acetylcarnosine lubricant eye drops and mitochondria-targeted antioxidant act as a powerful therapeutic platform for the treatment of cataracts and primary open-angle glaucoma.

Senile cataract is a clouding of the lens in the aging eye leading to a decrease in vision. Symptoms may include faded colors, blurry vision … brane in vivo. The authors developed and patented the new ophthalmic compositions including N-acetylcarnosine acting as a prodrug of naturally targeted to mitochondria l-carnosine endowed with pluripotent antioxidant activities, combined with mitochondria-targeted rechargeable antioxidant (either MitoVit E, Mito Q or SkQs) as a potent medicine to treat ocul …

Longitudinal characterization of serum metabolome and lipidome reveals that the ceramide profile is associated with metabolic health in early postpartum cows experiencing different lipolysis.

Reduced feed intake in early lactation prompts increased fat mobilization to meet dairy cow energy needs for milk production. The increased … m metabolome of the HFM cows was characterized by higher concentrations of glycine, acylcarnitines, carnosine, Cer(d20:0/18:0), Cer(d18:1/16:0), and Cer(t18:0/24:0) compared with LFM cows. The differential serum metabolites and lipids at different sampling times during the peripartum period were enriched in the sphingolipid metabolism. Differences in serum …

Longitudinal Analysis of the Microbiome and Metabolome in the 5xfAD Mouse Model of Alzheimer's Disease.

Recent reports implicate gut microbiome dysbiosis in the onset and progression of Alzheimer's disease (AD), yet studies involving model anim … pared to their WT littermates. 5xfAD animals exhibited significantly lower plasma concentrations of carnosine and the lysophospholipid lysoPC a C18:1. Correlations between the microbiome and metabolome were also explored. Taken together, these findings strengthen the link between Turicibacter abundance and AD, provide a basis for further microbiome studies …

Pharmacological and dietary-supplement treatments for autism spectrum disorder: a systematic review and network meta-analysis.

BACKGROUND: There is still no approved medication for the core symptoms of autism spectrum disorder (ASD). This network meta-analysis invest … risperidone (k = 1, RB: 0.97 [0.21,1.74]) in adults. There were some indications of improvement by carnosine, haloperidol, folinic acid, guanfacine, omega-3-fatty-acids, probiotics, sulforaphane, tideglusib and valproate, yet imprecise and not robust. Confidence in these estimates was very low or low, except moderate for oxytocin. Medications differed subs …

Zinc deficiency anemia and effects of zinc therapy in maintenance hemodialysis patients.

Quantitative adjuvant zinc therapy using polaprezinc was performed to examine the correlation between zinc concentration and anemia in maintenance hemodialysis patients to propose appropriate treatment. Anemia and serum zinc concentration were measured in 117 patients with chronic renal failure receiving outpatient maintenance hemodialysis at Tsuyama Chuo Kinen Hospital. Two bags of polaprezinc (containing zinc 34 mg/day) were administered to 58 patients with lower than normal zinc levels (Zn < 80 mg/dl) as adjuvant zinc therapy to assess anemia improvement. Zinc concentration and all anemia p

[Do the glutamate excitotoxicity theory and potential free radicals implication in schizophrenia aetiopathogenesis provide a new enlightenment to links between: genome, environment and biology in the determinism of that disorder?].

The aetiopathogenesis of schizophrenia constitutes nowadays one of the major points of interest for researchers on this cosmopolitan disorde … e at the presynaptic level in addition to a dysfunctioning of the antioxidizing system (glutathion, carnosine, superoxide dismutase, aspartate) to which dopamine and other monoamines might participate. The question is whether or not this theory contributes to shed light on links between: genome, environmental factors and biology in schizophrenia. Through th …

Efficacy of quadruple regimen with polaprezinc for gastric Helicobacter pylori infection eradication: protocol for a single-centre, single-blind, non-inferiority, randomised clinical trial.

INTRODUCTION: Helicobacter pylori (H. pylori) is the most well-known risk factor for gastric cancer. At present, H. pylori shows varying levels of resistance to different treatments, leading to a lower rate of H. pylori eradication. The aim of this study is to evaluate the efficacy of polaprezinc-containing quadruple therapy (PQT) for the eradication of H. pylori infection and, thus, to provide more evidence to inform the clinical treatment of H. pylori infection in China. METHODS AND ANALYSIS: This is a single-centre, single-blind, non-inferiority, randomised controlled trial, enrolling 158

A proton magnetic resonance spectroscopy study of metabolites in the occipital lobes in epilepsy.

PURPOSE: gamma-Amino butyric acid (GABA) and glutamate, respectively the principal inhibitory and excitatory neurochemicals in the brain, are visible to proton magnetic resonance spectroscopy (MRS). We report a study of GABA+ (GABA plus homocarnosine) and GLX (glutamate plus glutamine) concentrations in the occipital lobes in patients with idiopathic generalised epilepsy (IGE) and in patients with occipital lobe epilepsy (OLE). METHODS: Fifteen patients with IGE, 15 patients with OLE, and 15 healthy volunteers were studied. A single voxel was prescribed in the occipital lobes for each subject…

Antigenicity studies on catena-(S)-[mu-[N alpha-(3-aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc].

The antigenicity of Z-103 (catena-(S)-[mu[N alpha-(3-aminopropionyl) histidinato(2-)-N1,N2,O:N tau]-zinc], CAS 107667-60-7) was evaluated using the following assay procedures: 1. active systemic anaphylaxis (ASA) in guinea pigs. 2. passive cutaneous anaphylaxis (PCA) in guinea pigs with serum from guinea pigs sensitized with Z-103, 3. delayed type skin reaction (Maximization Test) in guinea pigs, 4. passive cutaneous anaphylaxis (PCA) in rats with serum from mice sensitized with Z-103 and 5. passive hemagglutination (PHA) with serum from mice sensitized with Z-103. In each test except for Maxi

Effects of polaprezinc on gastric mucosal damage and neurotransmitters in a rat model of chemotherapy-induced vomiting.

Objective To investigate the effects of polaprezinc (PZ) on cyclophosphamide (CTX)- or cisplatin (DDP)-induced gastric mucosal injury and on a rat model of neurotransmitter-mediated vomiting. Methods Sprague-Dawley rats were divided at random into Control, CTX, DDP, PZ+CTX, and PZ+DDP groups. After 20 days, brain tissues and sera were analyzed for the levels of dopamine (DA), 5-hydroxytryptamine (5-HT), and nuclear factor kappa B (NF-κB). Hematoxylin and eosin-stained sections of stomach, intestine, and brain tissues were examined using light microscopy. Results The levels of DA, 5-HT, and NF-

Insulin-like growth factor I plays a role in gastric wound healing: evidence using a zinc derivative, polaprezinc, and an in vitro rabbit wound repair model.

BACKGROUND: Although the detailed mechanism is unclear, zinc and its derivative, polaprezinc, have been reported to accelerate gastric ulcer healing in vivo. AIM: To investigate the detailed cellular mechanism of polaprezinc on gastric epithelial cells and fibroblasts with special attention to insulin-like growth factor I (IGF-I). METHODS: Isolated rabbit gastric epithelial cells formed a complete monolayer, from which a circular artificial wound with constant size was made. The restoration process was monitored by measuring wound size up to 48 h. Either polaprezinc, IGF-I, fibroblast condit

Metabolomics meets machine learning: Longitudinal metabolite profiling in serum of normal versus overconditioned cows and pathway analysis.

This study aimed to investigate the differences in the metabolic profiles in serum of dairy cows that were normal or overconditioned when dr … droxybutyryl-carnitine, glycine, leucine, phosphatidylcholine-diacyl-C40:3, trans-4-hydroxyproline, carnosine, and creatinine) were identified in this way. Pathway enrichment analysis showed that branched-chain AA degradation (before calving) and mitochondrial β-oxidation of long-chain fatty acids along with fatty acid metabolism, purine metabolism, and ala …

Oral zinc supplementation reduces the erythropoietin responsiveness index in patients on hemodialysis.

BACKGROUND: In hemodialysis (HD) patients, zinc depletion caused by inadequate intake, malabsorption, and removal by HD treatment leads to erythropoiesis-stimulating agent (ESA) hyporesponsiveness. This study investigated the effects of zinc supplementation in HD patients with zinc deficiency on changes in the erythropoietin responsiveness index (ERI). METHODS: Patients on HD with low serum zinc levels (<65 μg/dL) were randomly assigned to two groups: The polaprezinc group (who received daily polaprezinc, containing 34 mg/day of zinc) (n = 35) and the control group (no supplementation) (n = 3

Oral Administration of Polaprezinc Attenuates Fluorouracil-induced Intestinal Mucositis in a Mouse Model.

5-Fluorouracil (5-FU) has broadly been applied to treat colorectal cancer as one of the most effective chemotherapeutic agents. However, it frequently causes intestinal mucosal injury and related side effects, such as abdominal pain and diarrhoea, which limit the use of 5-FU in a clinic setting. Polaprezinc has gradually become known as a mucosal protective agent for the management of gastric ulcer. This study aimed to investigate the prophylactic efficacy of Polaprezinc administered orally against intestinal mucositis induced by 5-FU in mice on the condition that the antitumour effect could n

The Role of Oxidative Stress in Diabetic Neuropathy: Generation of Free Radical Species in the Glycation Reaction and Gene Polymorphisms Encoding Antioxidant Enzymes to Genetic Susceptibility to Diabetic Neuropathy in Population of Type I Diabetic Patients.

Diabetic neuropathy (DN) represents the main cause of morbidity and mortality among diabetic patients. Clinical data support the conclusion … n in formulations of transglycating imidazole-containing peptide-based antioxidants (non-hydrolyzed carnosine, carcinine, n-acetylcarcinine) scavenging ROS in the glycation reaction, modifying the activity of enzymic and non-enzymic antioxidant defenses that participate in metabolic processes with ability of controlling at transcriptional levels the differe …

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… Treatment group received daily oral carnosine supplementation. After 72 hr; animals were sacrificed. Plasma and urinary creatinine and urinary microprotein concentration were measured. … Picrosirius red stained slides revealed decreased collagen deposition with carnosine treatment. Venom treatment significantly increased renal fibrotic markers such as CTGF; TGF-β; α-SMA which is reduced after carnosine treatment. …

Cattle Encephalon Glycoside and Ignotin Protects Neurons Against Microglia-Induced Neuroinflammation via Elevating BDNF Expression and Inhibiting TLR4/NF-κB Pathway.

Neuroinflammation is involved in the pathology and progression of Alzheimer's disease (AD) and is closely related to microglial activation. We have previously reported that cattle encephalon glycoside and ignotin (CEGI) could inhibit the activation of microglia in APP/PS1 mice, a mouse model of familial AD. However, the anti-neuroinflammatory mechanisms of CEGI have not yet been fully elucidated. Here, we aimed to investigate the role of CEGI in microglia-mediated neuroinflammation in AD. APP/PS1 mice were treated with CEGI intraperitoneally for 30 days, and then their cognition was assessed.

Long-term treatment with a Yang-invigorating Chinese herbal formula produces generalized tissue protection against oxidative damage in rats.

Previous work in our laboratory has shown that long-term treatment with Vigconic 28 (VI-28), a Yang-invigorating Chinese herbal formula used for the promotion of overall wellness in Chinese medicine, can enhance the mitochondrial functional ability and antioxidant capacity in various tissues of both male and female rats. To investigate whether the VI-28 treatment regimen could afford tissue protection against oxidative injury, the effects of long-term VI-28 treatment (80 or 240 mg/kg/d x 30) on oxidative stress-induced tissue damage in various organs (brain, heart, liver, and kidney) were exam

Evaluation of topical external medicine for 5-fluorouracil-induced oral mucositis in hamsters.

Oral ulcerative mucositis is a common and painful toxicity associated with chemotherapy for cancer. Current treatment for chemotherapy-induced oral mucositis is largely palliative, and no adequate treatment with conclusive evidence exists. The purpose of this study was to evaluate the potential effectiveness of the topical external medicines used in clinical settings, and the authors investigated the effects of 1% azulene ointment, 0.12% dexamethasone ointment, and polaprezinc-sodium alginate suspension on an animal model for oral mucositis induced by chemotherapy. Oral mucositis was induced i

Replacing soybean meal with okara meal: Effects on production, milk fatty acid and plasma amino acid profile, and nutrient utilization in dairy cows.

Okara meal is a byproduct from the production of soymilk and tofu and can potentially replace soybean meal (SBM) in dairy diets due to its h … r significant changes in the plasma concentrations of AA were observed. The plasma concentration of carnosine was lowest in cows receiving the OKR diet. Overall, our results revealed that okara meal can completely replace SBM without negatively affecting production and nutrient digestibility in early- to mid-lactation Jersey cows. Further research is needed …