• MeSH
• Glycogen * chemistry   history   MeSH
• Glycogen Storage Disease Type III * history   MeSH
• Humans MeSH
• Check Tag
• Humans MeSH
• Publication type
• Historical Article MeSH
• Editorial MeSH

OBJECTIVE: To evaluate the effect of iatrogenic menopause on the physiology of the vagina of the ewe and to evaluate if vaginal changes in ewes can be translated to women with genitourinary syndrome of menopause (GSM). METHODS: Preclinical research with Dohne Merino ewes. Iatrogenic menopause was induced by bilateral ovariectomy (OVX). Animals were randomized for surgery, blinded for allocation and outcome assessment. Differences between groups were determined by linear regression analyses at 5 months after OVX. Outcome measures were vaginal epithelial thickness, pH, vaginal maturation value, vaginal maturation index, epithelial glycogen accumulation, content of elastin fibers, collagen, and vascularity. RESULTS: OVX ewes (n = 20) showed epithelial thinning of the vaginal wall from 146 μm to 47 μm (mean, P < 0.001). Furthermore, epithelial glycogen accumulation and vascularity of the vaginal wall significantly decreased (43% and 23%, respectively) as compared with the control group (no intervention; n = 5). No significant differences were found for other outcome measures. CONCLUSION: This study established the ewe as a suitable large animal model for GSM. Furthermore, the similar relevant outcomes in humans and ewes hold great value for future translational research for the evaluation and optimization of different treatment modalities for GSM.

• MeSH
• Glycogen MeSH
• Iatrogenic Disease MeSH
• Humans MeSH
• Menopause * MeSH
• Models, Animal MeSH
• Ovariectomy adverse effects   MeSH
• Sheep MeSH
• Vagina * surgery   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Glycogen-nucleic acid constructs i.e., glycoplexes are emerging promising platforms for the alteration of gene expression and transcription. Understanding the interaction of glycoplexes with human blood components, such as serum proteins and peripheral blood mononuclear cells (PBMCs), is important to overcome immune cell activation and control biodistribution upon administration of the glycoplexes in vivo. Herein, we investigated the interactions of polyethylene glycol (PEG)ylated and non-PEGylated glycoplexes carrying siRNA molecules with PBMCs isolated from the blood of healthy donors. We found that both types of glycoplexes were non-toxic and were primarily phagocytosed by monocytes without triggering a pro-inflammatory interleukin 6 cytokine production. Furthermore, we investigated the role of the protein corona on controlling the internalization efficiency in immune cells - we found that the adsorption of serum proteins, in particular haptoglobin, alpha-1-antitrypsin and apolipoprotein A-II, onto the non-PEGylated glycoplexes, significantly reduced the uptake of the glycoplexes by PBMCs. Moreover, the non-PEGylated glycoplexes were efficient in the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) knockdown in monocytic THP-1 cell line. This study provides an insight into the rational design of glycogen-based nanocarriers for the safe delivery of siRNA without eliciting unwanted immune cell activation and efficient siRNA activity upon its delivery.

• MeSH
• Glycogen metabolism   MeSH
• Blood Proteins metabolism   MeSH
• Leukocytes, Mononuclear metabolism   MeSH
• Humans MeSH
• RNA, Small Interfering genetics   MeSH
• Protein Corona * metabolism   MeSH
• Tissue Distribution MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Low production rates are still one limiting factor for the industrial climate-neutral production of biovaluable compounds in cyanobacteria. Next to optimized cultivation conditions, new production strategies are required. Hence, the use of established molecular tools could lead to increased product yields in the cyanobacterial model organism Synechocystis sp. PCC6803. Its main storage compound glycogen was chosen to be increased by the use of these tools. In this study, the three genes glgC, glgA1 and glgA2, which are part of the glycogen synthesis pathway, were combined with the Pcpc560 promoter and the neutral cloning site NSC1. The complete genome integration, protein formation, biomass production and glycogen accumulation were determined to select the most productive transformants. The overexpression of glgA2 did not increase the biomass or glycogen production in short-term trials compared to the other two genes but caused transformants death in long-term trials. The transformants glgA1_11 and glgC_2 showed significantly increased biomass (1.6-fold - 1.7-fold) and glycogen production (3.5-fold - 4-fold) compared to the wild type after 96 h making them a promising energy source for further applications. Those could include for example a two-stage production process, with first energy production (glycogen) and second increased product formation (e.g. ethanol).

• MeSH
• Glycogen MeSH
• Synechocystis * genetics   MeSH
• Publication type
• Journal Article MeSH

ETHNOPHARMACOLOGICAL RELEVANCE: Morus alba L. is used in traditional Chinese medicine for the treatment of various diseases, including bacterial infections and inflammation. As a rich source of phenolic compounds, the plant is an object of many phytochemical and pharmacological studies. AIM OF THE STUDY: The aim of the study was to isolate and evaluate possible parallel antiviral, antibacterial, and anti-inflammatory activities of phenolic mulberry compounds. MATERIALS AND METHODS: Extensive chromatographic separation of mulberry root bark extract and in vitro biological screening of 26 constituents identified promising candidates for further pharmacological research. Selected compounds were screened for anti-infective and anti-inflammatory activities. Antiviral activity was determined by the plaque number reduction assay and by the titer reduction assay, antibacterial using broth microdilution method, and anti-inflammatory activity using COX Colorimetric inhibitor screening assay kit. One compound was evaluated in vivo in carrageenan-induced paw-edema in mice. RESULTS: Five prenylated compounds 1, 2, 8, 9, and 11, together with a simple phenolic ester 13, exhibited inhibitory activity against the replication of herpes simplex virus 1 (HSV-1) or herpes simplex virus 2 (HSV-2), with IC50 values ranging from 0.64 to 1.93 μg/mL, and EC50 values 0.93 and 1.61 μg/mL. Molecular docking studies demonstrated the effects of the active compounds by targeting HSV-1 DNA polymerase and HSV-2 protease. In antibacterial assay, compounds 1, 4, 11, and 17 diminished the growth of all of the Gram-positive strains tested, with MIC values of 1-16 μg/mL. The anti-inflammatory ability of several compounds to inhibit cyclooxygenase 2 (COX-2) was tested in vitro, and compound 16 displayed greater activity than the indomethacin, positive control. Mulberrofuran B (11) showed anti-inflammatory activity in vivo against carrageenan-induced paw-edema in mice. CONCLUSIONS: Experimental investigation showed promising antiviral, antibacterial, and/or anti-inflammatory activities of the phenolic mulberry constituents, often with multiple inhibitory effects that might be used as a potential source of new medicine.

• MeSH
• Cell Line MeSH
• Diabetes Mellitus drug therapy   metabolism   MeSH
• Glucose metabolism   MeSH
• Glycogen metabolism   MeSH
• Hypoglycemic Agents pharmacology   therapeutic use   MeSH
• Insulin Resistance MeSH
• Liver drug effects   metabolism   MeSH
• Muscle, Skeletal drug effects   metabolism   MeSH
• Rats MeSH
• Plant Leaves MeSH
• Membrane Potential, Mitochondrial drug effects   MeSH
• Morus * MeSH
• Mice MeSH
• AMP-Activated Protein Kinases metabolism   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Plant Extracts pharmacology   therapeutic use   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

As a natural polysaccharide polymer, glycogen possesses suitable properties for use as a nanoparticle carrier in cancer theranostics. Not only it is inherently biocompatible, it can also be easily chemically modified with various moieties. Synthetic glycogen conjugates can passively accumulate in tumours due to enhanced permeability of tumour vessels and limited lymphatic drainage (the EPR effect). For this study, we developed and examined a glycogen-based carrier containing a gadolinium chelate and near-infrared fluorescent dye. Our aim was to monitor biodistribution and accumulation in tumour-bearing rats using magnetic resonance and fluorescence imaging. Our data clearly show that these conjugates possess suitable imaging and tumour-targeting properties, and are safe under both in vitro and in vivo conditions. Additional modification of glycogen polymers with poly(2-alkyl-2-oxazolines) led to a reduction in the elimination rate and lower uptake in internal organs (lower whole-body background: 45% and 27% lower MRI signals of oxazoline-based conjugates in the liver and kidneys, respectively compared to the unmodified version). Our results highlight the potential of multimodal glycogen-based nanopolymers as a carrier for drug delivery systems in tumour diagnosis and treatment.

• MeSH
• Glycogen administration & dosage   MeSH
• Rats MeSH
• Drug Delivery Systems * MeSH
• Cell Line, Tumor MeSH
• Neoplasms drug therapy   MeSH
• Antineoplastic Agents administration & dosage   MeSH
• Theranostic Nanomedicine * MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• MeSH
• Gluconeogenesis drug effects   MeSH
• Glucose analysis   metabolism   MeSH
• Glycogen metabolism   MeSH
• Glycogenolysis * MeSH
• Glycolysis * MeSH
• Cell Hypoxia MeSH
• Indoles pharmacology   MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Neoplastic Stem Cells metabolism   MeSH
• Tumor Microenvironment MeSH
• Oxidative Phosphorylation MeSH
• Propanols pharmacology   MeSH
• Triple Negative Breast Neoplasms metabolism   pathology   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

T-2 toxin, A trichothecenes mycotoxin, is immunotoxic to animals and humans. Although it is highly cardiotoxic, the pathogenesis of cardiomyopathy caused by T-2 toxin is not entirely clear. Hence, in our research, cardiomyopathy was induced by a single injection of T-2 mycotoxin (0.23 mg/kg s.c., 1 LD50) to Wistar rats. The cardiac tissue was carefully examinated by using basic histopathology, semiquantitative (tissue grading score scales) and imaging (a total number of mast cells - MCs) analyses on days 1, 7, 14, 21, 28 and 60 of the study. The most intensive myocardial alterations (cardiac damage score, CDS = 4.20-4.40), irregular glycogen distribution (glycogen distribution score, GDS = 4.07-4.17), haemorrhagic foci (vascular damage score, VDS = 4.57-4.90), diffuse accumulation and degranulation of MCs were observed on day 28 and 60 after treatment (p < 0.001 vs. control and 1st T-2-toxin-treated group, respectively). Besides, statistically significant positive correlations were obtained regarding myocardial injury, glycogen distribution and intensity of haemorrhage, and a negative correlation was found in the case of MCs. Obtained results are essential and crucial for further in vivo experimental studies, including the development of medications able to reduce T-2 toxin-induced cardiotoxicity.

• MeSH
• Glycogen metabolism   MeSH
• Myocytes, Cardiac metabolism   MeSH
• Cardiomyopathies chemically induced   etiology   pathology   MeSH
• Cardiotoxicity etiology   pathology   MeSH
• Mast Cells pathology   MeSH
• Myocardium metabolism   pathology   MeSH
• Rats, Wistar MeSH
• T-2 Toxin toxicity   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

The ultimate goal of this project is to improve care about the patients with cancer by developing new noninvasive diagnostic and possibly also theranostic imaging tools based on polysaccharide materials. They may serve as customizable toolbox-like carriers selectively delivering active imaging components (such as gadolinium complexes suitable for magnetic resonance imaging, fluorescent dyes or radionuclides) to the solid tumor tissue with self-targeting effect due to size (EPR effect) or due to selective binding to cancer cell-specific structures (ligand targeting). Polysaccharides represent nontoxic natural-sourced biodegradable biocompatible polymer carriers from renewable resources with promising properties for such use in medicine. The active ligand-based targeting will be due to affinity of D-galactosylated structures (such as guar gum itself) to asialoglycoprotein receptors highly overexpressed in hepatocellular carcinomas or based on muscarinic and benzodiazepine receptor ligands that tightly bind to melanoma cells.

Hlavním cílem projektu je zlepšení péče o onkologické pacienty vyvinutím nových diagnostik pro neinvazivní zobrazování založených na polysacharidických materiálech. Tyto systémy mohou sloužit jako adaptovatelné molekulární stavebnice pro cílené doručení aktivních komponent (gadoliniové komplexy pro zobrazování magnetickou rezonancí, fluorescenční barviva nebo radionuklidy) do tkáně pevných nádorů se samocílícím efektem díky velikosti (EPR efekt) nebo díky selektivní vazbě na nádorové buňky (ligandové cílení). Polysacharidy představují biodegradovatelné polymerní nosiče přírodního původu z obnovitelných zdrojů s výhodnými vlastnostmi pro taková použití v medicíně. Aktivní cílení bude dáno afinitou D-galaktosylovaných struktur k asialoglykoproteinovým receptorům, které jsou vysoce exprimované v hepatocelulárních karcinomech, a na pevné vazbě ligandů pro muskarinové a benzodiazepinové receptory na melanomové buňky.

• MeSH
• Glycogen MeSH
• Carcinoma diagnostic imaging   MeSH
• Magnetic Resonance Imaging methods   MeSH
• Melanoma diagnostic imaging   MeSH
• Neoplasms diagnostic imaging   MeSH
• Polysaccharides MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• onkologie
• radiologie, nukleární medicína a zobrazovací metody
• NML Publication type
• závěrečné zprávy o řešení grantu AZV MZ ČR

BACKGROUND: Troxerutin (TRX) has a beneficial effect on blood viscosity and platelet aggregation, and is currently used for the treatment of chronic varicosity. Recently, TRX can improve lipid abnormalities, glucose intolerance and oxidative stress in high-fat diet-induced metabolic disorders. In this study, we tested the effect of TRX on metabolic syndrome-associated disorders using a non-obese model of metabolic syndrome-the Hereditary Hypertriglyceridaemic rats (HHTg). METHODS: Adult male HHTg rats were fed standard diet without or with TRX (150 mg/kg bwt/day for 4 weeks). RESULTS: Compared to untreated rats, TRX supplementation in HHTg rats decreased serum glucose (p<0.05) and insulin (p<0.05). Although blood lipids were not affected, TRX decreased hepatic cholesterol concentrations (p<0.01) and reduced gene expression of HMGCR, SREBP2 and SCD1 (p<0.01), involved in cholesterol synthesis and lipid homeostasis. TRX-treated rats exhibited decreased lipoperoxidation and increased activity of antioxidant enzymes SOD and GPx (p<0.05) in the liver. In addition, TRX supplementation increased insulin sensitivity in muscles and epididymal adipose tissue (p<0.05). Elevated serum adiponectin (p<0.05) and decreased muscle triglyceride (p<0.05) helped improve insulin sensitivity. Among the beneficial effects of TRX were changes to cytochrome P450 family enzymes. Hepatic gene expression of CYP4A1, CYP4A3 and CYP5A1 (p<0.01) decreased, while there was a marked elevation in gene expression of CYP1A1 (p<0.01). CONCLUSION: Our results indicate that TRX improves hepatic lipid metabolism and insulin sensitivity in peripheral tissues. As well as ameliorating oxidative stress, TRX can reduce ectopic lipid deposition, affect genes involved in lipid metabolism, and influence the activity of CYP family enzymes.

• MeSH
• Glucose metabolism   MeSH
• Glycogen metabolism   MeSH
• Hydroxyethylrutoside analogs & derivatives   therapeutic use   MeSH
• Hypolipidemic Agents therapeutic use   MeSH
• Rats, Inbred Strains MeSH
• Insulin Resistance MeSH
• Muscle, Skeletal metabolism   MeSH
• Rats MeSH
• Real-Time Polymerase Chain Reaction MeSH
• Metabolic Syndrome drug therapy   MeSH
• Lipid Metabolism drug effects   MeSH
• Disease Models, Animal MeSH
• Oxidative Stress drug effects   MeSH
• Transcriptome drug effects   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH