Assessment of ATP metabolism to adenosine by ecto-nucleotidases carried by tumor-derived small extracellular vesicles.

Immunosuppression is a hallmark of cancer progression. Tumor-derived small extracellular vesicles (sEV), also known as TEX, produce adenosine (ADO) and can mediate tumor-induced immunosuppression.Here, the ATP pathway of ADO production (ATP  ADP  AMP  ADO) by ecto-nucleotidases carried on the sEV surface was evaluated by a method using N-etheno-ATP (eATP) and N-etheno-AMP (eAMP) as substrates for enzymatic activity.

Assessment of ATP Metabolism to Adenosine by Ecto-Nucleotidases Carried by Tumor-Derived Small Extracellular Vesicles.

Background: Immunosuppression is a hallmark of cancer progression. Tumor-derived small extracellular vesicles (sEV), also known as TEX, produce adenosine (ADO) and can mediate tumor-induced immunosuppression.

Methods: Here, the ATP pathway of ADO production (ATP◊ADP◊AMP◊ADO) by ecto-nucleotidases carried in sEV was evaluated by a novel method using N-etheno-ATP (eATP) and N-etheno-AMP (eAMP) as substrates.

Incidental Bleeding Gastrointestinal Stromal Tumor Identified on 99m Tc-RBC Scintigraphy.

Various pathologies could lead to occult gastrointestinal (GI) bleeding. Here we report the case of a 73-year-old woman who presented with hematochezia and syncope, and was found to have a large bleeding GI stromal tumor incidentally from 99m Tc-RBC scintigraphy. This study was done after negative workup with CT angiography, colonoscopy, and capsule endoscopy for the source of GI bleeding.

8-Aminoinosine and 8-Aminohypoxanthine Inhibit Purine Nucleoside Phosphorylase and Exert Diuretic and Natriuretic Activity.

8-Aminoguanine and 8-aminoguanosine (via metabolism to 8-aminoguanine) are endogenous 8-aminopurines that induce diuresis, natriuresis, and glucosuria by inhibiting purine nucleoside phosphorylase (PNPase); moreover, both 8-aminopurines cause antikaliuresis by other mechanisms. Because 8-aminoinosine and 8-aminohypoxanthine are structurally similar to 8-aminoguanosine and 8-aminoguanine, respectively, we sought to define their renal excretory effects. First, we compared the ability of 8-aminoguanine, 8-aminohypoxanthine, and 8-aminoinosine to inhibit recombinant PNPase.

Biochemical pathways of 8-aminoguanine production in Sprague-Dawley and Dahl salt-sensitive rats.

Background: 8-Aminoguanine exerts natriuretic and antihypertensive activity. Whether and how "free" 8-aminoguanine exists in vivo is unclear. Because 8-nitroguanosine is naturally occurring, we tested the hypothesis that 8-aminoguanine can arise from: pathway 1, 8-nitroguanosine → 8-aminoguanosine → 8-aminoguanine; and pathway 2, 8-nitroguanosine → 8-nitroguanine → 8-aminoguanine.

Novel Guidewire Design and Coating for Continuous Delivery of Adenosine During Interventional Procedures.

Background The "no-reflow phenomenon" compromises percutaneous coronary intervention outcomes. There is an unmet need for a device that prevents no-reflow phenomenon. Our goal was to develop a guidewire platform comprising a nondisruptive hydrophilic coating that allows continuous delivery of adenosine throughout a percutaneous coronary intervention.

Author Correction: Simultaneous Inhibition of Glycolysis and Oxidative Phosphorylation Triggers a Multi-Fold Increase in Secretion of Exosomes: Possible Role of 2',3'-cAMP.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Tumor-derived exosomes promote angiogenesis via adenosine A receptor signaling.

Rationale: One hallmark of tumor-derived exosomes (TEX) is the promotion of cancer progression by stimulating angiogenesis. This study was performed to evaluate the role of adenosine receptors in TEX-induced angiogenesis.

Methods: TEX produced by UMSCC47 head and neck cancer cell line were isolated by mini size exclusion chromatography (mini-SEC).

Characterization of the N-etheno-bridge method to assess extracellular metabolism of adenine nucleotides: detection of a possible role for purine nucleoside phosphorylase in adenosine metabolism.

The goal of this study was to determine the validity of using N-etheno-bridged adenine nucleotides to evaluate ecto-nucleotidase activity. We observed that the metabolism of N-etheno-ATP versus ATP was quantitatively similar when incubated with recombinant CD39, ENTPD2, ENTPD3, or ENPP-1, and the quantitative metabolism of N-etheno-AMP versus AMP was similar when incubated with recombinant CD73. This suggests that ecto-nucleotidases process N-etheno-bridged adenine nucleotides similarly to endogenous adenine nucleotides.

Simultaneous Inhibition of Glycolysis and Oxidative Phosphorylation Triggers a Multi-Fold Increase in Secretion of Exosomes: Possible Role of 2'3'-cAMP.

Exosome secretion by cells is a complex, poorly understood process. Studies of exosomes would be facilitated by a method for increasing their production and release. Here, we present a method for stimulating the secretion of exosomes.

Proximal tubule apical endocytosis is modulated by fluid shear stress via an mTOR-dependent pathway.

Cells lining the proximal tubule (PT) have unique membrane specializations that are required to maintain the high-capacity ion transport and endocytic functions of this nephron segment. PT cells in vivo acutely regulate ion transport in response to changes in glomerular filtration rate (GFR) to maintain glomerulotubular balance. PT cells in culture up-regulate endocytic capacity in response to acute changes in fluid shear stress (FSS); however, it is not known whether GFR modulates PT endocytosis to enable maximally efficient uptake of filtered proteins in vivo.

Adenosine production by brain cells.

Unlabelled: The early release of adenosine following traumatic brain injury (TBI) suppresses seizures and brain inflammation; thus, it is important to elucidate the cellular sources of adenosine following injurious stimuli triggered by TBI so that therapeutics for enhancing the early adenosine-release response can be optimized. Using mass spectrometry with C-labeled standards, we investigated in cultured rat neurons, astrocytes, and microglia the effects of oxygen-glucose deprivation (OGD; models energy failure), H O (produces oxidative stress), and glutamate (induces excitotoxicity) on intracellular and extracellular levels of 5'-AMP (adenosine precursor), adenosine, and inosine and hypoxanthine (adenosine metabolites). In neurons, OGD triggered increases in intracellular 5'-AMP (2.

Calorie Restriction-induced Weight Loss and Exercise Have Differential Effects on Skeletal Muscle Mitochondria Despite Similar Effects on Insulin Sensitivity.

Background: Skeletal muscle insulin resistance and reduced mitochondrial capacity have both been reported to be affected by aging. The purpose of this study was to compare the effects of calorie restriction-induced weight loss and exercise on insulin resistance, skeletal muscle mitochondrial content, and mitochondrial enzyme activities in older overweight to obese individuals.

Methods: Insulin-stimulated rates of glucose disposal (Rd) were determined using the hyperinsulinemic euglycemic clamp before and after completing 16 weeks of either calorie restriction to induce weight loss (N = 7) or moderate exercise (N = 10).

Renal 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase Is an Important Determinant of AKI Severity after Ischemia-Reperfusion.

A positional isomer of 3',5'-cAMP, 2',3'-cAMP, is produced by kidneys in response to energy depletion, and renal 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) metabolizes 2',3'-cAMP to 2'-AMP; 2',3'-cAMP is a potent opener of mitochondrial permeability transition pores (mPTPs), which can stimulate autophagy. Because autophagy protects against AKI, it is conceivable that inhibition of CNPase protects against ischemia-reperfusion (IR) -induced AKI. Therefore, we investigated renal outcomes, mitochondrial function, number, area, and autophagy in CNPase-knockout (CNPase(-/-)) versus wild-type (WT) mice using a unique two-kidney, hanging-weight model of renal bilateral IR (20 minutes of ischemia followed by 48 hours of reperfusion).

Exercise and Weight Loss Improve Muscle Mitochondrial Respiration, Lipid Partitioning, and Insulin Sensitivity After Gastric Bypass Surgery.

Both Roux-en-Y gastric bypass (RYGB) surgery and exercise can improve insulin sensitivity in individuals with severe obesity. However, the impact of RYGB with or without exercise on skeletal muscle mitochondria, intramyocellular lipids, and insulin sensitivity index (SI) is unknown. We conducted a randomized exercise trial in patients (n = 101) who underwent RYGB surgery and completed either a 6-month moderate exercise (EX) or a health education control (CON) intervention.

[Phenolic antioxidant TS-13 regulating ARE-dependent genes induces tumor cell death by mitochondria-dependent pathway].

Effects of water-soluble phenolic antioxidant sodium 3-(3'-tret-butyl-4'-hydroxyphenyl)-propyl thiosulfonate (TS-13), potassium 3,5-dimethyl-4-hydroxybenzyl thioetanoate (BEP-11-K) and potassium 3-(3',5'-ditretbutyl-4'-hydroxyphenyl)-propionate (potassium phenosan) on tumor cells proliferative activity and the role of redox-dependent and calcium-dependent signaling mechanisms in realization of tumor cell response to the antioxidant action were studied. Potassium phenosan and BEP-11-K were found to stimulate proliferation and ARE-inducing phenolic antioxidant TS-13 was found to inhibit tumor cell growth in culture. The tumor cell growth rate depended on the rate of intracellular reactive oxygen species production and was decreased by apocynin (a NADPH-oxidase inhibitor) and antimycin A (an ubiquinol-cytochrome c oxidoreductase inhibitor).

[Serologic study of experimental cholera polymer antigen diagnosticums].

Aim: Evaluation of quality indicators of constructed cholera antigen polymer diagnosticums by using a complex of specific anti-cholera sera. MATERIALS AND METHODS. Cell lysates of cholera vibrio strains Vibrio cholerae cholerae 1395, V.

Reduced skeletal muscle oxidative capacity and elevated ceramide but not diacylglycerol content in severe obesity.

Objective: The link between a reduced capacity for skeletal muscle mitochondrial fatty acid oxidation (FAO) and lipotoxicity in human insulin resistance has been the subject of intense debate. The objective of this study was to investigate whether reduced FAO is associated with elevated acyl CoA, ceramide, and diacylglycerol (DAG) in severely obese insulin resistant subjects.

Methods: Muscle biopsies were conducted in lean (L, 22.

[Taxonomic characteristics and mixed communities of wound infection agents in patients of reanimation and surgical departments of a hospital].

Aim: Study of taxonomical structure ofwound infection agents, prevalence of mixes, and detection of character of their possible connection with the results of various microorganisms population interaction in septic wounds.

Materials And Methods: A microbiological study of material from patients with wound infection (WI), 582 of those were cured in reanimation and intensive therapy departments (RITD; group 1) and 1455 - in surgical departments (SD; group 2), was performed. Taxonomic membership and ability to coexist was determined in 4129 microorganisms strains.

Fish consumption and socio-economic factors among residents of Arkhangelsk city and the rural Nenets autonomous area.

Objectives: The urban Russian and the rural Indigenous populations in the Russian European North have different lifestyles, living conditions and food supplies. The objective of this study was to investigate and compare fish consumption in relation to the socio-economic characteristics of 2 communities in Arkhangelsk County.

Study Design: A cross-sectional study.

[Microbiological diagnosis of gas gangrene caused by Clostridium septicum (a clinical case)].

Microscopy of gram-stained impression smears is used for the rapid diagnosis of microorganisms in the wound. The shin tissues of patient P. with suspected gas gangrene of lower extremity soft tissues were microscopically found to have gram-positive spore-forming bacteria that were morphologically similar to C.

[Redox-dependent signaling system Nrf2/are in inflammation].

Transcription factor Nrf2 plays a key role in cell defense against oxidative stress, as well as in counteracting chemical and physical factors that induce apoptosis and carcinogenesis. The mechanism of Nrf2/ARE redox regulation and ARE-mediated gene expression are analyzed in the review. Special attention was paid to anti-inflammatory effects of Nrf2/ARE system, which significantly manifest in Nrf2 knockout animal.

[Mono- and associated microflora during wound infection in patients with burns].

Aim: To study etiologic role of microorganisms during wound infection and elucidation of their populations interaction in patientswith burns.

Materials And Methods: 2137 patients with wound infection treated in burn center were studied. 3179 samples of wound exudates and 6501 strains of microorganisms were studied.

Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity.

Insulin resistance in skeletal muscle in obesity and T2DM is associated with reduced muscle oxidative capacity, reduced expression in nuclear genes responsible for oxidative metabolism, and reduced activity of mitochondrial electron transport chain. The presented study was undertaken to analyze mitochondrial content and mitochondrial enzyme profile in skeletal muscle of sedentary lean individuals and to compare that with our previous data on obese or obese T2DM group. Frozen skeletal muscle biopsies obtained from lean volunteers were used to estimate cardiolipin content, mtDNA (markers of mitochondrial mass), NADH oxidase activity of mitochondrial electron transport chain (ETC), and activity of citrate synthase and beta-hydroxyacyl-CoA dehydrogenase (beta-HAD), key enzymes of TCA cycle and beta-oxidation pathway, respectively.

[Characterization of the adhesive activity of cholera vibrions in mammalian red blood cells as an additional test for assessment of their epidemic significance].

The in vitro study of the adhesive properties of V. cholerae eltor and V. cholerae O139 on a model of mammalian red blood cells revealed a correlation of their adhesive properties, the presence of the ctx AB, tcpA genes, and their hemolytic activity when blood group A (II) red blood cells were used.