Impact of post RFA treatment on neosquamous epithelium microstructure.

Radiofrequency ablation (RFA) is effective treatment for Barrett's esophagus (BE). Product of successful RFA is neosquamous epithelium (NSE), which resembles native squamous epithelium and has lower risk for neoplastic transformation. Dilated intercellular spaces (IS) are common microscopic feature of reflux induced injury of esophagus.

Monolacunary Wells-Dawson Polyoxometalate as a Novel Contrast Agent for Computed Tomography: A Comprehensive Study on In Vivo Toxicity and Biodistribution.

Polyoxotungstate nanoclusters have recently emerged as promising contrast agents for computed tomography (CT). In order to evaluate their clinical potential, in this study, we evaluated the in vitro CT imaging properties, potential toxic effects in vivo, and tissue distribution of monolacunary Wells-Dawson polyoxometalate, α-KPWO20HO (mono-WD POM). Mono-WD POM showed superior X-ray attenuation compared to other tungsten-containing nanoclusters (its parent WD-POM and Keggin POM) and the standard iodine-based contrast agent (iohexol).

The presence of Mott cells in the lymph nodes of rats with experimental autoimmune encephalomyelitis.

Mott cells are plasma cells that have multiple spherical Russell bodies packed in their cytoplasm. Russell bodies are dilated endoplasmic reticulum cisternae filled with aggregates of immunoglobulins that are neither secreted nor degraded. Mott cells were observed in our study by light and electron microscope in the lymph nodes of rats with experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis.

In vivo toxicity evaluation of a polyoxotungstate nanocluster as a promising contrast agent for computed tomography.

In this study, we demonstrate for the first time, that a discrete metal-oxo cluster α-/β-KPWO (WD-POM) exhibits superior performance as a computed tomography (CT) contrast agent, in comparison to the standard contrast agent iohexol. A toxicity evaluation of WD-POM was performed according to standard toxicological protocols using Wistar albino rats. The maximum tolerable dose (MTD) of 2000 mg/kg was initially determined after oral WD-POM application.

Micromorphological features and interleukin 6, 8, and 18 expressions in post-mortem lung tissue in cases with acute respiratory distress syndrome.

The purpose of this study was to analyze the presence of interleukins 6, 8, and 18 in post-mortem lung tissue of subjects deceased due to polytrauma. In addition to this, we have described different micromorphological features of lung tissue in ARDS cases associated with fatal traffic trauma. A total of 18 autopsy cases with ARDS after polytrauma and 15 control autopsy cases were analyzed in this study.

Effects of metformin and simvastatin treatment on ultrastructural features of liver macrophages in HFD mice.

Type 2 diabetes is a major health burden to the society. Macrophages and liver inflammation emerged as important factors in its development. We investigated ultrastructural changes in the liver, with a special emphasis on macrophages in high fat diet (HFD) fed C57BL/6 J mice treated with metformin or simvastatin, two drugs that are used frequently in diabetes.

In vitro models of insulin resistance: Mitochondrial coupling is differently affected in liver and muscle cells.

Mitochondrial dysfunction in diabetes is a widely studied topic, but inconsistency in literature data suggests a need for valid and reproducible models that will help to clarify this interaction. We aimed to establish insulin resistance models using chronic high insulin treatment in two cell types: myocytes and hepatocytes, characterise them in terms of mitochondrial function and compare them to the widely used palmitate-induced model of insulin resistance. We found that insulin lowered phosphorylation of Akt while not affecting cell viability, ROS production, mitochondrial morphology or respiration, and caused decrease in mitochondrial coupling only in muscle but not in liver cells.

3-Methyladenine prevents energy stress-induced necrotic death of melanoma cells through autophagy-independent mechanisms.

We investigated the effect of 3-methyladenine (3MA), a class III phosphatidylinositol 3-kinase (PI3K)-blocking autophagy inhibitor, on cancer cell death induced by simultaneous inhibition of glycolysis by 2-deoxyglucose (2DG) and mitochondrial respiration by rotenone. 2DG/rotenone reduced ATP levels and increased mitochondrial superoxide production, causing mitochondrial swelling and necrotic death in various cancer cell lines. 2DG/rotenone failed to increase proautophagic beclin-1 and autophagic flux in melanoma cells despite the activation of AMP-activated protein kinase (AMPK) and inhibition of mechanistic target of rapamycin complex 1 (mTORC1).

The current state of bionic limbs from the surgeon's viewpoint.

Amputations have a devastating impact on patients' health with consequent psychological distress, economic loss, difficult reintegration into society, and often low embodiment of standard prosthetic replacement.The main characteristic of bionic limbs is that they establish an interface between the biological residuum and an electronic device, providing not only motor control of prosthesis but also sensitive feedback.Bionic limbs can be classified into three main groups, according to the type of the tissue interfaced: nerve-transferred muscle interfacing (targeted muscular reinnervation), direct muscle interfacing and direct nerve interfacing.

toxicity evaluation of two polyoxotungstates with potential antidiabetic activity using rats as a model system.

In this study, the hypoglycemic effect of a donut-shaped polyanion salt (NH)[Na@PWO]·31HO {NaPW} and its Ag-containing derivative K[Ag@PWO]·22HO·6KCl {AgPW}, as well as their hepatotoxicity and nephrotoxicity, was evaluated. In the screening hypoglycemic study, rats with streptozotocin induced diabetes were treated intraperitoneally with three single doses (5, 10, and 20 mg per kg per b.w.

Comparative analysis of cell death mechanisms induced by lysosomal autophagy inhibitors.

We performed a comparative analysis of molecular cytotoxic mechanisms of lysosomal autophagy inhibitors bafilomycin A1, chloroquine, and ammonium chloride in B16 mouse melanoma cells. All agents caused oxidative stress, mitochondrial depolarization, and caspase-dependent apoptotic death, which was not affected by genetic inactivation of autophagy. Cathepsin inhibition reduced only the cytotoxicity of chloroquine, indicating its ability to cause lysosomal membrane permeabilization.

β-catenin and PPAR-γ levels in bone marrow of myeloproliferative neoplasm: an immunohistochemical and ultrastructural study.

In accordance with increased proliferation in myeloproliferative neoplasm (MPN), the goal is to evaluate the immunoexpression of: β-catenin, PPAR-γ and Ki67 protein, to compare them with bone marrow ultrastructural characteristics in patients with MPN. Immunoexpression and electron microscopy of bone marrow was analyzed in 30 Ph-negative MPN patients, including per 10 patients with polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The quantity of β-catenin immunoreactive cells was significantly higher in PV then in ET (p < 0.

Graphene quantum dots inhibit T cell-mediated neuroinflammation in rats.

We investigated the therapeutic capacity of nano-sized graphene sheets, called graphene quantum dots (GQD), in experimental autoimmune encephalomyelitis (EAE), an animal model of immune-mediated central nervous system (CNS) damage. Intraperitoneally administered GQD (10 mg/kg/day) accumulated in the lymph node and CNS cells of Dark Agouti rats in which EAE was induced by immunization with spinal cord homogenate in complete Freund's adjuvant. GQD significantly reduced clinical signs of EAE when applied throughout the course of the disease (day 0-32), while the protection was less pronounced if the treatment was limited to the induction (day 0-7 post-immunization) or effector (from day 8 onwards) phase of the disease.

Metformin exacerbates and simvastatin attenuates myelin damage in high fat diet-fed C57BL/6 J mice.

Diabetic neuropathy is one of the most deleterious complications of diabetes mellitus in humans. High fat diet (HFD)-fed C57BL/6 J mice are a widely used animal model for type 2 diabetes mellitus and metabolic syndrome. We investigated the effects of metformin and simvastatin on the ultrastructural characteristics of sciatic nerve fibers in these mice.

Repeated penile girth enhancement with biodegradable scaffolds: Microscopic ultrastructural analysis and surgical benefits.

Autologous tissue engineering using biodegradable scaffolds as a carrier is a well-known procedure for penile girth enhancement. We evaluated a group of previously treated patients with the aim to analyze histomorphometric changes after tissue remodeling and to estimate the benefits of repeated procedure. Between February 2012 and December 2016, a group of 21 patients, aged 22-37 (mean 28.

In vitro and in vivo antimelanoma effect of ethyl ester cyclohexyl analog of ethylenediamine dipropanoic acid.

Melanoma, an aggressive skin tumor with high metastatic potential, is associated with high mortality and increasing morbidity. Multiple available chemotherapeutic and immunotherapeutic modalities failed to improve survival in advanced disease, and the search for new agents is ongoing. The aim of this study was to investigate antimelanoma effects of O,O-diethyl-(S,S)-ethylenediamine-N,N'di-2-(3-cyclohexyl) propanoate dihydrochloride (EE), a previously synthesized and characterized organic compound.

Graphene quantum dots suppress proinflammatory T cell responses via autophagy-dependent induction of tolerogenic dendritic cells.

Graphene quantum dots (GQD) are atom-thick nanodimensional carbon sheets with excellent physico-chemical and biological properties, making them attractive for application in theranostics. However, their immunoregulatory properties are insufficiently investigated, especially in human primary immune cells. We found that non-toxic doses of GQD inhibit the production of proinflammatory and T helper (Th)1 cytokines, and augment the production of anti-inflammatory and Th2 cytokines by human peripheral blood mononuclear cells.

Toxicity evaluation of two polyoxotungstates with anti-acetylcholinesterase activity.

A toxicity evaluation of two Keggin-type heteropolytungstates, K[TiPWO]·6HO and KH[SiVWO]·3HO, with different inhibitory potencies toward acetylcholinesterase activity (IC values of 1.04×10 and 4.80×10mol/L, respectively) was performed.

Autophagy suppression sensitizes glioma cells to IMP dehydrogenase inhibition-induced apoptotic death.

We investigated the role of autophagy, a process of controlled self-digestion, in the in vitro anticancer action of the inosine monophosphate dehydrogenase (IMPDH) inhibitor ribavirin. Ribavirin-triggered oxidative stress, caspase activation, and apoptotic death in U251 human glioma cells were associated with the induction of autophagy, as confirmed by intracellular acidification, appearance of autophagic vesicles, conversion of microtubule associated protein 1 light chain 3 (LC3)-I to autophagosome-associated LC3-II, and degradation of autophagic target p62/sequestosome 1. Ribavirin downregulated the activity of autophagy-inhibiting mammalian target of rapamycin complex 1 (mTORC1), as indicated by a decrease in phosphorylation of the mTORC1 substrate ribosomal p70S6 kinase and reduction of the mTORC1-activating Src/Akt signaling.

Aggressive human neuroblastomas show a massive increase in the numbers of autophagic vacuoles and damaged mitochondria.

Autophagy is activated in cancer cells in response to multiple stresses and has been demonstrated to promote tumor cell survival and drug resistance in neuroblastoma (NB). This study was conducted to analyze the ultrastructural features of peripheral neuroblastic tumors (pNTs) and identify the relation of the types of NTs, the proliferation rate, and MYCN gene amplification with a number of autophagic vacuoles. Our results indicate that aggressive human NBs show a massive increase in the number of autophagic vacuoles associated with proliferation rate and that alteration of the mitochondria might be an important factor for the induction of autophagy in NTs.

c-Jun N-terminal kinase-dependent apoptotic photocytotoxicity of solvent exchange-prepared curcumin nanoparticles.

Indian spice curcumin is known for its anticancer properties, but the anticancer mechanisms of nanoparticulate curcumin have not been completely elucidated. We here investigated the in vitro anticancer effect of blue light (470 nm, 1 W)-irradiated curcumin nanoparticles prepared by tetrahydrofuran/water solvent exchange, using U251 glioma, B16 melanoma, and H460 lung cancer cells as targets. The size of curcumin nanocrystals was approximately 250 nm, while photoexcitation induced their oxidation and partial agglomeration.

Statin-mediated inhibition of cholesterol synthesis induces cytoprotective autophagy in human leukemic cells.

Statins exhibit anti-leukemic properties due to suppression of the mevalonate pathway by the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase, and subsequent depletion of cholesterol, farnesylpyrophosphate, and geranylgeranylpyrophosphate. We investigated the role of autophagy, a controlled intracellular self-digestion, in the anti-leukemic action of statins. Treatment with low concentrations (≤6 µM) of statins, cholesterol depletion, and specific inhibition of cholesterol synthesis and protein farnesylation or geranylgeranylation, all inhibited proliferation of leukemic cell lines and primary leukemic cells without inducing overt cell death.