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Characterization of a Fetal Liver Cell Population Endowed with Long-Term Multiorgan Endothelial Reconstitution Potential.
2016
et al.
Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors
2017
Dominyka Dapkute,1,2 Simona Steponkiene,1 Danute Bulotiene,1 Liga Saulite,3 Una Riekstina,3 Ricardas Rotomskis1,4 1Biomedical Physics Laboratory, National Cancer Institute, Vilnius, Lithuania; 2Institute of Biosciences, Vilnius University, Vilnius, Lithuania; 3Faculty of Medicine, University of Latvia, Riga, Latvia; 4Biophotonics Group of Laser Research Center, Faculty of Physics, Vilnius University, Vilnius, Lithuania Purpose: Cell-mediated delivery of nanoparticles is emerging as a new method of cancer diagnostics and treatment. Due to their inherent regenerative properties, adult mesenchymal stem cells (MSCs) are naturally attracted to wounds and sites of inflammation, as well as tumors.…
New 1,4-Dihydropyridines Down-regulate Nitric Oxide in Animals with Streptozotocin-induced Diabetes Mellitus and Protect Deoxyribonucleic Acid agains…
2015
Diabetes mellitus (DM) and its complications cause numerous health and social problems throughout the world. Pathogenic actions of nitric oxide (NO) are responsible to a large extent for development of complications of DM. Search for compounds regulating NO production in patients with DM is thus important for the development of pharmacological drugs. Dihydropyridines (1,4-DHPs) are prospective compounds from this point of view. The goals of this study were to study the in vivo effects of new DHPs on NO and reactive nitrogen and oxygen species production in a streptozotocin (STZ)-induced model of DM in rats and to study their ability to protect DNA against nocive action of peroxynitrite. STZ…
Gut microbiota regulate hepatic von Willebrand factor synthesis and arterial thrombus formation via Toll-like receptor-2.
2016
The symbiotic gut microbiota play pivotal roles in host physiology and the development of cardiovascular diseases, but the microbiota-triggered pattern recognition signaling mechanisms that impact thrombosis are poorly defined. In this article, we show that germ-free (GF) and Toll-like receptor-2 (Tlr2)-deficient mice have reduced thrombus growth after carotid artery injury relative to conventionally raised controls. GF Tlr2-/- and wild-type (WT) mice were indistinguishable, but colonization with microbiota restored a significant difference in thrombus growth between the genotypes. We identify reduced plasma levels of von Willebrand factor (VWF) and reduced VWF synthesis, specifically in he…
Oleanolic acid improves diet-induced obesity by modulating fat preference and inflammation in mice.
2018
Obesity, triggered by high-fat diet (HFD), is associated to altered gustatory perception of dietary lipids. Oleanolic acid (OLA), a triterpene, has been reported to exert anti-obesity effects in animal models. Hence, we investigated the role of OLA in the modulation of oro-sensory perception of lipids in control and HFD-induced obese mice. As expected, OLA-treated obese mice exhibited a decrease in body, liver, and visceral adipose tissue weights. OLA treatment improved glucose tolerance, insulin level, plasma lipopolysaccharide (LPS), and hepatic cholesterol and triglyceride concentrations. OLA-treated obese mice exhibited higher fat preference compared to untreated obese mice, probably du…
Oleocanthal exerts antitumor effects on human liver and colon cancer cells through ROS generation
2017
The beneficial health properties of the Mediterranean diet are well recognized. The principle source of fat in Mediterranean diet is extra-virgin olive oil (EVOO). Oleocanthal (OC) is a naturally occurring minor phenolic compound isolated from EVOO, which has shown a potent anti-inflammatory activity, by means of its ability to inhibit the cyclooxygenase (COX) enzymes COX-1 and COX-2. A large body of evidence indicates that phenols exhibit anticancer activities. The aim of the present study was to evaluate the potential anticancer effects of OC in hepatocellular carcinoma (HCC) and colorectal carcinoma (CRC) models. A panel of human HCC (HepG2, Huh7, Hep3B and PLC/PRF/5) and CRC (HT29, SW48…
Context-Dependent Role of NF-κB Signaling in Primary Liver Cancer—from Tumor Development to Therapeutic Implications
2019
Chronic inflammatory cell death is a major risk factor for the development of diverse cancers including liver cancer. Herein, disruption of the hepatic microenvironment as well as the immune cell composition are major determinants of malignant transformation and progression in hepatocellular carcinomas (HCC). Considerable research efforts have focused on the identification of predisposing factors that promote induction of an oncogenic field effect within the inflammatory liver microenvironment. Among the most prominent factors involved in this so-called inflammation-fibrosis-cancer axis is the NF-κB pathway. The dominant role of this pathway for malignant transformation and progression…
A PDCD1 Role in the Genetic Predisposition to NAFLD-HCC?
2021
Obesity and non-alcoholic fatty liver disease (NAFLD) are contributing to the global rise in deaths from hepatocellular carcinoma (HCC). The pathogenesis of NAFLD-HCC is not well understood. The severity of hepatic steatosis, steatohepatitis and fibrosis are key pathogenic mechanisms, but animal studies suggest altered immune responses are also involved. Genetic studies have so far highlighted a major role of gene variants promoting fat deposition in the liver (PNPLA3 rs738409
Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver
2021
Metastasis is facilitated by the formation of a "premetastatic niche," which is fostered by primary tumor-derived factors. Colorectal cancer (CRC) metastasizes mainly to the liver. We show that the premetastatic niche in the liver is induced by bacteria dissemination from primary CRC. We report that tumor-resident bacteria Escherichia coli disrupt the gut vascular barrier (GVB), an anatomical structure controlling bacterial dissemination along the gut-liver axis, depending on the virulence regulator VirF. Upon GVB impairment, bacteria disseminate to the liver, boost the formation of a premetastatic niche, and favor the recruitment of metastatic cells. In training and validation cohorts of C…
Chemotherapeutic efficacy of curcumin and resveratrol against cancer: Chemoprevention, chemoprotection, drug synergism and clinical pharmacokinetics
2021
The frequent inefficiency of conventional cancer therapies due to drug resistance, non-targeted drug delivery, chemotherapy-associated toxic side effects turned the focus to bioactive phytochemicals. In this context, curcumin and resveratrol have emerged as potent chemopreventive and chemoprotective compounds modulating apoptotic and autophagic cell death pathways in cancer in vitro and in vivo. As synergistic agents in combination with clinically established anticancer drugs, the enhanced anticancer activity at reduced chemotherapy-associated toxicity towards normal organs can be explained by improved pharmacokinetics, pharmacodynamics, bioavailability and metabolism. With promising precli…