Colon adenocarcinoma is a major cause of cancer mortality worldwide. Type 2 diabetic people have an increased risk of developing colorectal cancer compared with nondiabetic people. There are studies showing that metformin inhibits angiogenesis, which is an important stage in cancer metastasis. Our aim was to identify the effects of metformin on miR-21, PTEN, and Akt gene expressions associated with angiogenesis in co-culture conditions established with human colorectal adenocarcinoma cells (HT -29) and human umbilical vein endothelial (HUVEC) cells. Cytotoxicity was evaluated via MTT assay, and PTEN, Akt, and miR-21 expressions were measured by real-time polymerase chain reaction in HUVEC cells under the effects of HT29 cells. Cell viability decreased with increasing doses of metformin, especially in the 160 mu g/mL metformin treatment group. According to real-time PCR results, PTEN was significantly upregulated in 80 and 160 mu g/mL metformintreated cells, and Akt, and miR-21 expressions were downregulated significantly in all metformin treatment groups. An inverse relation was found between PTEN, Akt and miR-21 levels in HUVEC cells under HT29-HUVEC co -culture conditions. Increased PTEN signalling was associated with the prevention of angiogenesis through reducing cell proliferation and migration. The miR-21/PTEN/Akt signalling pathway may have a crucial role in the molecular mechanism of metformin's antiangiogenic effect.

Deinoxanthin, the major carotenoid of bacterium Deinococcus radiodurans , is a unique C2 hydroxylated monocyclic ketocarotenoid. In the present review article composed based on articles retrieved from Medline/PubMed and Scopus following a systematic search, we discuss chemical, biological and pharmacological properties of the compound. Based on the literature, deinoxanthin possesses remarkable resistance against ultraviolet (UV) radiations, exhibits strong reactive oxygen speciesscavenging capacity, and exerts apoptotic effects on Saos-2, PC -3, HT -29 and, HepG2 cells. Interestingly, deinoxanthin has been detected following exposure to Mars -like solar UV spectrum in space when protected from solar radiation. Despite promising potential of deinoxanthin, it seems that few studies have evaluated its biological/pharmacological function and further in vivo / in vitro studies should be conducted to reveal signalling pathways modulated by this compound.

Proteasome inhibitor bortezomib is an anticancer agent approved for treatment of multiple myeloma and mantle cell lymphoma. However, its application in other types of cancer, primarily in solid tumors, is limited due to poor pharmacokinetics, inefficient tissue penetration, low stability and frequent adverse effects. In the present study, a novel micellar nano-scaled delivery system was manufactured, composed of amphiphilic poly(N-vinylpyrrolidone) nanoparticles loaded with bortezomib. Similar nanoparticles loaded with prothionamide, a drug without anticancer effect, were used as control. The size and zeta potential of the obtained polymeric micelles were measured by dynamic light scattering. Bortezomib-loaded micelles exhibited significant cytotoxic activity in vitro in monolayer tumor cell cultures (IC50 similar to 6.5 mu g/ml) and in 3D multicellular tumor spheroids (IC50 similar to 8.5 mu g/ml) of human glioblastoma cell lines U87 and T98G. Additionally, the toxic effects in vivo were studied in zebrafish Danio rerio embryos, with an estimated 50% lethal concentration of 0.1 mg/ml. Considering that bortezomib and other molecules from the class of proteasome inhibitors are potent antitumor agents, nanodelivery approach can help reduce adverse effects and expand the range of its applications for treatment of various oncological diseases.

One of the primary challenges regarding chronic kidney disease (CKD) diagnosis is the absence of reliable methods to detect early-stage kidney damage. A metabolomic approach is expected to broaden the current diagnostic modalities by enabling timely detection and making the prognosis more accurate. Analysis performed on urine has several advantages, such as the ease of collection using noninvasive methods and its lower protein and lipid content compared with other bodily fluids. This review highlights current trends in applied analytical methods, major discoveries concerning pathways, and investigated populations in the context of urine metabolomic research for CKD over the past five years. Also, we are presenting approaches, instrument upgrades, and sample preparation modifications that have improved the analytical parameters of methods. The onset of CKD leads to alterations in metabolism that are apparent in the molecular composition of urine. Recent works highlight the prevalence of alterations in the metabolic pathways related to the tricarboxylic acid cycle and amino acids. Including diverse patient cohorts, using numerous analytical techniques with modifications and the appropriate annotation and explanation of the discovered biomarkers will help develop effective diagnostic models for different subtypes of renal injury with clinical applications.

Several drug-delivery systems have been reported on and often successfully applied in cancer therapy. Cell-targeted delivery can reduce the overall toxicity of cytotoxic drugs and increase their effectiveness and selectivity. Besides traditional liposomal and micellar formulations, various nanocarrier systems have recently become the focus of developmental interest. This review discusses the preparation and targeting techniques as well as the properties of several liposome-, micelle-, solid-lipid nanoparticle-, dendrimer-, gold-, and magnetic-nanoparticle-based delivery systems. Approaches for targeted drug delivery and systems for drug release under a range of stimuli are also discussed.

INTRODUCTION:Alcohol, tobacco and illicit drug use combined are the largest modifiable health risk factors. Wastewater-based epidemiology (WBE) is a complementary approach for monitoring substance use in the population. In this study we applied WBE technique to a community in the Moscow region to estimate population-level consumption of alcohol, tobacco and morphine. METHODS:Wastewater sampling was carried out over 47 days, in 2018 and 2019, including the New Year period. Analysis of the samples for consumption biomarkers (ethyl sulphate, cotinine and morphine) were undertaken using liquid chromatography tandem mass spectrometry (LC-MS/MS). Daily consumption estimates were then compared with sales/production/prescription data and between different days of the week using Mann-Whitney U test. RESULTS:Alcohol consumption was significantly higher on Sundays and during the New Year and Russian Christmas period compared to weekdays and Saturdays. Tobacco consumption estimates were largely consistent throughout the week. Morphine was detected by WBE during the monitoring period but was inconsistent with prescription record data. DISCUSSION AND CONCLUSIONS:This study provides evidence for the feasibility of conducting WBE in Russia. Estimates of alcohol consumption derived from WBE were higher than average alcohol sales data for the country. The estimated consumption of nicotine is generally consistent with the production data, with estimates higher than in most other countries. Our results also suggest potential illegal use of opioids (morphine-based) in the population. Given the considerable health and economic costs of substance use in Russia, more extensive WBE testing is recommended to inform and evaluate public health policies.

Human multiforme glioblastoma is characterized by an unfavorable prognosis, low survival rate and extremely limited possibilities for therapy. Rat C6 glioma is an experimental model for the study of glioblastoma growth and invasion. It has been shown that the growth and development of the tumor is accompanied by changes in the surrounding normotypic tissues [1]. These changes create a favorable environment for the development of the tumor and give it an evolutionary advantage [2]. Description of changes occurring in normotypic cells of the body upon their contact with tumor cells is of great interest. We have grown C6 glioma cells and rat astrocytes, as well as astrocyte cells co-cultured together with C6 glioma. We performed proteome-wide LC-MS analysis of these experimental groups. The data includes LC-MS/MS raw files and exported MaxQuant and ProteinPilot search results with fasta. Dataset published in the PRIDE repository project accession PXD026776.

An association of vitamin D receptor (VDR) polymorphisms and vitiligo has been suggested. However, previous studies have reported contradictory results while including limited data among Caucasians. The aim of this single-center study was to evaluate the effect of three common VDR gene polymorphisms (FokI, TaqI and BsmI) on susceptibility and clinical aspects of vitiligo in a Southeastern European Caucasian population. A total of 110 unrelated vitiligo cases and 509 general population controls were enrolled from October 2018 to November 2019. Genomic DNA was extracted from whole blood after de-identification and anonymization of the samples and genotyped for the selected VDR polymorphisms by the qPCR (melting curve analysis). Subgroup analysis by clinical features among subsets of patients indicated that, compared to subjects with the FokI TT genotype or T allele, carriers of the FokI CC genotype or C allele exhibited significantly decreased risk of developing vitiligo before the age of 30 [TT vs.CC : odds ratio (OR)=0.286, 95% confidence interval (CI): 0.083-0.984, P=0.041; T vs.C : OR=0.545, 95%C I: 0.313-0.948, P=0.031]. Intra-patient analysis also revealed that, compared to T allele, the presence of TaqI C allele was adversely associated with the incidence of concurrent leukotrichia (T vs. C: OR=1.874, 95%C I: 1.018-3.451, P=0.042). Comparisons between the case and control groups showed no evidence to support an association between susceptibility to vitiligo and the VDR BsmI, TaqI, and FokI polymorphisms in this cohort. Thus, the studied VDR polymorphisms might indirectly impact the clinical course and treatment decision-making despite their lack of association with vitiligo per se. Further research with larger sample sizes, especially across Caucasian individuals, should be performed to confirm these findings.

Although fossil fuels remain the main source of energy, the volume of renewable sources of energy is constantly increasing. Biodiesel is a promising alternative fuel due to the number of advantages compared to fossil fuel and other types of biofuel. The specific objective of this study was to identify the difference between conventional and novel technologies applied during the whole life cycle of biodiesel production and consumption. The study offers some important insights into the recent advances in the biodiesel industry including biodiesel production from microalgal lipids, advanced homogenous and enzymatic transesterification, non-catalytic supercritical transesterification, application of microwave and ultrasound assisting technologies. Considering all the factors affecting the efficiency and safety of the biodiesel production process, here we reviewed the main principals and recent achievements in the environmental life cycle assessment of biodiesel production and consumption.

Health benefits of fish consumption could be counterbalanced by the intake of contaminants after long term fish consumption, burdened even in trace levels. The presence of the indicator PCBs (NDL-PCBs and PCB 118) in farmed and wild seabream and seabass was evaluated. For the determination of PCB, a GC-MS method was developed and evaluated. The association of PCB accumulation in fish with seasonality, locality, production mode and species was also investigated. A new approach for the risk characterisation after exposure to NDL-PCB through fish consumption in Greece was developed, based on the real exposure and the permitted maximum levels of both aggregated dietary exposure and exposure through fish consumption. PCB levels determined in fish were below established permitted limits (6.24 ng/g 95th percentile), while PCB levels and congener distribution varied significantly between farmed and wild fish (p = 0.001). Seasonality was highlighted as an important factor affecting NDL-PCBs accumulation, with high levels coinciding with the reproduction period of each species. Differences were also depicted for sampling sites, with PCB 118 presenting significantly higher values in open seas while NDL-PCB congeners in closed seas. Risk assessment of NDL-PCB intake through fish consumption corrected for the aggregated exposure revealed no risk for the consumers.

This study demonstrates the adsorptive recovery of high-concentration Iopamidol (TOP) from aqueous solution. IOP is a highly valuable X-ray iodinated contrast agent (ICA), and the reuse of the adsorbent activated carbon (AC) is via elution with alcohol. Of the adsorbents selected, coconut powder AC (CPAC) displayed the best adsorption performance for IOP. The results of batch investigation into adsorption kinetics, isotherms, activation energy, and thermodynamic calculations support the occurrence of a physisorption process. The adsorption mechanism has been determined using the intraparticle diffusion model. A Boyd plot has revealed that IOP adsorption onto CPAC was mainly governed by particle diffusion. CPAC also exhibited excellent adsorptive performance toward IOP, which was efficiently eluted and recovered using methanol in a semicontinuous flow system. Moreover, the spent CPAC was efficiently regenerated and reused in five adsorption/desorption cycles. The characterization of CPAC samples by SEM, DRIFT, and TGA shows that IOP is absorbed onto CPAC, leading to significant decreases in the BET surface area and pore volume and shift of the pore diameter. pi-pi, donor-acceptor complex, van der Waals, and hydrogen-bond interactions are governed by the IOP adsorption. Hydrogen-bond interactions between IOP and alcohols play a crucial role in the desorption process. IOP was completely eluted, and the surface properties of CPAC were recovered after elution in the flow system. This study demonstrates that many benefits can be achieved from adsorption/desorption processes, such as those in wastewater treatment and the recovery of valuable compounds, as adsorbent recycling simplifies the operations and reduces treatment costs.

Ginseng is one of the main representatives of traditional Chinese medicine and presents a wide range of pharmacological actions. Ginsenosides are the main class of active compounds found in ginseng. They demonstrate unique biological activity and medicinal value, namely anti-tumour, anti‑inflammatory and antioxidant properties, as well as anti-apoptotic properties. Increasing levels of stress in life are responsible for the increased incidence of nervous system diseases. Neurological diseases create a huge burden on the lives and health of individuals. In recent years, studies have indicated that ginsenosides play a pronounced positive role in the prevention and treatment of neurological diseases. Nevertheless, research is still at an early stage of development, and the complex mechanisms of action involved remain largely unknown. This review aimed to shed light into what is currently known about the mechanisms of action of ginsenosides in relation to Alzheimer's disease. Scientific material and theoretical bases for the treatment of nervous system diseases with purified Panax ginseng extracts are also discussed.

Glioblastoma multiforme is the most aggressive malignant tumor of the central nervous system. Due to the absence of effective pharmacological and surgical treatments, the identification of early diagnostic and prognostic biomarkers is of key importance to improve the survival rate of patients and to develop new personalized treatments. On these bases, the aim of this review article is to summarize the current knowledge regarding the application of molecular biology and proteomics techniques for the identification of novel biomarkers through the analysis of different biological samples obtained from glioblastoma patients, including DNA, microRNAs, proteins, small molecules, circulating tumor cells, extracellular vesicles, etc. Both benefits and pitfalls of molecular biology and proteomics analyses are discussed, including the different mass spectrometry-based analytical techniques, highlighting how these investigation strategies are powerful tools to study the biology of glioblastoma, as well as to develop advanced methods for the management of this pathology.

In recent years, the introduction of new molecular techniques in experimental and clinical settings has allowed researchers and clinicians to propose circulating-tumor DNA (ctDNA) analysis and liquid biopsy as novel promising strategies for the early diagnosis of cancer and for the definition of patients' prognosis. It was widely demonstrated that through the non-invasive analysis of ctDNA, it is possible to identify and characterize the mutational status of tumors while avoiding invasive diagnostic strategies. Although a number of studies on ctDNA in patients' samples significantly contributed to the improvement of oncology practice, some investigations generated conflicting data about the diagnostic and prognostic significance of ctDNA. Hence, to highlight the relevant achievements obtained so far in this field, a clearer description of the current methodologies used, as well as the obtained results, are strongly needed. On these bases, this review discusses the most relevant studies on ctDNA analysis in cancer, as well as the future directions and applications of liquid biopsy. In particular, special attention was paid to the early diagnosis of primary cancer, to the diagnosis of tumors with an unknown primary location, and finally to the prognosis of cancer patients. Furthermore, the current limitations of ctDNA-based approaches and possible strategies to overcome these limitations are presented.

The association between genetic variations in the cytochrome P450 (CYP) family genes and pathological conditions related to long-term exposure to organochlorine compounds (OCs) deserves further elucidation. OCs are persistent organic pollutants with bioaccumulative and lipophilic characteristics. They can act as endocrine disruptors and perturb cellular mechanisms. Prolonged exposure to OCs has been associated with different pathological manifestations. CYP genes are responsible for transcribing enzymes essential in xenobiotic metabolism. Therefore, polymorphisms in these genetic sequences a. alter the metabolic pathways, b. induce false cellular responses, and c. may provoke pathological conditions. The main aim of this review is to define the interaction between parameters a, b and c at a mechanistic/molecular level, with references in clinical cases.

Exposure to organophosphorus nerve agents, the most deadly chemical warfare agents, is possible in a variety of situations, such as destruction of chemical warfare agents, terrorist attacks, armed conflicts or accidents in research laboratories and storage facilities. Hundreds of thousands of tons of chemical munitions were disposed of at the sea in the post World War II period, with European, Russian, Japanese and US coasts being the most affected. Sulfur mustard, Lewisite and nerve agents appear to be the most frequently chemical warfare agents disposed of at the sea. Addressing the overall environmental risk, it has been one of the priorities of the world community since that time. Aside from confirming exposure to nerve agents in the alleged use for forensic purposes, the detection and identification of biological markers of exposure are also needed for the diagnosis and treatment of poisoning, in addition to occupational health monitoring for specific profiles of workers. When estimating detrimental effects of acute or potential chronic sub-lethal doses of organophosphorus nerve agents, released accidentally or intentionally into the environment, it is necessary to understand the wide spectra of physical, chemical and toxicological properties of these agents, and predict their ultimate fate in environmental systems.

The substance 4-methylimidazole (4-MEI) has raised several concerns regarding its toxicity to humans, although no harmonized classification has yet been decided. The regulatory limits for food products set by various authorities in Europe and the USA differ considerably. The purpose of the present study is to compare two liquid chromatography techniques in order to determine the levels of 4-MEI in food products from the Greek market and roughly estimate the possible exposure and relevant health risk for the consumers.A total of thirty-four samples (soft drinks, beers, balsamic vinegars, energy drinks and sauces) were collected and analyzed. The quality parameters for both analytical methodologies (linearity, accuracy, inter day precision, recovery) are presented. No detectable levels of 4-MEI are found in beers and soft drink samples, other than cola type. On the other hand, 4-MEI was detected in all cola type soft drinks (15.8-477.0 ng/ml), energy drinks (57.1%, 6.6-22.5 ng/ml) and vinegar samples (66.7%, 9.7-3034.7 ng/ml), while only one of the sauce samples was found to have a detectable level of 17.5 ng/ml 4-MEI. (C) 2017 Elsevier Ltd. All rights reserved.

Organophosphorus (OPs) and organochlorine (OCs) pesticides are synthetic organic compounds used mainly in agriculture to manage pest problems.Human is occupationally and environmentally exposed to pesticides via inhalation, ingestion and skin absorption.When the pollutant enters human body it is rapidly metabolized to more toxic compounds than the parent compound.Their ability to interfere with biochemical and metabolic pathways in humans makes them compounds of high concern.Acute and chronic exposure has been linked with neurological, cardiovascular, birth effects and male infertility.Human exposure to pesticides is estimated by measuring their metabolites in biological tissues and fluids such as blood, urine, amniotic fluid and hair.In this review study advances on biomonitoring of pesticides are presented.Measured levels of pesticides in urine matrices, amniotic fluid, meconium and hair are presented in order to monitor the human burden and biomonitoring data between occupationally and environmentally exposed populations are being compared.