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Background: Heterogenicity with high glycolysis rate and invasiveness are crucial markers of breast cancer that essentially participated in female high mortality rate globally. Although, the potential role of green tea and it constitutes to manage the tumor state including breast tumor, the precise pathway of this role still unclear and need to be elucidated. The current study therefore investigated the glucose regulatory role of Decaffeinated Green Tea Extract (DGTE) to promote antitumor and antimetastatic in MCF7 cells. Methods: The viable cells were assessed after 4h and 24h in response to DGTE/ dorsomorphin dihydrochloride (AMPK) selective inhibitor. Lactate and glucose uptake were investigated in addition to cellular migration. Results: Significant cytotoxicity of DGTE was seen after 24h but not 4h, while suppressed AMPK pathway induced further decreased in viable cells. Furthermore, DGTE significantly altered glucose metabolism through decreasing glucose uptake and consequently reduced the glycolysis. Moreover, these results were associated with significant reduction in the cellular migration in response to DGTE. Conclusion: To conclude, the DGTE interacted with MCF7 cells metabolism to induce the precise impact and therefore could be a potential additive therapeutic agent to manage the proliferation and invasion of various cancer cells including breast cancer. [ABSTRACT FROM AUTHOR]

Human T-cell Leukemia Virus (HTLV-1) is a human retrovirus that establishes a lifelong infection of host immune cells which may develop into Adult T-cell Leukemia (ATL). The process by which the virus transforms host cells into a cancerous state is not well understood, but the HTLV-1 basic leucine zipper factor (HBZ) protein has been shown to play an important role in carcinogenesis. HBZ is a viral transcriptional regulator that controls the expression of both viral and cellular genes. Numerous studies have shown that HBZ alters the gene expression of infected host cells in ways that promote carcinogenesis. However, it remains unclear how these genetic changes result in the metabolic reprogramming that is characteristic of cancer. Here, we evaluated the metabolic changes caused by the HBZ protein and whether these changes are reported to be involved in cancer progression. Recently, our lab has obtained preliminary data which suggests that polyamine biosynthesis is upregulated in cells expressing HBZ. Polyamines (including spermine and spermidine) act as positive regulators of the cell cycle and dysregulation of polyamine biosynthesis has been observed in several types of tumors. Further, polyamines have also been implicated in metastasis, which may make them possible therapeutic targets. This project aims to evaluate whether the upregulation in polyamines is due to HBZ-mediated changes in the expression of biosynthetic genes. We hypothesize that HBZ enhances the expression of the polyamine biosynthetic enzymes spermidine synthase (srm) and spermine synthase (sms). [ABSTRACT FROM AUTHOR]

The effects of glycans-capped AgNPs (30±5 nm average diameter, spherical shape) on biocompatibility and uptake was studied in relation to the glycan capping (glucose AgNPs-G, glucose/sucrose AgNPs-GS, glucose/fructose AgNPs-GF), and to the cell types (HeLa cells, lymphocytes, and HepG2 cells). Glycan capping and type of cells drive morphological changes, viability loss and type and extent of cell death induction; in addition cells response is largely influenced by the AgNPs amount. The MTT photometric method to determine cell metabolism and the analysis of the membrane integrity by Annexin V-Propidium Iodide labelling were used to quantify cell viability and cell death with different concentrations of NPs. It turns out that i) AgNPs-GF are the most toxic, whereas ii) AgNPs-GS are the less toxic NPs, probably due to the stability of glucose/sucrose capping up to 5 days in culture medium; iii) HepG2 cells are the most sensitive to the presence of NPs. A deeper investigation is necessary to explain the interesting PBLs proliferation increase observed in the presence of AgNPs-GS. [ABSTRACT FROM AUTHOR]

Salinity of drilling waste is a serious problem, and it is one of the biggest problems at the stage of selecting drilling waste utilization method. The high salinity of drilling waste results from a few causes, i.e. the use of drilling fluids (inorganic salts are commonly used as drilling fluids components) in the process of drilling, drilling in saline formations and also brine inflowing to the well. The investigations carried out on drilling waste has shown that their soluble salts of alkali metals in the form of chlorides, sulfates, hydrogen carbonates and carbonates occurring in above standard quantities are contaminants hazardous for the soil-water environment. Preventing or at least limiting a penetration of salts from drilling waste into the soil-water environment should be a priority issue as an excess of salts considerably affects ion equilibria in the sorption complex and cell metabolism of plants. Many metabolic processes, such as activity of enzymes, synthesis of proteins, activity of mitochondria and chloroplasts become disturb under saline conditions. The results of a feasibility analyses of drilling waste desalination through aqueous extraction are presented in the paper. The obtained extracts are aqueous solutions of mineral salts, mainly sodium chloride and potassium chloride. Owing to the high content of potassium salts, the NaCl and KCl were separated through crystallization. [ABSTRACT FROM AUTHOR]

We enlarge our results from the study of the hopping mechanism of the oscillation excitation transport in 1D model of one biologica-likel macromolecular chain to the case of a system composed from two 1D parallel macromolecular chains with consideration of the properties of intramolecular oscillation excitations. We suppose, that due to the exciton interaction with thermal oscillation (generated by mechanical phonon subsystem) of structural elements (consisting of the peptide group) of the chains, the exciton becomes by self trapped and forms the polaron state. We suggest a model which generalizes the modified Holstein polaron model to the case of two macromolecular chains and find that because of the interchain coupling, the exciton energy band is splitted into two subbands. The hopping process of exciton migration along the macromolecular chains is studied in dependence of system parameters and temperature. We pay an special attention to the temperature range (near T = 300 K) in which living cells operate. It is found that for the certain values of the system parameters there exists the abrupt change of the exciton migration nature from practically free (light) exciton motion to an immobile (heavy, dressed by phonon cloud) quasiparticle We discuss an application of the obtained results to the exciton transport both within deoxyribonucleic acid molecule and in the 2D polymer films organized from such macromolecular chains. [ABSTRACT FROM AUTHOR]

Patch-clamp technique becomes a powerful method in studying cell excitability, as well as mechanisms of their regulation by different metabolic factors, pharmacology and drug candidates. The main idea of this study is employing of unique properties of amorphous porous alumina layers to perform three-dimensional architecture of recording site. Increased throughput is achieved by automation and parallel measurements on several cells. Multisensor-systems on the basis of nanoporous anodic alumina: highly ordered arrays of nanoholes with several hundreds down to several tens of nanometer diameter; substrate thickness within 0.005-1 mm patterned down to ~20-50 nm, wide range of compositions providing different electrophysical and optical properties, flexible, reconfigurable with the possibility of embedding in mobile manufacturing line, enables mass production without the use of expensive lithographic tools. [ABSTRACT FROM AUTHOR]

In this paper we utilize a systematic method to optimize the topology of a line defect Photonic Crystal Wave guide (PCW), a very popular and effective optical device for realizing optical buffer in room temperate operation. In order to do this, we divide the unit cell PCW to 25 squares and utilize a Binary Particle Swarm Optimization (BPSO) algorithm to find the optimum topology. During the optimization process, we apply some constraints to avoid band mixing as well. Calculation results show that Normalized Delay-Bandwidth Product (NDBP) for the structure optimized is 0.27. This structure optimized possesses a high bandwidth (20.9 nm) with group index of 21.7 as well. [ABSTRACT FROM AUTHOR]

Re-engineering cellular behavior promises to advance the production of commercially significant biomolecules and to enhance cellular function for many applications. To achieve a desired cellular objective, it is necessary to identify within a metabolic network a set of reactions whose fluxes should be changed using gene modifications. We develop a computational method, CCOpt, to optimize the selection of an intervention set that consists of gene up/down-regulation using uncertainty-aware chance-constrained optimization. In contrast to deterministic approaches where constraints are met with 100% certainty, constraints in CCOpt are probabilistically met at a user-specified confidence level. We investigate the application of CCOpt to two case studies that utilize the Chinese Hamster Ovary (CHO) cell metabolism. Our results demonstrate that CCOpt is capable of identifying optimal intervention sets without the run-time cost of a sampling based (Monte Carlo) approach. [ABSTRACT FROM AUTHOR]

The tissue fluorescence gives the response of light emitting molecule signature, and characterizes the cell composition and peculiarities of metabolism. Both are useful for the biomedical diagnostics, as reported in previous our and others works. The present work demonstrates the results of application of laser excited autofluorescence for diagnostics of pathology in genital tissues, and the feasibility for the bedside at "point of care - off lab" application. A portable device using the USB spectrophotometer, micro laser (355 nm Nd:YAG, 0,5 ns pulse, repetition rate 10 kHz, output power 15 mW), three channel optical fiber and computer with diagnostic program was designed and ready for clinical trial to be used for cytology and biopsy specimen on site diagnostics, and for the endoscopy/puncture procedures. The biopsy and cytology samples, as well as intervertebral disc specimen were evaluated by pathology experts and the fluorescence spectra were investigated in the fresh and preserved specimens. The spectra were recorded in the spectral range 350-900 nm. At the initial stage the Gaussian components of spectra were found and the Mann- Whitney test was used for the groups' differentiation and the spectral regions for optimal diagnostics purpose were found. Then a formal dividing of spectra in the components or the definite width bands, where the main difference of the different group spectra was observed, was used to compare these groups. The ROC analysis based diagnostic algorithms were created for medical prognosis. The positive prognostic values and negative prediction values were determined for cervical Liquid PAP smear supernatant sediment diagnosis of being Cervicitis and Norma versus CIN2+. In a case of intervertebral disc the analysis allows to get the additional information about the disc degeneration status. All these results demonstrated an efficiency of the proposed procedure and the designed device could be tested at the point-of-care site or for intervertebral disc operations. [ABSTRACT FROM AUTHOR]

The tissue fluorescence gives the response of light emitting molecule signature, and characterizes the cell composition and peculiarities of metabolism. Both are useful for the biomedical diagnostics, as reported in previous our and others works. The present work demonstrates the results of application of laser excited autofluorescence for diagnostics of pathology in genital tissues, and the feasibility for the bedside at "point of care - off lab" application. A portable device using the USB spectrophotometer, micro laser (355 nm Nd:YAG, 0,5 ns pulse, repetition rate 10 kHz, output power 15 mW), three channel optical fiber and computer with diagnostic program was designed and ready for clinical trial to be used for cytology and biopsy specimen on site diagnostics, and for the endoscopy/puncture procedures. The biopsy and cytology samples, as well as intervertebral disc specimen were evaluated by pathology experts and the fluorescence spectra were investigated in the fresh and preserved specimens. The spectra were recorded in the spectral range 350-900 nm. At the initial stage the Gaussian components of spectra were found and the Mann- Whitney test was used for the groups' differentiation and the spectral regions for optimal diagnostics purpose were found. Then a formal dividing of spectra in the components or the definite width bands, where the main difference of the different group spectra was observed, was used to compare these groups. The ROC analysis based diagnostic algorithms were created for medical prognosis. The positive prognostic values and negative prediction values were determined for cervical Liquid PAP smear supernatant sediment diagnosis of being Cervicitis and Norma versus CIN2+. In a case of intervertebral disc the analysis allows to get the additional information about the disc degeneration status. All these results demonstrated an efficiency of the proposed procedure and the designed device could be tested at the point-of-care site or for intervertebral disc operations. [ABSTRACT FROM AUTHOR]

Cesium (Cs), as well as potassium (K), is a member of alkaline metal elements. In the study of transporter, Cs has been used as a K channel blockeron cells. Doses of CsCl by the intraperi-toneal route in mice indicated that a rapid transfer of Cs from blood to tissue compartments (Pinsky and Bose, 1984). Distribution of Cs in the whole bodies had been investigated. However, it is not clear that how the Cs is transported through which kinds of way at the molecular levels, and that the effect of Cs on the cell metabolisms. We examined the proliferation of HeLa cells cultured by Dulbecco's modified Eagle medium supplemented with 10% fatal bovine serum and 10 mM of different types of alkali metals such as Li, Na, K, Rb, and Cs at 37 degree C, 5% CO2. Among them, only Cs inhibited the proliferation of the cells. The proliferation decrease is dependent on Cs concentration. Microscopic examination of the Cs-treated cells, cell membrane was not smoothly. Two different methods of live and dead assay were performed (i.e., lactose dehy-drogenase-release assay and cytometry of Calcein-propidium iodide stained cells). In the Cs concentration that showed inhibition of cell proliferation, the HeLa cell membrane was not damaged by Cs. To confirm extracellular Cs uptake into the cell, intracellular cations were analyzed by capillary electrophoresis (P/ACETM MDQ). The intracellular cation content was analyzed as magnesium-based intracellular cation ratio. The intracellular Cs was detected in Cs-treated cells but not in control cell. The intracellular pH was measured by use of the pH-sensitive dye indicator BCECF. Alkalization of intracellular pH was occurred in the cells cultured with CsCl, but not in the cells cultured with the other alkali metals. Generally, intracellular pH of tumor cells was lower than normal cells. It is considered that Cs added to extracellular media uptake into the cells, and inhibition of cell proliferation possibly due to intracellular alkalization induced by Cs administration. [ABSTRACT FROM AUTHOR]

Sequestosome1/p62/A170 (SQSTM1) is a multifunctional regulator of cell signaling and metabolism with an ability to modulate targeted degradation of proteins through autophagy. SQSTM1 implements its functions through physical interactions with different types of proteins including atypical PKCs, non-receptor type tyrosine kinase p56Lck (Lck), polyubiquitin and autophagosomal factor LC3. One of the notable physiological functions of SQSTM1 is the regulation of redox sensitive voltage-gated potassium (Kv) channels which modulate membrane potential, signal integration and neurotransmitter release. Kv channels are composed of a and ß subunits, (Kva)4 and (Kvß)4. Previous studies have established that SQSTM1 scaffolds PKCζ, enhancing phosphorylation of Kvß. Both PKCζ and SQSTM1 play key roles in acute hypoxia-induced Kv channel inactivation in pulmonary artery. SQSTM1 is an oxidative stress inducible protein regulated by transcription factor Nrf2, a master regulator of antioxidant system (1). The expression levels of SQSTM1 in vascular cells are up-regulated by atherogenic stimuli, such as oxidized low density lipoprotein and 4-hydroxynonenal, suggesting SQSTM1 has a protective role against oxidative stress (2). We have examined the role of SQSTM1 in neointimal hyperplasia and vascular remodeling in vivo following carotid artery ligation. Neointimal hyperplasia was markedly enhanced near the ligation sites after 3 weeks in SQSTM1-/- compared with wild-type (SQSTM1+/+) mice. The intimal area and stenotic ratio were, respectively, 2.1- and 1.7-fold higher in SQSTM1-/- mice, indicating enhanced proliferation of vascular smooth muscle cells (SMCs). We found that migration of aortic SQSTM1-/- SMCs was enhanced compared to wild type SMCs and that they proliferated more rapidly in response to fetal calf serum and attained 2-3-fold higher cell densities compared to wild type SMCs. The enhanced proliferation of SQSTM1-/- aortic SMCs in vitro highlights a novel role for SQSTM1 in suppressing smooth muscle migration and proliferation following vascular injury (3). Recent studies have revealed the role of Kv1.3 channels in enhancing migration and proliferation of arterial SMCs (4). As Kv1.3 channels provide a signaling platform and may thereby modulate the migration and proliferation of arterial SMCs and are recognized as a therapeutic target for treatment of restenosis. Based on these studies, we highlight the molecular mechanisms by which SQSTM1 suppresses proliferation of arterial smooth muscle cells and neointimal hyperplasia following carotid artery ligation. [ABSTRACT FROM AUTHOR]

One essential hallmark of tumour cells is altered metabolism (1). Most tumour cells exhibit high rates of glycolysis, even in the presence of oxygen ("Warburg effect"), resulting in increased production of lactate, which is transported out of the cells, contributing to the acidic microenvironment encountered in tumours. The acidic microenvironment has been associated with invasive behaviour, mutagenesis as well as radio- and chemoresistance (2). More recently, several authors have proposed a metabolic complementarity between tumour and stroma. If the tumour is glycolytic, the associated stroma is more oxidative and vice-versa. The latter process is known as the "reverse Warburg effect" (3). Monocarboxylate transporters (MCTs), by performing the plasma membrane efflux of lactate coupled with a proton, especially the isoforms 1 (MCT1) and 4 (MCT4), play an important role in the maintenance of the metabolic phenotype of tumours and associated stroma. MCT1 has been more associated with cells exhibiting an oxidative phenotype, being involved in lactate uptake, while MCT4 has been associated with the glycolytic phenotype, being responsible for lactate efflux (4). Our group has been studying the expression of these MCT isoforms as well as their chaperone, CD147, essential for MCT activity and plasma membrane expression, in several series of human cancers (5). We found upregulation of MCT1 and MCT4 colorectal cancer, upregulation of MCT1, MCT4 and CD147 in cervical cancer, upregulation of MCT1 in breast cancer and upregulation of MCT1 and CD147 in glioblastomas, compared to the corresponding non-neoplastic tissues. On the other hand, there was downregulation of MCT4 in gastric cancer and downregulation of MCT1 in prostate cancer. We also found important associations between MCT overexpression and the clinicopathological data of the cases, mostly with aggressiveness parameters. Due to their role in the maintenance of tumour metabolism, MCTs are considered promising targets in cancer therapy. Thus, we are also studying the effects of MCT inhibition using different tumour models. In general, MCT inhibition in glycolytic tumour cells leads to a decrease in lactate production, cell proliferation, migration and invasiveness (6). In summary, MCT activity is essential for the maintenance of the metabolic phenotype of tumours, playing a key role in the crosstalk between tumour cells and microenvironment. However, MCTs are differentially expressed among the solid tumours and future strategies of MCT inhibition in cancer treatment should take this fact into account [ABSTRACT FROM AUTHOR]