Mesenchymal stem cell secretome and regenerative therapy after cancer

Cancer treatment generally relies on tumor ablative techniques that can lead to major functional or disfiguring defects. These post-therapy impairments require the development of safe regenerative therapy strategies during cancer remission. Many current tissue repair approaches exploit paracrine (immunomodulatory, pro-angiogenic, anti-apoptotic and pro-survival effects) or restoring (functional or structural tissue repair) properties of mesenchymal stem/stromal cells (MSC). Yet, a major concern in the application of regenerative therapies during cancer remission remains the possible triggering of cancer recurrence. Tumor relapse implies the persistence of rare subsets of tumor-initiating cancer cells which can escape anti-cancer therapies and lie dormant in specific niches awaiting reactivation via unknown stimuli. Many of the components required for successful regenerative therapy (revascularization, immunosuppression, cellular homing, tissue growth promotion) are also critical for tumor progression and metastasis. While bi-directional crosstalk between tumorigenic cells (especially aggressive cancer cell lines) and MSC (including tumor stroma-resident populations) has been demonstrated in a variety of cancers, the effects of local or systemic MSC delivery for regenerative purposes on persisting cancer cells during remission remain controversial. Both pro- and anti-tumorigenic effects of MSC have been reported in the literature. Our own data using breast cancer clinical isolates have suggested that dormant-like tumor-initiating cells do not respond to MSC signals, unlike actively dividing cancer cells which benefited from the presence of supportive MSC. The secretome of MSC isolated from various tissues may partially diverge, but it includes a core of cytokines (i.e. CCL2, CCL5, IL-6, TGFβ, VEGF), which have been implicated in tumor growth and/or metastasis. This article reviews published models for studying interactions between MSC and cancer cells with a focus on the impact of MSC secretome on cancer cell activity, and discusses the implications for regenerative therapy after cancer.     

Novel potential inhibitors for adenylylsulfate reductase to control souring of water in oil industries

The biogenic production of hydrogen sulfide gas by sulfate-reducing bacteria (SRB) causes serious economic problems for natural gas and oil industry. One of the key enzymes important in this biologic process is adenosine phosphosulfate reductase (APSr). Using virtual screening technique we have discovered 15 compounds that are novel potential APSr inhibitors. Three of them have been selected for molecular docking and microbiological studies which have shown good inhibition of SRB in the produced water from the oil industry.     

New insights into the chemical and isotopic composition of human-body biominerals. I: Cholesterol gallstones from England and Greece

We have analyzed gallstones from four patients of Europe and particularly from England (including samples from a mother and a daughter) and Greece. According to the XRD, FTIR, NMR and laser micro-Raman results the studied materials correspond to typical cholesterol monohydrate (ChM). The micro-morphology of cholesterol microcrystals was investigated by means of SEM–EDS. The XRF results revealed that Ca is the dominant non-organic metal in all gallstones (up to ～1.95 wt.%) together with Fe, Cu, Pb and Ni (up to ～19 ppm for each metal). Gallstones from England contain additional Mn (up to ～87 ppm) and Zn (up to ～6 ppm) while the sample of the mother contains negligible Zn and Mn, compared to that of her daughter, but significant As (～4.5 ppm). All cholesterol gallstones examined are well enriched in potentially toxic metals (Pb, as well as Ni in one case) and metalloids (As also in one case) as compared to the global average. The position of Zn, which is a characteristic biometal, in the structure of cholesterol, was investigated by molecular simulation using the Accelrys Materials Studio^® software. On the basis of IRMS results, all gallstones examined exhibit a very light δ¹³C signature (average δ¹³C ～?24‰ PDB). Gamma-ray spectrometry measurements indicate the presence of ²¹⁴Pb and ²¹⁴Bi natural radionuclides due to the ²³⁸U series as well as an additional amount of ⁴⁰K.     

Estimating Childhood Multi-Media Lead Exposure: Expanded Exposure/Uptake/Biokinetic Model

Abstract

Despite significant reductions over the past decade, lead exposure continues to be a problem for millions of children in the US. Minimizing further exposure to lead from its numerous and diverse sources is a priority of various regulatory components of the Environmental Protection Agency (EPA), as well as other Federal and State agencies. A critical step in assessing lead risks is the estimation of childhood lead exposure in the future under alternative regulatory scenarios. Using a wide variety of year- and age-specific data on lead concentrations in multiple media, exposure and activity patterns, absorption rates and biokinetics, an integrated uptake/biokinetic model was developed by EPA in its review of the lead National Ambient Air Quality Standard. The model can estimate blood lead distributions among childhood populations over time. It was validated using measured environmental and blood lead data around a primary lead smelter, and has been successfully applied to other point sources. An enhanced version of the model has been developed to deal with a wider variety of exposure situations, especially those at high levels. A personal computer (PC) compatible version is available for assessments of Superfund sites, paint lead abatement strategies, drinking water contamination and other problems.     

Comparative performance evaluation of a flat detector and an image intensifier angiographic system both used for interventional cardiology procedures in adult and pediatric patients

PurposeTo compare two angiography systems of different image capture technology, one with flat detector (FD) and one with image intensifier (II), in terms of entrance surface air kerma (ESAK) rate, detector dose (DD) rate and image quality (IQ), in interventional cardiology procedures concerning both adult and pediatric patients.Materials and methodsIn order to determine ESAK and DD rates, a digital dosimeter and polymethylmethacrylate (PMMA) plates were used. For the evaluation of IQ, two contrast objects (the Leeds TOR 18FG and a 5 mm-thick Aluminum plate) were used and two figures of merit were defined in fluoroscopy and cine acquisition modes. Measurements of ESAK, DD rates and IQ were made for various fields of view, pulse and frame acquisition rates.ResultsFor the particular setup used in this study was noted that ESAK values in the II system were generally larger than the respective values in the FD system (on average 70% for fluoro mode, 5 times for cine mode). When halving the fluoroscopy pulse rate, reduction in ESAK was not proportional, in fluoroscopy mode. Image quality evaluations indicated that II performs better in terms of low contrast sensitivity (LCS) and signal-to-noise ratio (SNR) than the FD system which performs better regarding high contrast resolution (HCR). However, when considering image quality in relation to ESAK the FD system performs better than the II system (with the exception of low thicknesses and zooms for high pulse rates in the fluoroscopy mode).ConclusionsThe FD system, generally, provides a better image quality–dose relation than the II system although II unit provides better LCS and SNR. This means that with the right adjustments to both systems, FD unit is able to provide same image quality with lower dose. However, newer technology does not automatically imply better image quality and further investigation is necessary for deriving safe conclusions for units which utilize different capture technology.     

Genome sequence of the mercury-methylating and pleomorphic Desulfovibrio africanus Strain Walvis Bay

Desulfovibrio africanus strain Walvis Bay is an anaerobic sulfate-reducing bacterium capable of producing methylmercury (MeHg), a potent human neurotoxin. The mechanism of methylation by this and other organisms is unknown. We present the 4.2-Mb genome sequence to provide further insight into microbial mercury methylation and sulfate-reducing bacteria.     

Genome sequence of the mercury-methylating strain Desulfovibrio desulfuricans ND132

Desulfovibrio desulfuricans strain ND132 is an anaerobic sulfate-reducing bacterium (SRB) capable of producing methylmercury (MeHg), a potent human neurotoxin. The mechanism of methylation by this and other organisms is unknown. We present the 3.8-Mb genome sequence to provide further insight into microbial mercury methylation.     

The ability of haemolysins expressed by atypical enteropathogenic Escherichia coli to bind to extracellular matrix components

Typical and atypical enteropathogenic Escherichia coli (EPEC) are considered important bacterial causes of diarrhoea. Considering the repertoire of virulence genes, atypical EPEC (aEPEC) is a heterogeneous group, harbouring genes that are found in other diarrheagenic E. coli pathotypes, such as those encoding haemolysins. Haemolysins are cytolytic toxins that lyse host cells disrupting the function of the plasma membrane. In addition, these cytolysins mediate a connection to vascular tissue and/or blood components, such as plasma and cellular fibronectin. Therefore, we investigated the haemolytic activity of 72 aEPEC isolates and determined the correlation of this phenotype with the presence of genes encoding enterohaemolysins (Ehly) and cytolysin A (ClyA). In addition, the correlation between the expression of haemolysins and the ability of these secreted proteins to adhere to extracellular matrix (ECM) components was also assessed in this study. Our findings demonstrate that a subset of aEPEC presents haemolytic activity due to the expression of Ehlys and/or ClyA and that this activity is closely related to the ability of these isolates to bind to ECM components.