Safety Study of Intravenously Administered Human Cord Blood Stem Cells in the Treatment of Symptoms Related to Chronic Inflammation

Numerous investigations suggest that Mesenchymal Stem Cells (MSCs) in general represent a valuable tool for therapy of symptoms related to chronic inflammatory diseases. Blue Horizon Stem Cell Therapy Program is a leading provider of adult and children’s stem cell therapies. Uniquely we have safely and efficiently treated more than 600 patients with documenting each procedure. The purpose of our study is primarily to monitor the immune response in order to validate the safety of intravenous infusion of human umbilical cord blood derived MSCs (UC-MSCs), and secondly, to evaluate effects on biomarkers associated with chronic inflammation. Nine patients were treated for conditions associated with chronic inflammation and for the purpose of antiaging. They have been given one intravenous infusion of UCMSCs. Our study of blood test markers of 9 patients with chronic inflammation before and within three months after MSCs treatment demonstrates that there is no significant changes and MSCs treatment was safe for the patients. Analysis of different indicators of chronic inflammation and aging included in initial, 24-hours, two weeks and three months protocols showed that stem cell treatment was safe for the patients; there were no adverse reactions. Moreover data from follow up protocols demonstrates significant improvement in energy level, hair, nails growth and skin conditions. Intravenously administered UC-MSCs were safe and effective in the improvement of symptoms related to chronic inflammation. Further close monitoring and inclusion of more patients are necessary to fully characterize the advantages of UC-MSCs application in treatment of symptoms related to chronic inflammation.

VHL, PBRM1 and SETD2 Genes in Kidney Cancer: A Molecular Investigation

Kidney cancer is the most lethal urological cancer accounting for 3% of adult malignancies. VHL, a tumor-suppressor gene, is best known to be associated with renal cell carcinoma (RCC). The VHL functions as negative regulator of hypoxia inducible factors. Recent sequencing efforts have identified several novel frequent mutations of histone modifying and chromatin remodeling genes in ccRCC (clear cell RCC) including PBRM1 and SETD2. The PBRM1 gene encodes the BAF180 protein, which involved in transcriptional activation and repression of selected genes. SETD2 encodes a histone methyltransferase, which may play a role in suppressing tumor development. In this study, RNAs of 30 paired tumor and normal samples that were grouped according to the types of kidney cancer and clinical characteristics of patients, including gender and average age were examined by RT-PCR, SSCP and sequencing techniques. VHL, PBRM1 and SETD2 expressions were relatively down-regulated. However, statistically no significance was found (Wilcoxon signed rank test, p>0.05). Interestingly, no mutation was observed on the contrary of previous studies. Understanding the molecular mechanisms involved in the pathogenesis of RCC has aided the development of molecular-targeted drugs for kidney cancer. Further analysis is required to identify the responsible genes rather than VHL, PBRM1 and SETD2 in kidney cancer.

Yawning and Cortisol as a Potential Biomarker for Early Detection of Multiple Sclerosis

Cortisol is essential to the regulation of the immune system and yawning is a pathological symptom of multiple sclerosis (MS). Electromyography activity (EMG) in the jaw muscles typically rises when the muscles are moved and with yawning is highly correlated with cortisol levels in healthy people. Saliva samples from 59 participants were collected at the start and after yawning, or at the end of the presentation of yawning-provoking stimuli, in the absence of a yawn, together with EMG data and questionnaire data: Hospital Anxiety and Depression Scale, Yawning Susceptibility Scale, General Health Questionnaire, demographic, health details. Exclusion criteria: chronic fatigue, diabetes, fibromyalgia, heart condition, high blood pressure, hormone replacement therapy, multiple sclerosis, stroke. Significant differences were found between the saliva cortisol samples for the yawners, t (23) = -4.263, p = 0.000, as compared with the non-yawners between rest and post-stimuli, which was nonsignificant. Significant evidence was found to support the Thompson Cortisol Hypothesis suggesting that rises in cortisol levels are associated with yawning. Further research is exploring the use of cortisol as an early diagnostic tool for MS. Ethics approval granted and professional code of conduct, confidentiality, and safety issues are approved therein.

Evaluation of Azo Dye Toxicity Using Some Haematological and Histopathological Alterations in Fish Catla catla

The textile industry plays a major role in the economy of India and on the other side of the coin it is the major source for water pollution. As azo dyes is the largest dye class they are extensively used in many fields such as textile industry, leather tanning industry, paper production, food, color photography, pharmaceuticals and medicine, cosmetic, hair colorings, wood staining, agricultural, biological and chemical research etc. In addition to these, they can have acute and/or chronic effects on organisms depending on their concentration and length of exposure when they discharged as effluent in the environment. The aim of this study was to assess the genotoxic and histotoxic potentials of environmentally relevant concentrations of C. I. Reactive Red 120 (RR 120) on Catla catla, important edible freshwater fingerlings. For this, healthy Catla catla fingerlings were procured from the Government Fish Farm and acclimatized in 100 L capacity and continuously aerated glass aquarium in laboratory for 15 days. According to APHA some physic-chemical parameters were measured and maintained such as temperature, pH, dissolve oxygen, alkalinity, total hardness. Water along with excreta had been changed every 24 hrs. All fingerlings were fed artificial food palates once a day @ body weight. After 15 days fingerlings were grouped in 5 (10 in each) and exposed to various concentrations of RR 120 (Control, 10, 20, 30 and 40 mg.l-1) and samples (peripheral blood and gills, kidney) were collected and analyzed at 96 hrs. All results were compared with the control. Micronuclei (MN), nuclear buds (NB), fragmented-apoptotic (FA) and bi-nucleated (BN) cells in blood smears and in tissues (gills and kidney cells) were observed. Prominent histopathological alterations were noticed in gills such as aneurism, hyperplasia, degenerated central axis, lifting of gill epithelium, curved secondary gill lamellae etc. Similarly kidney showed some detrimental changes like shrunken glomeruli with increased periglomerular space, degenerated renal tubules etc. Both haematological and histopathological changes clearly reveal the toxic potential of RR 120. This work concludes that water pollution assessment can be done by these two biomarkers which provide baseline to the further chromosomal or molecular work.

Depositional Environment and Source Potential of Devonian Source Rock, Ghadames Basin, Southern Tunisia

Depositional environment and source potential of the different organic-rich levels of Devonian age (up to 990m thick) from the onshore EC-1 well (Southern Tunisia) were investigated based on the analysis of more than 130 cutting samples by different geochemical techniques (Rock-Eval pyrolysis, GC-MS). The obtained results including Rock Eval Pyrolysis data and biomarker distribution (terpanes, steranes and aromatics) have been used to describe the depositional environment and to assess the thermal maturity of the Devonian organic matter. These results show that the Emsian deposits exhibit poor to fair TOC contents. The associated organic matter is composed of mixed kerogen (type II/III), as indicated by the predominance of C29 steranes over C27 and C28 homologous, that was deposited in a slightly reduced environment favoring organic matter preservation. Thermal maturity assessed from Tmax, TNR and MPI-1 values shows a mature stage of organic matter. The Middle Devonian (Eifelian) shales are rich in type II organic matter that was deposited in an open marine depositional environment. The TOC values are high and vary between 2 and 7% indicating good to excellent source rock. The relatively high HI values (reaching 547 mg HC/g TOC) and the low values of t19/t23 tricyclic terpane ratio (< 0.2) confirm the marine origin of the organic matter (type II). During the Upper Devonian, the organic matter was deposited under variable redox conditions, oxic to suboxic which is clearly indicated by the low C35/C34 hopanes ratio, immature to marginally mature with the vitrinite reflectance ranging from 0.5 to 0.7 Ro and Tmax value of 426°C-436 °C and the TOC values range between 0.8% to 4%.

Geochemical Study of Natural Bitumen, Condensate and Gas Seeps from Sousse Area, Central Tunisia

Natural hydrocarbon seepage has helped petroleum exploration as a direct indicator of gas and/or oil subsurface accumulations. Surface macro-seeps are generally an indication of a fault in an active Petroleum Seepage System belonging to a Total Petroleum System. This paper describes a case study in which multiple analytical techniques were used to identify and characterize trace petroleum-related hydrocarbons and other volatile organic compounds in groundwater samples collected from Sousse aquifer (Central Tunisia). The analytical techniques used for analyses of water samples included gas chromatography-mass spectrometry (GCMS), capillary GC with flame-ionization detection, Compound Specific Isotope Analysis, Rock Eval Pyrolysis. The objective of the study was to confirm the presence of gasoline and other petroleum products or other volatile organic pollutants in those samples in order to assess the respective implication of each of the potentially responsible parties to the contamination of the aquifer. In addition, the degree of contamination at different depths in the aquifer was also of interest. The oil and gas seeps have been investigated using biomarker and stable carbon isotope analyses to perform oil-oil and oil-source rock correlations. The seepage gases are characterized by high CH4 content, very low δ13CCH4 values (-71,9 ‰) and high C1/C1–5 ratios (0.95–1.0), light deuterium–hydrogen isotope ratios (- 198 ‰) and light δ13CC2 and δ13CCO2 values (-23,8‰ and-23,8‰ respectively) indicating a thermogenic origin with the contribution of the biogenic gas. An organic geochemistry study was carried out on the more ten oil seep samples. This study includes light hydrocarbon and biomarkers analyses (hopanes, steranes, n-alkanes, acyclic isoprenoids, and aromatic steroids) using GC and GC-MS. The studied samples show at least two distinct families, suggesting two different types of crude oil origins: the first oil seeps appears to be highly mature, showing evidence of chemical and/or biological degradation and was derived from a clay-rich source rock deposited in suboxic conditions. It has been sourced mainly by the lower Fahdene (Albian) source rocks. The second oil seeps was derived from a carbonate-rich source rock deposited in anoxic conditions, well correlated with the Bahloul (Cenomanian-Turonian) source rock.

Hepatotoxicity Induced by Arsenic Trioxide in Adult Mice and Their Progeny

In this investigation, we have evaluated the effects of arsenic trioxide on hepatic function in pregnant and lactating Swiss albino mice and their suckling pups. Experiments were carried out on female mice given 175 ppm As2O3 in their drinking water from the 14th day of pregnancy until day 14 after delivery. Our results showed a significant decrease in plasma levels of total protein and albumin, cholesterol and triglyceride in As2O3 treated mice and their pups. The hyperbilirubinemia and the increased plasma total alkaline phosphatase activity suggested the presence of cholestasis. Transaminase activities as well as lactate deshydrogenase activity in plasma, known as biomarkers of hepatocellular injury, were elevated indicating hepatic cells’ damage after treatment with As2O3. Exposure to arsenic led to an increase of liver thiobarbituric acid reactive substances level along with a concomitant decrease in the activities of superoxide dismutase, catalase and glutathione peroxidase and in glutathione.

Relations of Progression in Cognitive Decline with Initial EEG Resting-State Functional Network in Mild Cognitive Impairment

This study aimed at investigating whether the functional brain networks constructed using the initial EEG (obtained when patients first visited hospital) can be correlated with the progression of cognitive decline calculated as the changes of mini-mental state examination (MMSE) scores between the latest and initial examinations. We integrated the time–frequency cross mutual information (TFCMI) method to estimate the EEG functional connectivity between cortical regions, and the network analysis based on graph theory to investigate the organization of functional networks in aMCI. Our finding suggested that higher integrated functional network with sufficient connection strengths, dense connection between local regions, and high network efficiency in processing information at the initial stage may result in a better prognosis of the subsequent cognitive functions for aMCI. In conclusion, the functional connectivity can be a useful biomarker to assist in prediction of cognitive declines in aMCI.

Using Artificial Neural Networks for Optical Imaging of Fluorescent Biomarkers

The article presents the results of the application of artificial neural networks to separate the fluorescent contribution of nanodiamonds used as biomarkers, adsorbents and carriers of drugs in biomedicine, from a fluorescent background of own biological fluorophores. The principal possibility of solving this problem is shown. Use of neural network architecture let to detect fluorescence of nanodiamonds against the background autofluorescence of egg white with high accuracy - better than 3 ug/ml.

Vibratinal Spectroscopic Identification of Beta-Carotene in Usnic Acid and PAHs as a Potential Martian Analogue

Raman spectroscopy is currently a part of the instrumentation suite of the ESA ExoMars mission for the remote detection of life signatures in the Martian surface and subsurface. Terrestrial analogues of Martian sites have been identified and the biogeological modifications incurred as a result of extremophilic activity have been studied. Analytical instrumentation protocols for the unequivocal detection of biomarkers in suitable geological matrices are critical for future unmanned explorations, including the forthcoming ESA ExoMars mission to search for life on Mars scheduled for 2018 and Raman spectroscopy is currently a part of the Pasteur instrumentation suite of this mission. Here, Raman spectroscopy using 785nm excitation was evaluated for determining various concentrations of beta-carotene in admixture with polyaromatic hydrocarbons and usnic acid have been investigated by Raman microspectrometry to determine the lowest levels detectable in simulation of their potential identification remotely in geobiological conditions in Martian scenarios. Information from this study will be important for the development of a miniaturized Raman instrument for targetting Martian sites where the biosignatures of relict or extant life could remain in the geological record.

Application of EEG Wavelet Power to Prediction of Antidepressant Treatment Response

In clinical practice, the selection of an antidepressant often degrades to lengthy trial-and-error. In this work we employ a normalized wavelet power of alpha waves as a biomarker of antidepressant treatment response. This novel EEG metric takes into account both non-stationarity and intersubject variability of alpha waves. We recorded resting, 19-channel EEG (closed eyes) in 22 inpatients suffering from unipolar (UD, n=10) or bipolar (BD, n=12) depression. The EEG measurement was done at the end of the short washout period which followed previously unsuccessful pharmacotherapy. The normalized alpha wavelet power of 11 responders was markedly different than that of 11 nonresponders at several, mostly temporoparietal sites. Using the prediction of treatment response based on the normalized alpha wavelet power, we achieved 81.8% sensitivity and 81.8% specificity for channel T4.

Quantitative Analysis of Carcinoembryonic Antigen (CEA) Using Micromechanical Piezoresistive Cantilever

In this work, we have used arrays of micromechanical piezoresistive cantilever with different geometries to detect carcinoembryonic antigen (CEA), which is known as an important biomarker associated with various cancers such as colorectal, lung, breast, pancreatic, and bladder cancer. The sensing principle is based on the surface stress changes induced by antigen–antibody interaction on the microcantilevers surfaces. Different concentrations of CEA in a human serum albumin (HSA) solution were detected as a function of deflection of the beams. According to the experiments, it was revealed that microcantilevers have surface stress sensitivities in the order of 8 (mJ/m). This matter allows them to detect CEA concentrations as low as 3 ng/mL or 18 pM. This indicates the fact that the self-sensing microcantilevers approach is beneficial for pathological tests.

Mucus Secretion Responses to Various Sublethal Copper (II) Concentrations in the Mussel Perna perna

The purpose of this study was to evaluate the use of mucus production as a biomarker. This was done by exposing the mussel Perna perna to various sublethal concentrations of Cu. Mussels are effective as a bioindicator species as they accumulate Cu in their tissues. Differences in mucus production rates were evaluated at different Cu concentrations. The findings of this study indicate that increasing Cu concentrations had a significant effect on the mucus production rates over a 24 hour exposure. There were also significant differences between the mucus production rates at different Cu concentrations (p < 0.05). Thus, mucus is an essential detoxification mechanism.

Diagnostic Evaluation of Urinary Angiogenin (ANG) and Clusterin (CLU) as Biomarker for Bladder Cancer

Bladder carcinoma is an important worldwide health problem. Both cystoscopy and urine cytology used in detecting bladder cancer suffer from drawbacks where cystoscopy is an invasive method and urine cytology shows low sensitivity in low grade tumors. This study validates easier and less time-consuming techniques to evaluate the value of combined use of angiogenin and clusterin in comparison and combination with voided urine cytology in the detection of bladder cancer patients. This study includes malignant (bladder cancer patients, n= 50), benign (n=20) and healthy (n=20) groups. The studied groups were subjected to cystoscopic examination, detection of bilharzial antibodies, urine cytology, and estimation of urinary angiogenin and clusterin by ELISA. The overall sensitivity and specificity were 66% and 75% for angiogenin, 70% and 82.5% for clusterin and 46% and 80% for voided urine cytology. Combined sensitivity of angiogenin and clusterin with urine cytology increased from 82 to 88%. 

The Effects of Four Organic Cropping Sequences on Soil Phosphorous Cycling and Arbuscular Mycorrhizal Fungi

Organic farmers across Saskatchewan face soil phosphorus (P) shortages. Due to the restriction on inputs in organic systems, farmers rely on crop rotation and naturally-occurring arbuscular mycorrhizal fungi (AMF) for plant P supply. Crop rotation is important for disease, pest, and weed management. Crops that are not colonized by AMF (non-mycorrhizal) can decrease colonization of a following crop. An experiment was performed to quantify soil P cycling in four cropping sequences under organic management and determine if mustard (non-mycorrhizal) was delaying the colonization of subsequent wheat. Soils from the four cropping sequences were measured for inorganic soil P (Pi), AMF spore density (SD), phospholipid fatty acid analysis (PLFA, for AMF biomarker counts), and alkaline phosphatase activity (ALPase, related to AMF metabolic activity). Plants were measured for AMF colonization and P content and uptake of above-ground biomass. A lack of difference in AMF activity indicated that mustard was not depressing colonization. Instead, AMF colonization was largely determined by crop type and crop rotation.

Cereals' Products with Red Grape and Walnut Extracts as Functional Foods for Prevention of Kidney Dysfunction

In the present research, two nutraceuticals made from red grape and walnut that showed previously to improve kidney dysfunction were incorporated separately into functional foods' bread made from barley and rice bran. The functional foods were evaluated in rats in which chronic renal failure was induced through feeding diet rich in adenine and phosphate (APD). The evaluation based on assessing kidney function, oxidative stress, inflammatory biomarkers and body weight gain. Results showed induction of chronic kidney failure reflected in significant increase in plasma urea, creatinine, malondialdehyde, tumor necrosis factor- α and low density lipoprotein cholesterol along with significant reduction of plasma albumin, and total antioxidant and creatinine clearance and body weight gain on feeding APD compared to control healthy group. Feeding the functional foods produced amelioration in the different biochemical parameters and body weight gain indicating improvement in kidney function.

Changes to Oxidative Stress Levels Following Exposure to Formaldehyde in Lymphocytes

Formaldehyde is the illegal chemical substance used for food preservation in fish and vegetable. It can promote carcinogenesis. Superoxide dismutases are the important antioxidative enzymes that catalyze the dismutation of superoxide anion into oxygen and hydrogen peroxide. The resultant level of oxidative stress in formaldehyde-treated lymphocytes was investigated. The formaldehyde concentrations of 0, 20, 40, 60, 80 and 120μmol/L were treated in human lymphocytes for 12 hours. After 12 treated hours, the superoxide dismutase activity change was measured in formaldehyde-treated lymphocytes. The results showed that the formaldehyde concentrations of 60, 80 and 120μmol/L significantly decreased superoxide dismutase activities in lymphocytes (P < 0.05). The change of superoxide dismutase activity in formaldehyde-treated lymphocytes may be the biomarker for detect cellular injury, such as damage to DNA, due to formaldehyde exposure.

Pesticides Use in Rural Settings in Romania

The environment pollution with pesticides and heavy metals is a recognized problem nowadays, with extension to the global scale the tendency of amplification. Even with all the progress in the environmental field, both in the emphasize of the effect of the pollutants upon health, the linked studies environment-health are insufficient, not only in Romania but all over the world also. We aim to describe the particular situation in Romania regarding the uncontrolled use of pesticides, to identify and evaluate the risk zones for health and the environment in Romania, with the final goal of designing adequate programs for reduction and control of the risk sources. An exploratory study was conducted to determine the magnitude of the pesticide use problem in a population living in Saliste, a rural setting in Transylvania, Romania. The significant stakeholders in Saliste region were interviewed and a sample from the population living in Saliste area was selected to fill in a designed questionnaire. All the selected participants declared that they used pesticides in their activities for more than one purpose. They declared they annually applied pesticides for a period of time between 11 and 30 years, from 5 to 9 days per year on average, mainly on crops situated at some distance from the houses but high risk behavior was identified as the volunteers declared the use of pesticides in the backyard gardens, near their homes, where children were playing. The pesticide applicators did not have the necessary knowledge about safety and exposure. The health data must be correlated with exposure biomarkers in attempt to identify the possible health effects of the pesticides exposure. Future plans include educational campaigns to raise the awareness of the population on the danger of uncontrolled use of pesticides.

Protein Profiling in Alanine Aminotransferase Induced Patient cohort using Acetaminophen

Sensitive and predictive DILI (Drug Induced Liver Injury) biomarkers are needed in drug R&D to improve early detection of hepatotoxicity. The discovery of DILI biomarkers that demonstrate the predictive power to identify individuals at risk to DILI would represent a major advance in the development of personalized healthcare approaches. In this healthy volunteer acetaminophen study (4g/day for 7 days, with 3 monitored nontreatment days before and 4 after), 450 serum samples from 32 subjects were analyzed using protein profiling by antibody suspension bead arrays. Multiparallel protein profiles were generated using a DILI target protein array with 300 antibodies, where the antibodies were selected based on previous literature findings of putative DILI biomarkers and a screening process using pre dose samples from the same cohort. Of the 32 subjects, 16 were found to develop an elevated ALT value (2Xbaseline, responders). Using the plasma profiling approach together with multivariate statistical analysis some novel findings linked to lipid metabolism were found and more important, endogenous protein profiles in baseline samples (prior to treatment) with predictive power for ALT elevations were identified.

An Immunosensor for Bladder Cancer Screening

Nuclear matrix protein 22 (NMP22) is a FDA approved biomarker for bladder cancer. The objective of this study is to develop a simple NMP22 immumosensor (NMP22-IMS) for accurate measurement of NMP22. The NMP22-IMS was constructed with NMP22 antibody immobilized on screen-printed carbon electrodes. The construction procedures and antibody immobilization are simple. Results showed that the NMP22-IMS has an excellent (r2³0.95) response range (20 – 100 ng/mL). In conclusion, a simple and reliable NMP22-IMS was developed, capable of precisely determining urine NMP22 level.