Removal of polycyclic aromatic hydrocarbons (PAHs) by different physicochemical methods: A mini-review

PAHs are persistent organic pollutants spread worldwide in our environment, including air, soil, and water. They are a large class of organic pollutants released mainly from anthropogenic sources, including automobiles and incomplete combustion of fossil fuels, power plants, and natural sources like forest fires and volcanic eruptions. In recent years, a variety of treatment methods have been used to degrade PAHs in the environment. This paper reviewed the most frequent physicochemical methods for PAHs removal, including solvent extraction/soil washing, oxidation, ozone, solidification, and supercritical fluid extraction. The findings showed that combining physicochemical methods can be an effective option for better cleanup of PAH from contaminated areas

Design, modeling, expression, and chemoselective PEGylation of a new nanosize cysteine analog of erythropoietin

Reza Ahangari Cohan1, Armin Madadkar-Sobhani2,3, Hossein Khanahmad1, Farzin Roohvand4, Mohammad Reza Aghasadeghi4, Mohammad Hossein Hedayati5, Zahra Barghi5, Mehdi Shafiee Ardestani4, Davoud Nouri Inanlou1, Dariush Norouzian11Research and Development Department, Production and Research Complex, Pasteur Institute of Iran, Tehran, Iran; 2Department of Bioinformatics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran; 3Department of Life Sciences, Barcelona Supercomputing Center, Barcelona, Spain; 4Hepatitis and AIDS Department, Pasteur Institute of Iran, Tehran, Iran; 5Quality Control Department, Production and Research Complex, Pasteur Institute of Iran, Tehran, IranBackground: Recombinant human erythropoietin (rhEPO) is considered to be one of the most pivotal pharmaceutical drugs in the market because of its clinical application in the treatment of anemia-associated disorders worldwide. However, like other therapeutic proteins, it does not have suitable pharmacokinetic properties for it to be administrated at least two to three times per week. Chemoselective cysteine PEGylation, employing molecular dynamics and graphics in in silico studies, can be considered to overcome such a problem.Methods: A special kind of EPO analog was elicited based on a literature review, homology modeling, molecular dynamic simulation, and factors affecting the PEGylation reaction. Then, cDNA of the selected analog was generated by site-directed mutagenesis and subsequently cloned into the expression vector. The construct was transfected to Chinese hamster ovary/dhfr- cells, and highly expressed clones were selected via methotrexate amplification. Ion-immobilized affinity and size exclusion (SE) chromatography techniques were used to purify the expressed analog. Thereafter, chemoselective PEGylation was performed and a nanosize PEGylated EPO was obtained through dialysis. The in vitro biologic assay and in vivo pharmacokinetic parameters were studied. Finally, E31C analog Fourier transform infrared, analytical SE-high-performance liquid chromatography, zeta potential, and size before and after PEGylation were characterized.Results: The findings indicate that a novel nanosize EPO31-PEG has a five-fold longer terminal half-life in rats with similar biologic activity compared with unmodified rhEPO in proliferation cell assay. The results also show that EPO31-PEG size and charge versus unmodified protein was increased in a nanospectrum, and this may be one criterion of EPO biologic potency enhancement.Discussion: This kind of novel engineered nanosize PEGylated EPO has remarkable advantages over rhEPO.Keywords: nanoPEGylated EPO, cysteine PEGylation, pharmacokinetic propert

DNA Repair Defects in Sarcomas

DNA repair pathway is considered to be one of the most important mechanisms that protect cells from intrinsic and extrinsic stresses. It has been established that DNA repair activity has a crucial role in the way that cancer cells respond to treatment. Sarcomas are a group of tumors with mesenchymal origin in which their association with DNA repair aberrations has been reported in numerous studies. Special attention has been focused on exploiting these alterations to improve the patient’s overall survival and overcome drug resistance in cancer. While there is a large degree of heterogeneity among different types of sarcomas, DNA repair alteration is found to be a common defect in the majority of patients. In this chapter, we will introduce and review some of the most important dysregulated components involved in the DNA repair system, and discuss their association with tumorigenesis, cancer aggressiveness, drug resistance, and overall prognosis in the patients with sarcomas

The randomized shortened dental arch study (RaSDA): design and protocol

<p>Abstract</p> <p>Background</p> <p>Various treatment options for the prosthetic treatment of jaws where all molars are lost are under discussion. Besides the placement of implants, two main treatment types can be distinguished: replacement of the missing molars with removable dental prostheses and non-replacement of the molars, i.e. preservation of the shortened dental arch. Evidence is lacking regarding the long-term outcome and the clinical performance of these approaches. High treatment costs and the long time required for the treatment impede respective clinical trials.</p> <p>Methods/design</p> <p>This 14-center randomized controlled investigator-initiated trial is ongoing. Last patient out will be in 2010. Patients over 35 years of age with all molars missing in one jaw and with at least both canines and one premolar left on each side were eligible. One group received a treatment with removable dental prostheses for molar replacement (treatment A). The other group received a treatment limited to the replacement of all missing anterior and premolar teeth using fixed bridges (treatment B). A pilot trial with 32 patients was carried out. Two hundred and fifteen patients were enrolled in the main trial where 109 patients were randomized for treatment A and 106 for treatment B. The primary outcome measure is further tooth loss during the 5-year follow-up. The secondary outcome measures encompassed clinical, technical and subjective variables. The study is funded by the Deutsche Forschungsgemeinschaft (German Research Foundation, DFG WA 831/2-1, 2-2, 2-3, 2-4, 2-5).</p> <p>Discussion</p> <p>The particular value of this trial is the adaptation of common design components to the very specific features of complex dental prosthetic treatments. The pilot trial proved to be indispensable because it led to a number of adjustments in the study protocol that considerably improved the practicability. The expected results are of high clinical relevance and will show the efficacy of two common treatment approaches in terms of oral health. An array of secondary outcome measures will deliver valuable supplementary information. If the results can be implemented in the clinical practice, the daily dental care should strongly profit thereof.</p> <p>Trial registration</p> <p>The trial is registered at ClinicalTrials.gov under ISRCTN68590603 (pilot trial) and ISRCTN97265367 (main trial).</p

Innovation Across Cultures: Connecting Leadership, Identification, and Creative Behavior in Organizations

Innovation is considered essential for today's organizations to survive and thrive. Researchers have also stressed the importance of leadership as a driver of followers' innovative work behavior (FIB). Yet, despite a large amount of research, three areas remain understudied: (a) The relative importance of different forms of leadership for FIB; (b) the mechanisms through which leadership impacts FIB; and (c) the degree to which relationships between leadership and FIB are generalizable across cultures. To address these lacunae, we propose an integrated model connecting four types of positive leadership behaviors, two types of identification (as mediating variables), and FIB. We tested our model in a global data set comprising responses of N = 7,225 participants from 23 countries, grouped into nine cultural clusters. Our results indicate that perceived LMX quality was the strongest relative predictor of FIB. Furthermore, the relationships between both perceived LMX quality and identity leadership with FIB were mediated by social identification. The indirect effect of LMX on FIB via social identification was stable across clusters, whereas the indirect effects of the other forms of leadership on FIB via social identification were stronger in countries high versus low on collectivism. Power distance did not influence the relations

Systems Biology Approach Identifies Prognostic Signatures of Poor Overall Survival and Guides the Prioritization of Novel BET-CHK1 Combination Therapy for Osteosarcoma

Osteosarcoma (OS) patients exhibit poor overall survival, partly due to copy number variations (CNVs) resulting in dysregulated gene expression and therapeutic resistance. To identify actionable prognostic signatures of poor overall survival, we employed a systems biology approach using public databases to integrate CNVs, gene expression, and survival outcomes in pediatric, adolescent, and young adult OS patients. Chromosome 8 was a hotspot for poor prognostic signatures. The MYC-RAD21 copy number gain (8q24) correlated with increased gene expression and poor overall survival in 90% of the patients (n = 85). MYC and RAD21 play a role in replication-stress, which is a therapeutically actionable network. We prioritized replication-stress regulators, bromodomain and extra-terminal proteins (BETs), and CHK1, in order to test the hypothesis that the inhibition of BET + CHK1 in MYC-RAD21+ pediatric OS models would be efficacious and safe. We demonstrate that MYC-RAD21+ pediatric OS cell lines were sensitive to the inhibition of BET (BETi) and CHK1 (CHK1i) at clinically achievable concentrations. While the potentiation of CHK1i-mediated effects by BETi was BET-BRD4-dependent, MYC expression was BET-BRD4-independent. In MYC-RAD21+ pediatric OS xenografts, BETi + CHK1i significantly decreased tumor growth, increased survival, and was well tolerated. Therefore, targeting replication stress is a promising strategy to pursue as a therapeutic option for this devastating disease