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Mostafa Yusefi,1,2 Kamyar Shameli,3 Hossein Jahangirian,4 Sin-Yeang Teow,5 Leili Afsah-Hejri,6 Siti Nur Amalina Mohamad Sukri,1 Kamil Kuča1,7,8 1Malaysia-Japan International Institute of Technology, Universiti Teknologi Malaysia, Kuala Lumpur, Malaysia; 2Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur, 50603, Malaysia; 3Institute of Virology, School of Medicine, Technical University of Munich, Munich, 81675, Germany; 4CaroGen Corporation, Farmington, CT, USA; 5Department of Biology, College of Science, Mathematics and Technology, Wenzhou-Kean University, Wenzhou, Zhejiang Province, 325060, People’s Republic of China; 6Department of Food Safety and Quality, School of Business, Science and Technology, Lakeland University Plymouth, WI 53073, USA; 7Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic; 8Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech RepublicCorrespondence: Kamyar Shameli; Hossein Jahangirian, Tel +4917646555701 ; +16178608429, Email kamyarshameli@gmail.com; kamran.jahangirian@gmail.comAbstract: Chemotherapy is the most prominent route in cancer therapy for prolonging the lifespan of cancer patients. However, its non-target specificity and the resulting off-target cytotoxicities have been reported. Recent in vitro and in vivo studies using magnetic nanocomposites (MNCs) for magnetothermal chemotherapy may potentially improve the therapeutic outcome by increasing the target selectivity. In this review, magnetic hyperthermia therapy and magnetic targeting using drug-loaded MNCs are revisited, focusing on magnetism, the fabrication and structures of magnetic nanoparticles, surface modifications, biocompatible coating, shape, size, and other important physicochemical properties of MNCs, along with the parameters of the hyperthermia therapy and external magnetic field. Due to the limited drug-loading capacity and low biocompatibility, the use of magnetic nanoparticles (MNPs) as drug delivery system has lost traction. In contrast, MNCs show higher biocompatibility, multifunctional physicochemical properties, high drug encapsulation, and multi-stages of controlled release for localized synergistic chemo-thermotherapy. Further, combining various forms of magnetic cores and pH-sensitive coating agents can generate a more robust pH, magneto, and thermo-responsive drug delivery system. Thus, MNCs are ideal candidate as smart and remotely guided drug delivery system due to a) their magneto effects and guide-ability by the external magnetic fields, b) on-demand drug release performance, and c) thermo-chemosensitization under an applied alternating magnetic field where the tumor is selectively incinerated without harming surrounding non-tumor tissues. Given the important effects of synthesis methods, surface modifications, and coating of MNCs on their anticancer properties, we reviewed the most recent studies on magnetic hyperthermia, targeted drug delivery systems in cancer therapy, and magnetothermal chemotherapy to provide insights on the current development of MNC-based anticancer nanocarrier.Keywords: magnetic nanoparticles, polymer-based magnetic nanocomposites, hyperthermia, external magnetic field, targeted cancer treatments

Mostafa Yusefi,1 Kamyar Shameli,1 Ong Su Yee,1 Sin-Yeang Teow,2 Ziba Hedayatnasab,3,4 Hossein Jahangirian,5 Thomas J Webster,5 Kamil Kuča1,6 1Department of Chemical and Environmental Engineering, Malaysia-Japan International Institute of Technology, Universiti Teknologi Malaysia, Kuala Lumpur, 54100, Malaysia; 2Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Petaling Jaya, Selangor Darul Ehsan, 47500, Malaysia; 3Department of Chemical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur, 50603, Malaysia; 4Department of Chemical and Petroleum Engineering, Sharif University of Technology, Tehran, 11155-9465, Iran; 5Department of Chemical Engineering, College of Engineering, Northeastern University, Boston, MA, 02115, USA; 6Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech RepublicCorrespondence: Kamyar Shameli; Kamil Kuča Email kamyarshameli@gmail.com; kamil.kuca@uhk.czIntroduction: Fe3O4 nanoparticles (Fe3O4 NPs) with multiple functionalities are intriguing candidates for various biomedical applications.Materials and Methods: This study introduced a simple and green synthesis of Fe3O4 NPs using a low-cost stabilizer of plant waste extract rich in polyphenols content with a well-known antioxidant property as well as anticancer ability to eliminate colon cancer cells. Herein, Fe3O4 NPs were fabricated via a facile co-precipitation method using the crude extract of Garcinia mangostana fruit peel as a green stabilizer at different weight percentages (1, 2, 5, and 10 wt.%). The samples were analyzed for magnetic hyperthermia and then in vitro cytotoxicity assay was performed.Results: The XRD planes of the samples were corresponding to the standard magnetite Fe3O4 with high crystallinity. From TEM analysis, the green synthesized NPs were spherical with an average size of 13.42± 1.58 nm and displayed diffraction rings of the Fe3O4 phase, which was in good agreement with the obtained XRD results. FESEM images showed that the extract covered the surface of the Fe3O4 NPs well. The magnetization values for the magnetite samples were ranging from 49.80 emu/g to 69.42 emu/g. FTIR analysis verified the functional groups of the extract compounds and their interactions with the NPs. Based on DLS results, the hydrodynamic sizes of the Fe3O4 nanofluids were below 177 nm. Furthermore, the nanofluids indicated the zeta potential values up to − 34.92± 1.26 mV and remained stable during four weeks of storage, showing that the extract favorably improved the colloidal stability of the Fe3O4 NPs. In the hyperthermia experiment, the magnetic nanofluids showed the acceptable specific absorption rate (SAR) values and thermosensitive performances under exposure of various alternating magnetic fields. From results of in vitro cytotoxicity assay, the killing effects of the synthesized samples against HCT116 colon cancer cells were mostly higher compared to those against CCD112 colon normal cells. Remarkably, the Fe3O4 NPs containing 10 wt.% of the extract showed a lower IC50 value (99.80 μg/mL) in HCT116 colon cancer cell line than in CCD112 colon normal cell line (140.80 μg/mL).Discussion: This research, therefore, introduced a new stabilizer of Garcinia mangostana fruit peel extract for the biosynthesis of Fe3O4 NPs with desirable physiochemical properties for potential magnetic hyperthermia and colon cancer treatment.Keywords: green synthesis, Fe3O4 nanoparticles, Garcinia mangostana, magnetic hyperthermia, cytotoxicity assay

Petra Maresova,1 Michal Novotny,2,3 Blanka Klímová,4 Kamil Kuča3,51Department of Economics, Faculty of Informatics and Management, 2Department of Chemistry, Faculty of Science, University of Hradec Králové, 3Biomedical Research Center, University Hospital Hradec Králové, 4Department of Applied Linguistics, Faculty of Informatics and Management, 5Faculty of Informatics and Management, University of Hradec Králové, Hradec Králové, Czech Republic Background: Narcolepsy is a lifelong, rare neurological sleep disorder characterized by chronic, excessive attacks of daytime sleepiness. This disease is often extremely incapacitating, interfering with every aspect of life, in work and social settings.Objective: The purpose of this study is to specify the treatment costs of patients in the Central Europe (Czech Republic), while the attention is mainly paid to the drugs that were fully or partially covered by public health insurance. Furthermore, concomitant therapy is also evaluated, since it incurs a certain financial burden for patients and their family members. On the basis of the calculated costs, impact on the public budget is evaluated.Patients and methods: This study monitors the direct costs of the drugs for 13 patients, who represent ~1.3% of the total number of diagnosed patients in the Czech Republic, and evaluates the costs associated with their treatment during the period from January 9, 2011 to April 23, 2013.Results: Most of the treatment costs (~80%) were covered by publicly available sources. This finding is also true for the concomitant therapy of comorbidities. Additional payments for the drugs constitute about 20% of the total costs. Keywords: cataplexy, cost, narcolepsy, orphan drug, rare disease, sodium oxybate

Marek Bužga,1 Petra Maresova,2 Adela Seidlerová,1 Pavel Zonča,1 Pavol Holéczy,1 Kamil Kuča2,3 1Research Obesity Center, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic; 2Faculty of Informatics and Management, University of Hradec Kralove, Hradec Kralove, Czech Republic; 3Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic Abstract: The constantly growing incidence of obesity represents a risk of health complications for individuals, and is a growing economic burden for health care systems and society. The aim of this study was to evaluate the efficacy of bariatric surgery, specifically laparoscopic greater curve plication, laparoscopic sleeve gastrectomy, and Roux-en-Y gastric bypass, in patients with type 2 diabetes mellitus. The effect of bariatric surgery on the changes in blood pressure before, and 12 months after, surgery and in pharmacotherapy in the 12 months after surgery was analyzed. For achieving this purpose, 74 patients from the Obesity and Surgery Department of Vitkovice Hospital in Ostrava in the Czech Republic, were monitored. They were operated in 2011 and 2012. The Bonferroni method was used to test hypotheses about the impact of surgery on blood pressure and pharmacotherapy. One year after the surgery, systolic and diastolic blood pressure values decreased, both with no statistically significant difference between surgery types. Improvement was observed in 68% of cases, with 25% of patients discontinuing pharmacotherapy entirely. Keywords: type 2 diabetes mellitus, bariatric surgery, blood pressure, pharmacotherapy

With continued climate changes, soil drought stress has become the main limiting factor for crop growth in arid and semi‐arid regions. A typical characteristic of drought stress is the burst of reactive oxygen species (ROS), causing oxidative damage. Plant‐associated microbes, such as arbuscular mycorrhizal fungi (AMF), can regulate physiological and molecular responses to tolerate drought stress, and they have a strong ability to cope with drought‐induced oxidative damage via enhanced antioxidant defence systems. AMF produce a limited oxidative burst in the arbuscule‐containing root cortical cells. Similar to plants, AMF modulate a fungal network in enzymatic (e.g. GmarCuZnSOD and GintSOD1) and non‐enzymatic (e.g. GintMT1, GinPDX1 and GintGRX1) antioxidant defence systems to scavenge ROS. Plants also respond to mycorrhization to enhance stress tolerance via metabolites and the induction of genes. The present review provides an overview of the network of plant − arbuscular mycorrhizal fungus dialogue in mitigating oxidative stress. Future studies should involve identifying genes and transcription factors from both AMF and host plants in response to drought stress, and utilize transcriptomics, proteomics and metabolomics to clarify a clear dialogue mechanism between plants and AMF in mitigating oxidative burst. [ABSTRACT FROM AUTHOR]

Colorimetric dipsticks based on recognition capability of acetylcholinesterase enzyme (AChE) are a suitable tool for a fast and sensitive detection of nerve agents and some pesticides. In this review, the detectors are digestedly presented and basic biochemical methods appropriate for the colorimetric estimation of AChE enzymatic activity are included as well. Moreover, the available matrices suitable for construction of dipsticks and chemical, as well as physical protocols for AChE immobilization on detectors surface are introduced. [ABSTRACT FROM AUTHOR]

Oximes are cholinesterase reactivators used in organophosphorus poisoning. Clinical experience with pralidoxime (PRX) and other oximes is disappointing and their routine use has been questioned. In addition it is known that not all oximes are equally effective against all existing organophosphorus compounds. There is a demand for broad-spectrum reactivators with a higher efficacy than PRX. Based on our previous in vitro work the protection conferred by the various new oximes against inhibition by paraoxon as quantified by the IC50 shift (n m increase in the IC50 of the inhibitor per µ m oxime present) is: 0.3 (PRX), 0.4 (methoxime; MMC-4), 1 (K-33), 1.2 (BI-6), 1.5 (K-48) and 3.7 (K-27). The purpose of the study was to quantify in vivo the extent of oxime-conferred protection, using paraoxon (POX) as a cholinesterase inhibitor and to test whether in vitro efficacy translates to protection from mortality. There were seven groups of six rats in each cycle of the experiment. Group 1 (G1) received 1 µmol POX (≈ LD75), the other groups (G2-G7) received 1 µmol POX + of one the six reactivators. The animals were monitored for 48 h and the time of mortality was recorded. The procedure was repeated five times (cycles). All substances were applied i.p. The experiments were repeated using 2, 3, 5 and 10 µmol POX. Mortality data were compared and hazards ratios (relative risks) ranked using the Cox proportional hazards model using POX dose and group (reactivator) as time-independent covariables. The relative risk of death estimated by Cox analysis (95% CI) in oxime treated animals when compared with untreated animals, adjusted for POX dose (high/low) was K-27: 0.26 (0.19-0.35); K-48: 0.34 (0.25-0.45); methoxime: 0.38 (0.29-0.50); BI-6: 0.53 (0.41-0.69); PRX: 0.70 (0.54-0.91); K-33: 0.82 (0.63-1.07). It is concluded that K-27 and K-48 are the most promising new oximes. The compounds with the best results in vitro also confer the best protection in vivo. Further testing using methyl- and propyl-organophosphates are needed. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article presents a study which compared the importance of oximes and pralidoxime (PRX) for in vitro reactivation of red blood cell acetylcholinesterase inhibited by paraoxon (POX), a non-neuropathic organophosphate. The study found that the new cholinesterase reactivators are superior to PRX, methoxime and B1-6, K-27 oximes. It discovered the importance of in vivo testing in determining the efficacy of new oximes in treating organophosphorus compounds-induced poisoning.

In vitro as well as in vivo evaluation of the reactivating efficacy of various oximes against nerve agent-inhibited acetylcholinesterase has been usually done with the help of animal experiments. Nevertheless, previously published data indicate that the reactivation potency of oximes may be different in human and animal species, which may hamper the extrapolation of animal data to human data. Therefore, to better evaluate the efficacy of various oximes (pralidoxime, obidoxime, HI-6, K033) to reactivate brain acetylcholinesterase inhibited by sarin by in vitro methods, human, rat and pig brain acetylcholinesterase were used to calculate kinetic parameters for the reactivation. Our results show differences among the species, depending on the type of oxime, and indicate that data from animal experiments needs to be carefully evaluated before extrapolation to humans. [ABSTRACT FROM AUTHOR]