SYNTHESIS, CHARACTERIZATION, AND IN VIVO IMMUNOMODULATION OF CCR2 AND VASCULAR ENDOTHELIAL GROWTH FACTOR ANTAGONISTS-LOADED PEGYLATED NANOPARTICLES

Objective: Chemokine (C-C motif) ligand 2 (CCL2), a candidate of cytokines, orchestrates immune cell recruitment to inflamed organs. CCL2 has been shown to have direct angiogenic effects, so providing an anti-angiogenic agent, Avastin (AV), to be combined with the CCR2 antagonist (concentration ratio [CR]) plays an essential role in the hemostatic strategy for immunomodulation. Lack of targetability and the adverse effects of chemical treatments are the main obstacles led scientists to develop novel strategies using nano-delivery approaches such as pegylated nanoparticles (NPs) which exhibits reduced drug clearance rates. The rationale of the current study is to test the in vivo immunomodulatory effects of AV and/or CR in their NPs or free counterparts.Methods: These NPs were synthesized and characterized using different physicochemical techniques. Males Wistar rats (n=114) were used and divided into 7 groups treated with vehicle, AV, AVNP, CCR2 antagonist (CR), CCR2 antagonist NPs (CRNP), AV-CCR2 antagonist (AVCR), and AV-CCR2 antagonist NPs (AVCRNP). Groups were subdivided into three subgroups according to the administrated dose. Blood was taken from rats for differential leukocyte and platelet profile measurements. Sera were collected to test vascular endothelial growth factor (VEGF) levels. Autopsy samples from liver were taken for histopathological investigation.Results: The morphology of the NPs was spherical and had sizes ranging from 89.89 nm to 146 nm. Monocytes and lymphocytes accumulated in the blood circulation and VEGF levels were inhibited after AV and CR administrations. In addition, large platelets concentration ratio was elevated in the blood circulation.Conclusion: We concluded that AV ad CR therapeutic regimens have an immunomodulatory role through induction of monocyte-platelet aggregation and inhibition of VEGF

CLEMASTINE, THE H1 HISTAMINE RECEPTOR ANTAGONIST, ALTERS THE HUMAN SEX AND THYROID HORMONAL PROFILES

  Objective: Clemastine is widely used as an antihistaminic drug. However, clemastine effectively acts as an antagonist of H1 histamine receptor, it has significant burden adverse effects causing common nervous system, psychiatric, and gastrointestinal ailments, as well as rare cardiac and immune system disorders. The objective of this study is to investigate whether there is a remarkable impact of clemastine administration on the human hormonal pituitary-thyroid-adrenal axis.Methods: To achieve that, hormonal profile was tested in the sera of males and females treated and untreated individuals with clemastine. This is to measure serum estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin, progesterone, dehydroepiandrosterone sulfate, thyroid-stimulating hormone, triiodothyronine, thyroxine, fasting insulin, and cortisol levels. The circulating hormonal levels were measured quantitatively using enzyme-link immunosorbent assay.Results: We resulted that there were significant differences of the human hormonal profile on clemastine treatment.Conclusion: Hormonal profiling showed that there were remarkable signatures could be of great interest to underline some recommendations and guidelines optimizing the clemastine dosage to avoid burdens associated with the administration of this drug as well as maintain the physiological and psychological performances of both sexes exposing to clemastine during the period of allergic treatment

Mitigation Measures for Gaza Coastal Erosion

Coastal erosion is an ongoing hazard affecting Gaza beach, but is worsening due to a wide range of human activities such as the construction of Gaza fishing harbor in 1994-1998. The net annual alongshore sediment transport is about 190×103 m3, but can vary significantly depending on the severity of winter storms. According to the observed wave heights and directions, the net waves are cross-shore, therefore vast quantities of sediments may transfer to deep sea. The main objective of this study is to mitigate the erosion problem of Gaza coast. Change detection analysis was used to compute the spatial and temporal change of Gaza shoreline between 1972 and 2010. The results show negative rates in general, which means that the erosion was the predominant process. Gaza fishing harbor caused a serious damage to the Beach Camp shoreline. Consequently, several mitigation measures were considered in this study, which are: relocation of Gaza fishing harbor to offshore, groins, detached breakwaters, wide-crested submerged breakwaters and beach nourishment. Several numerical model tests associated with coastal structures are conducted to investigate the influence on morphodynamics. The results show that the relocation of the harbor is the best alternative to stop trapping of the sediments. If for any reason the relocation was not carried out, the wide-crested submerged breakwater alternative is an effective structure for preventing sandy beach erosion. The artificial reef type of submerged breakwaters with beach nourishment is recommended for Gaza beach, because it is an environmentally friendly and improving the ecosystem of marine life

How does long term exposure to base stations and mobile phones affect human 3 hormone profiles?

and safety for humans continuously exposed to radio frequency 51 radiation. 52 Design and methods 53 Study subjects 54 This study was conducted for 6 years on 82 mobile phone volun-55 teers with age ranges 14-22 years (n = 41) and 25-60 years 56 (n = 41). Those users were divided into three subgroups according 57 to the time of their exposure to RFR: (weak n = 19), (moderate 58 n = 9), and (strong n = 13) per day, in addition to 20 negative control 59 subjects. 60 On the other hand, volunteers exposed to RFR emitted from base 61 stations (n = 34) were selected with age ranges 14-22 years 62 (n = 17), and 25-60 years (n = 17) and living at distances 20-100 m 63 and 100-500 m apart from the base station. Additional 10 subjects 64 of each age range living at a distance more than 500 m apart from 65 the base station were considered as negative control group

Gene expression of IQGAPs and Ras families in an experimental mouse model for hepatocellular carcinoma: a mechanistic study of cancer progression

IQGAPs genes play critical role in either induction or suppression of cancer and its progression, however the relationship between Ras genes and these genes are still unclear. In this study, we tried to understand the mechanistic action of IQGAPs genes and its correlation with Ras genes in mouse hepatic cancer model. The genetic expressions of IQGAP1, IQGAP2, IQGAP3, Hras, Kras, Nras, Mras, Caspase3, and BAX were followed in both hepatocellular carcinoma and normal liver cells of Balbc mice. Genotoxic agent diethylnitrosamine (DEN)-induced hepatic cancer model was induced in male mice and recorded the occurrence of hepatocellular carcinoma by morphological and histological changes in the liver. It was observed that mRNA expressions of IQGAP1, Hras, Kras, Nras, Mras, Caspase3, and BAX genes were highly elevated in hepatocellular carcinoma cells when compared with normal liver cells, additionally their expressions increased by concentrating the dose of DEN. While, the expressions of IQGAP2 and IQGAP3 were significantly decreased in hepatocellular carcinoma cells when compared with normal liver cells, as well as their expressions decreased more with increasing the dose of DEN. It was concluded from this study that IQGAP1 has a strong signaling relationship with Ras genes in induction of cancer and it is considered as a key gene for induction or suppression of the hepatocellular carcinoma

Novel molecular approach to define pest species status and tritrophic interactions from historical Bemisia specimens

Museum specimens represent valuable genomic resources for understanding host-endosymbiont/parasitoid evolutionary relationships, resolving species complexes and nomenclatural problems. However, museum collections suffer DNA degradation, making them challenging for molecular-based studies. Here, the mitogenomes of a single 1912 Sri Lankan Bemisia emiliae cotype puparium, and of a 1942 Japanese Bemisia puparium are characterised using a Next-Generation Sequencing approach. Whiteflies are small sap-sucking insects including B. tabaci pest species complex. Bemisia emiliae’s draft mitogenome showed a high degree of homology with published B. tabaci mitogenomes, and exhibited 98–100% partial mitochondrial DNA Cytochrome Oxidase I (mtCOI) gene identity with the B. tabaci species known as Asia II-7. The partial mtCOI gene of the Japanese specimen shared 99% sequence identity with the Bemisia ‘JpL’ genetic group. Metagenomic analysis identified bacterial sequences in both Bemisia specimens, while hymenopteran sequences were also identified in the Japanese Bemisia puparium, including complete mtCOI and rRNA genes, and various partial mtDNA genes. At 88–90% mtCOI sequence identity to Aphelinidae wasps, we concluded that the 1942 Bemisia nymph was parasitized by an Eretmocerus parasitoid wasp. Our approach enables the characterisation of genomes and associated metagenomic communities of museum specimens using 1.5 ng gDNA, and to infer historical tritrophic relationships in Bemisia whiteflies.© The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. The attached file is the published pdf

Frankincense essential oil nanoemulsion specifically induces lung cancer apoptosis and inhibits survival pathways

Abstract Background The volatile fraction of frankincense (Boswellia sacra) oleogum was extracted, formulated in nanoemulsion and tested against lung cancer A549 cell line. First, the gum was hydro-distilled to isolate the volatile fraction (essential oil), which was analyzed via gas chromatography to identify its major volatile constituents. Then, the oil was formulated in two water-based nanoemulsions which differ from one another in the presence of propylene glycol (PG), which is used in the formulation step as a co-surfactant. The pure essential oil as well as its major volatile compound (α-pinene), its two nanoemulsions and a reference drug (Doxorubicin) were evaluated against lung cancer A549 cell lines and WI-38 normal lung cells. The evaluation included cytotoxicity (MTT and IC50), apoptosis (flow cytometric analysis) in addition to genetic assessments for some intrinsic and extrinsic genes relevant to apoptosis and survival pathways. Results Chromatographic analysis of frankincense essential oil revealed that α-pinene is the major volatile compound which constituent about 60% of that oil. Emulsification of the oil using the low energy technique gave nanoemulsions having major intense particles population (85–90%) with z-average diameter below 20.0 nm. Frankincense oil nanoemulsion fabricated with (PG) showed the best cytotoxic activity toward lung cancer A549 cell compared to PG-free nanoemulsion, α-pinene and the reference drug doxorubicin, along different incubation periods. Flow cytometric analysis also indicated that PG-containing nanoemulsion can induce cancer cells toward apoptosis better than the other formula and the pure oils. The same nanoemulsion was found to upregulate the pro-apoptotic genes [DR5, FAAD, Caspase 8 (Cas8), p53, and Bax] and downregulate the anti-apoptotic and reoccurrence genes (Bcl-2, NF-kB, and STAT-3). Most importantly, the PG-containing nanoemulsion had the least cytotoxic effect on the normal WI-38 lung cells. Conclusions These results point out to the potentials of frankincense essential oil (rich in α-pinene) and its PG-nanoemulsion as a promising adjuvant from plant-source to potentiate the activity of the systematic anti-lung cancer drugs

Bioactive glass doped with noble metal nanoparticles for bone regeneration: in vitro kinetics and proliferative impact on human bone cell line

International audienceThis work investigates the bioactivity of novel silver-doped (BG-Ag) and gold-doped (BG-Au) quaternary 46S6 bioactive glasses synthesized via a semi-solid-state technique. A pseudo-second-order kinetic model successfully predicted the in vitro uptake kinetic profiles of the initial ion-exchange release of Ca in simulated body fluid, the subsequent Si release, and finally, the adsorption of Ca and P onto the bioactive glasses. Doping with silver nanoparticles enhanced the rate of P uptake by up to approximately 90%; whereas doping with gold nanoparticles improved Ca and P uptake rates by up to about 7 and 2 times, respectively; as well as Ca uptake capacity by up to about 19%. The results revealed that the combined effect of Ca and Si release, and possibly the release of silver and gold ions into solution, influenced apatite formation due to their effect on Ca and P uptake rate and capacity. In general, gold-doped bioactive glasses are favoured for enhancing Ca and P uptake rates in addition to Ca uptake capacity. However, silver-doped bioactive glasses being less expensive can be utilized for applications targeting rapid healing. In vitro studies showed that BG, BG-Ag and BG-Au had no cytotoxic effects on osteosarcoma MG-63 cells, while they exhibited a remarkable cell proliferation even at low concentration. The prepared bioactive glass doped with noble metal nanoparticles could be potentially used in bone regeneration applications

Occurrence of Toxic Biogenic Amines in Various Types of Soft and Hard Cheeses and Their Control by Bacillus polymyxa D05-1

Egyptian cheeses are considered an important part of the Egyptian diet. This study aimed to examine 60 random samples of different types of commercial cheeses in Egypt, including soft cheeses (Domiati and Tallaga) and hard cheeses (Cheddar and Ras). The samples were subjected to chemical and microbial examination. Biogenic amines (BAs) are nitrogenous compounds found in a variety of foods; their presence is undesirable and related to spoilage, and can result in toxicological effects in humans. Thus, BAs were determined by using a high-performance liquid chromatography (HPLC) analysis. Moreover, the ability of Bacillus polymyxa D05-1 to reduce levels of experimentally added biogenic amines during the manufacturing of Tallaga cheese was investigated. The obtained results revealed variations in the chemical composition between the investigated samples. Furthermore, many cheese samples contained high levels of BAs, including histamine, tyramine and putrescine. Domiati cheese had the highest levels of BAs, followed by Tallaga and Cheddar, whereas Ras cheese had the lowest levels. The existence of yeasts, molds, coliforms and the high levels of BAs in cheese samples indicate the unsanitary conditions in which they were made and stored. Furthermore, addition of B. polymyxa D05-1 during Tallaga cheese manufacturing resulted in a reduction in BA levels

Occurrence of Toxic Biogenic Amines in Various Types of Soft and Hard Cheeses and Their Control by <i>Bacillus polymyxa</i> D05-1

Egyptian cheeses are considered an important part of the Egyptian diet. This study aimed to examine 60 random samples of different types of commercial cheeses in Egypt, including soft cheeses (Domiati and Tallaga) and hard cheeses (Cheddar and Ras). The samples were subjected to chemical and microbial examination. Biogenic amines (BAs) are nitrogenous compounds found in a variety of foods; their presence is undesirable and related to spoilage, and can result in toxicological effects in humans. Thus, BAs were determined by using a high-performance liquid chromatography (HPLC) analysis. Moreover, the ability of Bacillus polymyxa D05-1 to reduce levels of experimentally added biogenic amines during the manufacturing of Tallaga cheese was investigated. The obtained results revealed variations in the chemical composition between the investigated samples. Furthermore, many cheese samples contained high levels of BAs, including histamine, tyramine and putrescine. Domiati cheese had the highest levels of BAs, followed by Tallaga and Cheddar, whereas Ras cheese had the lowest levels. The existence of yeasts, molds, coliforms and the high levels of BAs in cheese samples indicate the unsanitary conditions in which they were made and stored. Furthermore, addition of B. polymyxa D05-1 during Tallaga cheese manufacturing resulted in a reduction in BA levels