Isolation and molecular characterization of novel glucarpidases:Enzymes to improve the antibody directed enzyme pro-drug therapy for cancer treatment

<div><p>Repeated cycles of antibody-directed enzyme pro-drug therapy (ADEPT) and the use of glucarpidase in the detoxification of cytotoxic methotrexate (MTX) are highly desirable during cancer therapy but are hampered by the induced human antibody response to glucarpidase. Novel variants of glucarpidase (formal name: carboxypeptidase G2, CPG2) with epitopes not recognized by the immune system are likely to allow repeated cycles of ADEPT for effective cancer therapy. Towards this aim, over two thousand soil samples were collected and screened for folate hydrolyzing bacteria using folate as the sole carbon source. The work led to the isolation and the characterization of three new glucarpidase producing strains, which were designated as: <i>Pseudomonas lubricans</i> strain SF168, <i>Stenotrophomonas</i> sp SA and <i>Xenophilus azovorans</i> SN213. The <i>CPG2</i> genes of <i>Xenophilus azovorans</i> SN213 (named <i>Xen CPG2</i>) and <i>Stenotrophomonas sp</i> SA (named <i>Sten CPG2</i>) were cloned and molecularly characterized. Both Xen CPG2 and Sten CPG2 share very close amino acid sequences (99%); we therefore, focused on the study of Xen CPG2. Finally, we demonstrated that a polyclonal antibody raised against our new CPG2, Xen CPG2, does not react with the CPG2 from <i>Pseudomonas sp</i>. strain RS-16 (Ps CPG2) that are currently in clinical use. The two enzymes, therefore could potentially be used consecutively in the ADEPT protocol to minimize the effect of the human antibody response that hampers current treatment with Ps CPG2. The identified novel CPG2 in this study will, therefore, pave the way for safer antibody directed enzyme pro-drug therapy for cancer treatment.</p></div

Bioactive Constituents of Juniperus turbinata Gussone from La Maddalena Archipelago

A comprehensive phytochemical study of Juniperus turbinata (Cupressaceae) collected from La Maddalena Archipelago (Sardinia, Italy) is reported. Both the essential oil and the ethanolic extract obtained from the aerial parts were analyzed. The essential oil appears to belong to a new chemotype compared to other Mediterranean juniper accessions, as it was favored by geographic isolation of the isles. It showed a low content of monoterpene hydrocarbons and a-terpineol, entmanoyl oxide, 1,10-di-epi-cubenol as the major constituents. The ethanolic fraction contained mainly diterpenoids. Among these, 15-formyloxyimbricatolic acid (7) is a new natural product since it has hitherto been obtained only by synthetic route. The phenolic fraction contained biflavonoids: cupressuflavone (9), followed by minor amounts of amentoflavone (10) and hinokiflavone (11). The essential oil and six purified compounds (1 – 4, 8 and 9) were assessed for biological activities, namely antioxidant (assessed by DPPH·, ABTS· + and FRAP methods) and cytotoxic effects towards selected human tumor cell lines (MDA-MB 231, A375 and HCT116 cells). Compound 3 exhibited higher radical scavenging activity against ABTS·+ radical than the reference Trolox. Noteworthy, compound 8 showed powerful effects towards tumor cell lines, with IC50 values in the range of 0.060 – 0.201 lM, which make it a promising anticancer drug candidate

Optimal Relay Selection using jellyfish Optimization Algorithm for Image Transmission over Multiuser Cooperative Communication Networks

A recent study and research have shown that the relay selection schemes for cooperative communication can achieve full cooperative diversity gains and still maintains energy efficiency. Multi-source and multi-relay networks frequently cooperate to transfer their own data to the destination, mainly the access point, in cooperative wireless networks. In this paper, we use a jellyfish optimizer to select the number of relays to transmit packets of the image depending on the order of the data in the image according to its importance and at a constant rate. First, the relationships between the number of relays, peak signal-to-noise ratio, and signal-to-noise ratio are analyzed. Second, the comparison between the performances of Equal Diversity (ED) and Unequal Diversity (UED) with Equal Error Protection(EEP) and Unequal Error Protection(UEP) is introduced using the set partitioning in hierarchical trees (SPIHT) image coder as a source coding. The jellyfish algorithm, as an efficient optimization technique, is applied for solving the problem of optimal relay selection method to reduce the bit error rate and to improve the transmitted image quality. Many useful and important results in the proposed work can be used in the enhancement of image transmission over cooperative networks. Relative to the traditional methods, the proposed method achieves better results for the transmission of images with high quality through cooperative communication networks

An overview on understanding the major bacterial fish diseases in freshwater salmonids

Exhaustive work on bacterial fish diseases provides a significant knowledge about the influence of bacterial infections in economically noteworthy freshwater fish species farmed around the world. However, it is still difficult to exactly pinpoint the causes of bacterial infections among wide diversity of fish species, although significant strides in this direction have been achieved with respect to different fish species. Various studies have demonstrated the growing prevalence of bacterial infections, concurrent with the rapid development of aquaculture worldwide, yet information regarding these infections, their influence on the host species, consequences of numerous environmental variables as well as social-economic impacts are still lacking, which warrant for a desperate need of detailed studies. Despite various efforts, the pathogenesis, appropriate diagnostic techniques and treatment measures of various diseases remains unclear and thus responsible for huge losses both in natural as well as aquaculture conditions. In addition, progress in control and prevention of these diseases is hampered by the lack of adequate epidemiological data on bacterial diseases in many countries. In the present review, an attempt has been made to bring together the scattered information available about the diverse features of most economically significant bacterial diseases affecting fresh water salmonids worldwide including: bacterial gill disease, columnaris disease, bacterial kidney disease, enteric red mouth disease, lactococcosis, furunculosis, bacterial coldwater disease, mycobacteriosis and photobacteriosis. Besides, we also tried to highlight a brief overview of the traditional techniques for isolating bacteria from their hosts along with the serological and/or genetic diagnostic tools. The development of immunisation techniques to stop certain bacterial infections is also discussed in this review paper. The study focuses on the latest fundamental knowledge linked to bacterial infections in freshwater systems covering epidemiology, clinical signs/pathogenesis, transmission, diagnosis and treatment measures while the pathogenesis data emphasizes the area calling for further investigation

Morphologic design of nanostructures for enhanced antimicrobial activity

Despite significant progress in synthetic polymer chemistry and in control over tuning the structures and morphologies of nanoparticles, studies on morphologic design of nanomaterials for the purpose of optimizing antimicrobial activity have yielded mixed results. When designing antimicrobial materials, it is important to consider two distinctly different modes and mechanisms of activity-those that involve direct interactions with bacterial cells, and those that promote the entry of nanomaterials into infected host cells to gain access to intracellular pathogens. Antibacterial activity of nanoparticles may involve direct interactions with organisms and/or release of antibacterial cargo, and these activities depend on attractive interactions and contact areas between particles and bacterial or host cell surfaces, local curvature and dynamics of the particles, all of which are functions of nanoparticle shape. Bacteria may exist as spheres, rods, helices, or even in uncommon shapes (e.g., box- and star-shaped) and, furthermore, may transform into other morphologies along their lifespan. For bacteria that invade host cells, multivalent interactions are involved and are dependent upon bacterial size and shape. Therefore, mimicking bacterial shapes has been hypothesized to impact intracellular delivery of antimicrobial nanostructures. Indeed, designing complementarities between the shapes of microorganisms with nanoparticle platforms that are designed for antimicrobial delivery offers interesting new perspectives toward future nanomedicines. Some studies have reported improved antimicrobial activities with spherical shapes compared to non-spherical constructs, whereas other studies have reported higher activity for non-spherical structures (e.g., rod, discoid, cylinder, etc.). The shapes of nano- and microparticles have also been shown to impact their rates and extents of uptake by mammalian cells (macrophages, epithelial cells, and others). However, in most of these studies, nanoparticle morphology was not intentionally designed to mimic specific bacterial shape. Herein, the morphologic designs of nanoparticles that possess antimicrobial activities per se and those designed to deliver antimicrobial agent cargoes are reviewed. Furthermore, hypotheses beyond shape dependence and additional factors that help to explain apparent discrepancies among studies are highlighted

Nurses\u27 Knowledge, Skills, and Attitudes Regarding Climate Change and Its Impact on Children\u27s Health in Egyptian Hospitals: A Comparative Study

Introduction: Pediatric nurses are believed to play a crucial role in mitigating and adapting to the impacts of climate change on children\u27s health. Consequently, this study aims to compare nurses\u27 knowledge, skills, and attitudes regarding climate change and its effects on children from hospitals in two provinces in Egypt. Methods: A cross-sectional comparative study was conducted involving staff nurses working in different pediatric units in hospitals across two provinces in Egypt. A total of 336 nurses were purposively selected as participants. Data collection utilized three tools: a designed structured questionnaire for knowledge, a climate health skills rating scale, and an attitude scale. Results: In Beni-Suef hospitals, a significant proportion of participants exhibited poor knowledge, skills, and attitudes (48.2%, 50.6%, and 54.2%, respectively). In contrast, most participants in Al Azhar hospitals demonstrated good knowledge, skills, and attitudes regarding climate change (69.6%, 29.2%, and 82.1%, respectively). These differences between the two provinces were highly statistically significant (P = 0.001). Conclusion: Nurses at Al Azhar Hospital exhibited higher levels of knowledge, skills, and attitudes regarding climate change compared to their counterparts at Beni-Suef Hospital

Effects of Chemically Characterized Fractions from Aerial Parts of Echinacea purpurea and E. angustifolia on Myelopoiesis in Rats

Echinacea species are used for beneficial effects on immune function, and various prevalent phytochemicals have immunomodulatory effects. Using a commercial E. purpurea (L.) Moench product, we have evaluated the myelopoietic effect on bone marrow of rats treated with various extracts and correlated this with their chemical class composition. Granulocyte/macrophage-colony forming cells (GM-CFCs) from femurs of female Sprague-Dawley rats were assessed at 24 h after 7 daily oral treatments. A 75 % ethanolic extract at 50 mg dried weight (derived from 227 mg aerial parts) per kg body weight increased GM-CFCs by 70 % but at 100 mg/kg was without effect. Ethanolic extracts from aerial parts of E. angustifolia DC. var. angustifolia andE. purpurea from the USDA North Central Regional Plant Introduction Station increased GM-CFCs by 3- and 2-fold, respectively, at 200 mg/kg (∼ 1400 mg/kg plant material). Extract from another USDA E. angustifoliawas inactive. Proton and APT NMR, MS, and TLC indicated alkylamides and caffeic-acid derivatives (CADs) present in ethanolic extracts of both the commercial and USDA-derived material. Cichoric and caftaric acids were prominent in both E. purpurea ethanolic extracts but absent in E. angustifolia. Aqueous extract of the commercial material exhibited polysaccharide and CAD signatures and was without effect on GM-CFCs. A methanol-CHCl3 fraction of commercial source, also inactive, was almost exclusively 1 : 4 nonanoic : decanoic acids, which were also abundant in commercial ethanolic extract but absent from USDA material. In conclusion, we have demonstrated an ethanol-extractable myelostimulatory activity in Echinacea aerial parts that, when obtained from commercial herbal supplements, may be antagonized by medium-chain fatty acids presumably derived from a non-plant additive

DEVELOPMENT OF SOME TOLERANT YEAST (SACCHAROMYCES CEREVISIAE) STRAINS TO HEAT AND SALT STRESSES

All living organisms are subjected to changing in conservational conditions, to which they must adapt to. Stress is defined as a threat refers to the physiological balance of systems critical to survival organisms. Five yeast strains (Saccharomyces cerevisiae) were subjected to different adverse environmental situations, such as thermal, osmotic and oxidative (salt) stresses. The objective of this work was to detect the most tolerant yeast strains under salt or heat stresses.  Five yeast strains were exposed in a first experiment to heat stress at 20°C or 40°C beside to the control at 30°C to detect the more tolerant strain. The same yeast strains were subjected in a second experiment to two different concentrations of salt stress (NaCl); 0.5 or 1.0 M, separately, for two days (at 30°C as normal temperature for growth), other strains were exposed to 0.5 M concentration of NaCl for 24 hours, then 1 M for another 24 hours. For the heat stress results, strain S4 was more tolerant at 40oCwith insignificant difference compared to the control (30oC), while it showed significant difference at 20°C. Strain S5 also was more tolerant at 20oC with insignificant difference compared to the control. For salt treatment, the only insignificant value was for strain S3at 0.5M NaCl compared with the control

Correction:Isolation and molecular characterization of novel glucarpidases: Enzymes to improve the antibody directed enzyme pro-drug therapy for cancer treatment

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