Nanoparticle-labeled stem cells: a novel therapeutic vehicle

Nanotechnology has been described as a general purpose technology. It has already generated a range of inventions and innovations. Development of nanotechnology will provide clinical medicine with a range of new diagnostic and therapeutic opportunities such as medical imaging, medical diagnosis, drug delivery, and cancer detection and management. Nanoparticles such as manganese, polystyrene, silica, titanium oxide, gold, silver, carbon, quantum dots, and iron oxide have received enormous attention in the creation of new types of analytical tools for biotechnology and life sciences. Labeling of stem cells with nanoparticles overcame the problems in homing and fixing stem cells to their desired site and guiding extension of stem cells to specific directions. Although the biologic effects of some nanoparticles have already been assessed, information on toxicity and possible mechanisms of various particle types remains inadequate. The aim of this review is to give an overview of the mechanisms of internalization and distribution of nanoparticles inside stem cells, as well as the influence of different types of nanoparticles on stem cell viability, proliferation, differentiation, and cytotoxicity, and to assess the role of nanoparticles in tracking the fate of stem cells used in tissue regeneration

Challenges in treating patients with inflammatory bowel disease and concurrent viral hepatitis infection

Introduction: Inflammatory bowel diseases (IBD) require long-term administration of immunomodulatory treatments to maintain disease remission. Due to the high worldwide prevalence of hepatitis B (HBV) or C (HCV) virus infections, presence of concurrent hepatitis can be a relevant clinical issue to manage when treating IBD. Areas covered: The paper summarizes epidemiological data about IBD and HBV/HCV infection and reviews current knowledge about the natural history of HBV and HCV in the IBD setting, concentrating on risk of hepatitis reactivation during immunosuppressive treatment. Most updated recommendations for management of HBV and HCV infections in IBD patients are discussed. Expert commentary: The development of new drugs for IBD with different molecular targets and the availability of potent and efficacious antiviral drugs for HBV and HCV will simplify management of hepatitis infection in IBD patients in the near future

Genotypic and Phenotypic Structure of the Population of Phytophthora infestans in Egypt Revealed the Presence of European Genotypes

Late blight disease of potato and tomato, caused by Phytophthora infestans, results in serious losses to Egyptian and global potato and tomato production. To understand the structure and dynamics of the Egyptian population of P. infestans, 205 isolates were collected from potato and tomato plants during three growing seasons in 2010–2012. The characterization was achieved by mating-type assay, metalaxyl sensitivity assay, and virulence pattern. Additionally, genotyping of 85 Egyptian isolates and 15 reference UK isolates was performed using 12 highly informative microsatellite (SSR) markers David E. L. Cooke and five effector (RxLR) genes. Mating-type testing showed that 58% (118 of 205) of the isolates belonged to mating type A1, 35% (71 isolates) to mating type A2, and the rest 8% (16 isolates) were self-fertile. The phenotype of metalaxyl response was represented as 45% resistant, 43% sensitive, and 12% as intermediate. Structure analysis grouped the 85 identified genotypes into two main clonal lineages. The first clonal lineage comprised 21 isolates belonging to A2 mating type and 8 self-fertile isolates. This clonal lineage was identified as Blue_13 or EU_13_A2. The second main clonal lineage comprised 55 isolates and was identified as EU_23_A1. A single isolate with a novel SSR genotype that formed a distinct genetic grouping was also identified. The effector sequencing showed good correspondence with the virulence data and highlighted differences in the presence and absence of loci as well as nucleotide polymorphism that affect gene function. This study indicated a changing population of P. infestans in Egypt and discusses the findings in the context of late blight management

Cyclic Dipeptides: The Biological and Structural Landscape with Special Focus on the Anti-Cancer Proline-Based Scaffold

Cyclic dipeptides, also know as diketopiperazines (DKP), the simplest cyclic forms of peptides widespread in nature, are unsurpassed in their structural and bio-functional diversity. DKPs, especially those containing proline, due to their unique features such as, inter alia, extra-rigid conformation, high resistance to enzyme degradation, increased cell permeability, and expandable ability to bind a diverse of targets with better affinity, have emerged in the last years as biologically pre-validated platforms for the drug discovery. Recent advances have revealed their enormous potential in the development of next-generation theranostics, smart delivery systems, and biomaterials. Here, we present an updated review on the biological and structural profile of these appealing biomolecules, with a particular emphasis on those with anticancer properties, since cancers are the main cause of death all over the world. Additionally, we provide a consideration on supramolecular structuring and synthons, based on the proline-based DKP privileged scaffold, for inspiration in the design of compound libraries in search of ideal ligands, innovative self-assembled nanomaterials, and bio-functional architectures

The ligational behavior of a phenolic quinolyl hydrazone towards copper(II)- ions

<p>Abstract</p> <p>Background</p> <p>The heterocyclic hydrazones constitute an important class of biologically active drug molecules. The hydrazones have also been used as herbicides, insecticides, nematocides, redenticides, and plant growth regulators as well as plasticizers and stabilizers for polymers. The importance of the phenolic quinolyl hydrazones arises from incorporating the quinoline ring with the phenolic compound; 2,4-dihydroxy benzaldehyde. Quinoline ring has therapeutic and biological activities whereas, phenols have antiseptic and disinfectants activities and are used in the preparation of dyes, bakelite and drugs. The present study is planned to check the effect of the counter anions on the type and geometry of the isolated copper(II)- complexes as well as the ligational behavior of the phenolic hydrazone; 4-[(2-(4,8-dimethylquinolin-2-yl)hydrazono)methyl] benzene-1,3-diol; (H₂L).</p> <p>Results</p> <p>A phenolic quinolyl hydrazone (H₂L) was allowed to react with various copper(II)- salts (Cl‾, Br‾, NO₃‾, ClO₄‾, AcO‾, SO₄^2-). The reactions afforded dimeric complexes (ClO₄‾, AcO‾ ), a binuclear complex (NO₃‾ ) and mononuclear complexes (the others; Cl‾, Br‾, SO₄^2-). The isolated copper(II)- complexes have octahedral, square pyramid and square planar geometries. Also, they reflect the strong coordinating ability of NO₃‾, Cl‾, Br‾, AcO‾ and SO₄^2-anions. Depending on the type of the anion, the ligand showed three different modes of bonding <it>viz</it>. (NN)⁰for the mononuclear complexes (<b>3, 4, 6</b>), (NO)^-with O- bridging for the dimeric complexes (<b>1, 5</b>) and a mixed mode [(NN)⁰+ (NO)^-with O- bridging] for the binuclear nitrato- complex (<b>2</b>).</p> <p>Conclusion</p> <p>The ligational behavior of the phenolic hydrazone (H₂L) is highly affected by the type of the anion. The isolated copper(II)- complexes reflect the strong coordinating power of the SO₄^2-, AcO‾, Br‾, Cl‾ and NO₃‾ anions. Also, they reflect the structural diversity (octahedral, square pyramid and square planar) depending on the type of the counter anion.</p

Ethylene responsive transcription factor ERF109 retards PCD and improves salt tolerance in plant

Semi-quantitative RT-PCR for tobacco VIGS lines of 13 knocked down TFs induced 2 h post oxalic acid treatment (20 mM) as compared to their WT and VIGS line with empty pTRV2 (V2) plants. Amplicon sizes of different genes and primers used are shown in Additional file 5: Table S3. The Nbactin gene was used as the house-keeping control. Gene codes refer to those indicated in Additional file 3: Table S2. (DOCX 684 kb

Identification and Validation of ERK5 as a DNA Damage Modulating Drug Target in Glioblastoma

YesBrain tumours kill more children and adults under 40 than any other cancer, with approximately half of primary brain tumours being diagnosed as high-grade malignancies known as glioblastomas. Despite de-bulking surgery combined with chemo-/radiotherapy regimens, the mean survival for these patients is only around 15 months, with less than 10% surviving over 5 years. This dismal prognosis highlights the urgent need to develop novel agents to improve the treatment of these tumours. To address this need, we carried out a human kinome siRNA screen to identify potential drug targets that augment the effectiveness of temozolomide (TMZ)-the standard-of-care chemotherapeutic agent used to treat glioblastoma. From this we identified ERK5/MAPK7, which we subsequently validated using a range of siRNA and small molecule inhibitors within a panel of glioma cells. Mechanistically, we find that ERK5 promotes efficient repair of TMZ-induced DNA lesions to confer cell survival and clonogenic capacity. Finally, using several glioblastoma patient cohorts we provide target validation data for ERK5 as a novel drug target, revealing that heightened ERK5 expression at both the mRNA and protein level is associated with increased tumour grade and poorer patient survival. Collectively, these findings provide a foundation to develop clinically effective ERK5 targeting strategies in glioblastomas and establish much-needed enhancement of the therapeutic repertoire used to treat this currently incurable disease

Analysis of transcriptional response to heat stress in Rhazya stricta

Clusters of assembled transcripts of R. stricta SRA in mature leaves (A5-L8) at different time points of the day (A, morning; F-H, midday & L, dusk). Grey lines indicate expression patterns of individual transcripts in a given cluster. Blue lines indicate overall expression pattern across different transcripts of a given cluster. (PDF 397 kb

Sudden cardiac death athletes: a systematic review

Previous events evidence that sudden cardiac death (SCD) in athletes is still a reality and it keeps challenging cardiologists. Considering the importance of SCD in athletes and the requisite for an update of this matter, we endeavored to describe SCD in athletes. The Medline (via PubMed) and SciELO databases were searched using the subject keywords "sudden death, athletes and mortality". The incidence of SCD is expected at one case for each 200,000 young athletes per year. Overall it is resulted of complex dealings of factors such as arrhythmogenic substrate, regulator and triggers factors. In great part of deaths caused by heart disease in athletes younger than 35 years old investigations evidence cardiac congenital abnormalities. Athletes above 35 years old possibly die due to impairments of coronary heart disease, frequently caused by atherosclerosis. Myocardial ischemia and myocardial infarction are responsible for the most cases of SCD above this age (80%). Pre-participatory athletes' evaluation helps to recognize situations that may put the athlete's life in risk including cardiovascular diseases. In summary, cardiologic examinations of athletes' pre-competition routine is an important way to minimize the risk of SCD