Application of FTIR microscopy for the characterization of malignancy: H-ras transfected murine fibroblasts as an example.

Recently, microscopic FTIR is widely used in the field of biology and medicine. FTIR can detect biomolecular changes in the cells and tissues responsible for various disorders. In this report, we characterize the H-ras transfected fibroblasts and its normal control using microscopic FTIR. The intensity of the normal fibroblasts was higher than that of H-ras transfected fibroblasts. Our studies showed significant differences occur in the concentration of vital metabolites upon transformation. The DNA and carbohydrates level decreased in the transformed cells compared to the controls. A linear correlation could be found between the levels of carbohydrates and phosphate, while the RNA/DNA ratio varied inversely with glucose/phosphate levels.     

Quantification of tyramine in different types of food using novel green synthesis of ficus carica quantum dots as fluorescent probe

Tyramine (TYM) is catecholamine releasing compound and TYM rich food causes hypertensive crisis due to a combination with monoamine oxidase inhibitor (MAOIs). Therefore, analysis of TYM in TYM rich food as (old cheese, cured meat, sausage, pickled olive and canned fish) and the environment is essential for hypertensive patients and to improvement of food industries. In this work, TYM was analyzed in different types of food using novel green synthesis carbon dots from Ficus carica (fig fruits). The gradual addition of TYM to polyamine carbon quantum dots (PA@CQDs) led to enhancement of the quantum dots fluorescence due to formation of hydrogen bonding between quantum dots and TYM. The calibration graph was plotted in the range 5–400 ng mL⁻¹. The method was applied for the determination of TYM in different types of food as old cheese, cured meat, sausage, pickled olive and canned fish. The lower limit of quantitation (LOQ) was found to be 1.68 ng mL⁻¹. The method was successfully applied for the quantification of TYM in varying types of food with high sensitivity and high economic effect due to the reusability of the quantum dots. The optical and morphological characters of quantum dots were studied carefully.     

A Meta-Analysis of the Prevalence of Toxoplasmosis in Livestock and Poultry Worldwide

EcoHealth - Toxoplasma gondii causes toxoplasmosis with a global prevalence in the world. A large proportion of human illness is most frequently associated with consuming raw and undercooked meat...     

Metronidazole aryloxy,carboxy and azole derivatives: Synthesis,anti-tumor activity,QSAR, molecular docking and dynamics studies

A series of novel metronidazole aryloxy, carboxy and azole derivatives has been synthesized and their cytotoxic activities on three cancer cell lines were evaluated by MTT assay. Compounds 4m, 4l and 4d showed the most potent cytotoxic activity (IC₅₀s?less than?100?µg/mL). Apoptosis was also detected for these compounds by flow cytometry. Docking studies were performed in order to propose the probable target protein. In the next step, molecular dynamics simulation was carried out on the proposed target protein, focal adhesion kinase (FAK, PDB code: 2ETM), bound to compound 4m. As, 4m showed a potent cytotoxic activity and an acceptable apoptotic effect, it can be a potential anticancer candidate that may work through inhibition of FAK.     

Middle East and North Africa consensus on osteoporosis

With the increasing life expectancy, osteoporosis is becoming a major worldwide health problem. The magnitude of the disease may become larger in developing countries, more particularly in the Middle East region where the prevalence of low bone mass is higher than in western countries. Although several local organizations and countries have developed guidelines for osteoporosis, no previous regional guidelines have been developed encompassing all Middle-Eastern and North African countries. The present document reviews all the regional published data on bone mineral density, risk factors, fracture prevalence and vitamin D status. It also gives simple recommendations applicable to all these countries. This document was endorsed by leading members of all the different regional countries including, Iran, Egypt, Tunisia, Jordan, Palestine, Syria, Iraq, Libya, Oman, Kuwait, Saudi Arabia and Bahrain.     

Yif1B Is Involved in the Anterograde Traffic Pathway and the Golgi Architecture

Yif1B is an intracellular membrane‐bound protein belonging to the Yip family, shown previously to control serotonin 5‐HT_1A receptor targeting to dendrites. Because some Yip proteins are involved in the intracellular traffic between the ER and the Golgi, here we investigated the precise localization of Yif1B in HeLa cells. We found that Yif1B is not resident into the Golgi, but rather belongs to the IC compartment. After analyzing the role of Yif1B in protein transport, we showed that the traffic of the VSVG protein marker was accelerated in Yif1B depleted HeLa cells, as well as in hippocampal neurons from Yif1B KO mice. Conversely, Yif1B depletion in HeLa cells did not change the retrograde traffic of ShTx. Interestingly, in long term depletion of Yif1B as in Yif1B KO mice, we observed a disorganized Golgi architecture in CA1 pyramidal hippocampal neurons, which was confirmed by electron microscopy. However, because short term depletion of Yif1B did not change Golgi structure, it is likely that the implication of Yif1B in anterograde traffic does not rely on its role in structural organization of the Golgi apparatus, but rather on its shuttling between the ER, the IC and the Golgi compartments.      

ICOS-Expressing CD4 T Cells Induced via TLR4 in the Nasal Mucosa Are Capable of Inhibiting Experimental Allergic Asthma

Modulation of adaptive immune responses via the innate immune pattern recognition receptors, such as the TLRs, is an emerging strategy for vaccine development. We investigated whether nasal rather than intrapulmonary application of Protollin, a mucosal adjuvant composed of TLR2 and TLR4 ligands, is sufficient to elicit protection against murine allergic lower airway disease. Wild-type, Tlr2(-/-), or Tlr4(-/-) BALB/c mice were sensitized to a birch pollen allergen extract (BPEx), then received either intranasal or intrapulmonary administrations of Protollin or Protollin admixed with BPEx, followed by consecutive daily BPEx challenges. Nasal application of Protollin or Protollin admixed with BPEx was sufficient to inhibit allergic lower airway disease with minimal collateral lung inflammation. Inhibition was dependent on TLR4 and was associated with the induction of ICOS in cells of the nasal mucosa and on both CD4(+)Foxp3(+) and CD4(+)Foxp3(-) T cells of the draining lymph nodes (LNs), as well as their recruitment to the lungs. Adoptive transfer of cervical LN CD4(+)ICOS(+), but not CD4(+)ICOS(-), cells inhibited BPEx-induced airway hyperresponsiveness and bronchoalveolar lavage eosinophilia. Thus, our data indicate that expansion of resident ICOS-expressing CD4(+) T cells of the cervical LNs by nasal mucosal TLR4 stimulation may inhibit the development of allergic lower airway disease in mice.     

Vascular binding of a pathogen under shear force through mechanistically distinct sequential interactions with host macromolecules

Systemic dissemination of microbial pathogens permits microbes to spread from the initial site of infection to secondary target tissues and is responsible for most mortality due to bacterial infections. Dissemination is a critical stage of disease progression by the Lyme spirochaete, Borrelia burgdorferi. However, many mechanistic features of the process are not yet understood. A key step is adhesion of circulating microbes to vascular surfaces in the face of the shear forces present in flowing blood. Using real‐time microscopic imaging of the Lyme spirochaete in living mice we previously identified the first bacterial protein (B. burgdorferi BBK32) shown to mediate vascular adhesion in vivo. Vascular adhesion is also dependent on host fibronectin (Fn) and glycosaminoglycans (GAGs). In the present study, we investigated the mechanisms of BBK32‐dependent vascular adhesion in vivo. We determined that BBK32–Fn interactions (tethering) function as a molecular braking mechanism that permits the formation of more stable BBK32–GAG interactions (dragging) between circulating bacteria and vascular surfaces. Since BBK32‐like proteins are expressed in a variety of pathogens we believe that the vascular adhesion mechanisms we have deciphered here may be critical for understanding the dissemination mechanisms of other bacterial pathogens.     

The "linker" region (amino acids 38-47) of the disintegrin elegantin is a novel inhibitory domain of integrin alpha5beta1-dependent cell adhesion on fibronectin: evidence for the negative regulation of fibronectin synergy site biological activity

Disintegrins are a family of potent inhibitors of cell-cell and cell-matrix adhesion. In this study we have identified a region of the disintegrin elegantin, termed the "linker domain" (amino acids 38-47), with inhibitory activity toward alpha(5)beta(1)-mediated cell adhesion on fibronectin (Fn). Using a chimeric structure-function approach in which sequences of the functionally distinct disintegrin kistrin were introduced into the elegantin template at targeted sites, a loss of inhibitory function toward alpha(5)beta(1)-mediated adhesion on Fn was observed when the elegantin linker domain was substituted. Subsequent analysis comparing the inhibitory efficacies of the panel of elegantin-kistrin chimeras toward CHO alpha(5) cell adhesion on recombinant Fn III(6-10) fragments showed that the loss of inhibitory activity associated with the disruption of the elegantin linker domain was dependent upon the presence of a functional Fn III(9) synergy site within the Fn III(6-10) substrate. This suggested that the elegantin linker domain inhibits primarily the activity of the Fn synergy domain in promoting alpha(5)beta(1) integrin-mediated cell adhesion. Construction of a cyclic peptide corresponding to the entire region of the elegantin linker domain showed that this domain has intrinsic alpha(5)beta(1) inhibitory activity comparable with the activity of the RGDS peptide. These data demonstrate a novel biological function for a disintegrin domain that antagonizes integrin-mediated cell adhesion.     

Engineering tissues for in vitro applications

Engineered tissues can be employed for studies on the fundamental mechanisms of embryology and adult physiology and for investigating the evolution of disease processes. They also provide platforms to evaluate the behavior of new chemical entities in drug development. The recent development of three specific technologies has greatly facilitated the engineering of tissues for in vitro applications: the microfabrication tools that serve to both define the cellular microenvironment and enable parallelization of cell-based assays; synthetic, tunable hydrogels to create three-dimensional microenvironments; and bioreactors to control nutrient transport and fluid shear stress. Furthermore, convergence of these tools is providing investigators with the opportunity to construct and study tissues in vitro with unprecedented levels of sophistication.