Breast Tumor Targeting in Mice Bearing 4T1 Tumor with Labeled CXCR4 Antagonist Analogue

International Journal of Peptide Research and Therapeutics - Chemokine receptor belongs to G-protein-coupled cell-surface receptors. CXCR4 as a chemokine receptor is over-expressed in many type of...     

Improvement of inflammatory and toxic stress biomarkers by silymarin in a murine model of type one diabetes mellitus

Type 1 diabetes mellitus (T1DM) is characterized by an impairment of the insulin-secreting beta cells with an immunologic base. Inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, and free radicals are believed to play key roles in destruction of pancreatic β cells. The present study was designed to investigate the effect of Silybum marianum seed extract (silymarin), a combination of several flavonolignans with immunomodulatory, anti-oxidant, and anti-inflammatory potential on streptozotocin (STZ)-induced T1DM in mouse. Experimental T1DM was induced in male albino mice by IV injection of multiplelow- doses of STZ for 5 days. Seventy-two male mice in separate groups received various doses of silymarin (20, 40, and 80 mg/kg) concomitant or after induction of diabetes for 21 days. Blood glucose and pancreatic biomarkers of inflammation and toxic stress (IL-1β, TNF-α, myeloperoxidase, lipid peroxidation, protein oxidation, thiol molecules, and total antioxidant capacity) were determined. Silymarin treatment reduced levels of inflammatory cytokines such as TNF-α and IL-1β and oxidative stress mediators like myeloperoxidase activity, lipid peroxidation, carbonyl and thiol content of pancreatic tissue in an almost dose dependent manner. No marked difference between the prevention of T1DM and the reversion of this disease by silymarin was found. Use of silymarin seems to be helpful in T1DM when used as pretreatment or treatment. Benefit of silymarin in human T1DM remains to be elucidated by clinical trials.     

VARIATION IN THE STRENGTH AND SOFTNESS OF SELECTION ON DELETERIOUS MUTATIONS

Deleterious alleles constantly enter populations through mutation. Understanding the nature of selection against such alleles is required to assess their impact on populations. In a subdivided population, two distinct aspects of selection are important: the strength and softness of selection. Using Drosophila melanogaster, we estimated both aspects of selection for each of eight loci across two environments. These data allow us to test conflicting predictions about the factors affecting the softness of selection. First, we show that the softness of selection is not determined by ecological conditions alone. Second, we find that resource limitation makes selection stronger but does not make it softer. Third, we find that wild‐type individuals tend to benefit more than mutants from being reared with competitors of low genetic quality. This means that selection is effectively “harder” on mutants than wild types. A model is presented showing that the sensitivities of mutants and wild types to local competitors differentially affect equilibrium mutation frequency and measures of load.     

Iodine deficiency and subclinical hypothyroidism are common in cystic fibrosis patients

BackgroundDisorders of thyroid function have been inconsistently described in cystic fibrosis (CF) patients and in CF transmembrane regulator protein knockout animals. The literature lacks reports on iodine status of CF individuals. We hypothesize, that iodine deficiency is common in CF and account for abnormal thyroid function in CF patients.MethodsWe investigated 129 children, adolescents, and adults with CF, who were living in the northern part of Bavaria/Germany. Malnutrition and lung function were analyzed. Urinary iodine excretion, TSH (thyroid-stimulating hormone), and ft4 (free thyroxine) were measured and set in relation to population-based, age-adjusted reference ranges.ResultsSubclinical hypothyroidism (normal fT4, elevated TSH) was found in 11.6% of subjects, and iodine deficiency in 83.7%. No correlations were found with age, BMI, status of malnutrition, or lung function.ConclusionDramatic iodine deficiency was found in our cohort of CF patients. This condition can cause subclinical hypothyroidism; therefore, an individual iodine supplementation program is necessary and should be started immediately.     

Fine-Tuning of the Cellular Signaling Pathways by Intracellular GTP Levels

It has become increasingly evident that among purine nucleotides, guanine based nucleotides specially guanosine-5′-triphosphate (GTP) serve as an important and independent regulatory factors for development and diverse cellular functions such as differentiation, metabolism, proliferation and survival in multiple tissues. In this brief review, it has been provided selective outline related to delicate regulation of signaling pathways by guanosine based nucleotides as intracellular signaling molecules. Although the exact mode of action of theses nucleotides in many biological processes and signaling pathways is still elusive, it has become well clear that intracellular guanosine based nucleotides content rather than adenosine based nucleotides could modulate the intensity and duration of signaling which ultimately impact on cell’s fate. It opens an entirely new perspective for developing new and potential therapeutic strategies to combat diseases like cancer, hypoxia, etc.     

Immobilization of acetylcholinesterase in nanofibrous PVA/BSA membranes by electrospinning

Electrospinning, a simple and versatile method to fabricate nanofibrous supports, has attracted continuous attention in the field of enzyme immobilization. In this study, acetylcholinesterase (AChE) has been successfully immobilized in PVA nanofibers via electrospinning of a mixture of AChE, BSA as an enzyme stabilizing additive and PVA. The maximum activity recovery of immobilized AChE was about 40%. In comparison with free enzyme, the immobilized AChE showed improved stability while retaining a considerable amount of activity at lower pH values. Moreover, the immobilized AChE retained >34% of its initial activity when stored at 30°C for 100 days and retained 70% of its initial activity after ten consecutive reactor batch cycles.