Compression-induced changes in the shape and volume of the chondrocyte nucleus

Changes in cell shape and volume are believed to play a role in the process of mechanical signal transduction by chondrocytes in articular cartilage. One proposed pathway through which chondrocyte deformation may be transduced to an intracellular signal is through cytoskeletally mediated deformation of intracellular organelles, and more specifically, of the cell nucleus. In this study, confocal scanning laser microscopy was used to perform in situ three-dimensional morphometric analyses of the nuclei of viable condrocytes during controlled compression of articular cartilage explants from the canine patellofemoral groove. Unconfined compression of the tissue to a 15% surface-to-surface strain resulted in a significant decrease of chondrocyte height and volume by 14.7 ± 6.4 and 11.4 ± 8.4%, respectively, and of nuclear height and volume by 8.8 ± 6.2% and 9.8 ± 8.8%, respectively. Disruption of the actin cytoskeleton using cytochalasin D altered the relationship between matrix deformation and changes in nuclear height and shape, but not volume. The morphology and deformation behavior of the chondrocytes were not affected by cytochalasin treatment. These results suggest that the actin cytoskeleton plays an important role in the link between compression of the extracellular matrix and deformation of the chondrocyte nuclei and imply that chondrocytes and their nuclei undergo significant changes in shape and volume in vivo.     

Metal Binding Antimicrobial Peptides in Nanoparticle Bio-functionalization: New Heights in Drug Delivery and Therapy

Probiotics and Antimicrobial Proteins - Peptides are considered very important due to the diversity expressed through their amino acid sequence, structure variation, large spectrum, and their...     

Some 3-(4-Aminophenyl)pyrrolidine-2,5-diones as All- trans -retinoic Acid Metabolising Enzyme Inhibitors (RAMBAs)

A series of (±) -3-(4-aminophenyl) pyrrolidin-2,5-diones substituted in the 1-, 3- or 1,3- position with an aryl or long chain alkyl function are weak inhibitors of the metabolism of all-trans retinoic acid (RA) by rat liver microsomes (68-75% inhibition) compared with ketoconazole (85%). Further studies with the 1-cyclohexyl analogue (1) (IC 50 = 98.8 μM, ketoconazole, 22.15 μM) showed that it was not stereoselective in its inhibition. (±) - (1) was not an inhibitor of pig brain microsomal enzyme (ketoconazole, IC 50 = 20.9 μM), had little effect on human liver microsomal enzyme (19.3%, ketoconazole, 81.6%) or human placental microsomal enzyme (9.8%, ketoconazole 73.9%) but was a weak inhibitor of human and rat skin homogenates (52.6% and IC 50 = 211.6 μM respectively; ketoconazole, 38.8% and 85.95 μM). In RA-induced cell cultures of human male genital fibroblasts and HaCat cells, (±) - (1) was a weak inhibitor (c. 53% at 200 μM) whereas ketoconazole showed high potency (c. 65% at 0.625 μM and 0.25 μM respectively). The nature of the induced target enzyme is discussed.     

Inhibition of Retinoic Acid Metabolising Enzymes by 2-(4-aminophenylmethyl)-6-hydroxy-3,4-dihydronaphthalen-1(2H)-one and Related Compounds

In a search for inhibitors of all-trans retinoic acid (RA)-metabolising enzymes as potential agents for the treatment of skin conditions and cancer we have examined 2-(4-aminophenylmethyl)-6-hydroxy-3,4-dihydronaphthalen-1(2H)-one (5). Compound (5) is a moderate inhibitor of RA-metabolising enzymes in mammalian cadaverous tissue microsomes and homogenates as well as RA-induced enzymes in cultured human genital fibroblasts and HaCat cells. Overall (5) was more potent than or equipotent with ketoconazole, a standard inhibitor, in the cadaverous systems but less active towards the RA-induced cell culture systems. Examination of the data suggests that RA-induction generates metabolising enzymes not present in the cadaverous systems, which are more susceptible to inhibition by ketoconazole than (5).     

Genotyping of –374A/T, –429A/G,And 63 bp Ins/Del Polymorphisms of Rage By Rapid One-Step Hexaprimer Amplification Refractory Mutation System Polymerase Chain Reaction in Breast Cancer Patients

Several studies have focused on the RAGE genetic background and have demonstrated that its polymorphisms affect the receptor's activity, expression, and downstream signaling. However, there is only little information regarding RAGE polymorphism in breast cancer. In the present study, the authors studied RAGE polymorphisms in 71 patients with breast cancer and 93 healthy women. RAGE –374T/A, –429T/C, and 63 bp Ins/del polymorphisms were analyzed using a hexaprimer amplification refractory mutation system PCR (H-ARMS-PCR). The results showed that RAGE polymorphisms are not associated with breast cancer in the current study population. Larger studies are required to confirm these data in other populations.     

Human umbilical cord mesenchymal stem cell-derived extracellular vesicles: A novel therapeutic paradigm

Mesenchymal stem cells (MSCs) have been revealed to hold great potential for the development of new treatment approaches for various diseases. However, the clinical use of these cells is limited due to their tumorigenic effects. The therapeutic benefits of MSCs are largely dependent on paracrine factors including extracellular vesicles (EVs). EVs are nano-sized bilayer membrane structures containing lipids, microRNAs and proteins which play key roles in cell-to-cell communications. Because of their lower immunogenicity, tumorigenicity, and easier management, EVs have emerged as a new promising alternative to whole-cell therapy. Therefore, this paper reviews current preclinical studies on the use of EVs derived from human umbilical cord MSCs (hucMSCs) as a therapeutic approach in treatment of several diseases including neurological, cardiovascular, liver, kidney, and bone diseases as well as the cutaneous wound, inflammatory bowel disease, cancers, infertility, and other disorders.     

Distribution and impact of virus associated diseases of common bean (Phaseolus vulgaris L.) in northern Iran

Different viral diseases infect common bean crops in Iran. A total of 248 symptomatic samples were collected from common bean fields throughout main growing fields of Guilan province in Iran during the summer of 2006. Eight viruses were detected using double antibody-sandwich – enzyme-linked immunosorbent assay (DAS-ELISA). Bean common mosaic virus – BCMV (1%), Bean leaf roll virus – BLRV (9%), Cowpea mild mottle virus – CpMMV (6%), Southern bean mosaic virus – SBMV (3%), Cucumber mosaic virus – CMV (15%), Bean golden mosaic virus – BGMV (2%), Bean common mosaic necrosis virus – BCMNV (1%) and Bean yellow mosaic virus – BYMV (1%) were detected. Comparatively CMV (15%) was found to be more prevalent in Guilan province. Multiple infections of viruses were recorded in many samples. Weed species belonging to Chenopodiaceae, Solanaceae, Malvaceae and Amaranthaceae families were also found to be infected with the viruses.     

Feeding corn germ instead of corn grain on the performance of Holstein dairy cows fed low-forage diet and human-edible feed conversion efficiency

Using corn germ (CG) instead of corn grain could maintain dairy cow performance and might increase the efficiency of human food production. The primary objective of this study was to evaluate the effects of replacing corn grain with CG on the performance, nutrient intake, and digestibility of dairy cows. It also aimed to investigate the effect of CG on the efficiency of human food production in high-producing Holstein dairy cows in early lactation. Nine multiparous Holstein cows with 65.6 ± 8.5 DIM, milk yield of 55.6 ± 4.5 kg/d, and body weight of 611.3 ± 43.3 kg (mean ± SD) were used in a 3 × 3 Latin square design with 21-d periods. Treatments were (1) control treatment (CT, diet contains corn grain), (2) alternative treatment (AT, diet where corn grain was replaced with CG), and (3) balanced treatment (BT, diet where corn grain was replaced with CG but with the same energy content as CT). Control and balanced diets were isoenergetic (6.61 MJ/kg of DM); however, AT had higher energy (6.77 MJ/kg of DM). Treatments had no effect on dry and organic matter intake. NDF intake, however, was higher in CG diets compared with CT (P = 0.0001). Total-tract digestibility of DM tended to be reduced (P = 0.08), and OM digestibility was reduced (P = 0.05) by the inclusion of CG in diets. Whole and energy-corrected milk production were greater in AT compared with CT and BT (P < 0.05). Milk yield was similar in cows fed CT and BT. Treatments had no effect on milk composition or feed efficiency. Diet CT, when compared with CG diets, had lower efficiency in terms of human-edible feed conversion efficiency (HeFCE) and net food production (P < 0.05). Diet BT had greater HeFCE and net production of human-edible CP than AT (P < 0.05). Plasma BHBA, non-esterified fatty acids, and glucose concentrations were not affected by treatments, but plasma cholesterol was higher in cows that consumed CG diets (P = 0.04). The results indicate that, in high-producing early lactation dairy cows fed high concentrate diets, net food protein production can be substantially improved without lowering milk production through the reduction of dietary starch from 30.2 to 24.8% by replacing corn grain with CG.     

Genome-Wide Analysis of Alternative Splicing in Zea mays during Maize Iranian Mosaic Virus Infection

Plant Molecular Biology Reporter - Maize Iranian mosaic virus (MIMV) infects several gramineous plants and is an economically important nucleorhabdovirus in Iran. Maize responds to MIMV infection...