Collagen and non-collagenous proteins molecular crosstalk in the pathophysiology of osteoporosis

Collagenous and non-collagenous proteins (NCPs) in the extracellular matrix, as well as the coupling mechanisms between osteoclasts and osteoblasts, work together to ensure normal bone metabolism. Each protein plays one or more critical roles in bone metabolism, sometimes even contradictory, thus affecting the final mechanical, physical and chemical properties of bone tissue. Anomalies in the amount and structure of one or more of these proteins can cause abnormalities in bone formation and resorption, which consequently leads to malformations and defects, such as osteoporosis (OP). The connections between key proteins involved in matrix formation and resorption are far from being elucidated. In this review, we resume knowledge on the crosstalk between collagen type I and selected NCPs (Transforming Growth Factor-β, Insulin-like Growth Factor-1, Decorin, Osteonectin, Osteopontin, Bone Sialoprotein and Osteocalcin) of bone matrix, focusing on their possible involvement and role in OP. The different elements of this network can be pharmacologically targeted or used for the design/development of innovative regenerative strategies to modulate a feedback loop in bone remodelling.     

Evaluation of different commercial feeds on grow-out silver black porgy,Sparidentex hasta (Valenciennes), for optimum growth performance,fillet quality,and cost of production

The objective of the study was to find a cost-effective feed from three commercial feeds, namely, Arasco (Saudi Arabia), Skretting (Turkey), and Biomar (Greece) for commercially producing silver black porgy (sobaity bream), Sparidentex hasta in Kuwait. For confidentiality, these feeds were randomly given code names, diets 1, 2, and 3, which were known only to the investigating staffs. The trash fish (diet 4) was used as the control. The experiment was conducted for 28 wk with grow-out sobaity bream (210.0 ± 0.51 g) using a flow-through system consisting of twelve 1-m³ tanks. There were three replicates for each treatment. Fish were fed two times daily at satiation level. The results showed that fish fed diet 2 resulted in significantly (P > 0.05) better growth performance, feed utilization, and higher fillet eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content compared to other diets. A comparison of fillet quality of cultured and wild sobaity bream showed no significant (P > 0.05) difference between sensory attributes, except that of ‘flavor’ in cooked fillets of wild sobaity bream. A simple economic analysis showed that the cost per kilogram of fish production was significantly (P > 0.05) the lowest in diet 2 (USD4.13), followed by diet 1 (USD5.70), diet 4 (USD6.33), and diet 3 (USD6.92). Thus, based on growth performance, feed utilization, cost of production, and nutritional quality of fillet, it is concluded that diet 2 may be recommended for commercial culture of sobaity bream in Kuwait. However, future research should focus on how to improve fillet quality of the cultured fish at par with wild fish by manipulating the feed formulation.     

Improvement of γ-decalactone production by stimulating the import of ricinoleic acid and suppressing the degradation of γ-decalactone in Saccharomyces cerevisiae

A number of yeast species can transform ricinoleic acid into γ-decalactone, a high-value compound with fruity aroma, through β-oxidation. This study investigated the effect of l-carnitine on γ-decalactone production by Saccharomyces cerevisiae MF013 to increase the β-oxidation rate. Results showed that l-carnitine shortened the biotransformation period by approximately 10?h and increased γ-decalactone production by 19.5%. γ-Caprolactone, γ-octalactone, and γ-dodecalactone were separately added to the medium to prevent γ-decalactone degradation by yeast cells at the end of biotransformation. γ-Octalactone competitively inhibited γ-decalactone from binding to lactonase, resulting in an 11% increase in γ-decalactone production. This research proposed an effective approach to improve the γ-decalactone production rate, shorten the biotransformation period, and suppress the γ-decalactone degradation in S. cerevisiae.     

The presence of 12β-deoxydecarbamoylsaxitoxin in the Japanese toxic dinoflagellate Alexandrium determined by simultaneous analysis for paralytic shellfish toxins using HILIC-LC–MS/MS

A differential screening study using high-resolution (HR)-hydrophilic interaction chromatography (HILIC)-electrospray ionization (ESI)–quadrupole time-of-flight mass spectrometry (Q-TOF MS) was conducted to identify saxitoxin (STX) analogues in the marine dinoflagellate toxic sub-clone Alexandrium tamarense Axat-2 and the non-toxic sub-clone UAT-014-009 derived from the same Japanese isolate. One unknown compound was identified only in the toxic sub-clone and was found to have the molecular formula C₉H₁₆N₆O₂. This structure differed from that of decarbamoyl STX (dcSTX; C₉H₁₆N₆O₃) by the loss of a single oxygen. A 12-deoxy-dcSTX standard (a mixture of 12α- and β-deoxy-dcSTX) was chemically prepared from dcSTX by reduction with sodium borohydride. The unknown compound in the toxic strain of A. tamarense was identified as 12β-deoxy-dcSTX by comparison of its HR-HILIC-LC–MS retention time and HR–MS/MS spectrum with those of the chemically prepared standard, and the identification was confirmed by high-sensitivity HPLC analysis with post-column fluorescent derivatization. Moreover, two Japanese isolates of A. catenella showing toxin profiles different from that of A. tamarense were also found to contain 12β-deoxy-dcSTX. Previously, 12β-deoxy-dcSTX was isolated from the freshwater cyanobacterium Lyngbya wollei, which produces a unique set of STX analogues. This study is the first evidence of the presence of 12β-deoxy-dcSTX in marine dinoflagellates.     

Comparative growth,cross stress resistance,transcriptomics of Streptococcus pyogenes cultured under low shear modeled microgravity and normal gravity

Streptococcus pyogenes is commonly found on pharynx, mouth and rarely on skin, lower gastrointestinal tract. It is a potential pathogen causing tonsillitis, pneumonia, endocarditis. The present study was undertaken to study the effects of low shear modeled microgravity on growth, morphology, antibiotic resistance, cross-stress resistance to various stresses and alteration in gene expression of S. pyogenes. The growth analysis performed using UV–Visible spectroscopy indicated decrease in growth of S. pyogenes under low shear modeled microgravity. Morphological analysis by Bio-transmission electron microscopy (TEM), Bio-scanning electron microscopy (SEM) did not reveal much difference between normal and low shear modeled microgravity grown S. pyogenes. The sensitivity of S. pyogenes to antibiotics ampicillin, penicillin, streptomycin, kanamycin, hygromycin, rifampicin indicates that the bacterium is resistant to hygromycin. Further S. pyogenes cultured under low shear modeled microgravity was found to be more sensitive to ampicillin and rifampicin as compared with normal gravity grown S. pyogenes. The bacteria were tested for the acid, osmotic, temperature and oxidative cross stress resistances. The gene expression of S. pyogenes under low shear modeled microgravity analyzed by microarray revealed upregulation of 26 genes and down regulation of 22 genes by a fold change of 1.5.     

KLF4在内毒素血症小鼠中的表达模式及其意义

目的探讨Kruppel样因子4（Kruppel-like factor 4，KLF4）在内毒素血症小鼠中的表达模式及意义。方法运用实时荧光PCR技术和Western blot技术，分别从mRNA水平和蛋白水平探讨内毒素血症小鼠肝脏和肺脏中KLF4的表达；运用生物信息学技术，对启动子区含有KLF4的结合位点的炎症介质基因进行了预测；运用RT-PCR技术，从mRNA水平探讨内毒素血症小鼠肝脏和肺脏中IL1β的表达模式。结果内毒素血症小鼠肝脏和肺脏中KLF4 mRNA的表达下凋，KLF4蛋白的表达先下凋后升高；IL-18、IL-15、IL-12、IL-18、IL-10等炎症介质基因的启动子区均含有KLF4的结合元件，这些炎症基因的表达可能直接受到KLF4的调控；内毒素血症小鼠肝脏和肺脏中IL-IB的表达模式与KLF4的表达模式呈相反趋势。结论内毒素血症小鼠肝脏和肺脏中KLF4表达下调，KLF4在炎症介质基因表达调控中可能具有重要作用。     

Ecological variations and role of heat shock protein in Artemisia judaica L. in response to temperature regimes of Tabuk,Saudi Arabia

Artemisia judaica L. (Compositae) are shrubby herbs growing wildly in Tabuk region and distributed in the desert regions. This region is characterized by extremely variable environmental conditions where the temperature varies from extreme low to extreme high. These temperature regimes have a profound effect on morphology, growth physiology and biochemistry of the plants. The plant samples were collected from Tabuk–Jordan road (760 m above sea level) in the month of January, April, July and October 2013 to evaluate the effect of temperature dynamics on A. judaica L. in four different seasons. Physiological, biochemical alterations and heat shock proteins (HSPs) were studied during these seasons in order to evaluate the environmental adaptation and stress tolerance in response to temperature variations. Plant growth parameters showed a significant increase in height, fresh and dry matter accumulation, total chlorophyll, nitrogen, phosphorus, potassium, artemisinin and leaf relative water contents investigated in the month of April and October. Growth of plant was suppressed and an active role of carbonic anhydrase (CA), catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) was observed to cope with the extreme low temperature in January and extreme high temperature in July 2013. However, the plants collected in October and April did not show a statistical difference. Inductions in the expression of HSP90 were recorded in all the plants collected during April and October 2013 with no statistically significant difference. Therefore, based on the results it is recommended that during April and October the environmental conditions are best suitable for growth, development and medicinal use of Artemisia.     

Insulin Receptor Substrate 2-mediated Phosphatidylinositol 3-kinase Signaling Selectively Inhibits Glycogen Synthase Kinase 3β to Regulate Aerobic Glycolysis

Insulin receptor substrate 1 (IRS-1) and IRS-2 are cytoplasmic adaptor proteins that mediate the activation of signaling pathways in response to ligand stimulation of upstream cell surface receptors. Despite sharing a high level of homology and the ability to activate PI3K, only Irs-2 positively regulates aerobic glycolysis in mammary tumor cells. To determine the contribution of Irs-2-dependent PI3K signaling to this selective regulation, we generated an Irs-2 mutant deficient in the recruitment of PI3K. We identified four tyrosine residues (Tyr-649, Tyr-671, Tyr-734, and Tyr-814) that are essential for the association of PI3K with Irs-2 and demonstrate that combined mutation of these tyrosines inhibits glucose uptake and lactate production, two measures of aerobic glycolysis. Irs-2-dependent activation of PI3K regulates the phosphorylation of specific Akt substrates, most notably glycogen synthase kinase 3β (Gsk-3β). Inhibition of Gsk-3β by Irs-2-dependent PI3K signaling promotes glucose uptake and aerobic glycolysis. The regulation of unique subsets of Akt substrates by Irs-1 and Irs-2 may explain their non-redundant roles in mammary tumor biology. Taken together, our study reveals a novel mechanism by which Irs-2 signaling preferentially regulates tumor cell metabolism and adds to our understanding of how this adaptor protein contributes to breast cancer progression.     

The Mitogen-activated Protein (MAP) Kinases p38 and Extracellular Signal-regulated Kinase (ERK) Are Involved in Hepatocyte-mediated Phenotypic Switching in Prostate Cancer Cells

The greatest challenge for the seeding of cancer in metastatic sites is integration into the ectopic microenvironment despite the lack of an orthotopic supportive environment and presence of pro-death signals concomitant with a localized “foreign-body” inflammatory response. In this metastatic location, many carcinoma cells display a reversion of the epithelial-to-mesenchymal transition that marks dissemination in the primary tumor mass. This mesenchymal to epithelial reverting transition (MErT) is thought to help seeding and colonization by protecting against cell death. We have previously shown that hepatocyte coculture induces the re-expression of E-cadherin via abrogation of autocrine EGFR signaling pathway in prostate cancer (PCa) cells and that this confers a survival advantage. Herein, we show that hepatocytes educate PCa to undergo MErT by modulating the activity of p38 and ERK1/2. Hepatocytes inhibited p38 and ERK1/2 activity in prostate cancer cells, which allowed E-cadherin re-expression. Introduction of constitutively active MEK6 and MEK1 to DU145 cells cocultured with hepatocytes abrogated E-cadherin re-expression. At least a partial phenotypic reversion can be achieved by suppression of p38 and ERK1/2 activation in DU145 cells even in the absence of hepatocytes. Interestingly, these mitogen-activated protein kinase activities were also triggered by re-expressed E-cadherin leading to p38 and ERK1/2 activity in PCa cells; these signals provide protection to PCa cells upon challenge with chemotherapy and cell death-inducing cytokines. We propose that distinct p38/ERK pathways are related to E-cadherin levels and function downstream of E-cadherin allowing, respectively, for hepatocyte-mediated MErT and tumor cell survival in the face of death signals.