Oncostatin M regulates hematopoietic stem cell (HSC) niches in the bone marrow to restrict HSC mobilization.

We show that pro-inflammatory oncostatin M (OSM) is an important regulator of hematopoietic stem cell (HSC) niches in the bone marrow (BM). Treatment of healthy humans and mice with granulocyte colony-stimulating factor (G-CSF) dramatically increases OSM release in blood and BM. Using mice null for the OSM receptor (OSMR) gene, we demonstrate that OSM provides a negative feed-back acting as a brake on HSPC mobilization in response to clinically relevant mobilizing molecules G-CSF and CXCR4 antagonist. Likewise, injection of a recombinant OSM molecular trap made of OSMR complex extracellular domains enhances HSC mobilization in poor mobilizing C57BL/6 and NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ mice. Mechanistically, OSM attenuates HSC chemotactic response to CXCL12 and increases HSC homing to the BM signaling indirectly via BM endothelial and mesenchymal cells which are the only cells expressing OSMR in the BM. OSM up-regulates E-selectin expression on BM endothelial cells indirectly increasing HSC proliferation. RNA sequencing of HSCs from Osmr-/- and wild-type mice suggest that HSCs have altered cytoskeleton reorganization, energy usage and cycling in the absence of OSM signaling in niches. Therefore OSM is an important regulator of HSC niche function restraining HSC mobilization and anti-OSM therapy combined with current mobilizing regimens may improve HSPC mobilization for transplantation.

The Effect of Sustainability-Related Information on the Sensory Evaluation and Purchase Behavior towards Salami Products.

Consumer's interest in sustainable livestock farming methods has grown in response to concerns for the environment and animal welfare. The purpose of this study is to examine the different influences of sustainability product information on sensory characteristics and purchase behaviors. To accomplish this aim, the study used salami, which is an Italian-style sausage processed by fermentation and drying. Three different types of information were provided: salami made from the pork of an antibiotic-free pig (SMAFP), of an animal welfare pig (SMAWP), and of a grazing pig (SMGP). This study was conducted as an off-line experiment with Korean participants (n=140). As a result, there were sensory differences according to the sustainability information. For the SMAFP, it had a significant difference in, sourness (p<0.05). With the SMAWP, there was a difference in gumminess (p<0.10), and the SMGP had significant differences in sourness (p<0.01), sweetness (p<0.01), andmoisture (p<0.05). Moreover, the purchase intention and willingness to pay were significantly higher when the sustainability information was given. Especially, among the three types of salamis, participants were willing to pay the most for the SMAWP. This is one of the first consumer studies to investigate sensory evaluation and purchase behavior for various types of sustainable livestock production. These results contribute by helping sustainable meat producers and marketers become aware of the kind of sustainable information to which consumers are sensitive.

Donor-intrinsic variables determine mobilization efficiency: analyses from a cohort of sixty twice-mobilized stem cell donors.

BACKGROUND: Healthy volunteer registry donors have become the backbone of stem cell transplantation programs. While most registrants will never become actual donors, a small minority are called upon twice, most commonly for the same patient because of poor graft function. Anecdotal evidence provides no hard reasons to disallow second-time mobilized apheresis, but few centers have treated enough two-time donors for definitive conclusions. Moreover, for reasons unknown, the efficiency of G-CSF varies greatly between donations. METHODS: Comparison of outcomes of first vs. second donations can formally confirm G-CSF responsiveness as intrinsically, likely genetically, determined. In our database, we identified 60 donors (1.3%) who received two cycles of G-CSF 24 days to 4 years apart and systematically compared mobilization outcomes. RESULTS: First and second mobilization and collection proceeded without severe or unusual adverse effects. First-time mobilization efficiency was highly predictive of second-time mobilization. Neither mobilization efficiency nor time lag between donations affected the similarity of first- and second-time mobilization outcomes. CONCLUSIONS: With the caveat that only donors with an unremarkable first donation were cleared for a second, our data indicate that a second donation is feasible, equally tolerable as a first donation, and efficient. Moreover, the data strongly support the notion of donor-intrinsic variables dictating mobilization response and argue against relevant damage to the stem cell compartment during mobilization with rhG-CSF.

Modest and nonessential roles of the endocannabinoid system in immature hematopoiesis of mice.

Endocannabinoids are lipid mediators that signal via several seven-transmembrane domain G protein-coupled receptors. The endocannabinoid receptor CB2 is expressed on blood cells, including stem cells, and mediates the effects of cannabinoids on the immune system. The role of the endocannabinoid system in immature hematopoiesis is largely elusive. Both direct effects of endocannabinoids on stem cells and indirect effects through endocannabinoid-responsive niche cells like macrophages have been reported. Using two different CB2-deficient mouse models, we studied the role of the endocannabinoid system in immature hematopoiesis. Moreover, we utilized both models to assess the specificity of putative CB2 agonists. As heterodimerization of CB2 and CXCR4, which is highly expressed on hematopoietic stem cells, has already been described, we also assessed potential consequences of CB2 loss for CXCR4/CXCL12 signaling. Overall, no differential effects were observed with any of the compounds tested; the compounds barely induced signaling by themselves, whereas they attenuated CXCL12-induced signals in both CB2-competent and CB2-deficient cells. In vivo experiments were therefore by necessity restricted to loss-of-function studies in knockout (CB2-/-) mice: Except for mild lymphocytosis and slightly elevated circulating progenitor cells, homeostatic hematopoiesis in CB2-/- mice appears to be entirely normal. Mobilization in response to pharmacological stimuli, Plerixafor or G-CSF, was equally potent in wild-type and CB2-/- mice. CB2-/- bone marrow cells reconstituted hematopoiesis in lethally irradiated recipients with engraftment kinetics indistinguishable from those of wild-type grafts. In summary, we found the endocannabinoid system to be largely dispensable for normal murine hematopoiesis.

Advanced strategy to produce insecticidal destruxins from lignocellulosic biomass Miscanthus.

BACKGROUND: Biorefineries are widely recognized as the most feasible solution to the problem of achieving environmental sustainability along with economic growth. Furthermore, pine wilt disease has caused severe environmental and economic damage worldwide to date. Herein, a highly efficient, advanced process for producing destruxins (DTXs) from Miscanthus (MCT) is reported, along with an application strategy. RESULTS: The acetic acid-sodium chlorite pretreatment of MCT (AASC-MCT) is found to improve the monosaccharide production. Through biocatalytic conversion processes (simultaneous saccharification and cultivation), Metarhizium anisopliae JEF-279 can efficiently produce DTXs from 1% (w/v) AASC-MCT, i.e., DTX E (334.8 mg/L), A (288.8 mg/L), and B (48.6 mg/L). Monochamus alternatus (MA, Japanese pine sawyer) is known to act as a mediator transferring Bursaphelenchus xylophilus to pinewood. As B. xylophilus is associated with the occurrence of pine wilt disease, biological control of MA is a major strategy or controlling this disease. In this study, upon the application of a mixture of DTXs and protease-containing culture filtrate (PCF), complete mortality of MA is observed after a 5-day incubation. The MA immune system response is believed to cause an overexpression of actin and tropomyosin as a defense mechanism against the flaccid paralysis induced by the DTXs and PCF treatment. CONCLUSIONS: These results suggest that MCT can be used as a major feedstock in the biorefinery industry and that DTXs can be applied as an insecticide for biological control of pine wilt disease via MA termination.

Biorefining Process of Carbohydrate Feedstock (Agricultural Onion Waste) to Acetic Acid.

The biorefining of agricultural waste into green chemicals has clear potential for improving global environmental sustainability. In this study, we evaluated the potential of acetic acid production from carbohydrate feedstock (onion waste, OW) as a more environmentally friendly source than feedstock produced from natural gas. In particular, OW is an ideal feedstock for the biorefining process as it contains a sufficient amount of carbohydrates (69.7%). Five days of the simultaneous saccharification and two-step fermentation (SSTF) process produced acetic acid from OW more efficiently than the simultaneous saccharification and cofermentation (SSCF) process. SSTF produced 19.3 g/L acetic acid and recorded the highest conversion yield (90.5%) from OW (6% substrate loading, w/v). These results suggested that acetic acid can be efficiently and sustainably produced from OW by the SSTF process.

Biological properties of butanol extracts from green pine cone of Pinus densiflora.

This study examined the biological functions of the butanol extracts of green pine cones (GPCs) that had not ripened completely. The butanol extracts of GPC showed 78.22% DPPH-scavenging activity, 53.55% TEAC and 71.50% hyaluronidase (HAase) inhibition activity. They also exhibited inhibition activity against food poisoning microorganisms. The contents of total phenolic compounds and total flavonoids were 296.75 and 26.07 mg/g, respectively. Biologically active compounds were analyzed and separated using HPLC related to the DPPH-scavenging and HAase inhibition activities. Gallotannin was the primary biologically active compound with DPPH-scavenging and HAase inhibition activities in the GPC butanol extracts.

Optimal Fermentation Conditions of Hyaluronidase Inhibition Activity on Asparagus cochinchinensis Merrill by Weissella cibaria.

This study was conducted to evaluate the hyaluronidase (HAase) inhibition activity of Asparagus cochinchinesis (AC) extracts following fermentation by Weissella cibaria through response surface methodology. To optimize the HAase inhibition activity, a central composite design was introduced based on four variables: the concentration of AC extract (X1: 1-5%), amount of starter culture (X2: 1-5%), pH (X3: 4-8), and fermentation time (X4: 0-10 days). The experimental data were fitted to quadratic regression equations, the accuracy of the equations was analyzed by ANOVA, and the regression coefficients for the surface quadratic model of HAase inhibition activity in the fermented AC extract were estimated by the F test and the corresponding p values. The HAase inhibition activity indicated that fermentation time was most significant among the parameters within the conditions tested. To validate the model, two different conditions among those generated by the Design Expert program were selected. Under both conditions, predicted and experimental data agreed well. Moreover, the content of protodioscin (a well-known compound related to anti-inflammation activity) was elevated after fermentation of the AC extract at the optimized fermentation condition.

Inhibition of cyclooxygenase-1 and -2 activity in keratinocytes inhibits PGE2 formation and impairs vascular endothelial growth factor release and neovascularisation in skin wounds.

Inhibition of cyclooxygenase (Cox) enzymatic activity by non-steroidal anti-inflammatory drugs (NSAIDs) provides the molecular basis of analgesia following wounding or surgery. This study investigated the role of Cox activity in the regulation of vascular endothelial growth factor (VEGF) expression in keratinocytes and the formation of new blood vessels in acute wounds in mice. To this end, human HaCaT keratinocytes were stimulated with epidermal growth factor (EGF). EGF increased Cox-1 mRNA in the presence of the constitutively expressed Cox-1 protein in keratinocytes. EGF coinduced Cox-2 and VEGF165 mRNA and protein expression and an accumulation of prostaglandin E2 (PGE2 ) in cell culture supernatants. Inhibition of Cox isozyme activity by Cox-1 and -2 siRNA or ibuprofen reduced PGE2 and VEGF165 release from keratinocytes. In a mouse model of excisional wound healing, Cox-2 and VEGF165 expression were colocalized in the granulation tissue of acute wounds. Oral treatment of mice with the Cox-1 and -2 inhibitor diclofenac was associated with reduced levels of VEGF165 protein and an impaired blood vessel formation in acute wound tissue. In summary, our data suggest that a reduction of PGE2 -triggered VEGF165 protein expression in wound keratinocytes is likely to contribute to the observed impairment of wound neovascularisation upon Cox inhibition.