Methylbenzoxime as a therapeutic agent for glucocorticoid-induced osteoporosis in rats

Purpose: To investigate the effect of methylbenzoxime on dexamethasone-induced rat model of osteoporosis. Methods: Osteoporosis rat model was prepared by administration of dexamethasone to rats for sixty days. The rats were then divided into five groups of five animals each: normal control, untreated, and 2, 5 and 10 mg/kg treatment groups. All rats were administered dexamethasone for 60 days. Thereafter, rats in the three treatment groups received daily doses of 2, 5 or 10 mg/kg methylbenzoxime for 15 days, while rats in normal control and untreated groups were given equivalent volumes of normal saline in place of methylbenzoxime. After treatment, the rats were sacrificed, and the femur removed for histological assessment of pathological changes using H&E staining. Expressions of Wntn signalling pathway proteins in osteoblasts were assayed using reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot assays. Results: Methylbenzoxime inhibited osteoblast proliferation, as revealed from 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide (MTT) assay. It increased the expression of osteoprotegerin and downregulated receptor activator for nuclear factor-kappa B ligand. Dexamethasone decreased the expression of Wnt signalling pathway proteins in osteoblasts. However, treatment of the dexamethasone-exposed osteoblasts with methylbenzoxime reversed the inhibition of expressions of Wnt signalling pathway proteins. In vivo studies showed that methylbenzoxime treatment mitigated dexamethasone-induced pathological features in femur. In osteoporotic rats, methylbenzoxime significantly up-regulated the expression of osteocalcin but down-regulated the level of collagen-type I fragments, relative to the untreated group. The effect was significant in the 5 and 10 mg/kg treatment groups, when compared with 2 mg/kg group. Conclusion: Methylbenzoxime prevents dexamethasone-induced osteoporosis in vitro and in rats. Therefore, it is a potential therapeutic agent for the management of osteoporosis

Petrology, geochemistry and geochronology of the Zhongcang ophiolite, northern Tibet: implications for the evolution of the Bangong-Nujiang Ocean

Ophiolites are widespread along the Bangong-Nujiang suture zone, northern Tibet. However, it is still debated on the formation ages and tectonic evolution process of these ophiolites. The Zhongcang ophiolite is a typical ophiolite in the western part of the Bangong-Nujiang suture zone. It is composed of serpentinized peridotite, cumulate and isotropic gabbros, massive and pillow basalts, basaltic volcanic breccia, and minor red chert. Zircon SHRIMP U–Pb dating for the isotropic gabbro yielded weighted mean age of 163.4 ± 1.8 Ma. Positive zircon ɛHf(t) values (+15.0 to +20.2) and mantle-like δ18O values (5.29 ± 0.21)‰ indicate that the isotropic gabbros were derived from a long-term depleted mantle source. The isotropic gabbros have normal mid-ocean ridge basalt (N-MORB) like immobile element patterns with high MgO, low TiO2 and moderate rare earth element (REE) abundances, and negative Nb, Ti, Zr and Hf anomalies. Basalts show typical oceanic island basalt (OIB) geochemical features, and they are similar to those of OIB-type rocks of the Early Cretaceous Zhongcang oceanic plateau within the Bangong-Nujiang Ocean. Together with these data, we suggest that the Zhongcang ophiolite was probably formed by the subduction of the Bangong-Nujiang Ocean during the Middle Jurassic. The subduction of the Bangong-Nujiang Tethyan Ocean could begin in the Early–Middle Jurassic and continue to the Early Cretaceous, and finally continental collision between the Lhasa and Qiangtang terranes at the west Bangong-Nujiang suture zone probably has taken place later than the Early Cretaceous (ca. 110 Ma). Keywords: Tibetan plateau, Bangong-Nujiang suture zone, Ophiolite, Geochronology, Geochemistry, Subductio

SAMHD1 Attenuates Acute Inflammation by Maintaining Mitochondrial Function in Macrophages via Interaction with VDAC1

Over-activation of Toll-like receptor 4 (TLR4) is the key mechanism in Gram-negative bacterial infection-induced sepsis. SAM and HD domain-containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) inhibits multiple viruses, but whether it plays a role during bacterial invasion remains unelucidated. Monocyte-macrophage specific Samhd1 knockout (Samhd1−/−) mice and Samhd1−/− macrophage cell line RAW264.7 were constructed and used as research models to evaluate the role of SAMHD1 in TLR4-activated inflammation. In vivo, LPS-challenged Samhd1−/− mice showed higher serum inflammatory factors, accompanied with more severe inflammation infiltration and lower survival rate. In vitro, Samhd1−/− peritoneal macrophages had more activated TLR4 pathway upon LPS-stimulation, accompanied with mitochondrial depolarization and dysfunction and a higher tendency to be M1-polarized. These results could be rescued by overexpressing full-length wild-type SAMHD1 or its phospho-mimetic T634D mutant into Samhd1−/− RAW264.7 cells, whereas the mutants, dNTP hydrolase-function-deprived H238A and phospho-ablative T634A, did not exert the same effect. Lastly, co-IP and immunofluorescence assays confirmed that SAMHD1 interacted with an outer mitochondrial membrane-localized protein, voltage-dependent anion channel-1 (VDAC1). SAMHD1 inhibits TLR4-induced acute inflammation and M1 polarization of macrophages by interacting with VDAC1 and maintaining mitochondria function, which outlines a novel regulatory mechanism of TLR signaling upon LPS stimulation

Solutions of food polysaccharide blends for edible films production

The study of the rheological properties of aqueous solutions of starch blends with sodium alginate and agar-agar as well as the physico-mechanical properties of bicomponent films on their basis has been carried out. The extreme behavior of polymer blends with low content of one of the polymers is described in terms of mutual solubility or thermodynamic compatibility. There is a tendency of mechanical properties and water solubility increase with the increasing of SA and AA polymers in corn starch matrix. Obtained data evidence the benefits of bicomponent films production instead of starch-based films

Solutions of food polysaccharide blends for edible films production

The study of the rheological properties of aqueous solutions of starch blends with sodium alginate and agar-agar as well as the physico-mechanical properties of bicomponent films on their basis has been carried out. The extreme behavior of polymer blends with low content of one of the polymers is described in terms of mutual solubility or thermodynamic compatibility. There is a tendency of mechanical properties and water solubility increase with the increasing of SA and AA polymers in corn starch matrix. Obtained data evidence the benefits of bicomponent films production instead of starch-based films