The miR-665/SOST Axis Regulates the Phenotypes of Bone Marrow Mesenchymal Stem Cells and Osteoporotic Symptoms in Female Mice.

Osteoporosis is a common degenerative skeletal disease among older people, especially postmenopausal women. Bone marrow mesenchymal stem cells (BMSCs), the progenitors of osteoblasts, are essential to the pathophysiology of osteoporosis. Herein, targeting miRNAs with differential expression in dysfunctional BMSCs was accomplished by bioinformatics analysis based on public databases. Target mRNAs were predicted and applied for signaling pathway and function enrichment annotations. In vitro and in vivo effects of selected miRNA on BMSC proliferation and osteogenesis were investigated, the putative binding between selected miRNA and predicted target mRNA was verified, and the co-effects of the miRNA/mRNA axis on BMSCs were determined. miRNA 665 (miR-665) was down-regulated in osteoporotic BMSCs compared with normal BMSCs and elevated in BMSCs experiencing osteogenic differentiation. In BMSCs, miR-665 overexpression promoted cell proliferation and osteogenic differentiation. miR-665 targeted the Wnt signaling inhibitor sclerostin (SOST) and inhibited SOST mRNA and protein expression. SOST overexpression inhibited BMSC cell proliferation and osteogenic differentiation. When co-transduced to BMSCs, SOST knockdown significantly reversed the effects of miR-665 on BMSCs. In ovariectomy (OVX)-induced osteoporosis model mice, OVX remarkably decreased bone mass, whereas miR-665 overexpression partially improved OVX-induced bone mass loss. miR-665 was down-regulated in osteoporotic BMSCs and up-regulated in osteogenically differentiated BMSCs. In conclusion, the miR-665/SOST axis modulates BMSC proliferation, osteogenic differentiation, and OVX-induced osteoporosis in mice, possibly through Wnt signaling.

Synthesis of α-allenic aldehydes/ketones from homopropargylic alcohols using a visible-light irradiation system.

A visible-light irradiation tandem oxidative aryl migration/carbonyl formation reaction, mediated by K2S2O8 and visible-light photoredox catalysis, has been discovered. The presented transformation provides a straightforward access to important α-allenic aldehyde/ketone derivatives from readily available homopropargylic alcohol derivatives in a regioselective manner of 1,4-aryl shift concomitant with carbonyl formation. The operational simplicity and broad substrate scope demonstrate the great potential of this method for the synthesis of highly functional α-allenic aldehyde/ketone derivatives.

Effect of konjac glucomannan-based preservation pads on quality changes in refrigerated large yellow croaker (Pseudosciaena crocea).

The purpose of this study was to evaluate the preservation effects of konjac glucomannan (KGM)/oregano essential oil (OEO) Pickering emulsion-based pads (K/OPE pads) on large yellow croaker (Pseudosciaena crocea) fillets stored at 4 °C. The K/OPE pads were fabricated using a freeze-drying technique. The homogeneous distribution of the OEO Pickering emulsions in the KGM matrix was observed using scanning electron microscopy. Fourier transform infrared spectroscopy confirmed that the OEO emulsions were encapsulated in the KGM and there was hydrogen bonding interaction between them. Compared with the KGM pads, the K/OPE pad groups demonstrated enhanced antioxidant and antimicrobial properties. When the content of OPE was increased from 20 % to 40 %, the antioxidant performance of the K/OPE pads increased from 48.09 % ± 0.03 % to 86.65 % ± 0.02 % and the inhibition range of Escherichia coli and Staphylococcus aureus increased to 13.84 ± 0.81 and 16.87 ± 1.53 mm, respectively. At the same time, K/OPE pads were more effective in inhibiting the formation of total volatile alkaline nitrogen and the production of thiobarbituric acid-reactive substances, thereby helping in reducing water loss and maintaining the muscle tissue structure of fish fillets for a longer storage time. Consequently, these K/OPE40 pads extended the shelf life of the fish fillets by an additional 4 days and delayed spoilage during refrigerated storage. The findings suggest that the K/OPE pads can effectively safeguard the quality of refrigerated large yellow croaker fillets, presenting their potential as an active packaging material in the fish preservation industry.

Decreased cerebral perfusion and oxidative stress result in acute and delayed cognitive impairment.

Chronic cerebral hypoperfusion (CCH) is common in the pathogenesis of cognitive impairment, in which oxidative stress plays an important role. Here we describe an alternative rat model for CCH that involves two-stage, three-vessel occlusion (2s-3VO) and compare its effects with those of permanent bilateral occlusion (2VO) of the common carotid arteries. Real-time cerebral blood flow (CBF) during the surgery was monitored. Spatial learning and memory were tested with the Morris water maze, and oxidative damage was evaluated by measuring malondialdehyde (MDA) levels in both the hippocampus and cortex. We found that the CBF drop in the early stage of the 2s-3VO model was more modest than that in the 2VO model. Like 2VO rats, 2s-3VO rats showed impaired spatial learning and memory and increased MDA levels 8 weeks after surgery. Interestingly, when pooling observations from previous studies, we confirmed that oxidative damage appeared later than spatial learning and memory deficits but lasted longer than did cerebral hypoperfusion. Thus, the 2s-3VO model appears to be a suitable model for the study of CCH. Moreover, data support the notion that cognitive impairment in CCH rat models may be induced early by cerebral hypoperfusion early and in a later phase by oxidative stress.

An enriched environment reverses the synaptic plasticity deficit induced by chronic cerebral hypoperfusion.

Chronic cerebral hypoperfusion (CCH) leads to a long-term, inadequate blood supply in the brain, which eventually causes cognitive impairment. An enriched environment (EE) improves learning and memory by improving synaptic plasticity. The impact of an EE on cognitive impairment induced by CCH is not, however, well known. To investigate this possible effect, we permanently occluded the bilateral common carotid arteries (2-vessel occlusion) in rats to induce CCH and studied EE effects on cognitive impairment and synaptic plasticity following CCH. We found that EE treatment reversed spatial memory deficits induced by CCH. An EE also reversed the deficit in long-term potentiation following CCH, but the input-output curves and paired-pulse facilitation were not affected. CCH led to reduced expression of phosphorylated CREB in the rats, but EE reversed this reduction. In addition, CCH reduced the expression of synaptophysin and microtubule-associated protein 2, whereas EE reversed this reduced expression. Thus, EE reversed CCH-induced spatial cognitive impairment without affecting basal synaptic transmission or the release probability of presynaptic neurotransmitters. The EE effect probably resulted from the regulation of postsynaptic potentiation.