Poly-L-ornithine blocks the inhibitory effects of fibronectin on oligodendrocyte differentiation and promotes myelin repair

The extracellular matrix surrounding oligodendrocytes plays an important role during myelination and remyelination in the brain.In many cases,the microenvironment surrounding demyelination lesions contains inhibitory molecules,which lead to repair failure.Accordingly,blocking the activity of these inhibitory factors in the extracellular matrix should lead to more successful remyelination.In the central nervous system,oligodendrocytes form the myelin sheath.We performed primary cell culture and found that a natural increase in fibronectin promoted the proliferation of oligodendrocyte progenitors during the initial stage of remyelination while inhibiting oligodendrocyte differentiation.Poly-L-ornithine blocked these inhibitory effects without compromising fibronectin’s pro-proliferation function.Experiments showed that poly-L-ornithine activated the Erk1/2 signaling pathway that is necessary in the early stages of differentiation,as well as PI3K signaling pathways that are needed in the mid-late stages.When poly-L-ornithine was tested in a lysolecithin-induced animal model of focal demyelination,it enhanced myelin regeneration and promoted motor function recovery.These findings suggest that poly-L-ornithine has the potential to be a treatment option for clinical myelin sheath injury.

Quantum entangled fractional Fourier transform based on the IWOP technique

In our previous papers,the classical fractional Fourier transform theory was incorporated into the quantum theoretical system using the theoretical method of quantum optics,and the calculation produced quantum mechanical operators corresponding to the generation of fractional Fourier transform.The core function of the coordinate-momentum exchange operators in the addition law of fractional Fourier transform was analyzed too.In this paper,the bivariate operator Hermite polynomial theory and the technique of integration within an ordered product of operators(IWOP)are used to establish the entanglement fractional Fourier transform theory to the extent of quantum.A new function generating formula and an operator for generating quantum entangled fractional Fourier transform are obtained using the fractional Fourier transform relationship in a pair of conjugated entangled state representations.

Human adipose tissue-and umbilical cord-derived stem cells: which is a better alternative to treat spinal cord injury?

Multiple types of stem cells have been proposed for the treatment of spinal cord injury,but their comparative information remains elusive.In this study,a rat model of T10 contusion spinal cord injury was established by the impactor method.Human umbilical cord-derived mesenchymal stem cells(UCMSCs)or human adipose tissue-derived mesenchymal stem cells(ADMSCs)(2.5μL/injection site,1×10^5 cells/μL)was injected on rostral and caudal of the injury segment on the ninth day after injury.Rats injected with mesenchymal stem cell culture medium were used as controls.Our results show that although transplanted UCMSCs and ADMSCs failed to differentiate into neurons or glial cells in vivo,both significantly improved motor and sensory function.After spinal cord injury,UCMSCs and ADMSCs similarly promoted spinal neuron survival and axonal regeneration,decreased glial scar and lesion cavity formation,and reduced numbers of active macrophages.BioPlex analysis of spinal samples showed a specific increase of interleukin-10 and decrease of tumor necrosis factorαin the ADMSC group,as well as a downregulation of macrophage inflammatory protein 3αin both UCMSC and ADMSC groups at 3 days after cell transplantation.Upregulation of interleukin-10 and interleukin-13 was observed in both UCMSC and ADMSC groups at 7 days after cell transplantation.Isobaric tagging for relative and absolute quantitation proteomics analyses showed that UCMSCs and ADMSCs induced changes of multiple genes related to axonal regeneration,neurotrophy,and cell apoptosis in common and specific manners.In conclusion,UCMSC and ADMSC transplants yielded quite similar contributions to motor and sensory recovery after spinal cord injury via anti-inflammation and improved axonal growth.However,there were some differences in cytokine and gene expression induced by these two types of transplanted cells.Animal experiments were approved by the Laboratory Animal Ethics Committee at Jinan University(approval No.20180228026)on February 28,2018,and the application of human stem cells was approved by the Medical Ethics Committee of Medical College of Jinan University of China(approval No.2016041303)on April 13,2016.

Lentiviral vector-mediated down-regulation of IL-17A receptor in hepatic stellate cells results in decreased secretion of IL-6

AIM: To investigate the mechanism of interleukin (IL)-6 secretion through blocking the IL-17A/IL-17A recepto (IL-17RA) signaling pathway with a short hairpin RNA (shRNA) in hepatic stellate cells (HSCs) in vitro . METHODS: HSCs were derived from the livers of adul male Sprague-Dawley rats. IL-6 expression was evalu ated using real-time quantitative polymerase chain reaction and enzyme linked immunosorbent assay. The phosphorylation activity of p38 mitogen activated pro tein kinases (MAPK) and extracellular regulated pro tein kinases (ERK) 1/2 upon induction by IL-17A and suppression by IL-17RA shRNA were examined using Western blotting.RESULTS: IL-6 expression induced by IL-17A was significantly increased compared to control in HSCs (P < 0.01 in a dose-dependent manner). Suppression of IL17RA using lentiviral-mediated shRNA inhibited IL-6 expression induced by IL-17A compared to group with only IL-17A treatment (1.44 ± 0.17 vs 4.07 ± 0.43, P < 0.01). IL-17A induced rapid phosphorylation of p38 MAPK and ERK1/2 after 5 min exposure, and showed the strongest levels of phosphorylation of p38 MAPK and ERK1/2 at 15 min in IL-17A-treated HSCs. IL-6 mRNA expression induced by IL-17A (100 ng/mL) for 3 h exposure was inhibited by preincubation with specific inhibitors of p38 MAPK (SB-203580) and ERK1/2 (PD-98059) compared to groups without inhibitors preincubation (1.67 ± 0.24, 2.01 ± 0.10 vs 4.08 ± 0.59, P < 0.01). Moreover, lentiviral-mediated IL-17RA shRNA 1 inhibited IL-17A-induced IL-6 mRNA expression compared to random shRNA in HSCs (1.44 ± 0.17 vs 3.98 ± 0.68, P < 0.01). Lentiviral-mediated IL17RA shRNA 1 inhibited phosphorylation of p38 MAPK and ERK1/2 induced by 15 min IL-17A (100 ng/mL) exposure. CONCLUSION: Down-regulation of the IL-17RA receptor by shRNA decreased IL-6 expression induced by IL-17A via p38 MAPK and ERK1/2 phosphorylation in HSCs. Suppression of IL-17RA expression may be a strategy to reduce the inflammatory response induced by IL-17A in the liver.

牛乳酪蛋白源ACE抑制肽的稳定性和毒理特性研究(英文)

研究目的：创新要点：研究方法：重要结论：酸碱热处理对牛乳酪蛋白源血管紧张素转化酶（ACE）抑制肽的抑制活性、游离氨基、色泽及其毒理特性的影响。在pn9.0-12．0的热处理条件下，牛乳酪蛋白源ACE抑制肽的抑制活性降低，色泽加深。热处理后的ACE抑制肽对Caco-2细胞和ECV-304细胞没有毒性作用。以ACE抑制活性、游离氨基、色差值和细胞存活率为检测指标，研究了酸碱热处理对ACE抑制肽的稳定性和毒理特性影响。高温和碱性热处理能破坏酪蛋白源ACE抑制肽的稳定性（见图1～3）。