Pure single-mode Rayleigh-Taylor instability for arbitrary Atwood numbers.

The validity of theoretical investigation on Rayleigh-Taylor instability (RTI) with nonlinearity is quite important, especially for the simplest and the commonest case of a pure single-mode RTI, while its previous explicit solution in weakly nonlinear scheme is found to have several defections. In this paper, this RTI is strictly solved by the method of the potential functions up to the third order at the weakly nonlinear stage for arbitrary Atwood numbers. It is found that the potential solution includes terms of both the stimulating and inhibiting RTI, while the terms of the decreasing RTI are omitted in the classical solution of the weakly nonlinear scheme, resulting in a big difference between these two results. For the pure single-mode cosine perturbation, comparisons among the classical result, the present potential result and numerical simulations, in which the two dimensional Euler equations are used, are carefully performed. Our result is in a better agreement with the numerical simulations than the classical one before the saturation time. To avoid the tedious expressions and improve a larger valid range of the solution, the method of the Taylor expansion is employed and the velocities of the bubble and spike are, respectively, obtained. Comparisons between the improved and the simulation results show that the improved theory can better predict the evolution of the interface from the linear to weakly nonlinear, even to later of the nonlinear stages.

Sca1+Lin-CD117- Mouse Bone Marrow-Derived Mesenchymal Stem Cells Regulate Immature Dendritic Cell Maturation by Inhibiting TLR4-IRF8 Signaling Via the Notch-RBP-J Pathway.

Mesenchymal stem cells (MSCs) have a superior immunomodulatory capacity compared to other cells of the immune system, and they hold great promise for treating various immune disorders. However, their regulatory effects on the maturation of immature dendritic cells (imDCs) are not fully understood. In this study, we show that Sca-1+Lin-CD117-MSCs restrain the lipopolysaccharide-stimulated maturation transition of imDCs cocultured without exogenous cytokines. The Notch signaling pathway plays a critical role in the process by controlling interferon regulatory factor 8 (IRF8) expression in an RBP-J-dependent manner. We observed a high degree of H3K27me3 modification mediated by SUZ12 and a relatively low degree of H3K4me3 modification regulated by WDR5 at the IRF8 promoter during coculture. These data reveal a possible mechanism by which Sca-1+Lin-CD117-MSCs modulate imDC maturation and further support the role of MSCs in treating immune disorders.

Qualitative and quantitative analysis of catechin and quercetin in flavonoids extracted from Rosa roxburghii Tratt.

PURPOSE: To perform a qualitative and quantitative analysis of catechin and quercetin in flavonoids extracted from Rosa roxburghii Tratt. METHODS: Total flavonoids were determined using ultraviolet spectrophotometry (UV) at 500 nm. The optimal gradient program started with 15 % methanol and was kept within a period of 0 - 20 min, while 25 % methanol was kept within 20 - 33 min. Subsequently, the concentration of methanol was reduced to 15 % and was held for 10 min until the next injection. Mass spectrometry spray voltage was 4,000 V, ionization temperature 350 °C, atomizer pressure 35 psi, nitrogen flow rate 8 L/min, and mass scan range 200 - 800 m/z. The detection wavelength used for catechin and quercetin was 270 and 368 nm, respectively. RESULTS: Based on the UV results, Rosa roxburghii Tratt content was 73.85 %, which is in agreement with the national standard. Liquid chromatography-mass spectrometry (LC-MS) results indicate that Rosa roxburghii Tratt flavonoids contained quercetin, 34.26 %, with relative standard deviation (RSD) of 2.88 % and catechin content of 2.97 % with RSD of 1.49 %. CONCLUSION: The proposed measurement method for determining the content of flavonoids in Rosa roxburghii Tratt has the advantage of simplicity, feasibility, good repeatability, and rapid and accurate analysis.

Flavonoids of Rosa roxburghii Tratt Exhibit Anti-Apoptosis Properties by Regulating PARP-1/AIF.

Radioprotection is an important approach to reduce the side-effects of radiotherapy. The radioprotective effect of the flavonoids of Rosa roxburghii Tratt (FRT) has been confirmed, and the mechanism has been identified as theBcl-2/caspase-3/PARP-1 signaling pathway. In this study, we investigated the effects of FRT on the intercellular adhesion molecule (ICAM), and vascular cell adhesion protein (VCAM) in addition to apoptosis-related proteins such as Bax/Bcl-2, p-ERK/ERK, p-p53/p53, and p-p38/p38. In the present study, we focused on the effect of FRT on PARP-1/AIF. Ionizing radiation triggered the activation of PARP-1 and AIF translocation from the mitochondrion to the nucleus. The inhibition of PARP-1/AIF signaling pathway by FRT was investigated. Our results showed that the expressions of Bax/Bcl-2, p-ERK/ ERK, p-p53/p53, and p-p38/p38 were decreased after FRT treatment compared with the radiation-treated group. FRT inhibited PARP-1 activation to inhibit AIF translocation from mitochondrion to nucleus. Pretreatment with FRT diminished the comet's tail and reduced fragments in six Gy-irradiated thymocytes compared with the irradiated cells without FRT treatment. We conclude that FRT enhanced radioprotection at least partially by regulating PARP-1/AIF to reduce apoptosis. J. Cell. Biochem. 118: 3943-3952, 2017. © 2017 Wiley Periodicals, Inc.

Sca-1+Lin-CD117- mesenchymal stem/stromal cells induce the generation of novel IRF8-controlled regulatory dendritic cells through Notch-RBP-J signaling.

Mesenchymal stem/stromal cells (MSCs) can influence the destiny of hematopoietic stem/progenitor cells (HSCs) and exert broadly immunomodulatory effects on immune cells. However, how MSCs regulate the differentiation of regulatory dendritic cells (regDCs) from HSCs remains incompletely understood. In this study, we show that mouse bone marrow-derived Sca-1(+)Lin(-)CD117(-) MSCs can drive HSCs to differentiate into a novel IFN regulatory factor (IRF)8-controlled regDC population (Sca(+) BM-MSC-driven DC [sBM-DCs]) when cocultured without exogenous cytokines. The Notch pathway plays a critical role in the generation of the sBM-DCs by controlling IRF8 expression in an RBP-J-dependent way. We observed a high level of H3K27me3 methylation and a low level of H3K4me3 methylation at the Irf8 promoter during sBM-DC induction. Importantly, infusion of sBM-DCs could alleviate colitis in mice with inflammatory bowel disease by inhibiting lymphocyte proliferation and increasing the numbers of CD4(+)CD25(+) regulatory T cells. Thus, these data infer a possible mechanism for the development of regDCs and further support the role of MSCs in treating immune disorders.

Mesenchymal stem cells inhibit Th17 cells differentiation via IFN-γ-mediated SOCS3 activation.

Mesenchymal stem cells (MSCs) are immunoregulatory, and the administration of them has been shown to ameliorate inflammation caused by Th17 cells. However, the mechanisms that contribute to MSC regulation on Th17 cell development are unclear. Here, we found that MSCs could inhibit Th17 cell differentiation through the activation of suppressors of cytokine signaling 3 (SOCS3) when coculture of MSCs and CD4(+)CD25(low)CD44(low)CD62L(high) T cells. Further analysis demonstrated that the inhibitory action was mediated via interferon gamma (IFN-γ), which activated signal transducer and activator of transcription-1 (STAT1) to enhance the expression of SOCS3, leading to STAT3 inhibition. Moreover, stable and reciprocal changes in H3K4me3 and H3K27me3 at the promoters of STAT1, STAT3 and RORγt determined the fate of Th17 cells. These results demonstrate that MSCs may inhibit Th17 differentiation via IFN-γ that activates SOCS3 leading to immunomodulatory effects, suggesting a possible mechanism by which MSCs could act as a cellular approach to attenuate the clinical and pathological manifestations of some autoimmune diseases.

Mesenchymal stem/stromal cells induce the generation of novel IL-10-dependent regulatory dendritic cells by SOCS3 activation.

Suppression of immune response by mesenchymal stem/stromal cells (MSCs) is well documented. However, their regulatory effects on immune cells, especially regulatory dendritic cells, are not fully understood. We have identified a novel Sca-1(+)Lin(-)CD117(-) MSC population isolated from mouse embryonic fibroblasts (MEF) that suppressed lymphocyte proliferation in vitro. Moreover, the Sca-1(+)Lin(-)CD117(-) MEF-MSCs induced hematopoietic stem/progenitor cells to differentiate into novel regulatory dendritic cells (DCs) (Sca-1(+)Lin(-)CD117(-) MEF-MSC-induced DCs) when cocultured in the absence of exogenous cytokines. Small interfering RNA silencing showed that Sca-1(+)Lin(-)CD117(-) MEF-MSCs induced the generation of Sca-1(+)Lin(-)CD117(-) MEF-MSC-induced DCs via IL-10-activated SOCS3, whose expression was regulated by the JAK-STAT pathway. We observed a high degree of H3K4me3 modification mediated by MLL1 and a relatively low degree of H3K27me3 modification regulated by SUZ12 on the promoter of SOCS3 during SOCS3 activation. Importantly, infusion of Sca-1(+)CD117(-)Lin(-) MEF-MSCs suppressed the inflammatory response by increasing DCs with a regulatory phenotype. Thus, our results shed new light on the role of MSCs in modulating regulatory DC production and support the clinical application of MSCs to reduce the inflammatory response in numerous disease states.

Mesenchymal stem cells inhibit Th17 cell differentiation by IL-10 secretion.

Recent findings indicate that mesenchymal stem cells (MSCs) may act as a regulator of Th17 cell differentiation, however, the underlying mechanism is still under debate. To investigate the underlying mechanisms of MSCs' regulatory effect, mouse bone marrow-derived MSCs were cocultured with mouse CD4(+)CD25(low)CD44(low)CD62L(high) T cells in vitro, and the proportion of induced Th17 cells, cytokines secretion, and transcription factors expression were examined by flow cytometry, enzyme-linked immunosorbent assay, quantitative reverse transcription polymerase chain reaction, and Western blotting. For the first time, our results showed that bone marrow-derived MSCs were able to inhibit Th17 cell differentiation via interleukin (IL)-10 secretion as the Th17 cell proportion was significantly regained when IL-10 was neutralized, or expression of IL-10 by bone marrow-derived MSCs was downregulated by RNA interference technique. Furthermore, IL-10 may suppress expression of Rorγt, the key transcription factor for Th17 cells, both by activating suppressor of cytokine signaling 3 through signal transducers and activators of transcription 5 phosphorylation, and decreasing signal transducers and activators of transcription 3 binding, which is at the promoter of Rorγt. Thus, our results demonstrate the inhibitory effect of MSCs on Th17 cells differentiation, and suggest increased IL-10 secretion might be the key factor.

Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2-dependent regulatory dendritic cell population.

Mesenchymal stem cells (MSCs), in addition to their multilineage differentiation, exert immunomodulatory effects on immune cells, even dendritic cells (DCs). However, whether they influence the destiny of full mature DCs (maDCs) remains controversial. Here we report that MSCs vigorously promote proliferation of maDCs, significantly reduce their expression of Ia, CD11c, CD80, CD86, and CD40 while increasing CD11b expression. Interestingly, though these phenotypes clearly suggest their skew to immature status, bacterial lipopolysaccharide (LPS) stimulation could not reverse this trend. Moreover, high endocytosic capacity, low immunogenicity, and strong immunoregulatory function of MSC-treated maDCs (MSC-DCs) were also observed. Furthermore we found that MSCs, partly via cell-cell contact, drive maDCs to differentiate into a novel Jagged-2-dependent regulatory DC population and escape their apoptotic fate. These results further support the role of MSCs in preventing rejection in organ transplantation and treatment of autoimmune disease.

Double chimerism in recipient by transplantation of two allogeneic MHC-mismatched mouse fetal blood units.

We have constituted a mouse model for fetal blood transplantation (FBT) to cross over major histocompatibility complex (MHC) without causing serious GVHD. It seems that full matching at the MHC appears not necessary for FBT, while the nucleated cell dose is critical. Two fetal blood units were combined from different donors to increase the stem/progenitor cell dose so as to explore the possibility of MHC-mismatched allogeneic transplantation. 26 out of 40 mice in mixed FBT group survived in the observation period of 60 days after transplantation without obvious GVHD. Double chimerism was demonstrated by PCR and flow cytometric analysis; and skin transplantation test proved the induction of donor specific immune tolerance. Our data suggest that two MHC-mismatched allogeneic donor fetal blood units could simultaneously engraft and reconstitute immune and hematopoietic system in a mouse model. The result may be beneficial for the expansion of cord blood application and enables more patients to share the advantages of cord blood transplantation.

[Effects of HLA disparity of two umbilical cord blood units on human engraftment in SCID mice].

OBJECTIVE: To evaluate the feasibility and characteristics of human engraftment in HLA disparate cord blood transplantation. METHODS: Two human HLA-haploidentical or HLA-mismatched cord blood units were transplanted into sublethally irradiated severe combined immunodeficiency (SCID) mice. The characteristics of engraftment, hematopoietic and immunological reconstitution between the two groups were compared. RESULTS: Two mixed cord blood units can engraft in SCID mice with donor-recipient chimerism and reconstitute hematopoiesis and immunological functions. No unfavorable factors had been observed. Only one of the two cord blood units which had higher colony forming ability in vitro could engraft in most SCID mice as shown by HLA-DQB(1) gene detection. Two HLA-haploidentical cord blood units were simultaneously engrafted in 3 SCID mice. CONCLUSION: Double HLA-haploidentical or HLA-mismatched cord blood can engraft in SCID mice and reconstitute hematopoietic and immunological functions. HLA disparity has no significant effect on survival and engrafting rate. However, in less HLA disparity group, two cord blood units were prone to engraft simultaneously.