Effect of mechanical loading and substrate elasticity on the osteogenic and adipogenic differentiation of mesenchymal stem cells

Mesenchymal stem cells (MSCs) are highly sensitive to biomechanics of their extracellular environment. Generally, a higher elasticity of culture substrates can drive cells into the osteogenic lineage, whereas low substrate elasticity results in adipogenesis. Applied mechanical loading by cyclic strain is another major variable influencing cell fate. Yet, little is known about the simultaneous effect of both cues. Therefore, the present study investigated the relative importance of both cues on differentiation. MSCs were cultured in an osteogenic and also an adipogenic environment on soft polyacrylamide (PAAm; E = 23 ± 0.3 kPa), stiff PAAm (111 ± 2 kPa), and polydimethylsiloxane (PDMS; E = 1,5 ± 0.07 MPa) either unstrained or with 8% cyclic strain at 1 Hz. Without strain, the relative expression of the early osteogenic marker alkaline phosphatase (ALP) was significantly higher (78%) on PDMS than on both PAAm. With 8% cyclic strain, ALP expression increased for all groups in comparison with unstrained controls. The highest increase was observed for the soft PAAm by 36%. Moreover, relative oil red O (ORO) expression—indicating adipogenesis—was the highest for unstrained soft PAAm. On the other hand, the percentage of ORO positive cells significantly decreased by 57% and 69% for soft and stiff PAAm when strained. In conclusion, biomaterial elasticity and mechanical loading can act simultaneously on cell differentiation. Substrate elasticity is an important factor, regulating the differentiation, but cyclic strain can drive MSCs towards the osteogenesis even on the softest substrate. As such, the osteogenic effect of mechanical loading can overrule the adipogenic effect of soft substrates, thereby acting as an inhibitor.     

NK026680 inhibits T-cell function in an IL-2-dependent manner and prolongs cardiac allograft survival in rats

NK026680 is a triazolopyrimidine derivative that has been shown to inhibit dendritic cell maturation and activation. Here, we examined the immunosuppressive properties of NK026680 on T-cell function and assessed its immunosuppressive efficacy in an ACI (RT1^av1 haplotype) to Lewis (RT1^l) rat heart transplantation model. The effects of NK026680 on T-cell proliferation, activation, and cytokine production were investigated in vitro. Heart transplant recipient rats were administered NK026680 daily for 14 days post-transplantation. In addition to graft survival time, alloimmune responses and graft histology at 4-10 days post-transplantation were assessed. NK026680 was found to inhibit proliferation, CD25 upregulation, IL-2 production, and cell cycle progression in αCD3/αCD28-stimulated murine T cells. These effects were likely due to suppression of the p38 mitogen-activated protein kinase pathway and the subsequent inhibition of p65, c-Fos, and to a lesser extent, c-Jun. Daily NK026680 treatment suppressed alloimmune responses, prevented cellular infiltration into allografts, and prolonged graft survival. The anti-rejection effects of NK026680 were enhanced by tacrolimus. In conclusion, NK026680 inhibits the activation of T cells and prolongs cardiac allograft survival in rats. These features make it a potential candidate immunosuppressant for the treatment of organ transplant patients in the future.     

Extracellular vesicles and female reproduction

Extracellular vesicles (EVs) are nano-sized membrane bound complexes that have been identified as a mean for intercellular communication between cells and tissues both in physiological and pathological conditions. These vesicles contain numerous molecules involved in signal transduction including microRNAs, mRNAs, DNA, proteins, lipids, and cytokines and can affect the behavior of recipient cells. Female reproduction is dependent on extremely fine-tuned endocrine regulation, and EVs may represent an added layer that contributes to this regulation. This narrative review article provides an update on the research of the role of EVs in female reproduction including folliculogenesis, fertilization, embryo quality, and implantation. We also highlight potential pitfalls in typical EV studies and discuss gaps in the current literature.     

miR-101在宫颈癌组织中的表达及其临床意义

目的:探讨miR-101在宫颈癌组织中的表达及与宫颈癌临床病理特征的关系。方法:应用逆转录实时荧光定量聚合酶链反应(RT-PCR)检测40例宫颈癌组织miR-101水平,以30例子宫肌瘤患者作为正常对照,探讨其表达与宫颈癌临床病理特征的关系。结果:与正常宫颈组织比较,miR-101在宫颈癌组织中表达下调(0.54±0.32)倍,差异有统计学意义(P<0.05)。不同病理分级、间质浸润深度、淋巴结转移宫颈癌患者miR-101表达水平分别比较差异均具有统计学意义(P<0.05),而不同年龄、临床分期、肿瘤直径、绝经与否的宫颈癌患者miR-101表达水平分别比较差异均无统计学意义(P>0.05)。结论:miR-101的表达与宫颈癌的发生、转移和侵袭能力有关,可作为治疗及评价预后的参考指标,并可为肿瘤靶向治疗提供新靶点。     

miR-155和循环系统疾病关系的研究进展

microRNA是一类近年来研究热门的微小RNA分子,在人类多种生理和病理过程中起重要的调节作用,其家族成员miR．155和循环系统疾病关系的研究日益深入而广泛,本文就miR．155和循环系统疾病的诊断、治疗、预后等多方面的关系及其作用机制作一综述。     

Leishmaniasis: vaccine candidates and perspectives

Leishmania is a protozoan parasite and a causative agent of the various clinical forms of leishmaniasis. High cost, resistance and toxic side effects of traditional drugs entail identification and development of therapeutic alternatives. The sound understanding of parasite biology is key for identifying novel drug targets, that can induce the cell mediated immunity (mainly CD4+ and CD8+ IFN-gamma mediated responses) polarized towards a Th1 response. These aspects are important in designing a new vaccine along with the consideration of the candidates with respect to their ability to raise memory response in order to improve the vaccine performance. This review is an effort to identify molecules according to their homology with the host and their ability to be used as potent vaccine candidates.     

Cultivated ginseng suppresses ultraviolet B–induced collagenase activation via mitogen-activated protein kinases and nuclear factor κB/activator protein-1–dependent signaling in human dermal fibroblasts

Cultivated ginseng (CG) (Panax ginseng C.A. Meyer), an herb used in Korean herbal medicine, has been widely used in China and Japan to treat fatigue and to enhance resistance to many diseases. It contains many bioactive constituents, including various ginsenosides that are believed to have antioxidant, immunostimulatory, and antiaging activities. Previous studies have revealed that treatment with Panax ginseng is significantly associated with reduced photoaging, but the underlying mode of action has not been elucidated. In this study, we hypothesized that CG inhibits ultraviolet B (UVB)–induced collagenase activation through mitogen-activated protein kinases (MAPKs) and nuclear factor κB (NF-κB)/activator protein-1 (AP-1)–dependent signaling in human skin fibroblasts. HS68 cells were treated with CG, followed by irradiation with UVB. Those effects were assessed by semiquantitative polymerase chain reaction, Western blotting, and enzymic activity assays. We found that CG increased cell viability and inhibited the production of reactive oxygen species in HS68 cells exposed to UVB irradiation. Pretreatment of HS68 cells with CG inhibited UVB-induced production of matrix metalloproteinase (MMP) 1 and MMP-13. Western blot analysis further revealed that CG markedly suppressed the enhancement of collagen degradation in UVB-exposed HS68 cells. Cultivated ginseng also suppressed UVB-induced activation of NF-κB, c-Jun, and c-Fos and the phosphorylation of MAPKs, which are upstream modulators of NF-κB and AP-1. These results indicate that CG inhibits UVB-induced collagenolytic MMP production by interfering with MAPK/AP-1 and NF-κB signaling and thus may be useful in the prevention and treatment of skin photoaging.