Accuracy Improvement of Braking Force via Deceleration Feedback Functions Applied to Braking Systems.

Currently, braking control systems used in regional railways are open-loop systems, such as metro and tramways. Given that the performance of braking can be influenced by issues such as wheel sliding or the properties of the friction components present in brake systems, our study puts forward a novel closed-loop mechanism to autonomously stabilize braking performance. It is able to keep train deceleration close to the target values required by the braking control unit (BCU), especially in terms of the electrical-pneumatic braking transform process. This method fully considers the friction efficiency characteristics of brake pads and encompasses running tests using rolling stock. The test results show that the technique is able to stabilize the actual deceleration at a closer rate to the target deceleration than before and avoid wheel sliding protection (WSP) action, especially during low-speed periods.

Recent advances in the therapeutic efficacy of hepatocyte growth factor gene-modified mesenchymal stem cells in multiple disease settings.

Mesenchymal stem cell (MSC) therapy is considered a new treatment for a wide range of diseases and injuries, but challenges remain, such as poor survival, homing and engraftment rates, thus limiting the therapeutic efficacy of the transplanted MSCs. Many strategies have been developed to enhance the therapeutic efficacy of MSCs, such as preconditioning, co-transplantation with graft materials and gene modification. Hepatocyte growth factor (HGF) is secreted by MSCs, which plays an important role in MSC therapy. It has been reported that the modification of the HGF gene is beneficial to the therapeutic efficacy of MSCs, including diseases of the heart, lung, liver, urinary system, bone and skin, lower limb ischaemia and immune-related diseases. This review focused on studies involving HGF/MSCs both in vitro and in vivo. The characteristics of HGF/MSCs were summarized, and the mechanisms of their improved therapeutic efficacy were analysed. Furthermore, some insights are provided for HGF/MSCs' clinical application based on our understanding of the HGF gene and MSC therapy.

Long-term hypoxia inhibits the passage-dependent stemness decrease and senescence increase of human dental pulp stem cells.

Dental pulp stem cells (DPSCs) derived from discarded orthodontic teeth are easily obtained and have become a promising source for mesenchymal stem cell-based therapy. However, the pulp tissue is limited, and long-term culture induces cell senescence. Hypoxic culture was expected to be suitable for DPSC expansion, but the results have been contradictory. The aim of this study was to verify the effect of hypoxic culture on human DPSCs (hDPSCs). hDPSCs were isolated and cultured in normoxic (ambient O2 concentration) and hypoxic (5% O2) environments from passage 3 (P3) to P6. The biological characteristics of the cells at P4 (short-term culture) and P6 (long-term culture) were evaluated, including the expression of surface markers, cellular proliferation activity, cellular senescence, and spontaneous and induced differentiation. The results showed that the morphology, phenotype, and proliferation activity of hDPSCs were not affected by hypoxic culture. Long-term normoxic culture of hDPSCs induced cell stemness loss and cell senescence, while hypoxic culture could alleviate these effects. The expression of the stemness markers STRO-1 and OCT4 was increased and the number of senescent cells and the expression of the senescence-related genes P53 and TGF-ß were reduced by long-term hypoxic culture. Spontaneous osteogenic and adipogenic differentiation did not occur during long-term normoxic culture. However, hypoxic culture suppressed the expression of the osteogenic markers ALP and RUNX-2 and the adipogenic markers PPAR-γ and FABP4. The induced osteogenic and adipogenic differentiation was apparently reduced by hypoxic culture as well. Our findings indicate that long-term hypoxia culture is beneficial to the maintenance of hDPSCs' biological characteristics and provide some insights into their large-scale expansion.

Overexpression of Hepatocyte Growth Factor in Dental Pulp Stem Cells Ameliorates the Severity of Psoriasis by Reducing Inflammatory Responses.

Psoriasis is an autoimmune disease still lacking standard treatment, and it has been demonstrated that mesenchymal stem cells (MSCs) are capable of immunoregulation. The underlying mechanism might involve the secretion of soluble cytokines, such as hepatocyte growth factor (HGF). This study aims to investigate the therapeutic effect of HGF-overexpressed dental pulp stem cells (DPSCs) [DPSCs; HGF overexpressed DPSCs (HGF-DPSCs)] on imiquimod-induced psoriasis. DPSCs were isolated and transfected by adenovirus vector carrying HGF gene (Ad-HGF). The immunoregulatry abilities of DPSCs and HGF-DPSCs were investigated by coculture of the MSCs with peripheral blood mononuclear cells (PBMCs) under appropriated stimulation. The psoriatic mice were treated with saline control, DPSCs, or HGF-DPSCs. Then the mice spleens were collected and weighted. The psoriatic skin lesions were analyzed by Hematoxylin/Eosin and immunohistochemical staining for histopathological changes, and quantitative real-time polymerase chain reaction to detect the expression levels of CD4+ T cell-related transcription factors and cytokines. The mice blood serum was measured by MILLIPLEX analysis and enzyme-linked immunosorbent assay to evaluate the expression levels of inflammation cytokines. The coculture experiments showed HGF overexpression enhanced the immunoregulation abilities of DPSCs not by suppressing PBMCs' proliferation, but by downregulating T helper 1 (Th1), Th17 cells, and upregulating regulatory T (Treg) cells. In psoriatic skin lesions, the psoriasis-like erythema, scaling, and thickening were ameliorated; and the expression of cytokeratin 6 (CK6), and cytokeratin 17 (CK17) were downregulated by DPSCs and HGF-DPSCs treatment. HGF overexpression enhanced the decrease of spleen masses; enhanced the downregulation of the expression levels of interferon-gamma (IFN-γ), tumor necrosis factor-α, and interleukin (IL)-17A in the blood serums; enhanced the downregulation of T-box transcription factor 21 (T-bet), IFN-γ, retinoic acid-related orphan receptor-γt (RORγt), IL-17A, IL-17F, IL-23, and upregulation of Foxp3 and IL-10 in the psoriatic skin lesions. Therefore, HGF overexpression enhanced DPSCs' treatment effect on psoriasis mainly by reducing inflammatory responses. These findings might provide new immunoregulation strategies for psoriasis treatment.

A Sandwich Structure of Human Dental Pulp Stem Cell Sheet, Treated Dentin Matrix, and Matrigel for Tooth Root Regeneration.

Tooth loss can cause a lot of physiological and psychological suffering. And tooth root engineering is a promising way for tooth loss treatment. Two kinds of seed cells are usually adopted for tooth root regeneration. In this study, a practical sandwich structure for tooth root regeneration was developed, which was constituted by only one kind of seed cell: human dental pulp stem cells (hDPSCs) and three kinds of graft materials: Vitamin C (VC) induced hDPSC sheet, human treated dentin matrix (hTDM), and Matrigel. It was found that VC could induce hDPSCs to form a cell sheet with two or three cell layers and promote their collagen type I (COL1) mRNA expression obviously. hDPSCs could attach and grow on hTDM, and the mRNA expression of osteocalcin (OCN), dentin sialophosphoprotein (DSPP), vascular endothelial growth factor receptor 1 (VEGFR1), and Nestin in hDPSCs was obviously upregulated by hTDM leaching solution. hDPSCs could stretch and proliferate in Matrigel. And when cultured in Matrigel condition medium, they positively expressed CD31, ß3-Tubulin, and Nestin proteins, as well as increased the mRNA expression of OCN, ALP, and Nestin. Furthermore, periodontium, dentin, and pulp-like tissues were successfully regenerated after the sandwich structure of hDPSC sheet/TDM/Matrigel was transplanted in nude mice subcutaneously for 3 months. Periodontium-like dense connective tissue was regenerated around the hTDM, and a great mass of predentin was formed on the cavity side of hTDM. Odontoblast-like cells and blood vessel-like structures, even nerve-like fibers, were observed in the pulp cavity. In summary, the above results showed that hDPSCs could be used as seed cells for the whole tooth root regeneration, and the sandwich structure constituted by hDPSC sheet, TDM/hDPSCs, and Matrigel/hDPSCs could be utilized for tooth root regeneration.

Mesenchymal stem cells promote colorectal cancer progression through AMPK/mTOR-mediated NF-κB activation.

Mesenchymal stem cells (MSCs) exert a tumor-promoting effect in a variety of human cancers. This study was designed to identify the molecular mechanisms related to the tumor-promoting effect of MSCs in colorectal cancer. In vitro analysis of colorectal cancer cell lines cultured in MSC conditioned media (MSC-CM) showed that MSC-CM significantly promoted the progression of the cancer cells by enhancing cell proliferation, migration and colony formation. The tumorigenic effect of MSC-CM was attributed to altered expression of cell cycle regulatory proteins and inhibition of apoptosis. Furthermore, MSC-CM induced high level expression of a number of pluripotency factors in the cancer cells. ELISAs revealed MSC-CM contained higher levels of IL-6 and IL-8, which are associated with the progression of cancer. Moreover, MSC-CM downregulated AMPK mRNA and protein phosphorylation, but upregulated mTOR mRNA and protein phosphorylation. The NF-κB pathway was activated after addition of MSC-CM. An in vivo model in Balb/C mice confirmed the ability of MSC-CM to promote the invasion and proliferation of colorectal cancer cells. This study indicates that MSCs promote the progression of colorectal cancer via AMPK/mTOR-mediated NF-κB activation.