Mesenchymal stromal/stem cells (MSCs) have been developed as a promising source for cell-based therapies of ischemic disease. However, there are some hurdles in their clinical application such as ...poor cell engraftment and inconsistent stem cell potency. In this study, we sought to find biomarkers for predicting potency of MSCs for proangiogenic therapy to improve their beneficial effects. Large variations were observed in proangiogenic factor secretion profiles of conditioned media derived from nine different donor-derived Wharton's jelly (WJ)-derived MSCs and 8 factors among 55 angiogenesis-related factors were secreted at considerable levels. Two distinct WJ-MSCs that had the lowest or the highest secretion of these eight factors showed corresponding proangiogenic activities in in vitro angiogenesis assays. When four additional different donor-derived WJ-MSCs were further examined, proangiogenic activities in migration and tube formation of endothelial cells and in in vivo Matrigel plug assay were highly consistent with secretion levels of four major factors (angiogenin, interleukin-8, monocyte chemoattractant protein-1, and vascular endothelial growth factor). Such correlation was also observed in vascular regenerative effect in a mouse hind limb ischemia model. Blocking of these four factors by neutralizing antibodies or knockdown of them by siRNA treatment resulted in significant inhibition of proangiogenic activities of not only WJ-MSCs, but also bone marrow-derived MSCs. These results suggest that these four factors may represent efficient biomarkers for predicting vascular regenerative efficacy of MSCs. Stem Cells 2019;37:77-88.
Aim
To examine the effects of a rural community-based program integrating health education and self-directed home-based resistance training on the mobility function of older women with knee ...osteoarthritis (OA).
Methods
Participants were assigned to the control (CON) or intervention (INT) group. Participants completed a mobility function assessment and questionnaire evaluation. The CON group received only the health education program and the INT group also participated in resistance training for 5 months. Primary outcomes were mobility function measured using a timed chair stand (TCS), timed up & go (TUG), gait speed (GS), and knee extensor strength (KES). We evaluated body composition and questionnaire results (WOMAC score, SARC-F scale, and SOF index) as secondary outcomes.
Results
There were significant differences in the interactions of group-by-time effects for TCS (
p
< 0.001), TUG (
p
= 0.006), GS (
p
= 0.020), and knee strength (
p
= 0.010). In the CON group, TCS (
p
= 0.003) and TUG (
p
= 0.005) increased compared with baseline, while in the INT group, TCS decreased significantly (
p
< 0.001) and TUG tended to decrease after the intervention. The INT group showed improvement in GS (
p
< 0.001) and KES (
p
= 0.003) after the intervention. By contrast, the CON group showed decreasing GS (
p
= 0.021) and KES (
p
= 0.011) compared with baseline. The SARC-F scale differed significantly in the interaction of group-by-time effects (
p
= 0.030), while the body composition, SOF index, and WOMAC score did not differ.
Conclusion
These results suggest that an integrated intervention program combining self-directed home-based resistance training with health education effectively improves the mobility function of older adults with knee OA dwelling in rural areas.
A 7.5 Gb/s/pin 8-Gb LPDDR5 SDRAM is implemented in a 1× nm DRAM process. Various techniques are applied to achieve higher bandwidth and lower power than LPDDR4X. To increase data rate, a WCK clocking ...scheme that is less vulnerable to power noise is adopted and a non-target ODT mode is proposed to reduce reflection noise in a two-rank system. A couple of techniques are proposed for saving power. To reduce self-refresh power, this chip supports deep sleep mode (DSM). In DSM, the leakage current of internal voltages decreases by disabling internal voltage generators that are not related with a self-refresh operation. Dynamic voltage frequency scaling (DVFS) is adopted to reduce read and write operation power and when writing all zeros data, an internal data copy function can be used for reducing write operation power. Last, a ZQ calibration scheme that shares one ZQ resistor (RZQ) and automatically executes ZQ calibration is presented. The proposed LPDDR5 DRAM operates up to 7.5 Gb/s on an automatic test equipment (ATE) and 6.4 Gb/s on a prototype system. Read and write power decrease by 21% and 33% compared to LPDDR4X at 4.266 Gb/s, and self-refresh power is reduced by 25% in DSM.
Inhibition of mitochondrial reactive oxygen species (ROS) and subsequent damage‐associated molecular patterns (DAMPs)‐induced inflammatory responses could be a novel target in clinical islet ...transplantation. We investigated the protective effects of NecroX‐7, a novel clinical‐grade necrosis inhibitor that specifically targets mitochondrial ROS, against primary islet graft failure. Islets from heterozygote human islet amyloid polypeptide transgenic (hIAPP+/−) mice and nonhuman primates (NHPs) were isolated or cultured with or without NecroX‐7 in serum‐deprived medium. Supplementation with NecroX‐7 during hIAPP+/− mouse islet isolation markedly increased islet viability and adenosine triphosphate content, and attenuated ROS, transcription of c‐Jun N‐terminal kinases, high mobility group box 1, interleukin‐1beta (IL‐1 β), IL‐6, and tumor necrosis factor‐alpha. Supplementation of NecroX‐7 during serum‐deprived culture also protected hIAPP+/− mouse and NHP islets against impaired viability, serum deprivation‐induced ROS, proinflammatory response, and accumulation of toxic IAPP oligomer. Supplementation with NecroX‐7 during isolation or serum‐deprived culture of hIAPP+/− mouse and NHP islets also improved posttransplant glycemia in the recipient streptozotocin‐induced diabetic hIAPP−/− mice and BALB/c‐nu/nu mice, respectively. In conclusion, pretransplant administration of NecroX‐7 during islet isolation and serum‐deprived culture suppressed mitochondrial ROS injury, generation of DAMPs‐induced proinflammatory responses, and accumulation of toxic IAPP oligomers ex vivo, and improved posttransplant glycemia in vivo.
NecroX‐7, a novel clinical‐grade necrosis inhibitor, protects against primary islet graft failure in murine and nonhuman primate models through inhibition of mitochondrial reactive oxygen species and subsequent inflammatory responses induced by damage‐associated molecular patterns.
Although serum bile acid concentrations are approximately 10 µM in healthy subjects, the crosstalk between the biliary system and vascular repair has never been investigated. In this study, ...tauroursodeoxycholic acid (TUDCA) induced dissociation of CD34(+) hematopoietic stem cells (HSCs) from stromal cells by reducing adhesion molecule expression. TUDCA increased CD34(+) /Sca1(+) progenitors in mice peripheral blood (PB), and CD34(+) , CD31(+) , and c-kit(+) progenitors in human PB. In addition, TUDCA increased differentiation of CD34(+) HSCs into EPC lineage cells via Akt activation. EPC invasion was increased by TUDCA, which was mediated by fibroblast activating protein via Akt activation. Interestingly, TUDCA induced integration of EPCs into human aortic endothelial cells (HAECs) by increasing adhesion molecule expression. In the mouse hind limb ischemia model, TUDCA promoted blood perfusion by enhancing angiogenesis through recruitment of Flk-1(+) /CD34(+) and Sca-1(+) /c-kit(+) progenitors into damaged tissue. In GFP(+) bone marrow-transplanted hind limb ischemia, TUDCA induced recruitment of GFP(+) /c-kit(+) progenitors to the ischemic area, resulting in an increased blood perfusion ratio. Histological analysis suggested that GFP(+) progenitors mobilized from bone marrow, integrated into blood vessels, and differentiated into VEGFR(+) cells. In addition, TUDCA decreased cellular senescence by reducing levels of p53, p21, and reactive oxygen species and increased nitric oxide. Transplantation of TUDCA-primed senescent EPCs in hind limb ischemia significantly improved blood vessel regeneration, as compared with senescent EPCs. Our results suggested that TUDCA promoted neovascularization by enhancing the mobilization of stem/progenitor cells from bone marrow, their differentiation into EPCs, and their integration with preexisting endothelial cells.
An unusually large bandgap modulation of 1.23–2.65 eV in monolayer MoS2 on a SiO2/Si substrate is found due to the inherent local bending strain induced by the surface roughness of the substrate, ...reaching the direct‐to‐indirect bandgap transition. Approximately 80% of the surface area reveals an indirect bandgap, which is confirmed further by the degraded photoluminescence compared to that from suspended MoS2.
Rab escort protein 1 (REP1) is a component of Rab geranyl-geranyl transferase 2 complex. Mutations in REP1 cause a disease called choroideremia (CHM), which is an X-linked eye disease. Although it is ...postulated that REP1 has functions in cell survival or death of various tissues in addition to the eye, how REP1 functions in normal and cancer cells remains to be elucidated. Here, we demonstrated that REP1 is required for the survival of intestinal cells in addition to eyes or a variety of cells in zebrafish, and also has important roles in tumorigenesis. Notably, REP1 is highly expressed in colon cancer tissues and cell lines, and silencing of REP1 sensitizes colon cancer cells to serum starvation- and 5-FU-induced apoptosis. In an effort to elucidate the molecular mechanisms underlying REP1-mediated cell survival under those stress conditions, we identified FOXO3 as a binding partner of REP1 using a yeast two-hybrid (Y2H) assay system, and we demonstrated that REP1 blocked the nuclear trans-localization of FOXO3 through physically interacting with FOXO3, thereby suppressing FOXO3-mediated apoptosis. Importantly, the inhibition of REP1 combined with 5-FU treatment could lead to significant retarded tumor growth in a xenograft tumor model of human cancer cells. Thus, our results suggest that REP1 could be a new therapeutic target in combination treatment for colon cancer patients.
Recently, wind power plants that generate wind energy with electricity are attracting a lot of attention thanks to their smaller installation area and cheaper power generation costs. In wind power ...generation, it is important to predict the amount of generated electricity because the power system would be unstable due to uncertainty in supply. However, it is difficult to accurately predict the amount of wind power generation because the power varies due to several causes, such as wind speed, wind direction, temperature, etc. In this study, we deal with a mid-term (one day ahead) wind power forecasting problem with a data-driven approach. In particular, it is intended to solve the problem of a newly completed wind power generator that makes it very difficult to predict the amount of electricity generated due to the lack of data on past power generation. To this end, a deep learning based transfer learning model was proposed and compared with other models, such as a deep learning model without transfer learning and Light Gradient Boosting Machine (LGBM). As per the experimental results, when the proposed transfer learning model was applied to a similar wind power complex in the same region, it was confirmed that the low predictive performance of the newly constructed generator could be supplemented.
Highly angiogenic bone marrow mononuclear cell-derived spheroids (BM-spheroids), formed by selective proliferation of the CD31
CD14
CD34
monocyte subset via three-dimensional (3D) culture, have had ...robust angiogenetic capacity in rodent syngeneic renal subcapsular islet transplantation. We wondered whether the efficacy of BM-spheroids could be demonstrated in clinically relevant intraportal islet transplantation models without increasing the risk of portal thrombosis. The thrombogenic potential of intraportally infused BM-spheroids was compared with that of mesenchymal stem cells (MSCs) and MSC-derived spheroids (MSC-spheroids). The angiogenic efficacy and persistence in portal sinusoids of BM-spheroids were examined in rodent syngeneic and primate allogeneic intraportal islet transplantation models. In contrast to MSCs and MSC-spheroids, intraportal infusion of BM-spheroids did not evoke portal thrombosis. BM-spheroids had robust angiogenetic capacity in both the rodent and primate intraportal islet transplantation models and improved posttransplant glycemic outcomes. MRI and intravital microscopy findings revealed the persistence of intraportally infused BM-spheroids in portal sinusoids. Intraportal cotransplantation of allogeneic islets with autologous BM-spheroids in nonhuman primates further confirmed the clinical feasibility of this approach. In conclusion, cotransplantation of BM-spheroids enhances intraportal islet transplantation outcome without portal thrombosis in mice and nonhuman primates. Generating BM-spheroids by 3D culture prevented the rapid migration and disappearance of intraportally infused therapeutic cells.
Direct injection and solid‐phase extraction methods for the determination of diquat and paraquat in surface and drinking water were developed using liquid chromatography with tandem mass ...spectrometry. The signal intensities of analytes based on six ion‐pairing reagents were compared with each other, and 12.5 mM nonafluoropentanoic acid was selected as the best suited amongst them. A clean‐up method was developed using Oasis hydrophilic–lipophilic balance; this was compared to the direct injection method, with respect to limits of detection, interference, precision, and accuracy. Limits of quantification of diquat and paraquat were 0.03 and 0.01 μg/L using the direct injection method, and 0.002 and 0.001 μg/L using the hydrophilic–lipophilic balance method. When the hydrophilic–lipophilic balance method was used to analyze target compounds in 114 surface water and 30 drinking water samples, paraquat and diquat were detected within a concentration range of 0.001–0.12 and 0.002–0.038 μg/L in surface water, respectively. When the direct injection method was used to analyze target compounds in the same samples, the detected concentrations of paraquat and diquat were within 25% in samples being >0.015 μg/L using the hydrophilic–lipophilic balance method. The liquid chromatography with tandem mass spectrometry method using direct injection can thus be used for routine monitoring of paraquat and diquat in surface and drinking water.
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