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171.
Chung-Hwa Park Si Hyun Bae Hee Yeon Kim Ja Kyung Kim Eun Sun Jung Ho Jong Chun Myeong Jun Song Sung-Eun Lee Seok Goo Cho Jong Wook Lee Jong Young Choi Seung Kew Yoon Nam Ik Han Young Sok Lee 《Cytotherapy》2013,15(12):1571-1579
Background aimsMany rodent experiments and human studies on stem cell therapy have shown promising therapeutic approaches to liver diseases. We investigated the clinical outcomes of five patients with liver failure of various causes who received autologous CD34-depleted bone marrow-derived mononuclear cell (BM-MNC) transplantation, including mesenchymal stromal cells, through the hepatic artery.MethodsCD34-depleted BM-MNCs were obtained from five patients waiting for liver transplantation by bone marrow aspiration and using the CliniMACS CD34 Reagent System (Miltenyi Biotech, Bergisch Gladbach, Germany), and autologous hepatic artery infusion was performed. The causes of hepatic decompensation were hepatitis B virus (HBV), hepatitis C virus (HCV), propylthiouracil-induced toxic hepatitis and Wilson disease.ResultsSerum albumin levels improved 1 week after transplantation from 2.8 g/dL, 2.4 g/dL, 2.7 g/dL and 1.9 g/dL to 3.3 g/dL, 3.1 g/dL, 2.8 g/dL and 2.6 g/dL. Transient liver elastography data showed some change from 65 kPa, 33 kPa, 34.8 kPa and undetectable to 46.4 kPa, 19.8 kPa, 29.1 kPa and 67.8 kPa at 4 weeks after transplantation in a patient with Wilson disease, a patient with HCV, and two patients with HBV. Ascites decreased in two patients. One of the patients with HBV underwent liver transplantation 4 months after the infusion, and the hepatic progenitor markers (cytokeratin [CD]-7, CD-8, CD-9, CD-18, CD-19, c-Kit and epithelial cell adhesion molecule [EpCAM]) were highly expressed in the explanted liver.ConclusionsSerum albumin levels, liver stiffness, liver volume, subjective healthiness and quality of life improved in the study patients. Although these findings were observed in a small population, the results may suggest a promising future for autologous CD34-depleted BM-MNC transplantation as a bridge to liver transplantation in patients with liver failure. 相似文献
172.
Shin Ae Park Christopher M. Reilly Joshua A. Wood Dai Jung Chung Danielle D. Carrade Sarah L. Deremer Rebecca L. Seraphin Kaitlin C. Clark Allison L. Zwingenberger Dori L. Borjesson Kei Hayashi Paul Russell Christopher J. Murphy 《Cytotherapy》2013,15(12):1498-1510
Background aimsMesenchymal stromal cells (MSCs) have been extensively studied as a cellular therapeutic for various pathologic conditions. However, there remains a paucity of data regarding regional and systemic safety of MSC transplantations, particularly with multiple deliveries of allogeneic cells. The purpose of this study was to investigate the safety and systemic immunomodulatory effects of repeated local delivery of allogeneic MSCs into the region of the lacrimal gland, the gland of the third eyelid and the knee joint in dogs.MethodsAllogeneic adipose tissue-derived canine MSCs were delivered to the regions of the lacrimal gland and the third eyelid gland as well as in the knee joints of six healthy laboratory beagles as follows: six times with 1-week intervals for delivery to the lacrimal gland and the third eyelid gland regions and three to four times with 1- to 2-week intervals for intra-articular transplantations. Dogs were sequentially evaluated by clinical examination. At the conclusion of the study, dogs were humanely euthanized, and a complete gross and histopathologic examination of all organ systems was performed. Mixed leukocyte reactions were also performed before the first transplantation and after the final transplantation.ResultsClinical and pathologic examinations found no severe consequences after repeated MSC transplantations. Results of mixed leukocyte reactions demonstrated suppression of T-cell proliferation after MSC transplantations.ConclusionsThis is the first study to demonstrate regional and systemic safety and systemic immunomodulatory effects of repeated local delivery of allogeneic MSCs in vivo. 相似文献
173.
Jun Seo Goo Yo Na Kim Kyung Mi Choi In Sik Hwang Ji Eun Kim Young Ju Lee Moon Hwa Kwak Sun Bo Shim Seung Wan Jee Chul Joo Lim Je Kyung Seong Dae Youn Hwang 《Clinical proteomics》2013,10(1):10
Background
To characterize changes in global protein expression in kidneys of transgenic rats overexpressing human selenoprotein M (SelM) in response to increased bioabivility of selenium (Sel), total proteins extracted from kidneys of 10-week-old CMV/hSelM Tg and wild-type rats were separated by 2-dimensional gel electrophoresis and measured for changes in expression.Results
Ten and three proteins showing high antioxidant enzymatic activity were up- and down-regulated, respectively, in SelM-overexpressing CMV/hSelM Tg rats compared to controls based on an arbitrary 2-fold difference. Up-regulated proteins included LAP3, BAIAP2L1, CRP2, CD73 antigen, PDGF D, KIAA143 homolog, PRPPS-AP2, ZFP313, HSP-60, and N-WASP, whereas down-regulated proteins included ALKDH3, rMCP-3, and STC-1. After Sel treatment, five of the up-regulated proteins were significantly increased in expression in wild-type rats, whereas there were no changes in CMV/hSelM Tg rats. Only two of the down-regulated proteins showed reduced expression in wild-type and Tg rats after Sel treatment.Conclusions
These results show the primary novel biological evidences that new functional protein groups and individual proteins in kidneys of Tg rats relate to Sel biology including the response to Sel treatment and SelM expression. 相似文献174.
Development of induced pluripotent stem cell (iPSC) technology introduced a novel way to derive pluripotent stem cells, but the genetic manipulation required to generate iPSCs may lead to uncontrolled tumorigenesis of the established cells and thus limit clinical feasibility of the technology. Numerous attempts have been made to date, and alternative reprogramming of somatic cells to reactivate cellular plasticity after differentiation has been suggested. As a result, it had become clear that cell-to-cell interactions and specific acellular environments can be utilized for somatic cell reprogramming. In our previous studies, embryonic stem cell (ESC)-like cells could be derived from transforming ovarian cells and fetal fibroblasts by cell-to-cell interaction or specific cell-mediated microenvironmental factor(s). This cellular event was induced without undertaking genetic manipulation of progenitor cells. Several differences were found between the cellular properties of niche-induced, ESC-like cells and those of genetically manipulated iPSCs and the referenced ESCs. Thus, we provided evidence that terminally differentiated somatic cells either acquire pluripotency-like activity or possess cellular and genetic plasticity under a specific microenvironment and/or cell-to-cell interaction. In this minireview, we discuss derivation of stem cell-like cells under specific microenvironmental conditions in terms of technical perspectives and limitations. 相似文献
175.
Ataxia-telangiectasia mutated (ATM) is a Ser/Thr protein kinase that plays a critical role in DNA damage-induced signaling and initiation of cell cycle checkpoint signaling in response to DNA-damaging agents such as ionizing radiation. We have previously reported the ATM protein loss by immunohistochemistry (IHC) in 16% of human gastric cancer (GC) tissue. We hypothesized that ATM gene intron mutations targeted by microsatellite instability (MSI) cause ATM protein loss in a subset of GC. We studied mononucleotide mutations at the intron of ATM gene, ATM IHC and MSI in GC. Ten human gastric cancer cell lines were studied for the ATM gene mutation at introns, RT-PCR, direct sequencing, and immunohistochemistry. GC tissues of 839 patients were analyzed for MSI and ATM IHC. Among them, 604 cases were analyzed for the ATM mutations at introns preceding exon 6, exon 10 and exon 20. Two human GC cell lines (SNU-1 and -638) showed ATM intron mutations, deletion in RT-PCR and direct sequencing, and ATM protein loss by IHC. The frequencies of ATM mutation, MSI, and ATM protein loss were 12.9% (78/604), 9.2% (81/882) and 15.2% (134/839), respectively. Analysis of associations among MSI, ATM gene mutation, and ATM protein loss revealed highly co-existing ATM gene alterations and MSI. ATM intron mutation and ATM protein loss were detected in 69.3% (52/75) and 53.3% (40/75) of MSI positive GC. MSI positivity and ATM protein loss were present in 68.4% (52/76) and 48.7% (37/76) of GC with ATM intron mutation. ATM mutation and ATM protein loss had characteristics of old age, distal location of tumor, large tumor size, and histologic intestinal type. Our study might be interpreted as that ATM gene mutation at intron might be targeted by MSI and lead to ATM protein loss in a selected group of GC. 相似文献
176.
Tih-Shih Lee Siau Juinn Alexa Goh Shin Yi Quek Rachel Phillips Cuntai Guan Yin Bun Cheung Lei Feng Stephanie Sze Wei Teng Chuan Chu Wang Zheng Yang Chin Haihong Zhang Tze Pin Ng Jimmy Lee Richard Keefe K. Ranga Rama Krishnan 《PloS one》2013,8(11)
Cognitive decline in aging is a pressing issue associated with significant healthcare costs and deterioration in quality of life. Previously, we reported the successful use of a novel brain-computer interface (BCI) training system in improving symptoms of attention deficit hyperactivity disorder. Here, we examine the feasibility of the BCI system with a new game that incorporates memory training in improving memory and attention in a pilot sample of healthy elderly. This study investigates the safety, usability and acceptability of our BCI system to elderly, and obtains an efficacy estimate to warrant a phase III trial. Thirty-one healthy elderly were randomized into intervention (n = 15) and waitlist control arms (n = 16). Intervention consisted of an 8-week training comprising 24 half-hour sessions. A usability and acceptability questionnaire was administered at the end of training. Safety was investigated by querying users about adverse events after every session. Efficacy of the system was measured by the change of total score from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) before and after training. Feedback on the usability and acceptability questionnaire was positive. No adverse events were reported for all participants across all sessions. Though the median difference in the RBANS change scores between arms was not statistically significant, an effect size of 0.6SD was obtained, which reflects potential clinical utility according to Simon’s randomized phase II trial design. Pooled data from both arms also showed that the median change in total scores pre and post-training was statistically significant (Mdn = 4.0; p<0.001). Specifically, there were significant improvements in immediate memory (p = 0.038), visuospatial/constructional (p = 0.014), attention (p = 0.039), and delayed memory (p<0.001) scores. Our BCI-based system shows promise in improving memory and attention in healthy elderly, and appears to be safe, user-friendly and acceptable to senior users. Given the efficacy signal, a phase III trial is warranted.
Trial Registration
ClinicalTrials.gov NCT01661894相似文献177.
Sung-Min Kim Heejaung Kim Jeong-Seon Lee Kyung Seok Park Gye Sun Jeon Jeeheun Shon Suk-Won Ahn Seung Hyun Kim Kyung Min Lee Jung-Joon Sung Kwang-Woo Lee 《PloS one》2013,8(11)
Background
Patients with ALS may be exposed to variable degrees of chronic intermittent hypoxia. However, all previous experimental studies on the effects of hypoxia in ALS have only used a sustained hypoxia model and it is possible that chronic intermittent hypoxia exerts effects via a different molecular mechanism from that of sustained hypoxia. No study has yet shown that hypoxia (either chronic intermittent or sustained) can affect the loss of motor neurons or cognitive function in an in vivo model of ALS.Objective
To evaluate the effects of chronic intermittent hypoxia on motor and cognitive function in ALS mice.Methods
Sixteen ALS mice and 16 wild-type mice were divided into 2 groups and subjected to either chronic intermittent hypoxia or normoxia for 2 weeks. The effects of chronic intermittent hypoxia on ALS mice were evaluated using the rotarod, Y-maze, and wire-hanging tests. In addition, numbers of motor neurons in the ventral horn of the spinal cord were counted and western blot analyses were performed for markers of oxidative stress and inflammatory pathway activation.Results
Compared to ALS mice kept in normoxic conditions, ALS mice that experienced chronic intermittent hypoxia had poorer motor learning on the rotarod test, poorer spatial memory on the Y-maze test, shorter wire hanging time, and fewer motor neurons in the ventral spinal cord. Compared to ALS-normoxic and wild-type mice, ALS mice that experienced chronic intermittent hypoxia had higher levels of oxidative stress and inflammation.Conclusions
Chronic intermittent hypoxia can aggravate motor neuronal death, neuromuscular weakness, and probably cognitive dysfunction in ALS mice. The generation of oxidative stress with activation of inflammatory pathways may be associated with this mechanism. Our study will provide insight into the association of hypoxia with disease progression, and in turn, the rationale for an early non-invasive ventilation treatment in patients with ALS. 相似文献178.
Seung Mi Lee Jeong Woo Park Byoung Jae Kim Chan-Wook Park Joong Shin Park Jong Kwan Jun Bo Hyun Yoon 《PloS one》2013,8(12)
Background
The objective of this study was to determine whether acute histologic chorioamnionitis is associated with adverse neonatal outcomes in late preterm infants who were born after preterm PROM.Methodology/Principal Findings
The relationship between the presence of acute histologic chorioamnionitis and adverse neonatal outcome was examined in patients with preterm PROM who delivered singleton preterm newborns between 34 weeks and 36 6/7 weeks of gestation. Nonparametric statistics were used for data analysis. The frequency of acute histologic chorioamnionitis was 24% in patients with preterm PROM who delivered preterm newborns between 34 weeks and 36 6/7 weeks of gestation. Newborns born to mothers with histologic chorioamnionitis had significantly higher rates of adverse neonatal outcome (74% vs 51%; p<0.005) than those without histologic chorioamnionitis. This relationship remained significant after adjustment for gestational age at preterm PROM, gestational age at delivery, and exposure to antenatal corticosteroids.Conclusions/Significance
The presence of acute histologic chorioamnionitis is associated with adverse neonatal outcome in late preterm infants born to mothers with preterm PROM. 相似文献179.
180.
Pengcheng Bu Kai-Yuan Chen Joyce Huan Chen Lihua Wang Jewell Walters Yong Jun Shin Julian P. Goerger Jian Sun Mavee Witherspoon Nikolai Rakhilin Jiahe Li Herman Yang Jeff Milsom Sang Lee Warren Zipfel Moonsoo M. Jin Zeynep H. Gümüş Steven M. Lipkin Xiling Shen 《Cell Stem Cell》2013,12(5):602-615
Highlights? miR-34a regulates colon cancer stem cell asymmetric division ? miR-34a generates a sharp threshold response ? miR-34a converts Notch signaling into a toggle switch ? Binary Notch levels specify self-renewal versus differentiation 相似文献