Exogenous rhTRX reduces lipid accumulation under LPS-induced inflammation.
Abstract Redox-regulating molecule, recombinant human thioredoxin (rhTRX) which shows anti-inflammatory, and anti-oxidative effects against lipopolysaccharide (LPS)-stimulated inflammation and regulate protein expression levels. LPS-induced reactive oxygen intermediates (ROI) and NO production were inhibited by exogenous rhTRX. We identified up/downregulated intracellular proteins under the LPS-treated condition in exogenous rhTRX-treated A375 cells compared with non-LPS-treated cells via 2-DE proteomic analysis. Also, we quantitatively measured cytokines of in vivo mouse inflammation models using cytometr...
Source: exp Mol Med - January 14, 2014 Category: Molecular Biology Authors: Han GY, Lee EK, Park HW, Kim HJ, Kim CW Tags: Exp Mol Med Source Type: research

Serotonin contracts the rat mesenteric artery by inhibiting 4-aminopyridine-sensitive Kv channels via the 5-HT2A receptor and Src tyrosine kinase.
Abstract Serotonin (5-hydroxytryptamine (5-HT)) is a neurotransmitter that regulates a variety of functions in the nervous, gastrointestinal and cardiovascular systems. Despite such importance, 5-HT signaling pathways are not entirely clear. We demonstrated previously that 4-aminopyridine (4-AP)-sensitive voltage-gated K(+) (Kv) channels determine the resting membrane potential of arterial smooth muscle cells and that the Kv channels are inhibited by 5-HT, which depolarizes the membranes. Therefore, we hypothesized that 5-HT contracts arteries by inhibiting Kv channels. Here we studied 5-HT signaling and t...
Source: exp Mol Med - December 21, 2013 Category: Molecular Biology Authors: Sung DJ, Noh HJ, Kim JG, Park SW, Kim B, Cho H, Bae YM Tags: Exp Mol Med Source Type: research

The application of an in situ karyotyping technique for mesenchymal stromal cells: a validation and comparison study with classical G-banding.
Abstract The cytogenetic analysis of mesenchymal stromal cells (MSCs) is essential for verifying the safety and stability of MSCs. An in situ technique, which uses cells grown on coverslips for karyotyping and minimizes cell manipulation, is the standard protocol for the chromosome analysis of amniotic fluids. Therefore, we applied the in situ karyotyping technique in MSCs and compared the quality of metaphases and karyotyping results with classical G-banding and chromosomal abnormalities with fluorescence in situ hybridization (FISH). Human adipose- and umbilical cord-derived MSC cell lines (American Type...
Source: exp Mol Med - December 21, 2013 Category: Molecular Biology Authors: Hwang SM, See CJ, Choi J, Kim SY, Choi Q, Kim JA, Kwon J, Park SN, Im K, Oh IH, Lee DS Tags: Exp Mol Med Source Type: research

Apoptosis signal-regulating kinase 1 (ASK1) is linked to neural stem cell differentiation after ischemic brain injury.
Abstract Neural stem cells (NSCs) have been suggested as a groundbreaking solution for stroke patients because they have the potential for self-renewal and differentiation into neurons. The differentiation of NSCs into neurons is integral for increasing the therapeutic efficiency of NSCs during inflammation. Apoptosis signal-regulating kinase 1 (ASK1) is preferentially activated by oxidative stress and inflammation, which is the fundamental pathology of brain damage in stroke. ASK1 may be involved in the early inflammation response after stroke and may be related to the differentiation of NSCs because of t...
Source: exp Mol Med - December 21, 2013 Category: Molecular Biology Authors: Song J, Cho KJ, Cheon SY, Kim SH, Park KA, Lee WT, Lee JE Tags: Exp Mol Med Source Type: research

Recognition of lipopolysaccharide pattern by TLR4 complexes.
Abstract Lipopolysaccharide (LPS) is a major component of the outer membrane of Gram-negative bacteria. Minute amounts of LPS released from infecting pathogens can initiate potent innate immune responses that prime the immune system against further infection. However, when the LPS response is not properly controlled it can lead to fatal septic shock syndrome. The common structural pattern of LPS in diverse bacterial species is recognized by a cascade of LPS receptors and accessory proteins, LPS binding protein (LBP), CD14 and the Toll-like receptor4 (TLR4)-MD-2 complex. The structures of these proteins acc...
Source: exp Mol Med - December 7, 2013 Category: Molecular Biology Authors: Park BS, Lee JO Tags: Exp Mol Med Source Type: research

PPARγ modulates vascular smooth muscle cell phenotype via a protein kinase G-dependent pathway and reduces neointimal hyperplasia after vascular injury.
In this study, we examined whether rosiglitazone, a peroxisome proliferator-activated receptor (PPAR)-γ agonist, could modulate VSMC phenotype through the PKG pathway to reduce neointimal hyperplasia after angioplasty. In vitro experiments showed that rosiglitazone inhibited the phenotype change of VSMCs from a contractile to a synthetic form. The platelet-derived growth factor (PDGF)-induced reduction of PKG level was reversed by rosiglitazone treatment, resulting in increased PKG activity. This increased activity of PKG resulted in phosphorylation of vasodilator-stimulated phosphoprotein at serine 239, leading to inhibi...
Source: exp Mol Med - December 2, 2013 Category: Molecular Biology Authors: Yang HM, Kim BK, Kim JY, Kwon YW, Jin S, Lee JE, Cho HJ, Lee HY, Kang HJ, Oh BH, Park YB, Kim HS Tags: Exp Mol Med Source Type: research

Phosphoproteomic analysis identifies activated MET-axis PI3K/AKT and MAPK/ERK in lapatinib-resistant cancer cell line.
Abstract Lapatinib, a dual inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) tyrosine kinases, has shown promising results as a growth inhibitor of HER2-positive cancer cells in vitro. However, similar to other EGFR-targeting drugs, acquired resistance to lapatinib by HER2-positive cancer cells remains a major clinical challenge. To elucidate resistance mechanisms to EGFR/HER2-targeting agents, we performed a systematic quantitative comparison of the phosphoproteome of lapatinib-resistant (LR) human gastric cancer cells (SNU216-LR) versus parental cell...
Source: exp Mol Med - November 23, 2013 Category: Molecular Biology Authors: Lee YY, Kim HP, Kang MJ, Cho BK, Han SW, Kim TY, Yi EC Tags: Exp Mol Med Source Type: research

Contralaterally transplanted human embryonic stem cell-derived neural precursor cells (ENStem-A) migrate and improve brain functions in stroke-damaged rats.
In this study, we investigated the fates of human embryonic stem cell (hESC)-derived NPCs (ENStem-A) for 8 weeks following transplantation into the side contralateral to the infarct region using 7.0T animal magnetic resonance imaging (MRI). T2- and T2*-weighted MRI analyses indicated that the migrating cells were clearly detectable at the infarct boundary zone by 1 week, and the intensity of the MRI signals robustly increased within 4 weeks after transplantation. Afterwards, the signals were slightly increased or unchanged. At 8 weeks, we performed Prussian blue staining and immunohistochemical staining using human-specifi...
Source: exp Mol Med - November 19, 2013 Category: Molecular Biology Authors: Chang DJ, Oh SH, Lee N, Choi C, Jeon I, Kim HS, Shin DA, Lee SE, Kim D, Song J Tags: Exp Mol Med Source Type: research

Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine.
Abstract Mesenchymal stem cells (MSCs) are partially defined by their ability to differentiate into tissues including bone, cartilage and adipose in vitro, but it is their trophic, paracrine and immunomodulatory functions that may have the greatest therapeutic impact in vivo. Unlike pharmaceutical treatments that deliver a single agent at a specific dose, MSCs are site regulated and secrete bioactive factors and signals at variable concentrations in response to local microenvironmental cues. Significant progress has been made in understanding the biochemical and metabolic mechanisms and feedback associated...
Source: exp Mol Med - November 19, 2013 Category: Molecular Biology Authors: Murphy MB, Moncivais K, Caplan AI Tags: Exp Mol Med Source Type: research

Developmental changes in hematopoietic stem cell properties.
Abstract Hematopoietic stem cells (HSCs) comprise a rare population of cells that can regenerate and maintain lifelong blood cell production. This functionality is achieved through their ability to undergo many divisions without activating a poised, but latent, capacity for differentiation into multiple blood cell types. Throughout life, HSCs undergo sequential changes in several key properties. These affect mechanisms that regulate the self-renewal, turnover and differentiation of HSCs as well as the properties of the committed progenitors and terminally differentiated cells derived from them. Recent find...
Source: exp Mol Med - November 19, 2013 Category: Molecular Biology Authors: Copley MR, Eaves CJ Tags: Exp Mol Med Source Type: research

Very small embryonic-like stem-cell optimization of isolation protocols: an update of molecular signatures and a review of current in vivo applications.
Abstract As the theory of stem cell plasticity was first proposed, we have explored an alternative hypothesis for this phenomenon: namely that adult bone marrow (BM) and umbilical cord blood (UCB) contain more developmentally primitive cells than hematopoietic stem cells (HSCs). In support of this notion, using multiparameter sorting we were able to isolate small Sca1(+)Lin(-)CD45(-) cells and CD133(+)Lin(-)CD45(-) cells from murine BM and human UCB, respectively, which were further enriched for the detection of various early developmental markers such as the SSEA antigen on the surface and the Oct4 and Na...
Source: exp Mol Med - November 19, 2013 Category: Molecular Biology Authors: Shin DM, Suszynska M, Mierzejewska K, Ratajczak J, Ratajczak MZ Tags: Exp Mol Med Source Type: research

In situ tissue regeneration through host stem cell recruitment.
Abstract The field of tissue engineering has made steady progress in translating various tissue applications. Although the classical tissue engineering strategy, which involves the use of culture-expanded cells and scaffolds to produce a tissue construct for implantation, has been validated, this approach involves extensive cell expansion steps, requiring a lot of time and laborious effort before implantation. To bypass this ex vivo process, a new approach has been introduced. In situ tissue regeneration utilizes the body's own regenerating capacity by mobilizing host endogenous stem cells or tissue-specif...
Source: exp Mol Med - November 19, 2013 Category: Molecular Biology Authors: Ko IK, Lee SJ, Atala A, Yoo JJ Tags: Exp Mol Med Source Type: research

Human salivary gland stem cells ameliorate hyposalivation of radiation-damaged rat salivary glands.
Abstract Salivary function in mammals may be defective for various reasons, such as aging, Sjogren's syndrome or radiation therapy in head and neck cancer patients. Recently, tissue-specific stem cell therapy has attracted public attention as a next-generation therapeutic reagent. In the present study, we isolated tissue-specific stem cells from the human submandibular salivary gland (hSGSCs). To efficiently isolate and amplify hSGSCs in large amounts, we developed a culture system (lasting 4-5 weeks) without any selection. After five passages, we obtained adherent cells that expressed mesenchymal stem cel...
Source: exp Mol Med - November 19, 2013 Category: Molecular Biology Authors: Jeong J, Baek H, Kim YJ, Choi Y, Lee H, Lee E, Kim ES, Hah JH, Kwon TK, Choi IJ, Kwon H Tags: Exp Mol Med Source Type: research

Implications and limitations of cellular reprogramming for psychiatric drug development.
Abstract Human-induced pluripotent stem cells (hiPSCs) derived from somatic cells of patients have opened possibilities for in vitro modeling of the physiology of neural (and other) cells in psychiatric disease states. Issues in early stages of technology development include (1) establishing a library of cells from adequately phenotyped patients, (2) streamlining laborious, costly hiPSC derivation and characterization, (3) assessing whether mutations or other alterations introduced by reprogramming confound interpretation, (4) developing efficient differentiation strategies to relevant cell types, (5) iden...
Source: exp Mol Med - November 19, 2013 Category: Molecular Biology Authors: Tobe BT, Brandel MG, Nye JS, Snyder EY Tags: Exp Mol Med Source Type: research

Amyloid-β oligomers regulate the properties of human neural stem cells through GSK-3β signaling.
Abstract Alzheimer's disease (AD) is the most common cause of age-related dementia. The neuropathological hallmarks of AD include extracellular deposition of amyloid-β peptides and neurofibrillary tangles that lead to intracellular hyperphosphorylated tau in the brain. Soluble amyloid-β oligomers are the primary pathogenic factor leading to cognitive impairment in AD. Neural stem cells (NSCs) are able to self-renew and give rise to multiple neural cell lineages in both developing and adult central nervous systems. To explore the relationship between AD-related pathology and the behaviors of NSCs that ena...
Source: exp Mol Med - November 19, 2013 Category: Molecular Biology Authors: Lee IS, Jung K, Kim IS, Park KI Tags: Exp Mol Med Source Type: research