BACKGROUND: Reactive oxygen species, such as superoxide (O(2)(-)), are involved in the abnormal growth of various cell types. Angiotensin II (Ang II) is one of the most potent inducers of oxidative stress in the vasculature. The molecular events involved in Ang II-induced proliferation of vascular smooth muscle cells (VSMCs) are ... More
Directed differentiation of pancreatic δ cells from human pluripotent stem cells.
Dysfunction of pancreatic δ cells contributes to the etiology of diabetes. Despite their important role, human δ cells are scarce, limiting physiological studies and drug discovery targeting δ cells. To date, no directed δ-cell differentiation method has been established. Here, we demonstrate that fibroblast growth factor (FGF) 7 promotes pancreatic ... More
Involvement of c-Src Tyrosine Kinase Upstream of Class I Phosphatidylinositol (PI) 3-Kinases in Salmonella Enteritidis Rck Protein-mediated Invasion.
AuthorsWiedemann A, Rosselin M, Mijouin L, Bottreau E, Velge P,
JournalJ Biol Chem
PubMed ID22810232
'The Salmonella outer membrane protein Rck mediates a Zipper entry mechanism controlled by tyrosine phosphorylation and class I phosphatidylinositol 3-kinase (PI 3-kinase). However, the underlying mechanism leading to this signaling cascade remains unclear. The present study showed that using Rck-coated beads or Rck-overexpressing Escherichia coli, Rck-mediated actin polymerization and invasion ... More
A differential role for the mitogen-activated protein kinases in lipopolysaccharide signaling: the MEK/ERK pathway is not essential for nitric oxide and interleukin 1beta production.
Authors Watters Jyoti J; Sommer Julie A; Pfeiffer Zachary A; Prabhu Usha; Guerra Alma N; Bertics Paul J;
JournalJ Biol Chem
PubMed ID11786532
'Endotoxin (lipopolysaccharide, LPS) is a component of the outer membrane of Gram-negative bacteria and promotes the activation of macrophages and microglia. Although these cells are highly LPS-responsive, they serve unique tissue-specific functions and exhibit different LPS sensitivities. Accordingly, it was of interest to evaluate whether these biological differences reside in ... More
Electrophoretic profiling of both RNA and protein from a single 250-pL sample.
Authors Zabzdyr Jennifer L; Lillard Sheri J;
JournalAnal Chem
PubMed ID11985318
'A novel approach is described that uses capillary electrophoresis (CE) to electrophoretically sample and separate both protein and RNA from a single injected plug of cell lysate. A 250-pL sample of lysate from Chinese hamster ovary cells (9.6 x 10(7) cells/mL) was hydrodynamically injected into a capillary containing a Tris-based ... More
Increases in free, unbound insulin-like growth factor I enhance insulin responsiveness in human hepatoma G2 cells in culture.
Authors Sakai Keiji; Lowman Henry B; Clemmons David R;
JournalJ Biol Chem
PubMed ID11834727
'Insulin-like growth factor-binding protein (IGFBP)-1 binds to insulin-like growth factor (IGF)-I and -II with high affinity and has been shown to modulate IGF-I actions in vivo and in vitro. The synthesis of IGFBP-1 is suppressed by insulin, and administration of IGFBP-1 to rats results in impaired glucose metabolism. A synthetic ... More
Fibrin inhibits peripheral nerve remyelination by regulating schwann cell differentiation.
'Remyelination is a critical step for functional nerve regeneration. Here we show that fibrin deposition in the peripheral nervous system after injury is a key regulator of remyelination. After sciatic nerve crush, fibrin is deposited and its clearance correlates with remyelination. Fibrin induces phosphorylation of ERK1/2 and production of p75 ... More
Molecular rearrangements of the extracellular vestibule in NMDAR channels during gating.
Authors Sobolevsky Alexander I; Beck Christine; Wollmuth Lonnie P;
JournalNeuron
PubMed ID11779481
Many N-methyl-D-aspartate receptor (NMDAR) channel blockers that have therapeutic potential can be trapped in the closed state. Using a combination of the substituted cysteine accessibility method and open channel blockers, we found that the M3 segment forms the core of the extracellular vestibule, including a deep site for trapping blockers. ... More
Influence of second and third cytoplasmic loops on binding, internalization, and coupling of chimeric bombesin/m3 muscarinic receptors.
Authors Tseng M J; Coon S; Stuenkel E; Struk V; Logsdon C D;
JournalJ Biol Chem
PubMed ID7629092
In order to investigate the molecular basis for differences in the characteristics of bombesin (Bn) and m3 muscarinic cholinergic (m3 ACh) receptors, chimeric Bn receptors possessing cytoplasmic domains from the m3 ACh receptor were produced. The receptors were expressed in CHO-K1 cells and binding, structural, and signal transduction characteristics were ... More
Reduced interleukin-18 levels in BAL specimens from patients with asthma compared to patients with sarcoidosis and healthy control subjects.
Authors Ho Ling-Pei; Davis Margaret; Denison Alan; Wood Fraser T; Greening Andrew P;
JournalChest
PubMed ID12006423
STUDY OBJECTIVES: To investigate whether differing airway interleukin (IL)-18 levels may be implicated in the pathogenesis of asthma and sarcoidosis. SETTING: University teaching hospital. Patients and methods: IL-18 levels were measured in BAL fluid and in the supernatant of lipopolysaccharide (LPS)-stimulated alveolar macrophages obtained by BAL from 15 patients with ... More
Brief exposure to high-dose transforming growth factor-beta1 enhances periosteal chondrogenesis in vitro: a preliminary report.
BACKGROUND: Articular cartilage has limited potential for repair. There have been various attempts aimed at improving the repair process in articular cartilage. Transforming growth factor-beta1 (TGF-beta1) has a stimulatory effect on chondrogenesis in periosteal explants. The purpose of the present study was to determine the effect of brief exposures (i.e., ... More
A 2-D liquid separations/mass mapping method for interlysate comparison of ovarian cancers.
Authors Kachman Maureen T; Wang Haixing; Schwartz Donald R; Cho Kathleen R; Lubman David M;
JournalAnal Chem
PubMed ID11985308
A two-dimensional liquid phase separation of proteins from whole cell lysates coupled on-line to an electrospray-ionization time-of-flight (ESI-TOF) mass spectrometer (MS) is used to map the protein content of ovarian surface epithelial cells (OSE) and an ovarian carcinoma-derived cell line (ES2). The two dimensions involve the use of liquid isoelectric ... More
BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: two randomised controlled studies.
Authors Black Gillian F; Weir Rosemary E; Floyd Sian; Bliss Lyn; Warndorff David K; Crampin Amelia C; Ngwira Bagrey; Sichali Lifted; Nazareth Bernadette; Blackwell Jenefer M; Branson Keith; Chaguluka Steven D; Donovan Linda; Jarman Elizabeth; King Elizabeth; Fine Paul E M; Dockrell Hazel M;
JournalLancet
PubMed ID11978337
BACKGROUND: The efficacy of BCG vaccines against pulmonary tuberculosis varies between populations, showing no protection in Malawi but 50-80% protection in the UK. To investigate the mechanism underlying these differences, randomised controlled studies were set up to measure vaccine-induced immune responsiveness to mycobacterial antigens in both populations. METHODS: 483 adolescents ... More
STAT3 Inhibitor ODZ10117 Suppresses Glioblastoma Malignancy and Prolongs Survival in a Glioblastoma Xenograft Model.
AuthorsKim BH, Lee H, Park CG, Jeong AJ, Lee SH, Noh KH, Park JB, Lee CG, Paek SH, Kim H, Ye SK
JournalCells
PubMed ID32183406
'Constitutively activated STAT3 plays an essential role in the initiation, progression, maintenance, malignancy, and drug resistance of cancer, including glioblastoma, suggesting that STAT3 is a potential therapeutic target for cancer therapy. We recently identified ODZ10117 as a small molecule inhibitor of STAT3 and suggested that it may have an effective ... More
Colonoscopy-based colorectal cancer modeling in mice with CRISPR-Cas9 genome editing and organoid transplantation.
AuthorsRoper J, Tammela T, Akkad A, Almeqdadi M, Santos SB, Jacks T, Yilmaz ÖH
JournalNat Protoc
PubMed ID29300388
'Most genetically engineered mouse models (GEMMs) of colorectal cancer are limited by tumor formation in the small intestine, a high tumor burden that limits metastasis, and the need to generate and cross mutant mice. Cell line or organoid transplantation models generally produce tumors in ectopic locations-such as the subcutaneous space, ... More
Establishment and characterization of induced pluripotent stem cells from placental mesenchymal stromal cells.
AuthorsParveen S
JournalStem Cell Res
PubMed ID29291511
Human term placenta is a bulky organ which harbours abundant mesenchymal stromal cells. This study reports isolation and characterization of placental mesenchymal stromal cells (PMSCs) followed by reprogramming of PMSCs to induced pluripotent stem cells (iPSCs). The placental human iPSC (PhiPSC) line is pluripotent with high telomerase activity, genetically identical ... More
LATS2 inhibits cell proliferation and metastasis through the Hippo signaling pathway in glioma.
AuthorsGuo C, Liang C, Yang J, Hu H, Fan B, Liu X
JournalOncol Rep
PubMed ID30896861
As a core kinase in the Hippo pathway, large tumor suppressor kinase 2 (LATS2) regulates cell proliferation, migration and invasion through numerous signaling pathways. However, its functions on cell proliferation, migration and invasion in glioma have yet to be elucidated. The present study revealed that LATS2 was downregulated in glioma ... More
Effect of early-stage autophagy inhibition in BRAF
AuthorsZahedi S, Fitzwalter BE, Morin A, Grob S, Desmarais M, Nellan A, Green AL, Vibhakar R, Hankinson TC, Foreman NK, Mulcahy Levy JM
JournalCell Death Dis
PubMed ID31515514
Autophagy is a multistage process. Progress within the field has led to the development of agents targeting both early (initiation) and late (fusion) stages of this process. The specific stage of autophagy targeted may influence cancer treatment outcomes. We have previously shown that central nervous system (CNS) tumors with the ... More
Exosome Treatment Enhances Anti-Inflammatory M2 Macrophages and Reduces Inflammation-Induced Pyroptosis in Doxorubicin-Induced Cardiomyopathy.
AuthorsSingla DK, Johnson TA, Tavakoli Dargani Z
JournalCells
PubMed ID31600901
Doxorubicin (Dox) is an effective antineoplastic agent used to treat cancers, but its use is limited as Dox induces adverse cardiotoxic effects. Dox-induced cardiotoxicity (DIC) can lead to heart failure and death. There is no study that investigates whether embryonic stem cell-derived exosomes (ES-Exos) in DIC can attenuate inflammation-induced pyroptosis, ... More
Oridonin induces Mdm2-p60 to promote p53-mediated apoptosis and cell cycle arrest in neuroblastoma.
AuthorsZhu HQ, Zhang C, Guo ZY, Yang JM, Guo JH, Chen C, Yao QH, Liu F, Zhang QW, Gao FH
JournalCancer Med
PubMed ID31339234
Oridonin could induce NB (neuroblastoma) cells growth inhibition by inducing apoptosis and cell cycle arrest, and the molecular mechanisms behind the effects deserve to be further explored. Here, oridonin was confirmed to cause the reactivation of p53 (cellular tumor antigen p53) to promote the expression of a series of apoptosis- ... More
Generation of integration free human iPSC line SORMi002-A from neonatal foreskin fibroblasts.
AuthorsShivaraj A, Parveen S
JournalStem Cell Res
PubMed ID31454679
Circumcision is a common surgical procedure usually performed on neonates worldwide. Skin removed after circumcision is abundant and often discarded. Neonatal foreskin fibroblasts (NFFs) can be easily isolated from it for application in biomedical research including induced pluripotent stem cell (iPSC) generation. In this study NFFs were reprogrammed to iPSCs ... More
Combining DNMT and HDAC6 inhibitors increases anti-tumor immune signaling and decreases tumor burden in ovarian cancer.
AuthorsMoufarrij S, Srivastava A, Gomez S, Hadley M, Palmer E, Austin PT, Chisholm S, Roche K, Yu A, Li J, Zhu W, Lopez-Acevedo M, Villagra A, Chiappinelli KB
JournalSci Rep
PubMed ID32103105
Novel therapies are urgently needed for ovarian cancer, the deadliest gynecologic malignancy. Ovarian cancer has thus far been refractory to immunotherapies that stimulate the host immune system to recognize and kill cancer cells. This may be because of a suppressive tumor immune microenvironment and lack of recruitment and activation of ... More
Heme Oxygenase-1 and Carbon Monoxide Regulate Growth and Progression in Glioblastoma Cells.
AuthorsCastruccio Castracani C, Longhitano L, Distefano A, Di Rosa M, Pittalà V, Lupo G, Caruso M, Corona D, Tibullo D, Li Volti G
JournalMol Neurobiol
PubMed ID32108290
In human glioma tumours, heme oxygenase-1 (HO-1) is overexpressed when compared with normal brain tissues and during oligodendroglioma progression. However, the molecular mechanisms mediated by HO-1 to promote glioblastoma remain unknown. We therefore aimed at investigating the effect of HO-1 expression and its selective enzymatic inhibition in two different cell ... More