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Yong Li, Qiu-Hua Yu, Ying Chu, Wei-Min Wu, Jian-Xiang Song, Xiao-Bo Zhu, Qiang Wang
Hypertension is a multifactorial chronic inflammatory disease that leads to cardiac remodeling. A-kinase anchor protein 12 (AKAP12) is a scaffolding protein that has multiple functions in various biological events, including the regulation of vessel integrity and differentiation of neural barriers in blood. However, the role of AKAP12 in angiotensin II (Ang II)-induced cardiac injury remains unclear. In the present study, Ang II infusion reduced AKAP12 expressions in the hearts of wild-type (WT) mice, and AKAP12 knockout (KO) enhanced the infiltration of inflammatory cells...
February 28, 2018: Biochemical and Biophysical Research Communications
Ping He, Ke Li, Shi-Bao Li, Ting-Ting Hu, Ming Guan, Fen-Yong Sun, Wei-Wei Liu
A-kinase anchor protein 12 (AKAP12; also known as Gravin) functions as a tumor suppressor in several human primary cancers. However, the potential correlation between histone deacetylase 3 (HDAC3) and AKAP12 and the underlying mechanisms remain unclear. Thus, in this study, in an aim to shed light into this matter, the expression levels of HDAC3 and AKAP12 in 96 colorectal cancer (CRC) and adjacent non-cancerous tissues, as well as in SW480 cells were examined by immunohistochemical, RT-qPCR and western blot analyses...
February 23, 2018: International Journal of Oncology
Carolina Angelica Parada, Joshua Osbun, Sumanpreet Kaur, Youssef Yakkioui, Min Shi, Catherine Pan, Tina Busald, Yigit Karasozen, Luis Francisco Gonzalez-Cuyar, Robert Rostomily, Jing Zhang, Manuel Ferreira
There is a need to better understand meningioma oncogenesis for biomarker discovery and development of targeted therapies. Histological or genetic criteria do not accurately predict aggressiveness. Post-translational studies in meningioma progression are lacking. In the present work, we introduce a combination of mass spectrometry-based phosphoproteomics and peptide array kinomics to profile atypical and anaplastic (high-grade) meningiomas. In the discovery set of fresh-frozen tissue specimens (14), the A-kinase anchor protein 12 (AKAP12) protein was found downregulated across the grades...
February 1, 2018: Scientific Reports
Takakuni Maki, Yoon Kyung Choi, Nobukazu Miyamoto, Akihiro Shindo, Anna C Liang, Bum Ju Ahn, Emiri T Mandeville, Seiji Kaji, Kanako Itoh, Ji Hae Seo, Irwin H Gelman, Josephine Lok, Ryosuke Takahashi, Kyu-Won Kim, Eng H Lo, Ken Arai
Oligodendrocyte precursor cells (OPCs) give rise to oligodendrocytes in cerebral white matter. However, the underlying mechanisms that regulate this process remain to be fully defined, especially in adult brains. Recently, it has been suggested that signaling via A-kinase anchor protein 12 (AKAP12), a scaffolding protein that associates with intracellular molecules such as protein kinase A, may be involved in Schwann cell homeostasis and peripheral myelination. Here, we asked whether AKAP12 also regulates the mechanisms of myelination in the CNS...
January 4, 2018: Stem Cells
Komal Ramani, Maria Lauda Tomasi, Joshua Berlind, Nirmala Mavila, Zhaoli Sun
Alcoholic liver injury is associated with hepatic stellate cell (HSC) activation. A-kinase anchoring protein 12 (AKAP12) scaffolds protein kinase C (PKC-α) and cyclin-D1, which is regulated by its phosphorylation, and spatiotemporally controls cell proliferation, invasiveness, and chemotaxis. HSC activation induces AKAP12 expression but the role of AKAP12's scaffolding activity in liver function is unknown. Since AKAP12 phosphorylation is enhanced in ethanol-treated HSCs, we examined AKAP12's scaffolding functions in alcohol-mediated HSC activation and liver injury...
January 2, 2018: American Journal of Pathology
Andreas Giannakou, Robert J Sicko, Wei Zhang, Paul Romitti, Marilyn L Browne, Michele Caggana, Lawrence C Brody, Laura Jelliffe-Pawlowski, Gary M Shaw, Denise M Kay, James L Mills
BACKGROUND: Ebstein anomaly (EA) is a rare congenital defect characterized by apical displacement of the septal tricuspid leaflets and atrialization of the right ventricle. The etiology of EA is unclear; however, recurrence in families and the association of EA with genetic syndromes and copy number variants (CNVs) suggest a genetic component. OBJECTIVE: We performed a population-based study to search for recurrent and novel CNVs in a previously unreported set of EA cases...
2017: PloS One
Xiaoqiang Yang
The aim of the present study was to identify risk genes in myocardial infarction. Microarray data GSE34198, containing data from the peripheral blood of 49 myocardial infarction samples and 48 corresponding control samples, were downloaded from the Gene Expression Omnibus database to screen the differentially expressed genes (DEGs). The DEGs were used to construct a protein‑protein interaction (PPI) network of patient samples, from which the feature genes were identified using the neighboring score method...
January 2018: Molecular Medicine Reports
Yi-Jen Chen, Wei-An Chang, Ya-Ling Hsu, Chia-Hsin Chen, Po-Lin Kuo
The role of osteoblasts in peri-articular bone loss and bone erosion in rheumatoid arthritis (RA) has gained much attention, and microRNAs are hypothesized to play critical roles in the regulation of osteoblast function in RA. The aim of this study is to explore novel microRNAs differentially expressed in RA osteoblasts and to identify genes potentially involved in the dysregulated bone homeostasis in RA. RNAs were extracted from cultured normal and RA osteoblasts for sequencing. Using the next generation sequencing and bioinformatics approaches, we identified 35 differentially expressed microRNAs and 13 differentially expressed genes with potential microRNA-mRNA interactions in RA osteoblasts...
November 11, 2017: International Journal of Molecular Sciences
Masashi Muramatsu, Lingqiu Gao, Jennifer Peresie, Benjamin Balderman, Shin Akakura, Irwin H Gelman
SSeCKS/Gravin/AKAP12 (SSeCKS) is a kinase scaffolding protein known to suppress metastasis by attenuating tumor-intrinsic PKC- and Src-mediated signaling pathways [1]. In addition to downregulation in metastatic cells, in silico analyses identified SSeCKS downregulation in prostate or breast cancer-derived stroma, suggesting a microenvironmental cell role in controlling malignancy. Although orthotopic B16F10 and SM1WT1[Braf(V600E)] mouse melanoma tumors grew similarly in syngeneic WT or SSeCKS-null (KO) mice, KO hosts exhibited 5- to 10-fold higher levels of peritoneal metastasis, and this enhancement could be adoptively transferred by pre-injecting naïve WT mice with peritoneal fluid (PF), but not non-adherent peritoneal cells (PC), from naïve KO mice...
September 19, 2017: Oncotarget
Pu Wang, Xinmiao Fan, Yibei Wang, Yue Fan, Yaping Liu, Shuyang Zhang, Xiaowei Chen
Microtia is a congenital malformation of the external ear caused by genetic and/or environmental factors. However, no causal genetic mutations have been identified in isolated microtia patients. In this study, we utilized targeted genomic capturing combined with next-generation sequencing to screen for mutations in 307 deafness genes in 32 microtia patients. Forty-two rare heterozygous mutations in 25 genes, including 22 novel mutations in 24 isolated unilateral microtia cases were identified. Pathway analysis found five pathways especially focal adhesion pathway and ECM-receptor interaction pathway were significantly associated with microtia...
September 8, 2017: Oncotarget
Stuart G Jarrett, Katharine M Carter, Brent J Shelton, John A D'Orazio
Using primary melanocytes and HEK293 cells, we found that cAMP signaling accelerates repair of bi- and mono-functional platinum-induced DNA damage. Elevating cAMP signaling either by the agonistic MC1R ligand melanocyte stimulating hormone (MSH) or by pharmacologic cAMP induction by forskolin enhanced clearance of intrastrand cisplatin-adducts in melanocytes or MC1R-transfected HEK293 cells. MC1R antagonists human beta-defensin 3 and agouti signaling protein blocked MSH- but not forskolin-mediated enhancement of platinum-induced DNA damage...
September 15, 2017: Scientific Reports
Z J Liu, W Liu, C H Cui, L K Gu, B C Xing, D J Deng
Objective: To study the association between the AKAP12 promoter methylation and recurrence of hepatocellular carcinoma. Methods: A total of 142 primary liver cancer patients underwent surgery in department of Hepatobiliary surgery in Peking University Cancer Hospital from 2003 to 2009 were selected as subjects in the survey; with the inclusion criteria as hepatocellular carcinoma, no cancer cells were observed in the surgical margin(SM) samples. All patients had neither lymph nor distant metastasis at the time of surgery, and receiving complete follow-up data for at least 3 years...
September 6, 2017: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
Wen Xie, Wei Su, Lijuan Zhang, Qingkun Shang, Bing Su
Metastasis remains the primary cause of prostate cancer related death. Cancer cells need to contact endothelial cells and disrupt endothelial junctions to cross the endothelium for invasion and metastasis. The suppression of heterotypic repulsion between cancer and endothelial cells allows cancer cells to invade into the surrounding tissue. Here, we demonstrate that SSeCKS/AKAP12 induced repulsion between human prostate cancer and microvessel endothelial cells, which was mediated by an angiogenesis inhibitor Semaphorin 3F...
September 2, 2017: Biochemical and Biophysical Research Communications
Pu Wang, Xinmiao Fan, Yibei Wang, Yue Fan, Yaping Liu, Shuyang Zhang, Xiaowei Chen
Microtia is a congenital malformation of the external ear caused by genetic and/or environmental factors. However, no causal genetic mutations have been identified in isolated microtia patients. In this study, we utilized targeted genomic capturing combined with next-generation sequencing to screen for mutations in 307 deafness genes in 32 microtia patients. Forty-two rare heterozygous mutations in 25 genes, including 22 novel mutations in 24 isolated unilateral microtia cases were identified. Pathway analysis found five pathways especially focal adhesion pathway and ECM-receptor interaction pathway were significantly associated with microtia...
June 28, 2017: Oncotarget
Won Tae Kim, Sung-Pil Seo, Young Joon Byun, Ho-Won Kang, Yong-June Kim, Sang-Cheol Lee, Pildu Jeong, Yoonhee Seo, Soo Young Choe, Dong-Joon Kim, Seon-Kyu Kim, Sung-Kwon Moon, Yung-Hyun Choi, Geun Taek Lee, Isaac Yi Kim, Seok Joong Yun, Wun-Jae Kim
There is a growing interest in the use of naturally occurring agents in cancer prevention. This study investigated the garlic extract affects in bladder cancer (BC) prevention. The effect of garlic extract in cancer prevention was evaluated using the T24 BC BALB/C-nude mouse xenograft model. Microarray analysis of tissues was performed to identify differences in gene expression between garlic extract intake and control diet, and gene network analysis was performed to assess candidate mechanisms of action. Furthermore, we investigated the expression value of selected genes in the data of 165 BC patients...
May 11, 2017: International Journal of Oncology
Jacob Kach, Tiha M Long, Phillip Selman, Eva Y Tonsing-Carter, Maria A Bacalao, Ricardo R Lastra, Larischa de Wet, Shane Comiskey, Marc Gillard, Calvin VanOpstall, Diana C West, Wen-Ching Chan, Donald Vander Griend, Suzanne D Conzen, Russell Z Szmulewitz
Increased glucocorticoid receptor (GR) expression and activity following androgen blockade can contribute to castration-resistant prostate cancer (CRPC) progression. Therefore, we hypothesized that GR antagonism will have therapeutic benefit in CRPC. However, the FDA-approved nonselective, steroidal GR antagonist, mifepristone, lacks GR specificity, reducing its therapeutic potential. Here, we report that two novel nonsteroidal and highly selective GR modulators (SGRM), CORT118335 and CORT108297, have the ability to block GR activity in prostate cancer and slow CRPC progression...
August 2017: Molecular Cancer Therapeutics
Zhitao Li, Sonal Singh, Santosh V Suryavanshi, Wengang Ding, Xiaoxu Shen, Cori S Wijaya, Wei Dong Gao, Bradley K McConnell
Gravin (AKAP12) is an A-kinase-anchoring-protein that scaffolds protein kinase A (PKA), β2 -adrenergic receptor (β2 -AR), protein phosphatase 2B and protein kinase C. Gravin facilitates β2 -AR-dependent signal transduction through PKA to modulate cardiac excitation-contraction coupling and its removal positively affects cardiac contraction. Trabeculae from the right ventricles of gravin mutant (gravin-t/t) mice were employed for force determination. Simultaneously, corresponding intracellular Ca2+ transient ([Ca2+ ]i ) were measured...
July 15, 2017: European Journal of Pharmacology
Vaithinathan Selvaraju, Sumanth C Suresh, Mahesh Thirunavukkarasu, Jayakanthan Mannu, Jocelyn L C Foye, Premendu P Mathur, J Alexander Palesty, Juan A Sanchez, David W McFadden, Nilanjana Maulik
We examined the effects of overexpressing HSPA12B on angiogenesis and myocardial function by intramyocardial administration of adenovirus encoding HSPA12B (Ad. HSPA12B) in a streptozotocin-induced diabetic rat subjected to myocardial infarction. Rats were divided randomly into six groups: control sham (CS) + Ad.LacZ, control myocardial infarction (CMI) + Ad.LacZ, control MI + Ad.HSPA12B, diabetic sham (DS) + Ad.LacZ, diabetic MI + Ad.LacZ and diabetic MI + Ad.HSPA12B. Following MI or sham surgery, the respective groups received either Ad...
April 2017: Journal of Cardiovascular Translational Research
Jun-Mo Yang, Hye Shin Lee, Ji Hae Seo, Ji-Hyeon Park, Irwin H Gelman, Eng H Lo, Kyu-Won Kim
Macrophages exhibit phenotypic plasticity, as they have the ability to switch their functional phenotypes during inflammation and recovery. Simultaneously, the mechanical environment actively changes. However, how these dynamic alterations affect the macrophage phenotype is unknown. Here, we observed that the extracellular matrix (ECM) constructed by AKAP12+ colon mesenchymal cells (CMCs) generated M2 macrophages by regulating their shape during recovery. Notably, rounded macrophages were present in the linear and loose ECM of inflamed colons and polarized to the M1 phenotype...
February 16, 2017: Scientific Reports
Guangru Xu, Minghui Zhang, Hongxing Zhu, Jinhua Xu
OBJECTIVE: To screen the gene signature for distinguishing patients with high risks from those with low-risks for colon cancer recurrence and predicting their prognosis. METHODS: Five microarray datasets of colon cancer samples were collected from Gene Expression Omnibus database and one was obtained from The Cancer Genome Atlas (TCGA). After preprocessing, data in GSE17537 were analyzed using the Linear Models for Microarray data (LIMMA) method to identify the differentially expressed genes (DEGs)...
March 10, 2017: Gene
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