作者机构：
[Li, Tony W. H.; Lu, Shelly C.; Wang, Jiaohong; Fan, Wei; Li, Yuan; Seki, Ekihiro; Zhang, Jing; Xiong, Ting; Tu, Jian; Lu, Liqing; Yang, Heping; Peng, Hui] Cedars Sinai Med Ctr, Div Digest & Liver Dis, Los Angeles, CA 90048 USA.;[Li, Yuan; Liu, Ting] Cent South Univ, Xiangya Hosp, Dept Gastroenterol, 78 Xiangya Rd, Changsha 410083, Hunan, Peoples R China.;[Xiong, Ting; Lu, Liqing; Chen, Yongheng; Liu, Ting] Cent South Univ, Xiangya Hosp, Chinese Minist Hlth, Key Lab Canc Prote, Changsha, Peoples R China.;[Tu, Jian] Univ South China, Inst Pharm & Pharmacol, Hengyang, Peoples R China.;[Zhang, Jing] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Oncol, Wuhan, Peoples R China.
通讯机构：
[Liu, Ting; Lu, Shelly C.; Yang, Heping] C;Cent South Univ, Xiangya Hosp, Dept Gastroenterol, 78 Xiangya Rd, Changsha 410083, Hunan, Peoples R China.;Cedars Sinai Med Ctr, Dept Med, Div Digest & Liver Dis, Davis Bldg,Room 2097,8700 Beverly Blvd, Los Angeles, CA 90048 USA.;Cedars Sinai Med Ctr, Dept Med, Div Digest & Liver Dis, Davis Bldg,Room 2094B,8700 Beverly Blvd, Los Angeles, CA 90048 USA.
摘要：
<jats:sec>
<jats:title>Background and Aims</jats:title>
<jats:p>Forkhead box M1 (FOXM1) and nuclear factor kappa B (NF‐ĸB) are oncogenic drivers in liver cancer that positively regulate each other. We showed that methionine adenosyltransferase 1A (MAT1A) is a tumor suppressor in the liver and inhibits NF‐ĸB activity. Here, we examined the interplay between FOXM1/NF‐κB and MAT1A in liver cancer.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Approach and Results</jats:title>
<jats:p>We examined gene and protein expression, effects on promoter activities and binding of proteins to promoter regions, as well as effects of FOXM1 inhibitors T0901317 (T0) and forkhead domain inhibitory‐6 (FDI‐6) <jats:italic toggle="yes">in vitro</jats:italic> and in xenograft and syngeneic models of liver cancer. We found, in both hepatocellular carcinoma and cholangiocarcinoma, that an induction in FOXM1 and NF‐κB expression is accompanied by a fall in MATα1 (protein encoded by MAT1A). The Cancer Genome Atlas data set confirmed the inverse correlation between FOXM1 and MAT1A. Interestingly, FOXM1 directly interacts with MATα1 and they negatively regulate each other. In contrast, FOXM1 positively regulates p50 and p65 expression through MATα1, given that the effect is lost in its absence. FOXM1, MATα1, and NF‐κB all bind to the FOX binding sites in the <jats:italic toggle="yes">FOXM1</jats:italic> and <jats:italic toggle="yes">MAT1A</jats:italic> promoters. However, binding of FOXM1 and NF‐κB repressed <jats:italic toggle="yes">MAT1A</jats:italic> promoter activity, but activated the <jats:italic toggle="yes">FOXM1</jats:italic> promoter. In contrast, binding of MATα1 repressed the <jats:italic toggle="yes">FOXM1</jats:italic> promoter. MATα1 also binds and represses the NF‐κB element in the presence of p65 or p50. Inhibiting FOXM1 with either T0 or FDI‐6 inhibited liver cancer cell growth <jats:italic toggle="yes">in vitro</jats:italic> and <jats:italic toggle="yes">in vivo</jats:italic>. However, inhibiting FOXM1 had minimal effects in liver cancer cells that do not express MAT1A.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>We have found a crosstalk between FOXM1/NF‐κB and MAT1A. Up‐regulation in FOXM1 lowers MAT1A, but raises NF‐κB, expression, and this is a feed‐forward loop that enhances tumorigenesis.</jats:p>
</jats:sec>
摘要：
Interferon-gamma (IFN-gamma), the sole member in type II IFN predominantly secreted by macrophages and T cells, is a critical regulator of immune function and provides a robust first line of defense against invading pathogens. Binding of IFN-gamma to its receptor complex can activate a variety of downstream signaling pathways, particularly the Janus kinase (JAK)/signal transducer and activator of transcription (STAT), to induce gene transcription within the target cells. This pro-inflammatory mediator is highly expressed in atherosclerotic lesions and promotes foam cell formation, but its effects on the atherogenesis are complex, with both pro- and anti-atherogenic properties. IFN-gamma also contributes to the development of myocardial infarction and stroke, the two main atherosclerotic diseases. Inhibition of IFN-gamma signaling may prevent the development of atherosclerosis and help treat atherosclerotic diseases. Since IFN-gamma may also exert anti-atherogenic effects, the safety and efficacy of anti-IFN-gamma treatment still require careful evaluation in the clinical setting. In the current review, we summarize recent progression on regulation and signaling pathways of IFN-gamma, and highlight its roles in foam cell formation, atherosclerosis, myocardial infarction as well as stroke. An increased understanding of these processes will help to develop novel IFN-gamma-centered therapies for atherosclerotic diseases. (C) 2014 Elsevier B.V. All rights reserved.
摘要：
Intervertebral disk degeneration (IDD) is the most common diagnosis in patients with low back pain, a main cause of musculoskeletal disability in the world. Interleukin-1 (IL-1) beta is the most important member of the IL-1 family, and has a strong pro-inflammatory activity by stimulating the secretion of multiple pro-inflammatory mediators. IL-1 beta is highly expressed in degenerative intervertebral disk (IVD) tissues and cells, and it has been shown to be involved in multiple pathological processes during disk degeneration, including inflammatory responses, matrix destruction, angiogenesis and innervation, cellular apoptosis, oxidative stress and cellular senescence. However, inhibition of IL-1 beta is found to promote extracellular matrix (ECM) repair and protect against disk regeneration. In this review, after a brief description of IL-1 beta signaling, we mainly focus on the expression profiles, roles and therapeutic potential of IL-1 beta in IDD. A better understanding will help develop novel IL-1 beta-based therapeutic interventions for degenerative disk disease. (C) 2015 Elsevier B.V. All rights reserved.
作者：
Jin Zhang;Guang-ya Zhang;Jin Xu;Wen-bo Wu;Xin-yang Sun;...
期刊：
African Journal of Psychiatry,2015年18(2):1-6 ISSN：1994-8220
通讯作者：
Zhang, L.-Y.
作者机构：
[Zhang J.] School of medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, China;[Zhang G.-Y.] Department of Psychiatry, Suzhou Psychiatric Hospital, Suzhou, Jiangsu, 215101, China;[Xu J.] Administration office, No.102 Hospital of Chinese People's Liberation Army, Changzhou, Jiangsu, 213003, China;[Wu W.-B.] Department of outpatients, No.102 Hospital of Chinese People's Liberation Army, Changzhou, Jiangsu, 213003, China;[Sun X.-Y.; Zhang L.-Y.] Prevention and Treatment Center for Psychological Diseases, No.102 Hospital of Chinese People's Liberation Army, Changzhou, Jiangsu, 213003, China
通讯机构：
[Zhang, L.-Y.] P;Prevention and Treatment Center for Psychological Diseases, No.102 hospital of Chinese People's Liberation Army, North Peace Road 55, Changzhou, Jiangsu, China
关键词：
Jin Zhang;Guang-ya Zhang;Jin Xu;Wen-bo Wu;Xin-yang Sun;Li-yi Zhang and Shu-ya He;Schizophrenia;miRNA-7;Target genes;Interaction
作者机构：
[Wang, Wen-Jun; Zhang, Jian; Zhang, Shu-Jun; Wang, Cheng; Yan, Yi-Guo] Univ South China, Affiliated Hosp 1, Dept Spine Surg, Hengyang 421001, Hunan, Peoples R China.;[Yu, Xiao-Hua] Univ South China, Life Sci Res Ctr, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Yu, Xiao-Hua] U;Univ South China, Life Sci Res Ctr, Hengyang 421001, Hunan, Peoples R China.
关键词：
Chemoresistance;Notch;OS;TP53;miRNAs
摘要：
Osteosarcoma (OS) is a primary malignant bone tumor with high morbidity that principally emerges in children and adolescents. Presently, the prognosis of OS patients remains poor due to resistance to chemotherapy, highlighting the need for new therapeutic approaches. MicroRNAs (miRNAs), a class of small noncoding RNA molecules, can negatively modulate protein expression at the post-transcriptional level. miRNAs regulate a variety of normal physiologic processes and are involved in tumorigenesis and development of multiple malignancies, including OS. Some miRNAs are differentially expressed in OS tissues, cell lines and serum, and have been shown to correlate with the malignant phenotype and prognosis. These altered miRNAs function as oncogenes or tumor suppressor genes in this process. Moreover, restoration of miRNA expression has shown promise for the treatment of OS. Here, we describe miRNA biochemistry with a focus on expression profile, role and therapeutic potential in OS. A better understanding will facilitate the identification and characterization of novel biomarkers and development of miRNA-targeted therapies. (C) 2015 Elsevier B.V. All rights reserved.
作者机构：
[Li K.; Sun A.; Zhang J.; Wang Q.; Pan Y.] Laboratory of Molecular Medicine, College of Pharmaceutical Science, Soochow University, Suzhou 215123, China;Suzhou Institute of Chinese Materia Medica, Suzhou 215123, China;Laboratory of Molecular Medicine, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China;[Zhou C.] Department of Pharmacology, Nanhua University, Hengyang, Hunan 421001, China;[Yi C.] College of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China
通讯机构：
[Li, K.] L;Laboratory of Molecular Medicine, , Suzhou 215123, China
关键词：
APC gene;Cancer;Mutation-sensitive switch
摘要：
Genetic polymorphisms and mutations of APC gene are associated with the development of cancer. Recently, a highly polymorphic 1493 code was identified by sequencing cancer tissues. The present study reported a mutation-sensitive switch based assay for code 1493 of APC gene. This assay has been applied in the analysis of both individual samples and DNA pool, showing an extremely high specificity (100% correctness) when compared with conventional sequencing analysis. Thus, this nanometerscale mutation-sensitive switch, consisting of high fidelity polymerase and phosphorothioate modified allele specific primers, can be used to replace DNA sequencing in the analysis of the specific genetic change of code 1493 of APC gene.
摘要：
Indels in evolutionary studies are rapidly decayed obeying a power law. The present study analyzed the length distribution of small insertions and deletions associated with human diseases and confirmed that the decay pattern of these small mutations is similar to that of indels when the mutation datasets are large enough. The describable decay pattern of somatic mutations may have application in the evaluation of varied penetrance of different mutations and in association study of gene mutation with carcinogenesis.
摘要：
We propose a short definition of GENOME: The full complement of genetic materials possessed by an intracellular parasite, a cell, or an organism. Accordingly, the human genome is the entire complement of inherited genetic materials possessed by an individual person, or possessed by a cell in an individual person. For higher species, the genomic makeup includes DNA in the nucleus and in the organelles regardless of the number of chromosomes and the homoplasmic or heteroplasmic status of the mitochondrial or chloroplastic DNA. Practically, GENOME can be referred to at the molecular, cellular, individual, and species levels, which has various implications in biotechnological research and molecular diagnostics.
关键词：
The current A(H1N1) flu has showed sub-population dependent susceptibility and fatality as early as April and May of 2009 in its first wave of spreading. After the pandemic outbreak spreads globally for more than seven months;the subpopulation dependence of this flu;including ethnicity;age and gender selectivity;has been recognized by several research groups. This paper attempts to discussed how to identify ethnic selectivity from the released data by WHO relevant to this ongoing flu;review some recently published papers describing the presence of ethnic differences in susceptibilities to the H1N1 flu virus and further raised an argument that ethnic differences in susceptibilities to a virus might be a piece of evidence reflecting a weak virulence of that specific virus.
作者机构：
[Xiao, L.; Li, Kai] Suzhou Univ, Mol Med Ctr, Suzhou 215006, Peoples R China.;[Xiao, L.; Li, Kai] Suzhou Univ, Second Affilated Hosp, Suzhou 215006, Peoples R China.;[Xiao, L.; Zhang, J.; Chen, C. L.; Li, Kai] Nanhua Univ, SNP Inst, Hengyang, Hunan, Peoples R China.;[Zhang, J.] Novartis Res Fdn, Genom Inst, San Diego, CA USA.;[Yin, Y. F.] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
通讯机构：
[Zhang, I ] ;Nanhua Univ, SNP Inst, Hengyang, Hunan, Peoples R China.
作者：
Zhang, Jia;Zhou, Cuilan;Yin, Yufang;Chen, Linling;Pardinas, Jose R.;...
期刊：
Current Pharmacogenomics and Personalized Medicine,2006年4(2):121-131 ISSN：1875-6913
通讯作者：
Li, K.
作者机构：
[Zhou, Cuilan; Yin, Yufang; Chen, Linling] SNP Institute, Nanhua University, Hengyang, Hunan, China;Genomapping Inc., Tianjin, China;Egea Biosciences, L.L.C., San Diego, CA 92121, USA;Department of Human Genetics, City of Hope National Medical Center, Duarte, CA 91010, USA;The changes in physical and chemical characteristics derived from genetic alteration are the basis for the development of mutation assays. Among the ever-increasing number of mutation assays available, most are variants of allele-specific primer extension targeting single nucleotide polymorphism (SNP) and point mutations. Conventional allele-specific primer extension was designed to work using exo polymerases exclusively, regardless that the fidelity of DNA polymerases has been recognized for more than three decades depending on the presence of proofreading activity provided by its internal 3’ exonuclease. Recently, exo polymerase with proofreading activity has been applied in mutation detection. The application of proofreading activity by DNA polymerase with 3’ to 5’ exonuclease provides two significant advantages: elimination of false positives and applicability to both real-time PCR as well as microarray platforms. Technologically, the high fidelity DNA polymerases offer a variety of applications in genetic analyses, including mutation detection, high fidelity expression profiling, and de novo sequencing. Some of these applications can be immediately applied in pharmacogenetics studies, particularly in the filed of somatic Pharmacogenetics.
通讯机构：
[Li, K.] D;Department of Human Genetics, , Duarte, CA 91010, United States
