// Miao Li 1 , Xi Li 2 , Yan Zhuang 3 , Yan Wang 4 , Matthew E. Burow 3 , Bridgette Collins-Burow 3 , Min Xue 5 , Chengjie Song 5 , Bin Shan 6 1 Department of Microbiology and Parasitology, College of Basic Medical Sciences, China Medical University, Shenyang, China 2 Department of Sports Medicine and Joint Surgery, The People's Hospital of Liaoning Province, Shenyang, China 3 Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA 4 Department of Biological Engineering, Zunyi Medical College Zhuhai Campus, Zhuhai, China 5 Department of Physiology, Xuzhou Medical College, Xuzhou, China 6 Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University Spokane, Spokane, WA, USA Correspondence to: Miao Li, email: sendtolm@126.com Bin Shan, email: bin.shan@wsu.edu Keywords: breast cancer, extracellular matrix, three-dimensional organotypic culture, gene expression, homeobox gene Received: February 05, 2016 Accepted: June 29, 2016 Published: July 08, 2016 ABSTRACT The gene expression signatures of the molecular intrinsic subtypes of breast cancer are regulated by epigenetic mechanisms such as methylation of CpG islands in gene promoters. Epigenetic codes can be regulated by the tumor microenvironment. The Claudin-low subtype is associated with triple-negative invasive ductal carcinomas in patients. Herein we explored epigenetic regulation of gene expression in the Claudin-low breast cancer cells by extracellular matrix (ECM), a key component of the tumor microenvironment. We modeled attachment to ECM using laminin rich ECM three-dimensional organotypic culture (lrECM 3D). In 2D and lrECM 3D cultures we examined expression of the homeobox (HOX) genes that epigenetically regulated in development and cancer. We demonstrated induction of the selected HOX genes in lrECM 3D culture of the Claudin-low breast cancer cells MDA-MB-231 and Hs578T. In particular activation of HOXA9 expression in lrECM 3D culture required binding of bromodomain containing 4 to the HOXA9 promoter and involved CpG hypomethylation. Our findings warrant further investigation of the ECM-regulated epigenetic coding of gene expression in the Claudin-low breast cancer.
Long non-coding RNAs (lncRNAs) play important roles in carcinogenesis and drug efficacy. Platinum-based chemotherapy is first-line treatment for lung cancer chemotherapy. In this study, we aimed to investigate the association of well-characterized lung cancer lncRNA genetic polymorphisms with the lung cancer susceptibility and platinum-based chemotherapy response. A total of 498 lung cancer patients and 213 healthy controls were recruited in the study. Among them, 467 patients received at least two cycles of platinum-based chemotherapy. Thirteen polymorphisms in HOXA distal transcript antisense RNA (HOTTIP), HOX transcript antisense intergenic RNA (HOTAIR), H19, CDKN2B antisense RNA 1 (ANRIL), colon cancer-associated transcript 2 (CCAT2), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and maternally expressed gene 3 (MEG3) genes were genotyped by allele-specific MALDI-TOF mass spectrometry. We found that patients with HOTTIP rs5883064 C allele or rs1859168 A allele had increased lung cancer risk (P = 0.01, P = 0.01, respectively). CCAT2 rs6983267 (P = 0.02, adenocarcinoma) and H19 rs2107425 (P = 0.02, age under 50 years) showed strong relationship with lung cancer susceptibility. CCAT2 rs6983267, H19 rs2839698, MALAT1 rs619586, and HOTAIR rs7958904 were associated with platinum-based chemotherapy response in dominant model ((P = 0.02, P = 0.04, P = 0.04, P = 0.01, respectively). ANRIL rs10120688 (P = 0.02, adenocarcinoma) and rs1333049 (P = 0.04, small-cell lung cancer), H19 rs2107425 (P = 0.02, small-cell lung cancer) and HOTAIR rs1899663 (P = 0.03, male; P = 0.03, smoker) were associated with response to platinum-based chemotherapy. HOTTIP, CCAT2, H19, HOTAIR, MALATI, ANRIL genetic polymorphisms were significantly associated with lung cancer susceptibility or platinum-based chemotherapy response. They may be potential clinical biomarkers to predict lung cancer risk and platinum-based chemotherapy response.
Objective Multiple linear regression (MLR) and machine learning techniques in pharmacogenetic algorithm-based warfarin dosing have been reported. However, performances of these algorithms in racially diverse group have never been objectively evaluated and compared. In this literature-based study, we compared the performances of eight machine learning techniques with those of MLR in a large, racially-diverse cohort. Methods MLR, artificial neural network (ANN), regression tree (RT), multivariate adaptive regression splines (MARS), boosted regression tree (BRT), support vector regression (SVR), random forest regression (RFR), lasso regression (LAR) and Bayesian additive regression trees (BART) were applied in warfarin dose algorithms in a cohort from the International Warfarin Pharmacogenetics Consortium database. Covariates obtained by stepwise regression from 80% of randomly selected patients were used to develop algorithms. To compare the performances of these algorithms, the mean percentage of patients whose predicted dose fell within 20% of the actual dose (mean percentage within 20%) and the mean absolute error (MAE) were calculated in the remaining 20% of patients. The performances of these techniques in different races, as well as the dose ranges of therapeutic warfarin were compared. Robust results were obtained after 100 rounds of resampling. Results BART, MARS and SVR were statistically indistinguishable and significantly out performed all the other approaches in the whole cohort (MAE: 8.84–8.96 mg/week, mean percentage within 20%: 45.88%–46.35%). In the White population, MARS and BART showed higher mean percentage within 20% and lower mean MAE than those of MLR (all p values < 0.05). In the Asian population, SVR, BART, MARS and LAR performed the same as MLR. MLR and LAR optimally performed among the Black population. When patients were grouped in terms of warfarin dose range, all machine learning techniques except ANN and LAR showed significantly higher mean percentage within 20%, and lower MAE (all p values < 0.05) than MLR in the low- and high- dose ranges. Conclusion Overall, machine learning-based techniques, BART, MARS and SVR performed superior than MLR in warfarin pharmacogenetic dosing. Differences of algorithms' performances exist among the races. Moreover, machine learning-based algorithms tended to perform better in the low- and high- dose ranges than MLR.
研究発表 1 Burden of caregivers for patients with mild Alzheimer's disease in Japan: difference in severity of dementia 林聪 2 Relationship between activities of daily living and Short Physical Performance Battery in elderly women with femoral neck fracture 龟山一义 3 以早期离床为目的的脑血管病患者站立动作练习用机器人的试开发 谷口敬道 4 在企业内对一例统合失调症(精神分裂症)对象进行就业支援 野﨑智仁 5 Development Process of Transfer Assist Robot based on the User Needs Concept Mio Nakamura 6 注意功能障碍和前额叶脑血流变化的相关研究-使用CPT和NIRS进行探讨 -黄富表 7 Changes of S-SEP by the upper limb immobilization during 10 hours Takuro Ikeda 8 针对膝关节前十字韧带重建术后本体感觉神经肌肉关节促通技术的即时介入效果 黄秋晨 9 Effects of the thickness of the transverse abdominal muscle in different tasks Kimiko TAJIRI 10 Reliability of lower Leg Proximal End Kinematics During Different Paces of Racewalking on a Treadmill Using a Motion Recorder (MVP-RF8-BC) Hongzhao
Many testis-specific and stage-specific genes are required for mouse spermatogenesis. In this study, semi-quantitative RT-PCR was used to confirm the tissue distribution of 12 mouse testicular genes, and fluorescence quantitative PCR labeled with SYBR GreenⅠ was applied to demonstrate the stage-specific expression of candidate genes at different spermatogenic stages. The results showed that all the genes examined were highly expressed in testis. The expression of Prm1, Prm2, Tnp1, and Tnp2 was predominant in elongating spermatids, 1.9-, 2.8-, 3.2-, and 2-fold increase as compared with that in pachytene spermatocytes, respectively. Dnajb3 expression was up-regulated 2.5-fold from pachytene spermatocytes to elongating spermatids. Akap4 was strongly expressed at elongating spermatid stage, with 5.5-fold increase than that in pachytene spermatocytes. Both Spata3 and Spata4 were equally expressed in round and elongating spermatids, 3-and 1.5-fold increase as compared with pachytene spermatocytes, respectively. The expression levels of hils1 and Tex24 were the highest in round spermatids, with 1.9-and 1.4-fold increase from pachytene spermatocytes, respectively. Spag4l and Papolb were down-regulated from pachytene spermatocytes to elongating spermatids, decreasing 45% and 34%, respectively. The results not only demonstrate the stage-specific expression of these genes, but also provide new data for further investigations into the functions of these specific genes during spermatogenesis.
Abstract Background: Early childhood growth and development is critical for long term health. Emerging science spotlights the significance of optimal gut microbiome and bone development during this period. The aim of the Bone And MicroBiOme Onset (BAMBOO) study is to determine age-appropriate trajectories for microbiome maturation and bone development, and to identify the influence of dietary factors in the process. This paper is to describe the rationale and study design, and reports study progress. Methods: BAMBOO is an ongoing prospective observational cohort study conducted in Tianjin, China. Children who meet the following requirements are invited to participate in this study: 1) full-term gestational birth (≥ 37 and ≤ 42 weeks); 2) singleton; and 3) signed informed consent by infant’s parents (or his/her legally accepted representative) and agree to fulfill the requirements of the study protocol. The exclusion criteria include pregnancy complication (such as pre-eclampsia, gestational diabetes), bowel disease, or currently participating or having participated in another clinical trial within 4 weeks prior to the start of this cohort. The study is composed of two groups of children: Group 1 includes children from birth to 12 months of age; group 2 includes children from 6 to 36 months of age. Questionnaires are used at different timepoints to collect information on infant feeding practice, medical history, concomitant medication, adverse events/serious adverse events and development benchmarks. Concurrent anthropometric measurements include length/height, weight, and bone measurements. Children’s dietary intake data are collected using 3-day-food diaries. Biological samples (stool, urine, and breastmilk) are also collected at different timepoints. Discussion: Recruitment of Bamboo started in September 2021 and is still ongoing. Data quality assessment and method validation have been conducted using early available samples. This study will provide unprecedented insights on early life microbiome maturation and bone development in Chinese infants and toddlers, and the impact of diet. The results may contribute to evidence-based policy making and inform nutrition healthcare programs for infants and toddlers aiming to benefit long-term health. Trial registration No.: ChiCTR2100049972 (August 16 th , 2021)
Pancreatic ductal adenocarcinoma (PDAC) patients' express higher levels of the orphan Nuclear Receptor 4A2 (NR4A2, NURR1) compared to normal pancreas and NR4A2 is a prognostic factor for patient survival. Knockdown of NR4A2 by RNA interference (RNAi) inhibited cell proliferation, invasion, and migration. RNA sequencing performed in NR4A2
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