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Target-to treat

Toshiaki Teratani, Kengo Tomita, Takahiro Suzuki, Hirotaka Furuhashi, Rie Irie, Makoto Nishikawa, Junji Yamamoto, Toshifumi Hibi, Soichiro Miura, Tohru Minamino, Yuichi Oike, Ryota Hokari, Takanori Kanai
Incidence of nonalcoholic steatohepatitis (NASH), which is considered a hepatic manifestation of metabolic syndrome, has been increasing worldwide with the rise in obesity; however, its pathological mechanism is poorly understood. Here, we demonstrate that the hepatic expression of aortic carboxypeptidase-like protein (ACLP), a glycosylated, secreted protein, increases in NASH in humans and mice. Furthermore, we elucidate that ACLP is a ligand, unrelated to WNT proteins, that activates the canonical WNT pathway and exacerbates NASH pathology...
March 19, 2018: Journal of Clinical Investigation
Adriely Goes, Gregor Fuhrmann
Biogenic and biomimetic therapeutics are a relatively new class of systems that are of physiological origin and/or take advantage of natural pathways, or aim at mimicking these to improve selective interaction with target tissue. The number of biogenic and bioengineered avenues for drug therapy and diagnostics has multiplied over the past years for many applications, indicating the high expectations associated with this biological route. Nevertheless, the use of "bio"-related approaches for treating or diagnosing infectious diseases is still rare...
March 19, 2018: ACS Infectious Diseases
Ting Zhang, Hao Zhang, Liang He, Zhihong Wang, Wenwu Dong, Wei Sun, Ping Zhang
BACKGROUND Low levels of 1-25-dihydroxyvitamin D3 [1,25(OH)2D3] in serum may be a risk factor for several tumor types. Also, high cathelicidin antimicrobial peptide (CAMP) expression is regarded to be important against tumor progression. We evaluated the potential importance of 1,25(OH)2D3 in the diagnosis and treatment of papillary thyroid cancer (PTC). MATERIAL AND METHODS The preoperative serum level of 1,25(OH)2D3 was measured using a double-antibody sandwich enzyme-linked immunosorbent assay. Vitamin D3 receptor (VDR) expression was detected by streptavidin-peroxidase immunohistochemical staining in PTC specimens...
March 19, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Conor P Kerley, Eamon Dolan, Philip E James, Liam Cormican
Dietary nitrate has been shown to increase nitrate/nitrite levels and decrease blood pressure (BP) in multiple populations. There are few reports among hypertensives and these reports have provided conflicting evidence. We aimed to assess the effect of daily nitrate compared with placebo in subjects with uncontrolled hypertension (HTN). On day 0, hypertensives wore an ambulatory BP monitor (ABPM) for 24 h and blood was taken. Subjects were then randomised to 7-d nitrate-rich beetroot juice (NO3 -) (12·9 mmol nitrate) followed by 7-d nitrate-depleted beetroot juice (0·5 mmol nitrate) or vice versa...
March 2018: British Journal of Nutrition
Damianos G Kokkinidis, Bejan Alvandi, Prio Hossain, T Raymond Foley, Caitlin E Kielhorn, Gagan D Singh, Stephen W Waldo, John R Laird, Ehrin J Armstrong
PURPOSE: To evaluate the association between a chronic total occlusion (CTO) and long-term outcomes among patients undergoing endovascular intervention to the external iliac artery (EIA). METHODS: A 2-center retrospective study was conducted of 331 patients (mean age 64.7±12.7 years; 221 men) who underwent endovascular intervention for 481 EIA atherosclerotic lesions between 2006 and 2016. A quarter of the lesions (115, 23.9%) were CTOs. The majority of patients (184, 60...
April 2018: Journal of Endovascular Therapy
Craig M Lilly, Omar Badawi, Xinggang Liu, Gill Christine S, Ilene Harris
OBJECTIVE: To determine whether patients transfused red blood cell (RBC) products according to guideline-specified pretransfusion hemoglobin (Hb) concentrations or for other reasons were more likely to survive their intensive care unit (ICU) stay. DESIGN: An observational study of 375 478 episodes of ICU care, over 5 years, was performed with ICU survival as the primary outcome. Outcomes were analyzed as a function of pretransfusion Hb concentration for groups with distinct transfusion indications while adjusting for potential confounders...
January 1, 2018: Journal of Intensive Care Medicine
Ya-Ping Xiao, Jie Zeng, Lin-Na Jiao, Xiao-Yu Xu
The treatment effect and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied, but there is no systematic summary currently. This review comprehensively collected and analyzed the traditional Chinese medicines on the treatment and signaling pathway regulation of osteoporosis in recent ten years, such as Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix. Based on the existing findings, the following conclusions were obtained: ①kidney-tonifying traditional Chinese medicine treated osteoporosis mainly through BMP-Smads, Wnt/ β -catenin, MAPK, PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/ RANK, estrogen, CTSK signaling pathway to inhibit osteoclasts of bone resorption...
January 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Lin Hai Kurahara, Keizo Hiraishi, Yaopeng Hu, Kaori Koga, Miki Onitsuka, Mayumi Doi, Kunihiko Aoyagi, Hidetoshi Takedatsu, Daibo Kojima, Yoshitaka Fujihara, Yuwen Jian, Ryuji Inoue
Background & Aims: The transient receptor potential ankyrin 1 (TRPA1) channel is highly expressed in the intestinal lamina propria, but its contribution to gut physiology/pathophysiology is unclear. Here, we evaluated the function of myofibroblast TRPA1 channels in intestinal remodeling. Methods: An intestinal myofibroblast cell line (InMyoFibs) was stimulated by transforming growth factor-β1 to induce in vitro fibrosis. Trpa1 knockout mice were generated using the Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
Hui Liu, Xin-Hua Cheng
Oxaliplatin is a commonly used chemotherapeutic drug for the treatment of advanced colorectal cancer. However, acquired drug resistance against oxaliplatin remains a major obstacle for efficient use of it, and mechanisms underlying oxaliplatin resistance are still required to be explored. In the present study, we exposed colorectal cancer cell line SW480 to oxaliplatin for a long time to obtain oxaliplatin-resistant colorectal cancer cell model (OR-SW480). We found that intracellular expression of miR-29b was decreased when the SW480 cells became oxaliplatin-resistant...
February 23, 2018: Oncotarget
Michelle Faria, Samaneh Karami, Sergio Granados-Principal, Prasenjit Dey, Akanksha Verma, Dong S Choi, Olivier Elemento, Tasneem Bawa-Khalfe, Jenny C Chang, Anders M Strom, Jan-Åke Gustafsson
Triple negative breast cancer (TNBC) still remains a challenge to treat in the clinic due to a lack of good targets for treatment. Although TNBC lacks expression of ERα, the expression of ERβ and its variants are detected quite frequently in this cancer type and can represent an avenue for treatment. We show that two of the variants of ERβ, namely ERβ2 and ERβ5, control aggressiveness of TNBC by regulating hypoxic signaling through stabilization of HIF-1α. RNA-seq of patient derived xenografts (PDX) from TNBC shows expression of ERβ2, ERβ4 and ERβ5 variants in more than half of the samples...
February 23, 2018: Oncotarget
Mengfan Qi, Ye Tian, Wang Li, Dan Li, Tian Zhao, Yuxin Yang, Qiwen Li, Sujun Chen, Yan Yang, Zhixiong Zhang, Liang Tang, Zhonghua Liu, Bo Su, Fei Li, Yonghong Feng, Ke Fei, Peng Zhang, Fan Zhang, Lei Zhang
Gefitinib, an EGFR tyrosine kinase inhibitor, is used to treat non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. However, the resistance to gefitinib eventually emerges in most of the patients. To understand its mechanism, we generated two acquired gefitinib-resistant NSCLC cell lines. The resistant cells have slower growth rates, but are more resistant to apoptosis in the presence of gefitinib, compared with their sensitive counterparts. In addition, our genome-wide transcriptome analysis reveals unexpected pathways, particularly autophagy, are dysregulated in the gefitinib-resistant cells...
February 23, 2018: Oncotarget
Xi Song, Qiyang Shen, Liting Fan, Qiuxiao Yu, Xiao Jia, Yu Sun, Wenpei Bai, Jihong Kang
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age and also an important metabolic disorder associated with insulin resistance (IR). Hyperandrogenism is a key feature of PCOS. However, whether hyperandrogenism can cause IR in PCOS remains largely unknown. The mammalian target of rapamycin complex 1 (mTORC1) and its regulated autophagy are closely associated with IR. In the present study, we investigated the role of mTORC1-autophagy pathway in skeletal muscle IR in a dehydroepiandrosterone (DHEA)-induced PCOS mouse model...
February 23, 2018: Oncotarget
Suolin Zhang, Yayan Wang
Expression of angiotensin II (Ang II), a key biological peptide in the renin-angiotensin system, is closely associated with the occurrence and development of cancer. Ang II binds two receptor subtypes, the Ang II type 1 receptor (AT1R) and the AT2R, to mediate a series of biological effects. Telmisartan, a specific AT1R blocker, has been reported to have potential as an anticancer drug for treating renal cancer. In the present study, whether telmisartan had an effect on non-small cell lung cancer (NSCLC) cell proliferation and migration was investigated...
April 2018: Oncology Letters
Zhanpeng Luo, Dawei Li, Xiaobo Luo, Litao Li, Suxi Gu, Long Yu, Yuanzheng Ma
The present study aimed to determine the mechanisms of action of curcumin in osteosarcoma. Human osteosarcoma U-2 OS cells was purchased from the Cell Bank of the Chinese Academy of Sciences. RNA sequencing analysis was performed for 2 curcumin-treated samples and 2 control samples using Illumina deep sequencing technology. The differentially expressed genes were identified using Cufflink software. Enrichment and protein-protein interaction network analyses were performed separately using cluster Profiler package and Cytoscape software to identify key genes...
April 2018: Oncology Letters
Yanhong Yang, Wenwen Zhou, Jiandong Wu, Lixin Yao, Lei Xue, Qianyi Zhang, Zhenzhen Wang, Xiaoyu Wang, Shu Dong, Jiangman Zhao, Duanduan Yin
Nimotuzumab, a humanized IgG1 monoclonal antibody against epidermal growth factor receptor (EGFR), increases radiosensitivity in lung cancer. Cisplatin is an effective antitumor agent in lung cancer. In the present study, the antitumor activity of nimotuzumab combined with cisplatin was investigated in A549 lung cancer cells. Viability, cell cycle distribution and cyclin D1 expression were assessed following treatment with nimotuzumab alone, cisplatin alone, nimotuzumab in combination with cisplatin, and nimotuzumab followed sequentially by cisplatin...
April 2018: Oncology Letters
Hui Di, Xinting Zhang, Yi Guo, Yanfang Shi, Chuan Fang, Yu Yuan, Jiwei Wang, Chao Shang, Wenzhe Guo, Chunhui Li
Glioblastoma multiforme (GBM) is a prevalent and aggressive disease, and the development of a novel therapy to better treat advanced GBM is urgently required. Lactate dehydrogenase A (LDHA), which functions as a key enzyme in transforming pyruvate into lactate, has attracted more attention in recent years due to its critical role in various types of advanced cancer. Previous data derived from the Oncomine database have shown that the expression of LDHA is higher in GBM tissues than that in corresponding normal control tissues...
April 2018: Oncology Letters
Tong Xie, Lingzhao Mo, Li Li, Naiquan Mao, Danrong Li, Deseng Liu, Chuantian Zuo, Dingming Huang, Qi Pan, Li Yang, Shoufeng Wang
The present study aimed to isolate and characterize side population (SP) cells in the human lung cancer A549 cell line, and elucidate the molecular mechanism of SP cells underlying lung cancer. The SP and non-SP (NSP) cells in A549 cells were isolated and their differentiation was analyzed by fluorescence-activated cell sorting. An in vitro plate clone assay, Matrigel® Transwell assay and chemoresistance analysis of the sorted SP and NSP cells were performed. In addition, the sorted SP and NSP cells were injected into BALB/c nude mice to detect their tumorigenic potential in vivo ...
April 2018: Oncology Letters
Zirong Pan, Jianmin Zhuang, Chenghong Ji, Zhezhen Cai, Weijia Liao, Zhengjie Huang
Morbidity and mortality owing to hepatocellular carcinoma (HCC), the most common primary liver cancer, has increased in recent years. Curcumin is a polyphenol compound that has been demonstrated to exert effective antiangiogenic, anti-inflammatory, antioxidant, and antitumor effects. However, its clinical effects in HCC remain elusive. The main aim of the present study was to determine the antiangiogenic effects of curcumin in HCC. H22HCC cells were treated with different concentrations of curcumin in vitro ...
April 2018: Oncology Letters
Andrew S Fister, Lena Landherr, Siela N Maximova, Mark J Guiltinan
Theobroma cacao , the source of cocoa, suffers significant losses to a variety of pathogens resulting in reduced incomes for millions of farmers in developing countries. Development of disease resistant cacao varieties is an essential strategy to combat this threat, but is limited by sources of genetic resistance and the slow generation time of this tropical tree crop. In this study, we present the first application of genome editing technology in cacao, using Agrobacterium-mediated transient transformation to introduce CRISPR/Cas9 components into cacao leaves and cotyledon cells...
2018: Frontiers in Plant Science
Robert A LaMothe, Pallavi N Kolte, Trinh Vo, Joseph D Ferrari, Tracy C Gelsinger, Jodie Wong, Victor T Chan, Sinthia Ahmed, Aditi Srinivasan, Patrick Deitemeyer, Roberto A Maldonado, Takashi K Kishimoto
T cells reacting to self-components can promote tissue damage when escaping tolerogenic control mechanisms which may result in autoimmune disease. The current treatments for these disorders are not antigen (Ag) specific and can compromise host immunity through chronic suppression. We have previously demonstrated that co-administration of encapsulated or free Ag with tolerogenic nanoparticles (tNPs) comprised of biodegradable polymers that encapsulate rapamycin are capable of inhibiting Ag-specific transgenic T cell proliferation and inducing Ag-specific regulatory T cells (Tregs)...
2018: Frontiers in Immunology
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