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Abigail K Corona, Holly M Saulsbery, Angel F Corona Velazquez, William T Jackson
Enterovirus D68 (EV-D68) is a medically important respiratory plus-strand RNA virus of children that has been linked to acute flaccid myelitis. We have determined that EV-D68 induces autophagic signaling and membrane formation. Autophagy, a homeostatic degradative process that breaks down protein aggregates and damaged organelles, promotes replication of multiple plus-strand viruses. Induction of autophagic signals promotes EV-D68 replication, but the virus inhibits the downstream degradative steps of autophagy in multiple ways...
March 20, 2018: Cell Reports
Román Rodríguez-Aguilar
The maternal mortality situation is analyzed in México as an indicator that reflects the social development level of the country and was one of the millennial development objectives. The effect of a maternal death in the related social group has multiplier effects, since it involves family dislocation, economic impact and disruption of the orphans' normal social development. Two perspectives that causes of maternal mortality were analyzed, on one hand, their relationship with social determinants and on the other, factors directly related to the health system...
2018: PloS One
Rajiv Gandhi Govindaraj, Misagh Naderi, Manali Singha, Jeffrey Lemoine, Michal Brylinski
Rare, or orphan, diseases are conditions afflicting a small subset of people in a population. Although these disorders collectively pose significant health care problems, drug companies require government incentives to develop drugs for rare diseases due to extremely limited individual markets. Computer-aided drug repositioning, i.e., finding new indications for existing drugs, is a cheaper and faster alternative to traditional drug discovery offering a promising venue for orphan drug research. Structure-based matching of drug-binding pockets is among the most promising computational techniques to inform drug repositioning...
2018: NPJ Systems Biology and Applications
Naiqian Zhao, Xiaoyan Li, Ying Feng, Jinxiang Han, Ziling Feng, Xifeng Li, Yanfang Wen
Excessive triglyceride accumulation in hepatocytes is the hallmark of obesity-associated nonalcoholic fatty liver disease (NAFLD). Elevated levels of the saturated free fatty acid palmitate in obesity are a major contributor to excessive hepatic lipid accumulation. The nuclear orphan receptor Nur77 is a transcriptional regulator and a lipotoxicity sensor. Using human HepG2 hepatoma cells, this study aimed to investigate the functional role of Nur77 in palmitate-induced hepatic steatosis. The results revealed that palmitate significantly induced lipid accumulation and suppressed lipolysis in hepatocytes...
March 19, 2018: Scientific Reports
Lin Jia, Dinglan Wu, Yuliang Wang, Wenxing You, Zhu Wang, Lijia Xiao, Ganhui Cai, Zhenyu Xu, Chang Zou, Fei Wang, Jeremy Yuen-Chun Teoh, Chi-Fai Ng, Shan Yu, Franky L Chan
The metastatic castration-resistant prostate cancer (CRPC) is a lethal form of prostate cancer, in which the expression of androgen receptor (AR) is highly heterogeneous. Indeed, lower AR expression and attenuated AR signature activity is shown in CRPC tissues, especially in the subset of neuroendocrine prostate cancer (NEPC) and prostate cancer stem-like cells (PCSCs). However, the significance of AR downregulation in androgen insensitivity and de-differentiation of tumor cells in CRPC is poorly understood and much neglected...
March 20, 2018: Oncogene
Ravi Gupta, Thomas J Bollyky, Matthew Cohen, Joseph S Ross, Aaron S Kesselheim
OBJECTIVES: To evaluate whether off-patent prescription drugs at risk of sudden price increases or shortages in the United States are available from independent manufacturers approved in other well regulated settings around the world. DESIGN: Observational study. SETTING: Off-patent drugs in the USA and approved by the Food and Drug Administration, up to 10 April 2017. STUDY COHORT: Novel tablet or capsule prescription drugs approved by the FDA since 1939 that were no longer protected by patents or other market exclusivity and had up to three generic versions...
March 19, 2018: BMJ: British Medical Journal
Corey Holt, Rachel Foster, Carly L Daniels, Mark van der Giezen, Stephen W Feist, Grant D Stentiford, David Bass
A parasite exhibiting Oomycete-like morphology and pathogenesis was isolated from discoloured eggs of the European lobster (Homarus gammarus) and later found in gill tissues of adults. Group-specific Oomycete primers were designed to amplify the 18S ribosomal small subunit (SSU), which initially identified the organism as the same as the 'Haliphthoros' sp. NJM 0034 strain (AB178865.1) previously isolated from abalone (imported from South Australia to Japan). However, in accordance with other published SSU-based phylogenies, the NJM 0034 isolate did not group with other known Haliphthoros species in our Maximum Likelihood and Bayesian phylogenies...
March 16, 2018: Journal of Invertebrate Pathology
Yuhong Li, Qi Ren, Lingyan Zhu, Yingshu Li, Jinfeng Li, Yiyang Zhang, Guoying Zheng, Tiesheng Han, Shufeng Sun, Fumin Feng
BACKGROUND: This investigation aimed to evaluate the role of methylation in the regulation of microRNA (miR)-122, miR-125b and miR-106b gene expression and the expression of their target genes during isoniazid (INH)-induced liver injury. METHODS: Rats were given INH 50 mg kg- 1 ·d- 1 once per day for 3, 7, 10, 14, 21 and 28 days and were sacrificed. Samples of blood and liver were obtained. RESULTS: We analysed the methylation and expression levels of miR-122, miR-125b and miR-106b and their potential gene targets in livers...
March 20, 2018: BMC Pharmacology & Toxicology
Shu-Long Li, Yun Yu, Peng Yang, Hui Wang, Cheng Zhang, Min Liu, Jia-Xiang Zhang, Tong Shen, Changhao Wu, Qi-Xing Zhu
The role of environmental factors in autoimmune diseases has been increasingly recognized. While major advance has been made in understanding biological pathogen-induced autoimmune diseases, chemically triggered autoimmunity is poorly understood. Trichloroethylene (TCE), a common environmental pollutant, has recently been shown to induce autoimmunity. This study explored whether TCE could cause imbalance of T helper (Th) cell subsets which would contribute to the pathogenesis of TCE-induced medicamentosa-like dermatitis...
January 1, 2018: International Journal of Toxicology
Linlin Dong, Xiaoyu Zheng, Kun Wang, Guonian Wang, Huichao Zou
BACKGROUND: The T-helper 17 (Th17)/regulatory T (Treg) balance is essential for immune homeostasis. But the effects of gastric surgery on this balance remain unclear. The aim of present study is to identify the influence of gastric surgery on Th17/Treg balance and the role of programmed death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway in this process. METHODS: Mice were divided into Control, Sham and Surgery group randomly. Animals in Surgery group accepted partial gastrectomy...
March 16, 2018: Journal of Trauma and Acute Care Surgery
Rong Liang, Yan Lin, Chun-Ling Yuan, Zhi-Hui Liu, Yong-Qiang Li, Xiao-Ling Luo, Jia-Zhou Ye, Hai-Hong Ye
Colorectal cancer (CRC) is one of the most common types of malignancy with high morbidity and mortality rates worldwide. This biologically heterogeneous disease results in diverse therapeutic responses, thus, novel prognostic biomarkers are required to improve CRC treatment. Estrogen-related receptor α (ERRα) is a nuclear orphan receptor, which is associated with estrogen receptor α. The present study aimed to investigate the expression of ERRα in patients with CRC, and explore the association between ERRα expression and clinicopathological factors, local recurrence and prognosis...
April 2018: Oncology Letters
Nicolas Daffern, Zhonglei Chen, Yongbo Zhang, Leslie Pick, Ishwar Radhakrishnan
The ligand-binding domains (LBD) of the NR5A subfamily of nuclear receptors activate transcription via ligand-dependent and ligand-independent mechanisms. The Drosophila Ftz-F1 receptor (NR5A3) belongs to the latter category and its ligand-independence is attributed to a short helical segment (6) within the protein that resides in the canonical ligand-binding pocket (LBP) in the crystalline state. Here, we show that the 6 helix is dynamic in solution when Ftz-F1 is bound to the LxxLL motif of its cofactor Ftz, undergoing motions on the fast (picosecond-nanosecond) as well as slow (microsecond-millisecond) timescales...
March 16, 2018: Biochemistry
Ahmet F Oner, Tiraje Celkan, Çetin Timur, Miranda Norton, Kaan Kavaklı
Hereditary factor X (FX) deficiency is a rare bleeding disorder more prevalent in countries with high rates of consanguineous marriage. In a prospective, open-label, multicentre, phase 3 study, 25 IU/kg pdFX was administered as on-demand treatment or short-term prophylaxis for 6 months-2 years. In Turkish subjects (N=6), 60.7% of bleeds were minor. A mean of 1.03 infusions was used to treat each bleed, and mean total dose per bleed was 25.38 IU/kg. Turkish subjects ratedpdFX efficacy as excellent or good for all 84 assessable bleeds; investigators judged overall pdFX efficacy to be excellent or good in all subjects...
March 16, 2018: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
Marie Madsen, Peter Riis Hansen, Lars Bo Nielsen, Renata Martins Cardoso, Miranda van Eck, Tanja Xenia Pedersen
Psoriasis is a chronic inflammatory skin disorder associated with several comorbidities including atherosclerosis. Disease mechanisms that may affect both psoriasis and atherosclerosis include activation of T helper 1 and T helper 17 cells. Imiquimod application is an established mouse model of psoriasis-like skin inflammation. The cardiac glycoside digoxin inhibits the master transcription factor of T helper 17 differentiation, retinoid acid receptor-related orphan nuclear receptor γt, and attenuates interleukin-17-dependent pathologies in mice...
March 12, 2018: American Journal of Pathology
Keigo Tsushida, Katsuyuki Tanabe, Kana Masuda, Satoshi Tanimura, Hiromasa Miyake, Yuka Arata, Hitoshi Sugiyama, Jun Wada
Acute kidney injury (AKI) has been associated with not only higher in-hospital mortality but also the subsequent development of chronic kidney disease (CKD). Recent evidence has suggested the involvement of mitochondrial dysfunction and impaired dynamics in the pathogenesis of AKI. Estrogen-related receptor α (ERRα) is an orphan nuclear receptor that acts as a transcription factor to regulate the transcription of genes required for mitochondrial biogenesis and oxidative phosphorylation. In the present study, we examined the effects of ERRα deficiency on the progression of AKI induced by cisplatin...
March 12, 2018: Biochemical and Biophysical Research Communications
Daniela Munro-Rojas, Esdras Fernandez-Morales, José Zarrabal-Meza, Ma Teresa Martínez-Cazares, Aurora Parissi-Crivelli, Javier Fuentes-Domínguez, Marie Nancy Séraphin, Michael Lauzardo, Jorge Alberto González-Y-Merchand, Sandra Rivera-Gutierrez, Roberto Zenteno-Cuevas
BACKGROUND: Mexico is one of the most important contributors of drug and multidrug-resistant tuberculosis in Latin America; however, knowledge of the genetic diversity of drug-resistant tuberculosis isolates is limited. METHODS: In this study, the genetic structure of 112 Mycobacterium tuberculosis strains from the southeastern Mexico was determined by spoligotyping and 24-loci MIRU-VNTRs. FINDINGS: The results show eight major lineages, the most of which was T1 (24%), followed by LAM (16%) and H (15%)...
2018: PloS One
Yiran Ao, Qin Zhao, Kai Yang, Gang Zheng, Xiaoqing Lv, Xiaoli Su
Clock genes are the core of the circadian rhythms in the human body and are important in regulating normal physiological functions. To date, research has indicated that the clock gene, period circadian clock 2 ( PER2 ), is downregulated in numerous types of cancer, and that it is associated with cancer occurrence and progression via the regulation of various downstream cell cycle genes. However, it remains unclear whether the decreased expression of PER2 influences the expression of other clock genes in cancer cells...
April 2018: Oncology Letters
Iwao Sugitani, Naoyoshi Onoda, Ken-Ichi Ito, Shinichi Suzuki
Anaplastic thyroid carcinoma (ATC) accounts for only 1 to 2% of all thyroid carcinomas, but it is one of the most lethal neoplasms in humans. To obtain further insights into this "orphan disease," we have established the ATC Research Consortium of Japan (ATCCJ) in 2009. It represents a multicenter registry for ATC that have been treated in Japan. To date, 67 institutions have taken part in the collaborative research system and over 1,200 cases have been accumulated in its database. Using this big data, several retrospective studies were carried out to evaluate 1) prognostic factors to determine initial treatment policy, 2) significance of extended radical surgery for Stage IVB cases, 3) characteristics of ATC incidentally found on pathological examination and 4) pathological features of ATC with long-term survival...
2018: Journal of Nippon Medical School, Nippon Ika Daigaku Zasshi
Andoni Ramirez-Garcia, Aize Pellon, Aitor Rementeria, Idoia Buldain, Eliana Barreto-Bergter, Rodrigo Rollin-Pinheiro, Jardel Vieira de Meirelles, Mariana Ingrid D S Xisto, Stephane Ranque, Vladimir Havlicek, Patrick Vandeputte, Yohann Le Govic, Jean-Philippe Bouchara, Sandrine Giraud, Sharon Chen, Johannes Rainer, Ana Alastruey-Izquierdo, Maria Teresa Martin-Gomez, Leyre M López-Soria, Javier Peman, Carsten Schwarz, Anne Bernhardt, Kathrin Tintelnot, Javier Capilla, Adela Martin-Vicente, Jose Cano-Lira, Markus Nagl, Michaela Lackner, Laszlo Irinyi, Wieland Meyer, Sybren de Hoog, Fernando L Hernando
Species of Scedosporium and Lomentospora are considered as emerging opportunists, affecting immunosuppressed and otherwise debilitated patients, although classically they are known from causing trauma-associated infections in healthy individuals. Clinical manifestations range from local infection to pulmonary colonization and severe invasive disease, in which mortality rates may be over 80%. These unacceptably high rates are due to the clinical status of patients, diagnostic difficulties, and to intrinsic antifungal resistance of these fungi...
April 1, 2018: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Ning Wei, Michelle L Gumz, Anita T Layton
Major renal functions such as renal blood flow, glomerular filtration rate, and urinary excretion are known to exhibit circadian oscillations. However, the underlying mechanisms that govern these variations have yet to be fully elucidated. To better understand the impact of the circadian clock on renal solute and water transport, we have developed a computational model of the renal circadian clock, and coupled that model to an epithelial transport model of the proximal convoluted cell of the rat kidney. The activity of the Na$^+$-H$^+$ exchanger 3 (NHE3) is assumed to be regulated by changes in transcription of the NHE3 mRNA due to regulation by circadian clock proteins...
March 14, 2018: American Journal of Physiology. Renal Physiology
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