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Reza Mohammadi, Zahra Mohammadi, Reza Abedi, Fatemeh Chireh, Abdolreza Balali, Parisa Mohamadynejad, Sadegh Shirian, Mehdi Moghanibashi
A large proportion of the transcriptome is sex biased in a wide range of taxa. Sexually dimorphic genes expression is highly tissue-dependent. Although gastric cancer exhibits sex bias to some extent, sexually dimorphic gene expression in the stomach is yet to be fully understood. The aim of the present study was to compare the expression levels of 12 genes in the gastric tissue between age-matched healthy men and women of different age groups. A total of 70 human antrum gastric tissue samples were obtained by endoscopy...
February 18, 2019: Molecular Biology Reports
Diego A Rojas, Pablo A Iturra, Andrea Méndez, Carolina A Ponce, Rebeca Bustamante, Miriam Gallo, Pamela Bórquez, Sergio L Vargas
Airway mucus responses to subclinical infections may explain variations in progression of chronic lung diseases and differences in clinical expression of respiratory infections across individuals. Pneumocystis associates to more severe Chronic Obstructive Pulmonary Disease (COPD), asthma, respiratory distress of premature newborns, and is a consistent subclinical infection between 2 and 5 months of age when hospitalizations for respiratory cause and infant mortality are higher. This atypical fungus associates to increased mucin 5AC (MUC5AC), a central effector of Th2-type allergic inflammation, in infant lungs...
February 14, 2019: Scientific Reports
Yang Yun, Yujie Zhang, Guangke Li, Shaoyu Chen, Nan Sang
Oxygenated polycyclic aromatic hydrocarbons (OPAHs) are a class of anthropogenic, persistent and very toxic PAH contaminant associated with developmental toxicity. Abnormal glucose metabolism disturbs energy balances that impair the early development of vertebrates, but the mechanisms by which maternal OPAH exposure alters glucose homeostasis in offspring are not well understood. Studies have suggested that epigenetic changes, particularly in DNA methylation, provide a memory of plastic developmental responses to the environment, leading to the generation of novel offspring phenotypes...
April 10, 2019: Science of the Total Environment
Dolors Cuevas, Joan Valls, Sònia Gatius, Berta Roman-Canal, Elena Estaran, Eduard Dorca, Maria Santacana, Marta Vaquero, Núria Eritja, Ana Velasco, Xavier Matias-Guiu
The two most frequent types of endometrial cancer (EC) are endometrioid (EEC) and serous carcinomas (SC). Differential diagnosis between them is not always easy. A subset of endometrial cancers shows misleading microscopical features, which cause problems in differential diagnosis, and may be a good scenario for next-generation sequencing. Previous studies have assessed the usefulness of targeted sequencing with panels of generic cancer-associated genes in EC histological typing. Based on the analysis of TCGA (The Cancer Genome Atlas), EEC and SC have different mutational profiles...
February 1, 2019: Virchows Archiv: An International Journal of Pathology
Charles E Mordaunt, Dorothy A Kieffer, Noreene M Shibata, Anna Członkowska, Tomasz Litwin, Karl-Heinz Weiss, Yihui Zhu, Christopher L Bowlus, Souvik Sarkar, Stewart Cooper, Yu-Jui Yvonne Wan, Mohamed R Ali, Janine M LaSalle, Valentina Medici
BACKGROUND: Wilson disease (WD) is an autosomal recessive disease caused by mutations in ATP7B encoding a copper transporter. Consequent copper accumulation results in a variable WD clinical phenotype involving hepatic, neurologic, and psychiatric symptoms, without clear genotype-phenotype correlations. The goal of this study was to analyze alterations in DNA methylation at the whole-genome level in liver and blood from patients with WD to investigate epigenomic alterations associated with WD diagnosis and phenotype...
February 1, 2019: Epigenetics & Chromatin
Caroline Stekelenburg, Karine Gerster, Jean-Louis Blouin, Mariarosaria Lang-Muritano, Michel Guipponi, Federico Santoni, Valerie M Schwitzgebel
OBJECTIVE: When diabetes is associated with congenital malformations, without autoimmune antibodies, a genetic cause is suspected. Here, we aimed to identify a defective gene that led to diabetes. RESEARCH DESIGN AND METHODS: We performed an exome analysis of an index case and his healthy parents. RESULTS: The child presented with childhood-onset diabetes, congenital hypopituitarism, cardiac malformation, and anal atresia. A DNA analysis revealed a heterozygous de novo pathogenic variant in the developmental transcription factor, forkhead box A2 (FOXA2)...
January 26, 2019: Pediatric Diabetes
Jing Lv, Lei Guo, Ji-Han Wang, Yu-Zhu Yan, Jun Zhang, Yang-Yang Wang, Yan Yu, Yun-Fei Huang, He-Ping Zhao
BACKGROUND: Esophageal adenocarcinoma (EAC) is an aggressive disease with high mortality and an overall 5-year survival rate of less than 20%. Barrett's esophagus (BE) is the only known precursor of EAC, and patients with BE have a persistent and excessive risk of EAC over time. Individuals with BE are up to 30-125 times more likely to develop EAC than the general population. Thus, early detection of EAC and BE could significantly improve the 5-year survival rate of EAC. Due to the limitations of endoscopic surveillance and the lack of clinical risk stratification strategies, molecular biomarkers should be considered and thoroughly investigated...
January 14, 2019: World Journal of Gastroenterology: WJG
Miao He, Hainan Zhang, Yuju Li, Changhai Tian, Beisha Tang, Yunlong Huang, Jialin Zheng
Transplantation of dopaminergic precursors (DPs) is a promising therapeutic strategy of Parkinson's disease (PD). However, limited cell source for dopaminergic precursors has become a major obstacle for transplantation therapy. Our group demonstrated previously that mouse fibroblasts can be reprogrammed into induced dopaminergic precursors (iDPs) with high differentiation efficiency. In the current study, we hypothesized that a similar strategy can be applied to generate human iDPs for future cell therapy of PD...
January 18, 2019: Neuroscience Letters
Xue Wang, Xue Jiang, Li Zhou, Zhuo Wang, He Huang, Mengqiao Wang
Neighboring enhancer of FOXA2 (NEF) is a newly discovered long non‑coding RNA (lncRNA) that serves an oncogenic function in the metastasis of hepatocellular carcinoma, while its involvement in other types of cancer and in tumor cell proliferation remain unknown. In the present study, tumor tissues and adjacent healthy tissues were obtained from patients with gastric carcinoma, and blood was extracted from patients with gastric carcinoma and healthy controls. Expression of NEF in those tissues was detected using a reverse transcription‑quantitative polymerase chain reaction...
January 16, 2019: Molecular Medicine Reports
Yeon Ji Chae, Dae Won Jun, Jai Sun Lee, Waqar Khalid Saeed, Hyeon Tae Kang, Kiseok Jang, Jin Ho Lee
Background/Aims: For the clinical application of stem cell therapy, functional enhancement is needed to increase the survival rate and the engraftment rate. The purpose of this study was to investigate functional enhancement of the paracrine effect using stem cells and hepatocyte-like cells and to minimize stem cell homing by using a scaffold system in a liver disease model. Methods: A microporator was used to overexpress Foxa2 in adipose tissue-derived stem cells (ADSCs), which were cultured in a poly(lactic-co-glycolic acid) (PLGA) scaffold...
December 24, 2018: Gut and Liver
Qian Peng, Chaomin Yue, Andy Chun Hang Chen, Kai Chuen Lee, Sze Wan Fong, William Shu Biu Yeung, Yin Lau Lee
Gap junctional intercellular communication (GJIC) is important for maintaining the pluripotency of mouse embryonic stem cells (mESC). However, human ESC (hESC) have a high level of connexin (Cx) molecules with unknown function. In this study, we found that the major Cx molecule, Cx43, was highly expressed in undifferentiated hESC. It was down-regulated upon spontaneously differentiation by embryoid body formation and induced differentiation along ectoderm, mesoderm and extraembryonic lineages, but up-regulated along endoderm differentiation...
December 19, 2018: Differentiation; Research in Biological Diversity
Sonam Dhamija, Andrea C Becker, Yogita Sharma, Ksenia Myacheva, Jeanette Seiler, Sven Diederichs
Lung cancer continues to be the leading cause of cancer-related deaths worldwide, with little improvement in patient survival rates in the past decade. Long non-coding RNAs (lncRNAs) are gaining importance as possible biomarkers with prognostic potential. By large-scale data mining, we identified LINC00261 as a lncRNA which was significantly downregulated in lung cancer. Low expression of LINC00261 was associated with recurrence and poor patient survival in lung adenocarcinoma. Moreover, the gene pair of LINC00261 and its neighbor FOXA2 were significantly co-regulated...
December 28, 2018: Non-Coding RNA
Lingxiang Zhu, Lingling An, Di Ran, Rosa Lizarraga, Cheryl Bondy, Xu Zhou, Richart W Harper, Shu-Yi Liao, Yin Chen
Human SCGB1A1 protein has been shown to be significantly reduced in bronchoalveolar lavage, sputum and serum from human asthmatics as compared to healthy individuals. However, the mechanism of this reduction and its functional impact have not been entirely elucidated. By mining online datasets, we found that the message RNA of SCGB1A1 was significantly repressed in brushed human airway epithelial cells from asthmatics and this repression appeared to be associated with the reduced expression of FOXA2. Consistently, both Scgb1A1 and FoxA2 were downregulated in an ovalbumin (OVA)-induced mouse model of asthma...
December 21, 2018: American Journal of Respiratory Cell and Molecular Biology
Susanta K Behura, Andrew M Kelleher, Thomas E Spencer
The placenta plays a pivotal role in the development of the fetal brain and also influences maternal brain function, but our understanding of communication between the placenta and brain remains limited. Using a gene expression and network analysis approach, we provide evidence that the placenta transcriptome is tightly interconnected with the maternal brain and fetal brain in d 15 pregnant C57BL/6J mice. Activation of serotonergic synapse signaling and inhibition of neurotrophin signaling were identified as potential mediators of crosstalk between the placenta and maternal brain and fetal brain, respectively...
December 6, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Naser Mobarra, Masoud Soleimani, Majid Ghayour-Mobarhan, Samaneh Safarpour, Gordon A Ferns, Reza Pakzad, Parvin Pasalar
A suitable alternative strategy for liver transplantation is the use of nanofibrous scaffolds together with stem cells. In this study, a random hybrid of poly-l-lactic acid (PLLA) and poly(ε-caprolactone) (PCL) was used as a three-dimensional (3D) culture for differentiation of hepatocyte-like cells and compared with routine culture (two-dimensional [2D]). The expression of the endodermal marker, forkhead box A2 (FOXA2), was assessed on Day 3 and the hepatic markers; albumin (ALB), α-1 antitrypsin (AAT), and cytokeratin-18 (CK-18) were evaluated on Day 18 using quantitative polymerase chain reaction qPCR...
December 4, 2018: Journal of Cellular Physiology
Zachary M Connelly, Shu Yang, Fenghua Chen, Yunshin Yeh, Nazih Khater, Renjie Jin, Robert Matusik, Xiuping Yu
Prostate cancer (PCa) is the leading cancer among men. Androgen Deprivation Therapy (ADT) is a common treatment for advanced PCa. However, ADT eventually fails and PCa relapses, developing into castration-resistant prostate cancer (CRPCa). Although alternative pathways such as cancer stem-cell pathway and neuroendocrine differentiation bypass androgen receptor (AR) signaling, AR remains the central player in mediating CRPCa. In this study, we identified a mechanism that retains AR signaling after androgen deprivation...
2018: American Journal of Clinical and Experimental Urology
Sara Ibrahim, Rania Dayoub, Sabrina Krautbauer, Gerhard Liebisch, Anja Kathrin Wege, Michael Melter, Thomas S Weiss
Cholestasis represents pathophysiologic syndromes defined as an impaired bile flow from the liver. As an outcome, bile acids accumulate and promote hepatocytes injury followed by liver cirrhosis and liver failure. Bile acids induce apoptosis, ER stress and mitochondrial membrane instability. In this study we aimed to investigate the role of cytosolic short form of ALR (Augmenter of Liver Regeneration) in the synthesis of bile acids and bile acid-induced apoptosis. Human hepatoma cells over-expressing the short form of ALR (sfALR, 15kDa) were incubated with glycochenodeoxycholic acid (GCDCA), and then primary bile acids' production and apoptosis were analyzed...
November 27, 2018: Experimental Cell Research
Jian Hou, Yan Long, Bo Hu, Shaojie Huang, Guangtao Xu, Tesheng Gao, Fenfang Wu, Yinxiong Li, Zhong-Kai Wu
BACKGROUND/AIMS: Hepatocyte-like cells derived from human pluripotent stem cells could be an important cell source for hepatocyte transplantation. The present study investigated the effect of retaining mTeSR1 medium during hepatic differentiation on hepatocyte-like cells in vitro. METHODS: Human embryonic stem cell line H1 were treated with activin A and bone morphogenetic protein 4 (BMP4) for definitive endoderm (DE) cell induction and subsequently treated with BMP2 and fibroblast growth factor 4 (FGF4) for early hepatic cell induction...
November 29, 2018: Cellular Physiology and Biochemistry
Soledad A Camolotto, Shrivatsav Pattabiraman, Timothy L Mosbruger, Alex Jones, Veronika K Belova, Grace Orstad, Mitchell Streiff, Lydia Salmond, Chris Stubben, Klaus H Kaestner, Eric Snyder
Changes in cancer cell identity can alter malignant potential and therapeutic response. Loss of the pulmonary lineage specifier NKX2-1 augments the growth of KRAS-driven lung adenocarcinoma and causes pulmonary to gastric transdifferentiation. Here we show that the transcription factors FoxA1 and FoxA2 are required for initiation of mucinous NKX2-1-negative lung adenocarcinomas in the mouse and for activation of their gastric differentiation program. Foxa1/2 deletion severely impairs tumor initiation and causes a proximal shift in cellular identity, yielding tumors expressing markers of the squamocolumnar junction of the gastrointestinal tract...
November 26, 2018: ELife
Irina Brokhman, Jie Xu, Brenda L K Coles, Rozita Razavi, Silvia Engert, Heiko Lickert, Robert Babona-Pilipos, Cindi M Morshead, Eric Sibley, Chin Chen, Derek van der Kooy
The enteric nervous system is thought to originate solely from the neural crest. Transgenic lineage tracing revealed a novel population of clonal pancreatic duodenal homeobox-1 (Pdx1)-Cre lineage progenitor cells in the tunica muscularis of the gut that produced pancreatic descendants as well as neurons upon differentiation in vitro. Additionally, an in vivo subpopulation of endoderm lineage enteric neurons, but not glial cells, was seen especially in the proximal gut. Analysis of early transgenic embryos revealed Pdx1-Cre progeny (as well as Sox-17-Cre and Foxa2-Cre progeny) migrating from the developing pancreas and duodenum at E11...
November 22, 2018: Developmental Biology
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