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Xin-Rui Han, Xin Wen, Yong-Jian Wang, Shan Wang, Min Shen, Zi-Feng Zhang, Shao-Hua Fan, Qun Shan, Liang Wang, Meng-Qiu Li, Bin Hu, Chun-Hui Sun, Dong-Mei Wu, Jun Lu, Yuan-Lin Zheng
Hypoxia-ischaemia (HI) remains a major cause of foetal brain damage presented a scarcity of effective therapeutic approaches. Dexmedetomidine (DEX) and microRNA-140-5p (miR-140-5p) have been highlighted due to its potentially significant role in the treatment of cerebral ischaemia. This study was to investigate the role by which miR-140-5p provides cerebral protection using DEX to treat hypoxic-ischaemic brain damage (HIBD) in neonatal rats via the Wnt/β-catenin signalling pathway. The HIBD rat models were established and allocated into various groups with different treatment plans, and eight SD rats into sham group...
March 13, 2018: Journal of Cellular and Molecular Medicine
Kelsey H Elliott, Grethel Millington, Samantha A Brugmann
BACKGROUND: Submandibular glands (SMGs) are specialized epithelial structures which generate saliva necessary for mastication and digestion. Loss of SMGs can lead to inflammation, oral lesions, fungal infections, problems with chewing/swallowing, and tooth decay. Understanding the development of the SMG is important for developing therapeutic options for patients with impaired SMG function. Recent studies have suggested Sonic hedgehog (Shh) signaling in the epithelium plays an integral role in SMG development; however, the mechanism by which Shh influences gland development remains nebulous...
March 13, 2018: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Roberto De Gregorio, Salvatore Pulcrano, Claudia De Sanctis, Floriana Volpicelli, Ezia Guatteo, Lars von Oerthel, Emanuele Claudio Latagliata, Roberta Esposito, Rosa Maria Piscitelli, Carla Perrone-Capano, Valerio Costa, Dario Greco, Stefano Puglisi-Allegra, Marten P Smidt, Umberto di Porzio, Massimiliano Caiazzo, Nicola Biagio Mercuri, Meng Li, Gian Carlo Bellenchi
The differentiation of dopaminergic neurons requires concerted action of morphogens and transcription factors acting in a precise and well-defined time window. Very little is known about the potential role of microRNA in these events. By performing a microRNA-mRNA paired microarray screening, we identified miR-34b/c among the most upregulated microRNAs during dopaminergic differentiation. Interestingly, miR-34b/c modulates Wnt1 expression, promotes cell cycle exit, and induces dopaminergic differentiation. When combined with transcription factors ASCL1 and NURR1, miR-34b/c doubled the yield of transdifferentiated fibroblasts into dopaminergic neurons...
March 2, 2018: Stem Cell Reports
Riikka E Mäkitie, Matthias Hackl, Riitta Niinimäki, Sakari Kakko, Johannes Grillari, Outi Mäkitie
Context: WNT signaling is fundamental to bone health and its aberrant activation leads to skeletal pathologies. A heterozygous missense mutation p.C218G in WNT1, a key WNT pathway ligand, leads to severe early-onset and progressive osteoporosis with multiple peripheral and spinal fractures. Despite the severe skeletal manifestations, conventional bone turnover markers are normal in mutation-positive patients. Objective: This study sought to explore the circulating miRNA pattern in patients with impaired WNT signaling...
March 1, 2018: Journal of Clinical Endocrinology and Metabolism
Fan Li, Yang Liu, Yingyu Cai, Xin Li, Min Bai, Ting Sun, Lianfang Du
This study investigated the impact of ultrasound (US) irradiation on the hepatic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) induced by hepatocyte growth factor (HGF) and the possible mechanisms. We treated hBMSCs, using HGF with and without US irradiation. Cell viability and stem cell surface markers were analyzed. Hepatocyte-like cell markers and functional markers including α-fetoprotein (αFP/AFP), cytokeratin 18 (CK18), albumin (ALB) and glycogen content were analyzed at the time point of day 1, 3 and 5 after treatment...
February 28, 2018: Ultrasound in Medicine & Biology
Julia Mrosk, SriLakshmi Bhavani Gandham, Hitesh Shah, Jochen Hecht, Ulrike Krüger, Anju Shukla, Uwe Kornak, Katta Mohan Girisha
Osteogenesis Imperfecta (OI) is a clinically and genetically heterogeneous disorder. Although differential diagnosis is greatly facilitated by next generation sequencing, its availability can vary considerably. In this study, we compared targeted gene panel or exome sequencing with clinical scoring and grouping in a cohort of 50 OI index patients recruited by a single Indian clinical center in an unselected fashion. In 48 patients we observed a total of 24 novel mutations and 24 known OI mutations, of which several were recurrent...
February 27, 2018: Bone
Katerina Koussoulas, Mathusi Swaminathan, Candice Fung, Joel C Bornstein, Jaime P P Foong
γ-Aminobutyric Acid (GABA) and its receptors, GABAA,B,C , are expressed in several locations along the gastrointestinal tract. Nevertheless, a role for GABA in enteric synaptic transmission remains elusive. In this study, we characterized the expression and function of GABA in the myenteric plexus of the mouse ileum. About 8% of all myenteric neurons were found to be GABA-immunoreactive (GABA+) including some Calretinin+ and some neuronal nitric oxide synthase (nNOS+) neurons. We used Wnt1-Cre;R26R-GCaMP3 mice, which express a genetically encoded fluorescent calcium indicator in all enteric neurons and glia...
2018: Frontiers in Physiology
Inusha Panigrahi, Siyaram Didel, Harita Kirpal, Ravishankara Bellampalli, Shabna Miyanath, Nandita Mullapudi, Sudha Rao
Osteogenesis imperfecta (OI) is an inherited disorder with osteoporosis and recurrent fractures. Children presenting with recurrent fractures and bowing of limbs have severe form of the disorder. Patients carrying homozygous WNT1 mutations have more frequent fractures while heterozygous carriers of the mutation in WNT1 gene are also found to have early onset osteoporosis. We identified a family with novel WNT1 mutation. The index case, a 6 month old child presented with fractures from early infancy. Next generation sequencing (NGS)done for the child didn't show any variations in other OI genes including COL1A1, COL1A2, SERPINH1, CRTAP, LEPRE1, PP1B, 1F1TM5 and BMP1 genes...
February 23, 2018: European Journal of Medical Genetics
Philip Tröster, Julia Haseleu, Jonas Petersen, Oliver Drees, Achim Schmidtko, Frederick Schwaller, Gary R Lewin, Gohar Ter-Avetisyan, York Winter, Stefanie Peters, Susanne Feil, Robert Feil, Fritz G Rathjen, Hannes Schmidt
A cGMP signaling cascade composed of C-type natriuretic peptide, the guanylyl cyclase receptor Npr2 and cGMP-dependent protein kinase I (cGKI) controls the bifurcation of sensory axons upon entering the spinal cord during embryonic development. However, the impact of axon bifurcation on sensory processing in adulthood remains poorly understood. To investigate the functional consequences of impaired axon bifurcation during adult stages we generated conditional mouse mutants of Npr2 and cGKI ( Npr2 fl / fl ;Wnt1 Cre and cGKI KO / fl ;Wnt1 Cre ) that lack sensory axon bifurcation in the absence of additional phenotypes observed in the global knockout mice...
2018: Frontiers in Molecular Neuroscience
Yu Zheng, Yi Zeng, Rongfang Qiu, Ruiqiong Liu, Wei Huang, Yongqiang Hou, Shuang Wang, Shuai Leng, Dandan Feng, Yang Yang, Yan Wang
The homeodomain transcription factor SIX3 was recently reported to be a negative regulator of the Wnt pathway and has an emerging role in cancer. However, how SIX3 contributes to tumorigenesis and metastasis is poorly understood. METHODS: We employed affinity purification and mass spectrometry (MS) to identify the proteins physically associated with SIX3. Genome-wide analysis of the SIX3/LSD1/NuRD(MTA3) complex using a chromatin immunoprecipitation-on-chip approach identified a cohort of target genes including WNT1 and FOXC2 , which are critically involved in cell proliferation and epithelial-to-mesenchymal transition...
2018: Theranostics
Wei Wang, Qing Li, Tao Yang, Dongsheng Li, Feng Ding, Hongzhi Sun, Guang Bai
Aquaporin 5 (AQP5) is a water channel protein that is over-expressed in many tumors. Elevated expression of AQP5 is associated with poor prognosis of colorectal cancer. Yet, whether AQP5 plays a role in epithelial-mesenchymal transition (EMT) of colorectal cancer has not been reported until now. Here we aim to investigate the function of AQP5 in the EMT process of colorectal cancer. We transfected HCT116 and SW480 cells with AQP5-specific shRNA and verified the knockdown efficiency through western blotting and real-time PCR...
February 17, 2018: Cytotechnology
Wenjun Zhang, Zheng Sun, Liang Su, Feng Wang, Yiming Jiang, Dengfeng Yu, Fujie Zhang, Zhe Sun, Wenbo Liang
Colon cancer is one of the deadliest cancers worldwide; abnormal microRNA expression is common during colon cancer development. The aim of the present study was to elucidate the role played by miR-185 in this context. We used quantitative real-time PCR (qRT-PCR) to measure miR-185 expression levels in colon cancer cell lines. The effects of miR-185 on colon cancer cell proliferation and invasion were assessed using the MTT, colony-forming, wound-healing, and transwell assays. A luciferase activity assay was used to confirm the target of miR-185...
February 15, 2018: European Journal of Pharmacology
Yue-Hui Wang, Cheng-Kuan Sun, Xiang-Lan Li, Yan Huang, Jing Sun
Persistent exposure to solar ultraviolet radiation (UVR) causes continuous damages to skin, including progressive impairment of epidermal stem cells (ESCs) capacities. Ghrelin is the only known endogenous orexigenic hormone, which has displayed its various pharmacological functions. In the current study, we found that the specific receptor of ghrelin, growth hormone secretagogue receptor (GHS-R), is expressed in ESCs. Interestingly, GHS-R expression is significantly upregulated in response to ultraviolet B (UVB) radiation...
February 5, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Huan Jing, Xiaoxia Su, Bo Gao, Yi Shuai, Ji Chen, Zhihong Deng, Li Liao, Yan Jin
Disrupted Wnt signaling in osteoblastic-lineage cells leads to bone formation defect in osteoporosis. However, the factors repressing Wnt signaling are unclear. In our study, we found that Wnt signaling was suppressed persistently in bone marrow-derived mesenchymal stem cells (BMSCs) during osteoporosis. Accordingly, histone acetylation levels on Wnt genes (Wnt1, Wnt6, Wnt10a, and Wnt10b) were declined in BMSCs from OVX mice. By screening the family of histone acetyltransferase, we identified that GCN5 expression increased during osteogenic differentiation of BMSCs, whereas decreased after osteoporosis...
February 7, 2018: Cell Death & Disease
Lei Zhang, Hailing Cheng, Yuxia Yue, Shuangzhan Li, Daping Zhang, Ruili He
BACKGROUND: Long non-coding RNAs (lncRNAs) have been identified as critical regulators in the development of atherosclerosis (AS). Here, we focused on discussing roles and molecular mechanisms of lncRNA H19 in vascular smooth muscle cells (VSMCs) progression. METHODS: RT-qPCR assay was used to detect the expression patterns of H19 and miR-148b in clinical samples and cells. Cell proliferative ability was evaluated by CCK-8 and colony formation assays. Cell apoptotic capacity was assessed by apoptotic cell percentage and the caspase-3 activity...
February 7, 2018: Journal of Biomedical Science
Yu-Hsiang Lin, Yi-Hsuan Hsiao, Shun-Fa Yang, Yu-Fan Liu, Chun-Fang Hsu, Po-Hui Wang
To date, no study has investigated the involvement of the single-nucleotide polymorphisms (SNPs) of WNT1 inducible signaling pathway protein 1 (WISP1) in uterine cervical cancer. Therefore, we conducted this study to explore the clinical implications of WISP1 SNPs in cervical cancer. One hundred and fifteen patients with invasive cervical cancer, 95 patients with preinvasive lesions, and 316 normal controls were enrolled. The WISP1 SNPs rs62514004, rs2929973, rs2977530, and rs2977537 were selected, and their genotypic distributions were determined through real-time polymerase chain reaction...
January 1, 2018: Reproductive Sciences
Joseph Chen, Christian M Nefzger, Fernando J Rossello, Yu B Y Sun, Sue Mei Lim, Xiaodong Liu, Suzan de Boer, Anja S Knaupp, Jinhua Li, Kathryn C Davidson, Jose M Polo, Tiziano Barberi
The canonical Wnt/β-catenin pathway is crucial for early embryonic patterning, tissue homeostasis, and regeneration. While canonical Wnt/β-catenin stimulation has been used extensively to modulate pluripotency and differentiation of pluripotent stem cells (PSCs), the mechanism of these two seemingly opposing roles has not been fully characterized and is currently largely attributed to activation of nuclear Wnt target genes. Here, we show that low levels of Wnt stimulation via ectopic expression of Wnt1 or administration of glycogen synthase kinase-3 inhibitor CHIR99021 significantly increases PSC differentiation into neurons, cardiomyocytes and early endodermal intermediates...
February 2, 2018: Stem Cells
Junko Ohtsuka, Hiroko Oshima, Issei Ezawa, Ryo Abe, Masanobu Oshima, Rieko Ohki
p53 mutations are frequently detected in malignant gastric cancers. However, the molecular mechanisms by which loss of p53 function promotes gastric cancer are not clear. We utilized Gan mice (K19-Wnt1/C2mE), which have functional p53 and develop intestinal-type gastric tumors, to investigate the role of p53 in gastric cancer progression by knocking out p53. We found that gastric epithelial cells acquire tumorigenicity in the subcutis of C57BL/6 mice as a result of Wnt activation, COX-2 activation and p53 deficiency...
February 2, 2018: Scientific Reports
Jia-Bing Tong, Xing-Xing Zhang, Xin-Heng Wang, Shi-Jie Zeng, Dan-Yang Wang, Zhi-Qiang Zhang, Jian Hu, Chen Yang, Ze-Geng Li
Lung cancer is one of the most fatal cancers due to its high metastatic rate. Traditional Chinese medicine has been used in cancer patients for decades to improve quality of life and prolong survival time. The present study used a novel Qiyusanlong (QYSL) decoction composed of 10 kinds of Chinese medicine including astragalus membranaceus (Huangqi), polygonatumod oratum (yuzu), scolopendra (tianlong), pberetima (dilong), solanum nigrum (longkui), herbahedyotis (baihushecao), semen coicis (yiyiren), euphorbia helioscopia (zeqi), curcuma longa (eshu) and tendril-leaved fritillary bulb (chuanbei)...
January 24, 2018: Molecular Medicine Reports
Anita Khadka, Marina Martínez-Bartolomé, Stephanie D Burr, Ryan C Range
The anterior neuroectoderm (ANE) in many deuterostome embryos (echinoderms, hemichordates, urochordates, cephalochordates, and vertebrates) is progressively restricted along the anterior-posterior axis to a domain around the anterior pole. In the sea urchin embryo, three integrated Wnt signaling branches (Wnt/β-catenin, Wnt/JNK, and Wnt/PKC) govern this progressive restriction process, which begins around the 32- to 60-cell stage and terminates by the early gastrula stage. We previously have established that several secreted Wnt modulators of the Dickkopf and secreted Frizzled-related protein families (Dkk1, Dkk3, and sFRP-1/5) are expressed within the ANE and play important roles in modulating the Wnt signaling network during this process...
2018: EvoDevo
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