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https://www.readbyqxmd.com/read/28713933/mir%C3%A2-146b%C3%A2-5p-promotes-the-neural-conversion-of-pluripotent-stem-cells-by-targeting-smad4
#1
Nianping Zhang, Ying Lyu, Xuebing Pan, Liping Xu, Aiguo Xuan, Xiaosong He, Wandan Huang, Dahong Long
Pluripotent stem cells (PSCs) are regarded as potential sources that provide specific neural cells for cell therapy in some nervous system diseases. However, the mechanisms underlying the neural differentiation of PSCs remain largely unknown. MicroRNAs (miRNAs or miRs) are a class of small non‑pro-tein-coding RNAs that act as critical regulatory molecules in many cellular processes. In this study, we found that miR‑146b‑5p expression was markedly increased following the neural induction of mouse embryonic stem cells (ESCs) or induced PSCs (iPSCs)...
July 11, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28711654/involvement-of-endoplasmic-reticulum-stress-and-neurite-outgrowth-in-the-model-mice-of-autism-spectrum-disorder
#2
Koichi Kawada, Seisuke Mimori, Yasunobu Okuma, Yasuyuki Nomura
Neurodevelopmental disorders are congenital impairments, impeding the growth and development of the central nervous system. These disorders include autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder in Diagnostic and Statistical Manual of Mental Disorders-5. ASD is caused by a gene defect and chromosomal duplication. Despite numerous reports on ASD, the pathogenic mechanisms are not clear. The optimal methods to prevent ASD and to treat it are also not clear. Other studies have reported that endoplasmic reticulum (ER) stress contributes to the pathogenesis of neurodegenerative diseases...
July 12, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28700649/autophagy-mediates-cell-cycle-response-by-regulating-nucleocytoplasmic-transport-of-pax6-in-limbal-stem-cells-under-ultraviolet-a-stress
#3
Maria Laggner, Andreas Pollreisz, Gerald Schmidinger, Ursula Schmidt-Erfurth, Ying-Ting Chen
Limbal stem cells (LSC) account for homeostasis and regeneration of corneal epithelium. Solar ultraviolet A (UVA) is the major source causing oxidative damage in the ocular surface. Autophagy, a lysosomal degradation mechanism, is essential for physiologic function and stress defense of stem cells. PAX6, a master transcription factor governing corneal homeostasis by regulating cell cycle and cell fate of LSC, responds to oxidative stress by nucleocytoplasmic shuttling. Impaired autophagy and deregulated PAX6 have been reported in oxidative stress-related ocular surface disorders...
2017: PloS One
https://www.readbyqxmd.com/read/28698011/clinical-and-morphological-manifestations-of-aniridia-associated-keratopathy-on-anterior-segment-optical-coherence-tomography-and-in-vivo-confocal-microscopy
#4
Anna Voskresenskaya, Nadezhda Pozdeyeva, Tatyana Vasilyeva, Yevgeniy Batkov, Aleksandr Shipunov, Boris Gagloev, Rena Zinchenko
PURPOSE: The study aimed to evaluate clinical and morphological changes in the limbal palisades of Vogt (POV) at different stages of aniridia-associated keratopathy (AAK) and to assess possible utility of anterior segment optical coherence tomography (AS-OCT) for the visualization of limbal progenitor structures as it correlates to laser scanning confocal microscopy (LSCM) data. METHODS: The study involved 32 patients (59 eyes) with congenital aniridia. AAK stage was defined based on biomicroscopy...
July 8, 2017: Ocular Surface
https://www.readbyqxmd.com/read/28697461/direct-induction-of-functional-neuronal-cells-from-fibroblast-like-cells-derived-from-adult-human-retina
#5
Lili Hao, Zhen Xu, Hui Sun, Wu Luo, Youchen Yan, Jing Wang, Jingyi Guo, Yizhi Liu, Shuyi Chen
Obtaining and manipulating neuronal cells are critical for neural biology basic mechanism studies and translational applications. Recent advances in protocol development and mechanism dissections have made direct induction of neuronal cells from other somatic cells (iN) a promising strategy for such purposes. In this study, we established a protocol to expand a population of fibroblast-like cells from adult human retinal tissues, which can be reprogrammed into iNs by forced expression of neurogenic transcription factors...
June 29, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28690640/wdr62-regulates-early-neural-and-glial-progenitor-specification-of-human-pluripotent-stem-cells
#6
Abdullah J Alshawaf, Ana Antonic, Efstratios Skafidas, Dominic Chi-Hung Ng, Mirella Dottori
Mutations in WD40-repeat protein 62 (WDR62) are commonly associated with primary microcephaly and other developmental cortical malformations. We used human pluripotent stem cells (hPSC) to examine WDR62 function during human neural differentiation and model early stages of human corticogenesis. Neurospheres lacking WDR62 expression showed decreased expression of intermediate progenitor marker, TBR2, and also glial marker, S100β. In contrast, inhibition of c-Jun N-terminal kinase (JNK) signalling during hPSC neural differentiation induced upregulation of WDR62 with a corresponding increase in neural and glial progenitor markers, PAX6 and EAAT1, respectively...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28688561/uncovering-the-pathogenesis-of-microtia-using-bioinformatics-approach
#7
Liu Lei, Liu Zhenzhong, Lin Lin, Pan Bo
OBJECTIVE: Bioinformatics is widely used in the field of cancer research, but in the research of pathogenesis of congenital malformations the situation is different. The aim of this study was to explore the underlying mechanism using bioinformatics approach. METHODS: The data were available from Mouse Genome Informatics and Pubmed. Protein-protein interaction (PPI) network of pathogenic genes was conducted using STRING. Gene ontology and pathway enrichment analyses were also performed to pathogenic genes...
August 2017: International Journal of Pediatric Otorhinolaryngology
https://www.readbyqxmd.com/read/28675567/a-modulatory-role-of-the-rax-homeobox-gene-in-mature-pineal-gland-function-investigating-the-photoneuroendocrine-circadian-system-of-a-rax-conditional-knockout-mouse
#8
Kristian Rohde, Tenna Bering, Takahisa Furukawa, Martin Fredensborg Rath
The retinal and anterior neural fold homeobox gene (Rax) controls development of the eye and the forebrain. Postnatal expression of Rax in the brain is restricted to the pineal gland, a forebrain structure devoted to melatonin synthesis. The role of Rax in pineal function is unknown. In order to investigate the role of Rax in pineal function while circumventing forebrain abnormalities of the global Rax knockout, we generated an eye and pineal-specific Rax conditional knockout mouse. Deletion of Rax in the pineal gland did not affect morphology of the gland, suggesting that Rax is not essential for pineal gland development...
July 4, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28670366/inhibitory-effect-of-dihydroartemisinin-on-chondrogenic-and-hypertrophic-differentiation-of-mesenchymal-stem-cells
#9
Zhen Cao, Chuan Liu, Yun Bai, Ce Dou, Jian-Mei Li, Duo-Wei Shi, Shi-Wu Dong, Qiang Xiang
Chondrocytes located in hyaline cartilage may maintain phenotype while the chondrocytes situated in calcified cartilage differentiate into hypertrophy. Chondrogenic and hypertrophic differentiation of mesenchymal stem cells (MSCs) are two subsequent processes during endochondral ossification. However, it is necessary for chondrocytes to hold homeostasis and to inhibit hypertrophic differentiation in stem cell-based regenerated cartilage. Dihydroartemisinin (DHA) is derived from artemisia apiacea which has many biological functions such as anti-malarial and anti-tumor...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28667292/identification-of-a-functionally-significant-tri-allelic-genotype-in-the-tyrosinase-gene-tyr-causing-hypomorphic-oculocutaneous-albinism-oca1b
#10
Chelsea S Norman, Luke O'Gorman, Jane Gibson, Reuben J Pengelly, Diana Baralle, J Arjuna Ratnayaka, Helen Griffiths, Matthew Rose-Zerilli, Megan Ranger, David Bunyan, Helena Lee, Rhiannon Page, Tutte Newall, Fatima Shawkat, Christopher Mattocks, Daniel Ward, Sarah Ennis, Jay E Self
Oculocutaneous albinism (OCA) and ocular albinism (OA) are inherited disorders of melanin biosynthesis, resulting in loss of pigment and severe visual deficits. OCA encompasses a range of subtypes with overlapping, often hypomorphic phenotypes. OCA1 is the most common cause of albinism in European populations and is inherited through autosomal recessive mutations in the Tyrosinase (TYR) gene. However, there is a high level of reported missing heritability, where only a single heterozygous mutation is found in TYR...
June 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28649419/identification-of-transcription-factors-that-promote-the-differentiation-of-human-pluripotent-stem-cells-into-lacrimal-gland-epithelium-like-cells
#11
Masatoshi Hirayama, Shigeru B H Ko, Tetsuya Kawakita, Tomohiko Akiyama, Sravan K Goparaju, Atsumi Soma, Yuhki Nakatake, Miki Sakota, Nana Chikazawa-Nohtomi, Shigeto Shimmura, Kazuo Tsubota, Minoru S H Ko
Dry eye disease is the most prevalent pathological condition in aging eyes. One potential therapeutic strategy is the transplantation of lacrimal glands, generated in vitro from pluripotent stem cells such as human embryonic stem cells, into patients. One of the preceding requirements is a method to differentiate human embryonic stem cells into lacrimal gland epithelium cells. As the first step for this approach, this study aims to identify a set of transcription factors whose overexpression can promote the differentiation of human embryonic stem cells into lacrimal gland epithelium-like cells...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/28647514/aqueous-cigarette-tar-extracts-disrupt-corticogenesis-from-human-embryonic-stem-cells-in-vitro
#12
Aynun N Begum, Jose S Aguilar, Yiling Hong
BACKGROUND: Cigarette butts are the most common form of litter in the world, and approximately 4.5 trillion smoked cigarettes are discarded every year worldwide. Cigarette butts contain over 4000 chemicals, many of which are known to have neurotoxic effects. Stem cell neuronal differentiation provides an excellent cellular model with which to examine the impact of aqueous cigarette tar extracts (ACTEs) on neurodevelopment. METHODS: We have developed a neurosphere-based stem cell neuronal differentiation protocol that can recapitulate corticogenesis and produce cell types that are similar to upper and lower layer cortical projection neurons found in the germinal zone of the developing human cortex...
June 22, 2017: Environmental Research
https://www.readbyqxmd.com/read/28632489/the-effects-of-platelet-gel-on-cultured-human-retinal-pigment-epithelial-cells
#13
Sahar Balagholi, Shaban Alizadeh, Abouzar Bagheri, Yashar Amizadeh, Mozhgan Rezaei Kanavi
The positive role of platelet gel (PG) in tissue regeneration is well known, however, other characteristics of PG still remain to be determined. We investigated cellular and molecular changes in cultured human retinal pigment epithelial (hRPE) cells when treated with different concentrations of PG named PG1, PG2, and PG3. hRPE cells were isolated from donor eyes of two newborn children, within 24 hours after their death. The cells were treated with three concentrations of PG for 7 days: 3 × 104/ml (PG1), 6 × 104/ml (PG2), and 9 × 104/ml (PG3)...
June 20, 2017: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28624217/efficacy-of-postnatal-in%C3%A2-vivo-nonsense-suppression-therapy-in-a-pax6-mouse-model-of-aniridia
#14
Xia Wang, Kevin Gregory-Evans, Kishor M Wasan, Olena Sivak, Xianghong Shan, Cheryl Y Gregory-Evans
Nonsense mutations leading to premature stop codons are common occurring in approximately 12% of all human genetic diseases. Thus, pharmacological nonsense mutation suppression strategies would be beneficial to a large number of patients if the drugs could be targeted to the affected tissues at the appropriate time. Here, we used nonsense suppression to manipulate Pax6 dosage at different developmental times in the eye of the small eye (Pax6(Sey/+); G194X) mouse model of aniridia. Efficacy was assessed by functional assays for visual capacity, including electroretinography and optokinetic tracking (OKT), in addition to histological and biochemical studies...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28615632/genome-wide-analysis-suggests-a-differential-microrna-signature-associated-with-normal-and-diabetic-human-corneal-limbus
#15
Mangesh Kulkarni, Aleksandra Leszczynska, Gabbie Wei, Michael A Winkler, Jie Tang, Vincent A Funari, Nan Deng, Zhenqiu Liu, Vasu Punj, Sophie X Deng, Alexander V Ljubimov, Mehrnoosh Saghizadeh
Small non-coding RNAs, in particular microRNAs (miRNAs), regulate fine-tuning of gene expression and can impact a wide range of biological processes. However, their roles in normal and diseased limbal epithelial stem cells (LESC) remain unknown. Using deep sequencing analysis, we investigated miRNA expression profiles in central and limbal regions of normal and diabetic human corneas. We identified differentially expressed miRNAs in limbus vs. central cornea in normal and diabetic (DM) corneas including both type 1 (T1DM/IDDM) and type 2 (T2DM/NIDDM) diabetes...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28607372/enhanced-derivation-of-human-pluripotent-stem-cell-derived-cortical-glutamatergic-neurons-by-a-small-molecule
#16
Shi-Ying Cao, Yao Hu, Cheng Chen, Fang Yuan, Min Xu, Qi Li, Kai-Heng Fang, Yaoyu Chen, Yan Liu
Human pluripotent stem cells (hPSCs) play important role in studying the function of human glutamatergic neurons and related disease pathogenesis. However, the current hPSC-derived cortical system produced a significant number of inhibitory GABAergic neurons that reduced the purity of excitatory neurons. In this study, we established a robust hPSC-derived cortical neurogenesis system by applying the SHH inhibitor cyclopamine. Cyclopamine specified the dorsal cortical fate in a dose-dependent manner and enhanced the generation of cortical glutamatergic neurons, expressing PAX6, TBR1, TBR2, CTIP2, SATB2, and vesicular glutamate transporters (vGLUT)...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28598868/pax6-aniridia-syndrome-clinics-genetics-and-therapeutics
#17
Hyun Taek Lim, Dae Hee Kim, Hyuna Kim
PURPOSE OF REVIEW: Aniridia is a rare and panocular disorder affecting most of the ocular structures which may have significant impact on vision. The purpose of this review is to describe the clinical features, genetics, and therapeutic options for this disease and to provide an update of current knowledge and latest research findings. RECENT FINDINGS: Aside from the ocular features, a variety of associated systemic abnormalities, including hormonal, metabolic, gastrointestinal, genitourinary, and neurologic disorders have been reported in children with aniridia...
June 8, 2017: Current Opinion in Ophthalmology
https://www.readbyqxmd.com/read/28597969/the-role-of-epigenetic-regulation-and-pluripotency-related-micrornas-in-differentiation-of-pancreatic-stem-cells-to-beta-cells
#18
Ediz Coskun, Merve Ercin, Selda Gezginci-Oktayoglu
In this study, we aimed to research class-I HDACs and glucose on differentiation of pancreatic islet derived mesenchymal stem cells (PI-MSCs) to beta cells. Beta cell differentiation determined by flow cytometric analysis and gene expression levels of PDX1, PAX4, PAX6, NKX6.1, NGN3, INS2, and GLUT2. The valproic acid, is an inhibitor of class I HDACs, caused the highest beta cell differentiation in PI-MSCs. However, the cells in this group were at early stages of differentiation. Glucose co-administration to this group carried the differentiation to higher levels, but these newly formed beta cells were not functional...
June 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28588695/canonical-and-alternative-transcript-expression-of-pax6-and-cxcr4-in-pancreatic-cancer
#19
Elizabeth C Little, Jennifer D Kubic, Ravi Salgia, Paul J Grippo, Deborah Lang
Pancreatic cancer is a lethal disease with a propensity for invading and metastasizing into the surrounding tissues, including the liver and intestines. A number of factors are aberrantly overexpressed in this tumor type and actively promote cancer progression and metastasis. The present study demonstrates that paired box transcription factor 6 (PAX6) and C-X-C chemokine receptor 4 (CXCR4) are frequently co-expressed in primary pancreatic adenocarcinoma tumors and established cell lines. Expression analysis methods used in the present study included evaluation of protein expression by western blot analysis and immunofluorescence, transcript expression levels by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and luciferase assays utilizing regulatory elements from the CXCR4 gene locus...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28588354/pax6-binds-to-promoter-sequence-elements-associated-with-immunological-surveillance-and-energy-homeostasis-in-brain-of-aging-mice
#20
Shashank Kumar Maurya, Rajnikant Mishra
BACKGROUND: Patients having mutations of Pax6 bear phenotypes that match age-associated neurological disorders. Mutations affect most cellular functions such as cell division, growth, differentiation, and cell death in brain, eyes, pituitary, pineal, and pancreas. The progressive reduction in the level of Pax6 during aging has also been observed. However, information about downstream targets of Pax6 in brain is unclear. Therefore, it is presumed that age-dependent alterations of Pax6 may also affect cascades of promoter sequence recognition in brain during aging...
May 2017: Annals of Neurosciences
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