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https://www.readbyqxmd.com/read/29932869/exosomes-derived-from-high-glucose-stimulated-schwann-cells-promote-development-of-diabetic-peripheral-neuropathy
#1
Longfei Jia, Michael Chopp, Lei Wang, Xuerong Lu, Alexandra Szalad, Zheng Gang Zhang
Schwann cells actively interact with axons of dorsal root ganglia (DRG) neurons. Exosomes mediate intercellular communication by transferring their biomaterials, including microRNAs (miRs) into recipient cells. We hypothesized that exosomes derived from Schwann cells stimulated by high glucose (HG) exosomes accelerate development of diabetic peripheral neuropathy and that exosomal cargo miRs contribute to this process. We found that HG exosomes contained high levels of miR-28, -31a, and -130a compared to exosomes derived from non-HG-stimulated Schwann cells...
June 22, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29924717/case-259
#2
Decai Tian, Xiaodong Zhu, Rong Xue, Peng Zhao, Yuanrong Yao
History In November 2012, a previously healthy 31-year-old woman was admitted to our hospital with a 2-month history of right-sided numbness, diplopia, and intermittent nausea and dizziness. She did not have a history of fever, weight loss, headache, photophobia, seizure, or extremity weakness. Physical examination revealed left abduction limitation and right-sided hypoesthesia. Kernig and Brudzinski signs were absent, and pathergy test results were negative. Laboratory evaluation revealed normal complete and differential blood counts, normal serum chemistry, and normal immune function...
July 2018: Radiology
https://www.readbyqxmd.com/read/29924024/systemic-lupus-erythematosus-with-guillian-barre-syndrome-a-case-report-and-literature-review
#3
Zhaoli Gao, Xianhua Li, Tao Peng, Zhao Hu, Jie Liu, Junhui Zhen, Yanxia Gao
INTRODUCTION: We report a case of systemic lupus erythematosus (SLE) with Guillian-Barre syndrome (GBS) as the first symptom. CASE PRESENTATION: A 30-year-old Chinese female with numbness and inductance of lower extremities 2 months previously. The electromyographic and cerebrospinal fluid findings supported inflammatory demyelinating disease, and the renal biopsy findings and rheumatoid-related results considered systemic lupus erythematosus. The patient received treatment with glucocorticoids and cyclophosphamide...
June 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29923987/ulcerative-colitis-with-guillain-barr%C3%A3-syndrome-a-case-report
#4
Zhengru Liu, Ke Zhou, Shan Tian, Weiguo Dong
RATIONALE: Ulcerative colitis is a chronic and recurrent inflammatory disease involving the intestine. It is reported that about 40% of patients with ulcerative colitis have extraintestinal manifestations, where as the literature on neurological involvement as extraintestinal manifestation is rather limited. Guillain-Barré syndrome is an abnormal immune-mediated and acute-acquired demyelinating disease that mainly affects the peripheral nervous system and often has a phenomenon of protein-cell separation of cerebrospinal fluid...
June 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29890853/numb-depletion-promotes-drp1-mediated-mitochondrial-fission-and-exacerbates-mitochondrial-fragmentation-and-dysfunction-in-acute-kidney-injury
#5
Ze Liu, Hao Li, Jianqun Su, Shihui Xu, Fengxin Zhu, Jun Ai, Zheng Hu, Miaomiao Zhou, Jianwei Tian, Zhiyuan Su, Peiliang Yang, Jing Nie
AIMS: Mitochondrial fragmentation is a crucial mechanism contributing to tubular cell apoptosis during acute kidney injury (AKI). However, the mechanism of modulating mitochondrial dynamics during AKI remains unclear. Numb is a multifunction adaptor protein that is expressed in renal tubules. The aim of the present study is to study the role of Numb in mitochondrial dysfunction during AKI. RESULTS: The expression of Numb was upregulated in both ischemia-reperfusion- and cisplatin-induced AKI...
June 11, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29862581/peripheral-neuropathy-in-diabetes-it-s-not-always-what-it-looks-like
#6
G Maltese, S V Tan, E Bruno, A Brackenridge, S Thomas
BACKGROUND: Hereditary Neuropathy with liability to Pressure Palsies (HNPP) is an autosomal dominant neuropathy, associated with deletion of the Peripheral Myelin Protein-22 (PMP-22) gene, causing recurrent painless palsies with age of onset between 10 and 30 years old. Only a few cases of Type 2 Diabetes and HNPP have been described and the coexistence of HNPP and Type 1 diabetes has never been reported. CASE REPORT: A 54-year old man with a history of Type 1 diabetes, managed with continuous subcutaneous insulin infusion (CSII), presented with deterioration of long-standing motor and sensory symptoms, previously attributed to golfer's elbow, diabetic neuropathy and spinal degenerative disease...
June 4, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/29843777/rare-copy-number-variants-analysis-identifies-novel-candidate-genes-in-heterotaxy-syndrome-patients-with-congenital-heart-defects
#7
Chunjie Liu, Ruixue Cao, Yuejuan Xu, Tingting Li, Fen Li, Sun Chen, Rang Xu, Kun Sun
BACKGROUND: Heterotaxy (Htx) syndrome comprises a class of congenital disorders resulting from malformations in left-right body patterning. Approximately 90% of patients with heterotaxy have serious congenital heart diseases; as a result, the survival rate and outcomes of Htx patients are not satisfactory. However, the underlying etiology and mechanisms in the majority of Htx cases remain unknown. The aim of this study was to investigate the function of rare copy number variants (CNVs) in the pathogenesis of Htx...
May 30, 2018: Genome Medicine
https://www.readbyqxmd.com/read/29787679/dynamic-proteome-alteration-and-functional-modulation-of-human-saliva-induced-by-dietary-chemosensory-stimuli
#8
Matthias Bader, Andreas Dunkel, Mareike Wenning, Bernd Kohler, Guillaume Medard, Estela Del Castillo, Amin Gholami, Bernhard Kuster, Siegfried Scherer, Thomas Hofmann
Saliva flow measurements and SDS-PAGE separation of human whole saliva freshly collected after oral stimulation with citric acid (sour), aspartame (sweet), iso-α-acids (bitter), mono sodium L-glutamate (umami), NaCl (salty), 6-gingerol (pungent), hydroxy-α-sanshool (tingling), and hydroxy-β-sanshool (numbing), followed by tryptic digestion, nano-HPLC-MS/MS, and label-free protein quantitation demonstrated a stimulus- and time-dependent influence of the dietary chemosensates on salivation and the salivary proteome composition...
May 22, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29784925/acrylamide-acute-neurotoxicity-in-adult-zebrafish
#9
Melissa Faria, Tamar Ziv, Cristian Gómez-Canela, Shani Ben-Lulu, Eva Prats, Karen Adriana Novoa-Luna, Arie Admon, Benjamin Piña, Romà Tauler, Leobardo Manuel Gómez-Oliván, Demetrio Raldúa
Acute exposure to acrylamide (ACR), a type-2 alkene, may lead to a ataxia, skeletal muscles weakness and numbness of the extremities in human and laboratory animals. In the present manuscript, ACR acute neurotoxicity has been characterized in adult zebrafish, a vertebrate model increasingly used in human neuropharmacology and toxicology research. At behavioral level, ACR-treated animals exhibited "depression-like" phenotype comorbid with anxiety behavior. At transcriptional level, ACR induced down-regulation of regeneration-associated genes and up-regulation of oligodendrocytes and reactive astrocytes markers, altering also the expression of genes involved in the presynaptic vesicle cycling...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29780224/correlative-study-between-c-reactive-protein-clinical-severity-and-nerve-conduction-studies-in-guillain-barr%C3%A3-syndrome
#10
Yosria A Altaweel, Sawsan Abdelaziz, Hala A Fathy, Shimaa AbdelBadea
Background: Guillain-Barre' syndrome (GBS) is a serious autoimmune disorder in which the immune system attacks healthy nerve cells of the peripheral nervous system causing polyradiculoneuropathy which leads to weakness, numbness, and tingling, and can eventually cause paralysis. Autoimmune conditions like GBS can induce a high level of inflammation resulting in an increase in the C-reactive protein( CRP) production. The aim of this study is to assess the relationship between CRP level and the clinical severity as well as the electrophysiological findings of nerve conduction studies in patients with GBS...
2018: The Egyptian journal of neurology, psychiatry and neurosurgery
https://www.readbyqxmd.com/read/29762249/numb-p72-but-not-numb-p65-contributes-to-the-trafficking-of-group-i-metabotropic-glutamate-receptors
#11
Na Wang, Xin-Yu Cai, Wei Gao, Ying Shen
The protein Numb localizes to clathrin-coated vesicles and participates in the trafficking of transmembrane receptors. We previous reported that Numb promotes the presence of metabotropic glutamate receptor 1 (mGlu1) on neuronal membrane, and Numb deficiency impairs synaptic expression of mGlu1. However, the actions of different Numb isoforms on mGlu1 trafficking are unknown. Here, we found that Numb-p72 and Numb-p65 are distinctly expressed in HEK293T cells. Interestingly, Numb-p72, but not Numb-p65, binds to mGlu1α and promotes the membrane expression of mGlu1α by antagonizing its internalization...
May 14, 2018: Neuroreport
https://www.readbyqxmd.com/read/29747452/cytokeratin-19-krt19-has-a-role-in-the-reprogramming-of-cancer-stem-cell-like-cells-to-less-aggressive-and-more-drug-sensitive-cells
#12
Subbroto Kumar Saha, Kyeongseok Kim, Gwang-Mo Yang, Hye Yeon Choi, Ssang-Goo Cho
Cytokeratin 19 ( KRT19 ) is a cytoplasmic intermediate filament protein, which is responsible for structural rigidity and multipurpose scaffolds. In several cancers, KRT19 is overexpressed and may play a crucial role in tumorigenic transformation. In our previous study, we revealed the role of KRT19 as signaling component which mediated Wnt/NOTCH crosstalk through NUMB transcription in breast cancer. Here, we investigated the function of KRT19 in cancer reprogramming and drug resistance in breast cancer cells...
May 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29738768/differential-effects-of-voluntary-wheel-running-and-toy-rotation-on-the-mrna-expression-of-neurotrophic-factors-and-fkbp5-in-a-post-traumatic-stress-disorder-rat-model-with-the-shuttle-box-task
#13
Masaaki Tanichi, Hiroyuki Toda, Kunio Shimizu, Minori Koga, Taku Saito, Shingo Enomoto, Shuken Boku, Fumiho Asai, Yumi Mitsui, Masanori Nagamine, Masanori Fujita, Aihide Yoshino
Life-threatening experiences can result in the development of post-traumatic stress disorder. We have developed an animal model for post-traumatic stress disorder (PTSD) using a shuttle box in rats. In this paradigm, the rats were exposed to inescapable foot-shock stress (IS) in a shuttle box, and then an avoidance/escape task was performed in the same box 2 weeks after IS. A previous study using this paradigm revealed that environmental enrichment (EE) ameliorated avoidance/numbing-like behaviors, but not hyperarousal-like behaviors, and EE also elevated hippocampal brain-derived neurotrophic factor (BDNF) expression...
May 5, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29732437/an-awake-minimally-invasive-fully-endoscopic-surgical-technique-for-treating-lumbar-radiculopathy-secondary-to-heterotopic-foraminal-bone-formation-after-a-minimally-invasive-transforaminal-lumbar-interbody-fusion-with-bmp-technical-note
#14
Albert Edward Telfeian
One complication associated with recombinant human bone morphogenetic protein (rhBMP-2) use in minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is heterotopic bone growth at the neural foramen which results in the compression of neural structures. Here we present an awake, minimally invasive surgical approach for treating the radiculopathy that results from this excessive bone growth in the foramen. A 42-year-old male underwent a lumbar 4-sacral 1 MIS-TLIF by another surgeon. He did well in the initial postoperative period, but he began to note right leg pain and numbness in an L5 dermatomal pattern...
March 2018: Journal of Spine Surgery (Hong Kong)
https://www.readbyqxmd.com/read/29644085/protein-molecular-modeling-shows-residue-t599-is-critical-to-wild-type-function-of-polg-and-description-of-a-novel-variant-associated-with-the-sando-phenotype
#15
John E Richter, Hector G Robles, Elizabeth Mauricio, Ahmed Mohammad, Paldeep S Atwal, Thomas R Caulfield
Sensory ataxic neuropathy with dysarthria and ophthalmoparesis (SANDO) is a rare phenotype resulting from pathogenic variants of mitochondrial DNA polymerase gamma ( POLG ). We modeled a novel POLG variant, T599P, that causes the SANDO phenotype and another variant at the same residue, p.T599E, to observe their effect on protein function and confirm the pathogenicity of T599P. Through neoteric molecular modeling techniques, we show that changes at the T599 residue position introduce extra rigidity into the surrounding helix-loop-helix, which places steric pressure on nearby nucleotides...
2018: Human Genome Variation
https://www.readbyqxmd.com/read/29581274/loss-of-tdp43-inhibits-progression-of-triple-negative-breast-cancer-in-coordination-with-srsf3
#16
Hao Ke, Limin Zhao, Honglei Zhang, Xu Feng, Haibo Xu, Junjun Hao, Shaowei Wang, Qin Yang, Li Zou, Xiaosan Su, Liqiong Wang, Chunlian Wu, Yang Wang, Jianyun Nie, Baowei Jiao
Aberrant alternative splicing has been highlighted as a potential hallmark of cancer. Here, we identify TDP43 (TAR DNA-binding protein 43) as an important splicing regulator responsible for the unique splicing profile in triple-negative breast cancer (TNBC). Clinical data demonstrate that TDP43 is highly expressed in TNBC with poor prognosis. Knockdown of TDP43 inhibits tumor progression, including proliferation and metastasis, and overexpression of TDP43 promotes proliferation and malignancy of mammary epithelial cells...
April 10, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29515366/the-activating-transcription-factor-3-atf3-homozygous-knockout-mice-exhibit-enhanced-conditioned-fear-and-down-regulation-of-hippocampal-gelsolin
#17
Chia-Sheng Pai, Pranao K Sharma, Hsien-Ting Huang, Srivaishnavi Loganathan, Heng Lin, Yu-Luan Hsu, Sarayut Phasuk, Ingrid Y Liu
The genetic and molecular basis underlying fear memory formation is a key theme in anxiety disorder research. Because activating transcription factor 3 ( ATF3 ) is induced under stress conditions and is highly expressed in the hippocampus, we hypothesize that ATF3 plays a role in fear memory formation. We used fear conditioning and various other paradigms to test Atf3 knockout mice and study the role of ATF3 in processing fear memory. The results demonstrated that the lack of ATF3 specifically enhanced the expression of fear memory, which was indicated by a higher incidence of the freeze response after fear conditioning, whereas the occurrence of spatial memory including Morris Water Maze and radial arm maze remained unchanged...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29507685/numb-and-numbl-differences-in-gene-regulation
#18
José Manuel García-Heredia, Amancio Carnero
NUMB, and its close homologue NUMBL, behave as tumor suppressor genes by regulating the Notch pathway. The downregulation of these genes in tumors is common, allowing aberrant Notch pathway activation and tumor progression. However, some known differences between NUMB and NUMBL have raised unanswered questions regarding the redundancy and/or combined regulation of the Notch pathway by these genes during the tumorigenic process. We have found that NUMB and NUMBL exhibit mutual exclusivity in human tumors, suggesting that the associated tumor suppressor role is regulated by only one of the two proteins in a specific cell, avoiding duplicate signaling and simplifying the regulatory network...
February 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29496391/structure-of-lnx1-ubc13-ubiquitin-complex-reveals-the-role-of-additional-motifs-for-the-e3-ligase-activity-of-lnx1
#19
Digant Nayak, J Sivaraman
LNX1 (ligand of numb protein-X1) is a RING and PDZ domain-containing E3 ubiquitin ligase that ubiquitinates human c-Src kinase. Here, we report the identification and structure of the ubiquitination domain of LNX1, the identification of Ubc13/Ube2V2 as a functional E2 in vitro, and the structural and functional studies of the Ubc13~Ub intermediate in complex with the ubiquitination domain of LNX1. The RING domain of LNX1 is embedded between two zinc-finger motifs (Zn-RING-Zn), both of which are crucial for its ubiquitination activity...
April 13, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29467404/basal-condensation-of-numb-and-pon-complex-via-phase-transition-during-drosophila-neuroblast-asymmetric-division
#20
Zelin Shan, Yuting Tu, Ying Yang, Ziheng Liu, Menglong Zeng, Huisha Xu, Jiafu Long, Mingjie Zhang, Yu Cai, Wenyu Wen
Uneven distribution and local concentration of protein complexes on distinct membrane cortices is a fundamental property in numerous biological processes, including Drosophila neuroblast (NB) asymmetric cell divisions and cell polarity in general. In NBs, the cell fate determinant Numb forms a basal crescent together with Pon and is segregated into the basal daughter cell to initiate its differentiation. Here we discover that Numb PTB domain, using two distinct binding surfaces, recognizes repeating motifs within Pon in a previously unrecognized mode...
February 21, 2018: Nature Communications
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