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https://www.readbyqxmd.com/read/27913094/hematopoietic-stem-cell-niches-produce-lineage-instructive-signals-to-control-multipotent-progenitor-differentiation
#1
Ana Cordeiro Gomes, Takahiro Hara, Vivian Y Lim, Dietmar Herndler-Brandstetter, Erin Nevius, Tatsuki Sugiyama, Shizue Tani-Ichi, Susan Schlenner, Ellen Richie, Hans-Reimer Rodewald, Richard A Flavell, Takashi Nagasawa, Koichi Ikuta, João Pedro Pereira
Hematopoietic stem cells (HSCs) self-renew in bone marrow niches formed by mesenchymal progenitors and endothelial cells expressing the chemokine CXCL12, but whether a separate niche instructs multipotent progenitor (MPP) differentiation remains unclear. We show that MPPs resided in HSC niches, where they encountered lineage-instructive differentiation signals. Conditional deletion of the chemokine receptor CXCR4 in MPPs reduced differentiation into common lymphoid progenitors (CLPs), which decreased lymphopoiesis...
November 23, 2016: Immunity
https://www.readbyqxmd.com/read/27908790/mpp-inhibits-mglur1-5-mediated-long-term-depression-in-mouse-hippocampus-by-calpain-activation
#2
Junyao Li, Hui Chen, Shengbing Wu, Yuefa Cheng, Qinglin Li, Jing Wang, Guoqi Zhu
Neurotoxins are harmful to nervous system and cause either neuronal cell death or impairment of synaptic activity, which contributes to Parkinson's disease or other neuronal disorders. Hippocampal synaptic plasticity was proposed as a cellular model for memory processing. In this study, we reported a novel effect of neurotoxin, 1-methyl-4-phenylpyridinium (MPP(+)), on metabotropic glutamate receptor 1/5 agonist, 3,5-dihydroxyphenylglycine (DHPG)-induced hippocampal synaptic plasticity, and MPP(+) incubation blocked DHPG-induced hippocampal long-term depression (LTD) in Schaffer collateral-CA1 synapses...
November 28, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27903454/effects-of-frequently-used-pharmaceutical-excipients-on-the-organic-cation-transporters-1-3-and-peptide-transporters-1-2-stably-expressed-in-mdckii-cells
#3
Marcus Otter, Stefan Oswald, Werner Siegmund, Markus Keiser
There is ample evidence that pharmaceutical excipients, which are supposed to be pharmacologically inactive, have an impact on drug metabolism and efflux transport. So far, little is known whether they also modulate uptake transporter proteins. We have recently shown that commonly used solubilizing agents exert significant effects on the function of organic anion uptake transporting polypeptides. Therefore, we investigated in this study the influence of frequently used pharmaceutical excipients on the transport activity of organic cation transporters OCT1, OCT2 and OCT3 and the peptide transporters PEPT1 and PEPT2...
November 26, 2016: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/27894919/resveratrol-attenuates-mpp-induced-mitochondrial-dysfunction-and-cell-apoptosis-via-akt-gsk-3%C3%AE-pathway-in-sn4741-cells
#4
Weijun Zeng, Wei Zhang, Fangfang Lu, Li Gao, Guodong Gao
Oxidative stress and mitochondrial dysfunction play crucial role in the dopaminergic neurons death, which is the pathological feature of Parkinson's disease (PD). Resveratrol (Res), a polyphenol derived from grapes and blueberries, has been reported to reduce oxidative stress injury and to restore mitochondrial function. In this study, we aimed to explore the underlying molecular mechanism of the beneficial effects of Res against MPP+- induced mitochondrial dysfunction and cell apoptosis in SN4741 cells. The data showed that Res significantly alleviated MPP+- induce cytotoxicity and restored MPP+- induced mitochondrial dysfunction in SN4741 cells...
November 26, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27893608/ape1-protects-against-mpp-induced-neurotoxicity-through-erk1-2-signaling-in-pc12-cells
#5
Bei Kang, Shengzhi Mu, Qian Yang, Shenglong Guo, Xiaoli Chen, Hena Guo
Oxidative stress, induced by reactive oxygen species (ROS), is an apoptosis activator. Oxidative stress causes dopaminergic neuron loss and plays a pivotal role in the pathogenesis of Parkinson's disease (PD). A recent study showed that apurinic/apyrimidinic endonuclease 1 (Ape1) decreases cytotoxicity and promotes neuron survival under oxidative stress. Furthermore, it has been proven that Ape1 is involved in the pathogenesis of PD. However, little is known about the contribution of Ape1 toward the development of PD...
January 1, 2017: Neuroreport
https://www.readbyqxmd.com/read/27882077/potential-protective-effects-of-autophagy-activated-in-mpp-treated-astrocytes
#6
Cunzhou Shen, Wenbiao Xian, Hongyan Zhou, Ling Chen, Zhong Pei
Astrocytes, which have various important functions, have previously been associated with Parkinsons disease (PD), particularly in 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models of PD. MPP+ is the toxic metabolite of MPTP and is generated by the enzymatic activity of monoamine oxidase B, which is predominantly located in astrocytes. MPP+ acts as a mitochondrial complex I inhibitor. Autophagy is an evolutionarily conserved self-digestion pathway in eukaryotic cells, which occurs in response to various types of stress, including starvation and oxidative stress...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27861351/small-amounts-of-tissue-preserve-pancreatic-function-long-term-follow-up-study-of-middle-segment-preserving-pancreatectomy
#7
Zipeng Lu, Jie Yin, Jishu Wei, Cuncai Dai, Junli Wu, Wentao Gao, Qing Xu, Hao Dai, Qiang Li, Feng Guo, Jianmin Chen, Chunhua Xi, Pengfei Wu, Kai Zhang, Kuirong Jiang, Yi Miao
Middle-segment preserving pancreatectomy (MPP) is a novel procedure for treating multifocal lesions of the pancreas while preserving pancreatic function. However, long-term pancreatic function after this procedure remains unclear.The aims of this current study are to investigate short- and long-term outcomes, especially long-term pancreatic endocrine function, after MPP.From September 2011 to December 2015, 7 patients underwent MPP in our institution, and 5 cases with long-term outcomes were further analyzed in a retrospective manner...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27844285/th17-cells-induce-dopaminergic-neuronal-death-via-lfa-1-icam-1-interaction-in-a-mouse-model-of-parkinson-s-disease
#8
Zhan Liu, Yan Huang, Bei-Bei Cao, Yi-Hua Qiu, Yu-Ping Peng
T helper (Th)17 cells, a subset of CD4(+) T lymphocytes, have strong pro-inflammatory property and appear to be essential in the pathogenesis of many inflammatory diseases. However, the involvement of Th17 cells in Parkinson's disease (PD) that is characterized by a progressive degeneration of dopaminergic (DAergic) neurons in the nigrostriatal system is unclear. Here, we aimed to demonstrate that Th17 cells infiltrate into the brain parenchyma and induce neuroinflammation and DAergic neuronal death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- or 1-methyl-4-phenylpyridinium (MPP(+))-induced PD models...
November 14, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27833154/cytokines-as-the-good-predictors-of-refractory-mycoplasma-pneumoniae-pneumonia-in-school-aged-children
#9
Yuanyuan Zhang, Shufen Mei, Yunlian Zhou, Meixia Huang, Guijuan Dong, Zhimin Chen
: Excessive immune response against pathogens may play an important role in refracory Mycoplasma pneumoniae pneumonia (RMPP). The aim of this study was to elucidate the associations between cytokines and the prediction of RMPP in school-aged patients. Retrospective analysis was performed on school-aged children with Mycoplasma pneumoniae pneumonia (MPP) hospitalized in our hospital between January 1, 2011 and December 31, 2015. The clinical charcteristics, including the cytokines in serum between the RMPP group and the general Mycoplasma pneumoniae pneumonia (GMPP) group were compared and the predictive values of RMPP were explored...
November 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27822849/physicochemical-properties-of-solid-phospholipid-particles-as-a-drug-delivery-platform-for-improving-oral-absorption-of-poorly-soluble-drugs
#10
Kohsaku Kawakami, Aoi Miyazaki, Mayuko Fukushima, Keiko Sato, Yuko Yamamura, Kohta Mohri, Shinji Sakuma
PURPOSE: A novel drug delivery platform, mesoporous phospholipid particle (MPP), is introduced. Its physicochemical properties and ability as a carrier for enhancing oral absorption of poorly soluble drugs are discussed. METHODS: MPP was prepared through freeze-drying a cyclohexane/t-butyl alcohol solution of phosphatidylcholine. Its basic properties were revealed using scanning electron microscopy, x-ray diffraction, thermal analysis, hygroscopicity measurement, and so on...
November 7, 2016: Pharmaceutical Research
https://www.readbyqxmd.com/read/27812757/counter-flow-suggests-transport-of-dantrolene-and-5-oh-dantrolene-by-the-organic-anion-transporters-2-oat2-and-3-oat3
#11
Birgitta C Burckhardt, Maja Henjakovic, Yohannes Hagos, Gerhard Burckhardt
Dantrolene is the only available drug for the treatment of malignant hyperthermia, a life-threatening inborn sensitivity of the ryanodine receptor (RyR1) in skeletal muscles to volatile anesthetics. Dantrolene is metabolized in the liver to 5-OH dantrolene. Both compounds are zwitterions or net negatively charged. Here, we investigated interactions of dantrolene and 5-OH dantrolene with solute carrier (SLC) family members occurring in skeletal muscle cells, hepatocytes, and renal proximal tubule cells. SLC22A8 (organic anion transporter 3, OAT3) was very sensitive to both compounds exhibiting IC50 values of 0...
November 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27811054/progressive-alterations-in-multipotent-hematopoietic-progenitors-underlie-lymphoid-cell-loss-in-aging
#12
Kira Young, Sneha Borikar, Rebecca Bell, Lauren Kuffler, Vivek Philip, Jennifer J Trowbridge
Declining immune function with age is associated with reduced lymphoid output of hematopoietic stem cells (HSCs). Currently, there is poor understanding of changes with age in the heterogeneous multipotent progenitor (MPP) cell compartment, which is long lived and responsible for dynamically regulating output of mature hematopoietic cells. In this study, we observe an early and progressive loss of lymphoid-primed MPP cells (LMPP/MPP4) with aging, concomitant with expansion of HSCs. Transcriptome and in vitro functional analyses at the single-cell level reveal a concurrent increase in cycling of aging LMPP/MPP4 with loss of lymphoid priming and differentiation potential...
October 17, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27809287/cx43-mediates-resistance-against-mpp%C3%A2-%C2%BA-induced-apoptosis-in-sh-sy5y-neuroblastoma-cells-via-modulating-the-mitochondrial-apoptosis-pathway
#13
In-Su Kim, Palanivel Ganesan, Dong-Kug Choi
Neuronal apoptosis in the substantia nigra par compacta (SNpc) appears to play an essential role in the pathogenesis of Parkinson's disease. However, the mechanisms responsible for the death of dopaminergic neurons are not fully understood yet. To explore the apoptotic mechanisms, we used a well-known parkinsonian toxin, 1-methyl-4-phenylpyridine (MPP⁺), to induce neuronal apoptosis in the human dopaminergic SH-SY5Y cell line. The most common method of interaction between cells is gap junctional intercellular communication (GJIC) mediated by gap junctions (GJs) formed by transmembrane proteins called connexins (Cx)...
November 1, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27799463/estrogen-receptors-and-esterol-dependent-neuroprotective-actions-a-pilot-study
#14
Ekaterine Tskitishvili, Christel Pequeux, Carine Munaut, Renaud Viellevoye, Michelle Nisolle, Agnes Noel, Jean-Michel Foidart
Estetrol (E4) has strong antioxidative, neuro- and angiogenic effects in neural system resulting in attenuation of neonatal hypoxic-ischemic encephalopathy. We aimed to define the role of estrogen receptors in E4-dependent actions in neuronal cell cultures and prove the promyelinating effect of E4. In vitro the antioxidative and cell survival/proliferating effects of E4 on H202-induced oxidative stress in primary hippocampal cell cultures were studied by using different combinations of specific inhibitors for ERα (MPP dihydrochloride), ERβ (PHTTP), GPR30 (G15) and palmytoilation (2-BR)...
October 31, 2016: Journal of Endocrinology
https://www.readbyqxmd.com/read/27797678/anorexia-nervosa-analysis-of-trabecular-texture-with-ct
#15
Azadeh Tabari, Martin Torriani, Karen K Miller, Anne Klibanski, Mannudeep K Kalra, Miriam A Bredella
Purpose To determine indexes of skeletal integrity by using computed tomographic (CT) trabecular texture analysis of the lumbar spine in patients with anorexia nervosa and normal-weight control subjects and to determine body composition predictors of trabecular texture. Materials and Methods This cross-sectional study was approved by the institutional review board and compliant with HIPAA. Written informed consent was obtained. The study included 30 women with anorexia nervosa (mean age ± standard deviation, 26 years ± 6) and 30 normal-weight age-matched women (control group)...
October 31, 2016: Radiology
https://www.readbyqxmd.com/read/27796870/gpr30-activation-contributes-to-the-puerarin-mediated-neuroprotection-in-mpp-induced-sh-sy5y-cell-death
#16
Yue-Fa Cheng, Guoqi Zhu, Qing-Wen Wu, Yue-Sheng Xie, Yan Jiang, Lan Guo, Ya-Li Guan, Ying-Shuo Liu, Jun Zhang
The neuroprotective action of puerarin in Parkinson's disease (PD) models has been well investigated. However, the mechanisms involved in protection have not been completely understood. G protein-coupled receptor 30 (GPR30) is a G protein-coupled estrogen receptor and considered a potential target in the neuroprotection against PD. In this study, we investigated whether puerarin prevented against 1-methyl-4-phenylpyridinium (MPP(+))-induced cell death via GPR30. Our results showed that the GPR30 agonist, G1, exhibited puerarin-mediated neuroprotection against MPP(+)-induced cell death of SH-SY5Y cells...
October 30, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27785754/nuclear-accumulation-of-histone-deacetylase-4-hdac4-exerts-neurotoxicity-in-models-of-parkinson-s-disease
#17
Qimei Wu, Xiaoyu Yang, Lei Zhang, Yu Zhang, Linyin Feng
Histone deacetylase 4 (HDAC4) is a class II HDAC which is highly expressed in the brain. Previous reports have shown that HDAC4 is essential for normal brain physiology and its deregulation leads to several neurodegenerative disorders. However, it remains unclear whether dysregulation of HDAC4 is specifically involved in the development of Parkinson's disease. In this study, we demonstrate that intracellular trafficking of HDAC4 is important in regulating dopaminergic cell death. While HDAC4 normally localizes to the cytoplasm, nuclear accumulation of HDAC4 was observed in dopaminergic neurons overexpressing A53T mutant α-synuclein treated with MPP(+)/MPTP in vitro and in vivo...
October 26, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27778023/icariin-protects-against-mpp-induced-neurotoxicity-in-mes23-5-cells
#18
Ai-Li Xu, Ming-Chun Jiang, Xiao-Han Chen, Wen-Fang Chen
Icariin is the major bioactive component of Epimedium and has been demonstrated to be a potential drug for age-related diseases. The present study was aimed to investigate the neuroprotective properties of icariin against 1-methyl-4-phenylpyridinium ion (MPP(+))-induced neurotoxicity in MES23.5 cells and the possible mechanisms. MTT assay showed that treatment with MPP(+) attenuated the cell viability in a dose-dependent manner in MES23.5 cells. Icariin pretreatment resulted in an enhancement of survival. Immunocytochemistry analysis revealed that icariin treatment attenuated MPP(+)-induced loss of tyrosine hydroxylase (TH) positive cells...
October 25, 2016: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/27777208/-anlysis-of-foot-biomechanics-characteristic-in-303-patients-with-type-2-diabetes-mellitus
#19
Wen-Xia Li, Ying Cao, Meng-Chen Zou, Ying Huang, Ping Hu, Xiang-Rong Luo, Ya Jiang, Yao-Ming Xue, Fang Gao
OBJECTIVE: To investigate foot biomechanics characteristic of patients with type 2 diabetes mellitus. METHODS: This study was conducted among 303 patients with type 2 diabetes. The whole foot was divided into 10 regions, namely the first toe (T1); the second to fifth toes (T2-5); the first, second, third, fourth, and fifth metatarsals (M1, M2, M3, M4, and M5, respectively); midfoot (MF), and the heel medial (HM). Foot arch index, foot angle and maximum peak pressure (MPP) of the 10 regions were measured using a Footscan gait system...
October 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/27774754/impact-of-elosulfase-alfa-in-patients-with-morquio-a-syndrome-who-have-limited-ambulation-an-open-label-phase-2-study
#20
Paul R Harmatz, Eugen Mengel, Tarekegn Geberhiwot, Nicole Muschol, Christian J Hendriksz, Barbara K Burton, Elisabeth Jameson, Kenneth I Berger, Andrea Jester, Marsha Treadwell, Zlatko Sisic, Celeste Decker
Efficacy and safety of elosulfase alfa enzyme replacement therapy (ERT) were assessed in an open-label, phase 2, multi-national study in Morquio A patients aged ≥5 years unable to walk ≥30 meters in the 6-min walk test. Patients received elosulfase alfa 2.0 mg/kg/week intravenously for 48 weeks. Efficacy measures were functional dexterity, pinch/grip strength, mobility in a modified timed 25-foot walk, pain, quality of life, respiratory function, and urine keratan sulfate (KS). Safety/tolerability was also assessed...
October 24, 2016: American Journal of Medical Genetics. Part A
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