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https://www.readbyqxmd.com/read/28342896/neuroprotective-and-axonal-outgrowth-promoting-effects-of-tetramethylpyrazine-nitrone-in-chronic-cerebral-hypoperfusion-rats-and-primary-hippocampal-neurons-exposed-to-hypoxia
#1
Tao Zhang, Jianbo Gu, Liangmiao Wu, Ning Li, Yewei Sun, Pei Yu, Yuqiang Wang, Gaoxiao Zhang, Zaijun Zhang
Chronic cerebral hypoperfusion is an important risk factor for vascular dementia and other brain dysfunctions, for which there are currently no effective medications available. We investigated the neuroprotective and axonal outgrowth promoting effects of tetramethylpyrazine nitrone (TBN) in a permanent bilateral occlusion of the common carotid arteries (2VO) rat model and in primary hippocampal neurons exposed to oxygen glucose deprivation (OGD). At 6th week after 2VO, TBN increased the time spent in novel arms in the Y-maze test and improved the discrimination ratio in object reorganization task...
March 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28342400/using-gene-expression-database-to-uncover-biology-functions-of-1-4-disubstituted-1-2-3-triazole-analogues-synthesized-via-a-copper-i-catalyzed-reaction
#2
Chun-Li Su, Chia-Ling Tseng, Chintakunta Ramesh, Hsiao-Sheng Liu, Chi-Ying F Huang, Ching-Fa Yao
We have synthesized bioactive 1,4-disubstituted 1,2,3-triazole analogues containing 2H-1,4-benzoxazin-3-(4H)-one derivatives via 1,3-dipolar cycloaddition in the presence of CuI. All the reactions proceeded smoothly and afforded its desired products in excellent yields. Among these analogues, 3y exhibited a better cytotoxic effect on human hepatocellular carcinoma (HCC) Hep 3B cells and displayed less cytotoxicity on normal human umbilical vein endothelial cells, compared with Sorafenib, a targeted therapy for advanced HCC...
March 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28339396/modulation-of-a%C3%AE-pp-and-gsk3%C3%AE-by-endoplasmic-reticulum-stress-and-involvement-in-alzheimer-s-disease
#3
Xin-Jun Liu, Jun Wei, Ying-Hui Shang, Han-Chang Huang, Feng-Xue Lao
Alzheimer's disease (AD) is a dementia disease with neuronal loss and synaptic impairment. This impairment is caused, at least partly, by the generation of two main AD hallmarks, namely the hyperphosphorylated tau protein comprising neurofibrillary tangles and senile plaques containing amyloid-β (Aβ) peptides. The amyloid-β protein precursor (AβPP) and glycogen synthase kinase-3β (GSK3β) are two main proteins associated with AD and are closely correlated with these hallmarks. Recently, both of the proteins were reported to be modulated by endoplasmic reticulum stress (ERS) and are involved in the pathogenesis of AD...
March 20, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28339060/chronological-changes-in-the-expression-of-phosphorylated-tau-and-5%C3%A2-amp%C3%A2-activated-protein-kinase-in-the-brain-of-senescence%C3%A2-accelerated-p8-mice
#4
Hak-Su Kim, Sohee Moon, Sujin Kim, Min-Jae Lee, Min Hwa Suk, Dong-Ho Park, Dong Wun Shin, Chang-Shin Park, Ju-Hee Kang
Senescence-accelerated mouse prone 8 (SAMP8), a non‑transgenic animal model used for researching sporadic Alzheimer's disease (AD), presents AD pathologies and overall dysregulation in brain energy metabolism, which is one of the early pathogenic characteristics of AD. In the present study, the authors examined chronological changes in the expression patterns of phosphorylated tau and of proteins related to energy metabolism to evaluate the association of tau phosphorylation and metabolism, using young‑ (2‑months‑old), middle‑ (5‑months‑old) and old‑aged (10‑months‑old) SAMP8...
March 23, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28338494/combined-knockdown-of-d-dopachrome-tautomerase-and-migration-inhibitory-factor-inhibits-the-proliferation-migration-and-invasion-in-human-cervical-cancer
#5
Qingying Wang, Yingze Wei, Jiawen Zhang
OBJECTIVE: D-dopachrome tautomerase (D-DT) is a homologue of macrophage migration inhibitory factor (MIF) with similar functions. However, the possible biological roles of D-DT in cervical cancer remain unknown so far. METHODS: D-dopachrome tautomerase was assessed by immunohistochemistry in 83 cervical cancer and 31 normal cervix tissues. The stable knockdown of D-DT and MIF by lentivirus-delivered short hairpin RNA was established, and tumor growth was examined in vitro and in vivo...
March 23, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28338397/clove-and-its-active-compound-attenuate-free-fatty-acid-mediated-insulin-resistance-in-skeletal-muscle-cells-and-in-mice
#6
Safina Ghaffar, Shabbir Khan Afridi, Meha Fatima Aftab, Munazza Murtaza, Rahman M Hafizur, Sara Sara, Sabira Begum, Rizwana Sanaullah Waraich
Several reports indicate anti-hyperglycemic effects of Syzygium aromaticum. In the present study, we report for the first time that clove extract (SAM) and its compound nigricin (NGC) decreases free fatty acid-mediated insulin resistance in mouse myoblasts. In addition, NGC was able to diminish insulin resistance in a diabetic mouse model. We observed that SAM and its compound NGC exhibited significant antioxidant activity in murine skeletal muscle cells. They also modulated stress signaling by reducing p38 MAP kinase phosphorylation...
March 24, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28337318/development-of-18-f-maleimide-based-glycogen-synthase-kinase-3%C3%AE-ligands-for-positron-emission-tomography-imaging
#7
Kongzhen Hu, Debasis Patnaik, Thomas Lee Collier, Katarzyna N Lee, Han Gao, Matthew R Swoyer, Benjamin H Rotstein, Hema S Krishnan, Steven H Liang, Jin Wang, Zhiqiang Yan, Jacob M Hooker, Neil Vasdev, Stephen J Haggarty, Ming-Yu Ngai
Dysregulation of glycogen synthase kinase-3β (GSK-3β) is implicated in the pathogenesis of neurodegenerative and psychiatric disorders. Thus, development of GSK-3β radiotracers for positron emission tomography (PET) imaging is of paramount importance, because such a noninvasive imaging technique would allow better understanding of the link between the activity of GSK-3β and central nervous system disorders in living organisms, and it would enable early detection of the enzyme's aberrant activity. Herein, we report the synthesis and biological evaluation of a series of fluorine-substituted maleimide derivatives that are high-affinity GSK-3β inhibitors...
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28337257/subcutaneous-liraglutide-ameliorates-methylglyoxal-induced-alzheimer-like-tau-pathology-and-cognitive-impairment-by-modulating-tau-hyperphosphorylation-and-glycogen-synthase-kinase-3%C3%AE
#8
Liqin Qi, Zhou Chen, Yanping Wang, Xiaoying Liu, Xiaohong Liu, Linfang Ke, Zhongjie Zheng, Xiaowei Lin, Yu Zhou, Lijuan Wu, Libin Liu
Memory deterioration and synapse damage with accumulation of β-amyloid and hyperphosphorylated tau are hallmark lesions of Alzheimer's disease (AD). Methylglyoxal (MG), a key intermediate of glucose metabolism, is elevated in AD brains and modifies Aβ42, increasing misfolding and leading to the accumulation of senile plaques. Liraglutide, an analog of glucagon-like peptide-1 (GLP-1), is neurotrophic and neuroprotective. However, whether liraglutide can protect against AD-like memory-related deficits and tau hyperphosphorylation caused by MG in vivo is not known...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28336261/methane-rescues-retinal-ganglion-cells-and-limits-retinal-mitochondrial-dysfunction-following-optic-nerve-crush
#9
Ruobing Wang, Qinglei Sun, Fangzhou Xia, Zeli Chen, Jiangchun Wu, Yuelu Zhang, Jiajun Xu, Lin Liu
Secondary degeneration is a common event in traumatic central nervous system disorders, which involves neuronal apoptosis and mitochondrial dysfunction. Exogenous methane exerts the therapeutic effects in many organ injury. Our study aims to investigate the potential neuroprotection of methane in a rat model of optic nerve crush (ONC). Adult male Sprague-Dawley rats were subjected to ONC and administrated intraperitoneally with methane-saturated or normal saline (10 ml/kg) once per day for one week after ONC...
March 20, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28335557/ros-production-and-erk-activity-are-involved-in-the-effects-of-d-%C3%AE-hydroxybutyrate-and-metformin-in-a-glucose-deficient-condition
#10
Santosh Lamichhane, Tonking Bastola, Ramesh Pariyar, Eun-Sol Lee, Ho-Sub Lee, Dae Ho Lee, Jungwon Seo
Hypoglycemia, a complication of insulin or sulfonylurea therapy in diabetic patients, leads to brain damage. Furthermore, glucose replenishment following hypoglycemic coma induces neuronal cell death. In this study, we investigated the molecular mechanism underlying glucose deficiency-induced cytotoxicity and the protective effect of d-β-hydroxybutyrate (D-BHB) using SH-SY5Y cells. The cytotoxic mechanism of metformin under glucose deficiency was also examined. Cell viability under 1 mM glucose (glucose deficiency) was significantly decreased which was accompanied by increased production of reactive oxygen species (ROS) and decreased phosphorylation of extracellular signal-regulated kinase (ERK) and glycogen synthase 3 (GSK3β)...
March 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28330809/piperine-attenuates-pathological-cardiac-fibrosis-via-ppar-%C3%AE-akt-pathways
#11
Zhen-Guo Ma, Yu-Pei Yuan, Xin Zhang, Si-Chi Xu, Sha-Sha Wang, Qi-Zhu Tang
Mitogen-activated protein kinases (MAPKs) and AMP-activated protein kinase α (AMPKα) play critical roles in the process of cardiac hypertrophy. Previous studies have demonstrated that piperine activates AMPKα and reduces the phosphorylation of extracellular signal-regulated kinase (ERK). However, the effect of piperine on cardiac hypertrophy remains completely unknown. Here, we show that piperine-treated mice had similar hypertrophic responses as mice treated with vehicle but exhibited significantly attenuated cardiac fibrosis after pressure overload or isoprenaline (ISO) injection...
March 14, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28328738/inhibition-of-hippocampal-long-term-potentiation-by-high-fat-diets-is-it-related-to-an-effect-of-palmitic-acid-involving-glycogen-synthase-kinase-3
#12
Ana Contreras, Danila Del Rio, Ana Martínez, Carmen Gil, Lidia Morales, Mariano Ruiz-Gayo, Nuria Del Olmo
High-fat diets (HFD) impair hippocampal-dependent learning and memory and produce important changes in synaptic transmission by enhancing glutamate uptake, decreasing synaptic efficacy, and inhibiting plasticity mechanisms such as N-methyl-D-aspartate-mediated long-term depression (LTD) within the hippocampus. Adolescent animals seem to be particularly susceptible to the detrimental effect of HFD as dietary treatments carried out between weaning and early adulthood are much more efficient in terms of hippocampal damage that those carried out during the adult period...
March 21, 2017: Neuroreport
https://www.readbyqxmd.com/read/28324237/cyclosporine-a-induces-endoplasmic-reticulum-stress-and-influences-pro-apoptotic-factors-in-human-gingival-fibroblasts
#13
Suresh Ranga Rao, Shiyamali Sundararajan, Rajasekaran Subbarayan, Dinesh Murugan Girija
Cyclosporine-A (CsA) induces gingival overgrowth. Cyclosporine's anti-apoptotic activity in human gingival fibroblast is due to desensitization of mitochondrial permeability transition pore (MPTP) and augmentation of anti-apoptotic, Bcl2. Alternative mechanisms of apoptosis exist involving enzymes like calcium-dependent Calpain and signaling events related to apoptosis, like Glycogen synthase kinase 3β (GSK3β) and protein kinase A (PKA). Cyclosporine-A in renal tubular cells induces endoplasmic reticulum stress (ER stress) which has not been explored in gingival overgrowth...
March 21, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28322909/paeoniflorin-ameliorates-cognitive-dysfunction-via-regulating-socs2-irs-1-pathway-in-diabetic-rats
#14
Xiaoxu Sun, Shanshan Li, Lixing Xu, Hao Wang, Zhanqiang Ma, Qiang Fu, Rong Qu, Shiping Ma
Paeoniflorin is a natural monoterpene glycoside in Paeonia lactiflora pall with various biological properties including promising anti-inflammatory activity. Current evidences support that inflammatory reaction, oxidative stress, as well as abnormal insulin signaling in the hippocampus are potential causes of tau hyperphosphorylation and finally induce cognitive dysfunction. The present study aims to explore the effects of paeoniflorin on the cognitive deficits and investigate the underlying mechanisms in diabetic rats induced by a high-sucrose, high-fat diet and low dose of streptozotocin (STZ)...
March 16, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28315454/astragaloside-iv-attenuates-lead-acetate-induced-inhibition-of-neurite-outgrowth-through-activation-of-akt-dependent-nrf2-pathway-in-vitro
#15
Chunlei Yu, Siwen Pan, Miaoxian Dong, Yingcai Niu
Recently, oxidative stress is strongly associated with lead (Pb)-induced neurotoxicity. We reported previously that Astragaloside IV (AS-IV) possesses potent antioxidant properties. Here, we evaluate the hypothesis that AS-IV attenuates lead acetate (PbAc)-mediated inhibition of neurite outgrowth might mainly result from its antioxidant property via serine/threonine protein kinase (Akt)-dependent activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Interestingly, AS-IV attenuates PbAc-induced inhibition of neurite outgrowth and displayed potential antioxidant properties by inhibiting reactive oxygen species (ROS)...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28301953/glucose-variability-aggravates-cardiac-fibrosis-by-altering-akt-signalling-path
#16
Changjiang Ying, Ting Liu, Hongwei Ling, Mingyue Cheng, Xiaoyan Zhou, Shanshan Wang, Yizhen Mao, Lei Chen, Runze Zhang, Wei Li
OBJECTIVE: To study the effect of blood glucose variability on cardiac fibrosis and its mechanism in a model of diabetic cardiomyopathy. METHODS: A total of 45 Sprague Dawley rats were randomly divided into three groups: control, control diabetes mellitus and fluctuated blood glucose groups. Fluctuated blood glucose was induced by daily subcutaneous insulin and intraperitoneal glucose injections at different time points. Blood lipids and glycosylated haemoglobin A1c were assessed...
March 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28301598/regulation-of-anti-apoptotic-bcl-2-family-protein-mcl-1-by-s6-kinase-2
#17
Alakananda Basu, Savitha Sridharan
The anti-apoptotic Bcl-2 family protein myeloid cell leukemia-1 (Mcl-1) plays an important role in breast cancer cell survival and chemoresistance. We have previously shown that knockdown of the 40S ribosomal protein S6 kinase-2 (S6K2), which acts downstream of the mechanistic target of rapamycin complex 1 (mTORC1), enhanced breast cancer cell death by apoptotic stimuli. The increase in cell death by S6K2 depletion was partly due to inactivation of Akt. In the present study, we investigated if S6K2 regulates Mcl-1, which acts downstream of Akt...
2017: PloS One
https://www.readbyqxmd.com/read/28299185/recent-advances-in-understanding-the-cellular-roles-of-gsk-3
#18
REVIEW
Kevin W Cormier, James R Woodgett
Glycogen synthase kinase-3 (GSK-3) is a ubiquitously expressed protein kinase that sits at the nexus of multiple signaling pathways. Its deep integration into cellular control circuits is consummate to its implication in diseases ranging from mood disorders to diabetes to neurodegenerative diseases and cancers. The selectivity and insulation of such a promiscuous kinase from unwanted crosstalk between pathways, while orchestrating a multifaceted response to cellular stimuli, offer key insights into more general mechanisms of cell regulation...
2017: F1000Research
https://www.readbyqxmd.com/read/28298517/phosphoproteomics-of-fgf1-signaling-in-chondrocytes-identifying-the-signature-of-inhibitory-response
#19
Jessica R Chapman, Olga Katsara, Rachel Ruoff, David Morgenstern, Shruti Nayak, Claudio Basilico, Beatrix Ueberheide, Victoria Kolupaeva
Fibroblast growth factor (FGF) signaling is vital for many biological processes, beginning with development. The importance of FGF signaling for skeleton formation was first discovered by the analysis of genetic FGFR mutations which cause several bone morphogenetic disorders, including achondroplasia, the most common form of human dwarfism. The formation of the long bones is mediated through proliferation and differentiation of highly specialized cells - chondrocytes. Chondrocytes respond to FGF with growth inhibition, a unique response which differs from the proliferative response of the majority of cell types; however its molecular determinants are still unclear...
March 15, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28298444/scffbxo17-e3-ligase-modulates-inflammation-by-regulating-proteasomal-degradation-of-glycogen-synthase-kinase-3%C3%AE-in-lung-epithelia
#20
Tomeka Suber, Jianxin Wei, Anastasia M Jacko, Ina Nikolli, Yutong Zhao, Jing Zhao, Rama K Mallampalli
Glycogen synthase kinase-3β (GSK3β) has diverse biological roles including effects on cellular differentiation, migration, and inflammation. GSK3β phosphorylates proteins to generate phosphodegrons necessary for recognition by Skip-1/Cullin-1/F-box (SCF) E3 ubiquitin ligases leading to subsequent proteasomal degradation of these substrates. However, little is known regarding how GSK3β protein stability itself is regulated and how its stability may influence inflammation. Here we show that GSK3β is degraded by the ubiquitin-proteasome pathway in murine lung epithelial (MLE) cells through lysine 183 as an acceptor site for K48 polyubiquitination...
March 15, 2017: Journal of Biological Chemistry
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