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https://www.readbyqxmd.com/read/28340322/immunogenicity-and-safety-of-primary-and-booster-vaccination-with-2-investigational-formulations-of-diphtheria-tetanus-and-haemophilus-influenzae-type-b-antigens-in-a-hexavalent-dtpa-hbv-ipv-hib-combination-vaccine-in-comparison-with-the-licensed-infanrix-hexa
#1
Timo Vesikari, Luis Rivera, Tiina Korhonen, Anitta Ahonen, Brigitte Cheuvart, Marjan Hezareh, Winnie Janssens, Narcisa Mesaros
Safety and immunogenicity of 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens of the combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Hib vaccine (DTPa-HBV-IPV/Hib) were evaluated in a Primary (NCT01248884) and a Booster vaccination (NCT01453998) study. In the Primary study, 721 healthy infants (randomized 1:1:1) received 3 doses of DTPa-HBV-IPV/Hib formulation A (DATAPa-HBV-IPV/Hib), or B (DBTBPa-HBV-IPV/Hib) or the licensed DTPa-HBV-IPV/Hib vaccine (Infanrix hexa, GSK; control group) at 2, 3, 4 months of age...
March 24, 2017: Human Vaccines & Immunotherapeutics
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
#2
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/28337336/sar-and-identification-of-2-quinolin-4-yloxy-acetamides-as-mycobacterium-tuberculosis-cytochrome-bc1-inhibitors
#3
Narisa Phummarin, Helena I Boshoff, Patricia S Tsang, James Dalton, Siouxsie Wiles, Clifton E Barry Rd, Brent R Copp
A previous phenotypic screen by GSK identified 2-(quinolin-4-yloxy)acetamides as potent growth inhibitors of Mycobacterium tuberculosis (Mtb). We report the results of a preliminary structure-activity relationship (SAR) study of the compound class which has yielded more potent inhibitors. An Mtb cytochrome bd oxidase deletion mutant (cydKO) was found to be hypersensitive to most members of the compound library, while strains carrying single-nucleotide polymorphisms of the qcrB gene, which encodes a subunit of the menaquinol cytochrome c oxidoreductase (bc1) complex, were resistant to the library...
November 1, 2016: MedChemComm
https://www.readbyqxmd.com/read/28337318/development-of-18-f-maleimide-based-glycogen-synthase-kinase-3%C3%AE-ligands-for-positron-emission-tomography-imaging
#4
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/28337268/geranylgeranylacetone-attenuates-myocardium-ischemic-reperfusion-injury-through-hsp70-and-akt-gsk-3%C3%AE-enos-pathway
#5
Chunxia Zhou, Jie Bai, Chuan Jiang, Lincai Ye, Yanjun Pan, Haibo Zhang
Early reperfusion of myocardial infarction area is the most effective and important therapy to acute myocardial infarction, but could induce reperfusion injury. Geranylgeranylacetone (GGA), an acyclic polyisoprenoid used as an oral anti-ulcer medication, has been reported to have protective effects on reperfusion injury. In the present study, we explored the protective effect of GGA against MIRI and the underlying mechanism. We pretreated rats with four daily GGA, and then observed its effects on heart function parameters following in situ ischemia/reperfusion...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28333124/bap31-is-involved-in-t-cell-activation-through-tcr-signal-pathways
#6
Kunwei Niu, Jialin Xu, Yuhua Cao, Yue Hou, Mu Shan, Yanqing Wang, Yang Xu, Mingyi Sun, Bing Wang
BAP31 is a ubiquitously expressed endoplasmic reticulum (ER) membrane protein. The functions of BAP31 in the immune system have not been investigated due to the lack of animal models. Therefore we created a BAP31 conditional knockdown mouse by performing a knockdown of BAP31 in the thymus. In doing so, we demonstrate that the maturation of T cells is normal but the number of T cells is less in the thymus of the knockout mouse. In addition, the spleen and lymph nodes of peripheral immune organs contained a lesser proportion of the mature T cells in the thymus specific BAP31 knockout mice...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28328977/jmjd3-aids-in-reprogramming-of-bone-marrow-progenitor-cells-to-hepatic-phenotype-through-epigenetic-activation-of-hepatic-transcription-factors
#7
Veena Kochat, Zaffar Equbal, Prakash Baligar, Vikash Kumar, Madhulika Srivastava, Asok Mukhopadhyay
The strictly regulated unidirectional differentiation program in some somatic stem/progenitor cells has been found to be modified in the ectopic site (tissue) undergoing regeneration. In these cases, the lineage barrier is crossed by either heterotypic cell fusion or direct differentiation. Though studies have shown the role of coordinated genetic and epigenetic mechanisms in cellular development and differentiation, how the lineage fate of adult bone marrow progenitor cells (BMPCs) is reprogrammed during liver regeneration and whether this lineage switch is stably maintained are not clearly understood...
2017: PloS One
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
#8
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/28324067/gestational-protein-restriction-impairs-glucose-disposal-in-the-gastrocnemius-muscles-of-female-rats
#9
C S Blesson, V Chinnathambi, S Kumar, C Yallampalli
Gestational low protein (LP) diet causes hyperglycemia and insulin resistance in adult offspring but the mechanism is not clearly understood. In this study, we explored the role of insulin signaling in gastrocnemius muscles of gestational LP exposed female offspring. Pregnant rats were fed control (20% protein) or isocaloric LP (6%) diet from gestational day 4 until delivery. Normal diet was given to mothers after delivery and to pups after weaning until necropsy. Offspring were euthanized at 4 months and gastrocnemius muscles were treated with insulin ex vivo for 30 min...
January 30, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324053/hepatic-insulin-resistance-and-altered-gluconeogenic-pathway-in-premature-baboons
#10
Lisa McGill-Vargas, Amalia Gastaldelli, Hanyu Liang, Diana Anzueto Guerra, Teresa Johnson-Pais, Steven Seidner, Donald McCurnin, Giovanna Muscogiuri, Ralph DeFronzo, Nicolas Musi, Cynthia Blanco
Premature infants have altered glucose regulation early in life and increased risk for diabetes in adulthood. Although prematurity leads to an increased risk of diabetes and metabolic syndrome in adult life, the role of hepatic glucose regulation and adaptation to an early extra-uterine environment in preterm infants remain unknown. The purpose of this study was to investigate developmental differences in glucose metabolism, hepatic protein content and gene expression of key insulin signaling/gluconeogenic molecules...
January 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28322909/paeoniflorin-ameliorates-cognitive-dysfunction-via-regulating-socs2-irs-1-pathway-in-diabetic-rats
#11
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/28321536/effect-of-sinapic-acid-on-hair-growth-promoting-in-human-hair-follicle-dermal-papilla-cells-via-akt-activation
#12
Hyunju Woo, Seungjun Lee, Seungbeom Kim, Deokhoon Park, Eunsun Jung
Hair loss known as alopecia is caused by abnormal hair follicle cycling including shortening of the anagen (growth) phase and changing of hair follicle morphology with miniaturization. In accordance with the life extension, the quality of life is considered to be a most important thing. The yearning for healthy and beautiful hair and low self esteem due to hair loss had negative influence on the quality of life with psychosocial maladjustment. The objective of this research was to identify new compound that can be used as a drug to promote hair growth...
March 20, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28320093/tmf-protects-chondrocytes-from-er-stress-induced-apoptosis-by-down-regulating-gsk-3%C3%AE
#13
Xiaoliang Yuan, Linfu Li, Weimei Shi, Hai Liu, Xianhua Huang, Zhiping Liu, Longhuo Wu
Endoplasmic reticulum (ER) stress-induced chondrocyte apoptosis plays a critical role in osteoarthritis cartilage degeneration. Previous studies showed that 5,7,3',4'-tetramethoxyflavone (TMF) exhibited chondroprotective activity through inhibiting PGE2-induced ER stress and down regulating the expression of GSK-3β. To further investigate the role of GSK-3β in ER stress-induced chondrocytes apoptosis and the protective role of TMF, GSK-3β siRNA and pcDNA3.1-myc-GSK-3β were employed to knock down and overexpress GSK-3β, respectively, in chondrocytes...
March 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28315854/mutation-of-n-linked-glycosylation-in-epcam-affected-cell-adhesion-in-breast-cancer-cells
#14
Xue Liu, Jiujiao Gao, Yan Sun, Dandan Zhang, Tingjiao Liu, Qiu Yan, Xuesong Yang
EpCAM expression is elevated in breast cancer tissue, and correlates with the cancer metastasis and cell adhesion. Although EpCAM glycosylation is supposed to be associated with its function, the contribution of N-glycosylation to its function remains unclear. Here we analyzed cell adhesion ability of EpCAM in breast cancer cells. The results showed that EpCAM expression was associated with cell adhesion and N-glycosylation mutation of EpCAM decreased adhesion capacity. N-glycosylation mutation of EpCAM was correlated with lower levels of integrin β1 and fibronectin...
March 18, 2017: Biological Chemistry
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/28315345/inositol-hexaphosphate-suppresses-colorectal-cancer-cell-proliferation-via-the-akt-gsk-3%C3%AE-%C3%AE-catenin-signaling-cascade-in-a-1-2-dimethylhydrazine-induced-rat-model
#16
Wenyang Yu, Cuiping Liu, Xin Li, Fuguo Yang, Lixue Cheng, Chang Liu, Yang Song
Colorectal cancer (CRC) is common worldwide, and most treatments for CRC have undesirable side effects. Many researchers have demonstrated that inositol hexaphosphate (IP6) has potent anticarcinogenic activity against CRC and no apparent toxicity to normal cells. However, the underlying mechanism is still unclear. In this study, we investigated the anticancer and anti-proliferative properties of IP6 in CRC and its possible mechanisms during this chemopreventive process. We examined the expression of genes related to the PI3K/Akt and Wnt pathways at the transcriptional and translational levels in a DMH-induced rat CRC model following IP6 administration...
March 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28314243/parthenolide-attenuates-cerebral-ischemia-reperfusion-injury-via-akt-gsk-3%C3%AE-pathway-in-pc12-cells
#17
Jun-Feng Zhang, Li Zhang, Li-Li Shi, Zhao-Hua Zhao, Hao Xu, Fei Liang, Hong-Bo Li, Yan Zhao, Xi Xu, Ke Yang, Ying-Fang Tian
Parthenolide (PN), a sesquiterpene lactone isolated from the herbal medicine feverfew (Tanacetum parthenium), was reported to possess neuroprotective activity. However, the neuroprotective effect of PN against cerebral ischemia/reperfusion (I/R) injury remains unclear. Therefore, the aim of the present study was to explore the neuroprotective effects of PN against oxygen-glucose deprivation (OGD)-induced apoptosis in PC12 cells and the underlying mechanisms. Our results demonstrated that PN ameliorated OGD/R-evoked neuronal injury and oxidative stress in PC12 cells...
March 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28300578/cellular-interactions-of-the-phosphorylated-form-of-akt-in-prostate-cancer
#18
Kai H Hammerich, Anna Frolov, Rile Li, Michael Ittmann, Gustavo E Ayala
Phospho-Akt (P-Akt1) promotes proliferation and increased survival in vitro and plays an important role in prostate cancer (PCa) progression as well as the prediction of the probability of recurrence. In this study, the goal was to demonstrate the involvement and impact of P-Akt1 on cellular interactions, biomechanisms and pathways in PCa. Tissue microarrays from 640 PCa patients were immunostained with various antibodies. Ki67 was used to measure proliferation index and Tunnel for apoptotic index. Increased expression of P-Akt1 was associated with an increased proliferation, but inversely correlated with apoptotic index...
March 11, 2017: Human Pathology
https://www.readbyqxmd.com/read/28299185/recent-advances-in-understanding-the-cellular-roles-of-gsk-3
#19
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/28292887/orai-and-trpc-channel-characterization-in-fc%C3%AE%C2%B5ri-mediated-calcium-signaling-and-mediator-secretion-in-human-mast-cells
#20
Hannah E Wajdner, Jasmine Farrington, Claire Barnard, Peter T Peachell, Christine G Schnackenberg, Joseph P Marino, Xiaoping Xu, Karen Affleck, Malcolm Begg, Elizabeth P Seward
Inappropriate activation of mast cells via the FcεRI receptor leads to the release of inflammatory mediators and symptoms of allergic disease. Calcium influx is a critical regulator of mast cell signaling and is required for exocytosis of preformed mediators and for synthesis of eicosanoids, cytokines and chemokines. Studies in rodent and human mast cells have identified Orai calcium channels as key contributors to FcεRI-initiated mediator release. However, until now the role of TRPC calcium channels in FcεRI-mediated human mast cell signaling has not been published...
March 2017: Physiological Reports
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