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https://www.readbyqxmd.com/read/29776017/pharmacokinetics-and-c-reactive-protein-modelling-of-anti-il-6-antibody-pf-04236921-in-healthy-volunteers-and-patients-with-autoimmune-disease
#1
Cheryl Li, Satoshi Shoji, Jean Beebe
AIMS: The purpose of this study was to characterize pharmacokinetics (PK) of PF-04236921, a novel anti-IL-6 monoclonal antibody, and its pharmacokinetics/pharmacodynamics (PK/PD) relationship on serum C-Reactive Protein (CRP) in healthy volunteers and patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Crohn's disease (CD) METHODS: Population modelling analyses were conducted using nonlinear mixed effects modelling. Data from 2 phase 1 healthy volunteer studies, a phase 1 RA study, a Phase 2 CD study, and a Phase 2 SLE study were included...
May 18, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29776015/delta-9-tetrahydrocannabinol-potentiates-fear-memory-salience-through-functional-modulation-of-mesolimbic-dopaminergic-activity-states
#2
Aurelie Fitoussi, Jordan Zunder, Huibing Tan, Steven R Laviolette
Chronic or acute exposure to delta-9-tetrahydrocannabinol (THC), the main psychoactive compound in cannabis, has been associated with numerous neuropsychiatric side-effects, including dysregulation of emotional processing and associative memory formation. Clinical and pre-clinical evidence suggests that the effects of THC are due to the ability to modulate mesolimbic dopamine (DA) activity states in the nucleus accumbens (NAc) and ventral tegmental area (VTA). Nevertheless, the mechanisms by which THC modulates mesolimbic DA function and emotional processing are not well understood...
May 18, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29776014/association-of-objectively-measured-physical-activity-with-brain-structure-uk-biobank-study
#3
Mark Hamer, Nikhil Sharma, G David Batty
BACKGROUND: Physical activity may be beneficial for cognition but mechanisms are unclear. We examined the association between objectively assessed physical activity and brain volume, with a focus on the hippocampus region. METHODS: We used data from UK Biobank (n=5,272; aged 55.4±7.5 yrs; 45.6% men) collected through 2013-2016. Participants wore the Axivity AX3 wrist-worn triaxial accelerometer for seven days to assess habitual physical activity. Structural magnetic resonance imaging was performed using a standard Siemens Skyra 3T running VD13A SP4 to obtain images of the brain...
May 18, 2018: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29775995/phosphorylation-alters-bim-mediated-mcl-1-stabilization-and-priming
#4
Jason E Conage-Pough, Lawrence H Boise
Mcl-1 is a highly labile protein, subject to extensive posttranslational regulation. This distinguishes Mcl-1 from other anti-apoptotic proteins and necessitates further study to better understand how interactions with pro-apoptotic Bcl-2 proteins affect its regulation. One such protein, Bim, is known to stabilize Mcl-1, and Bim phosphorylation has been associated with increased Mcl-1 binding. Consequently, we investigated the potential impact of Bim phosphorylation on Mcl-1 stability. We found that Bim stabilizes and primes Mcl-1 in RPCI-WM1 cells and is constitutively phosphorylated...
May 18, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29775984/static-postural-stability-in-chronic-ankle-instability-an-ankle-sprain-and-healthy-ankles
#5
Yong Ung Kwon
To identify the single leg balance (SLB) test that discriminates among healthy, coper, and chronic ankle instability (CAI) groups and to determine effects of ankle muscles on the balance error scoring system (BESS) among the three populations. 60 subjects (20 per group) performed the SLB test with eyes open (EO) and eyes closed (EC). Normalized mean amplitude (NMA) of the tibia anterior (TA), fibularis longus (FL), and medial gastrocnemius (MG) muscles and BESS were measured while performing the SLB test. The coper group had a lower error score than the CAI group in the EC...
May 18, 2018: International Journal of Sports Medicine
https://www.readbyqxmd.com/read/29775968/in-silico-structure-prediction-and-inhibition-mechanism-studies-of-athda14-as-revealed-by-homology-modeling-docking-molecular-dynamics-simulation
#6
Ming-Lang Zhao, Wang Wang, Hu Nie, Sha-Sha Cao, Lin-Fang Du
Histone deacetylases (HDACs) play a significant role in the epigenetic mechanism by catalyzing deacetylation of lysine on histone in both animals and plants. HDACs involved in growth, development and response to stresses in plants. Arabidopsis thaliana histone deacetylase 14 (AtHDA14) is found to localize in the mitochondria and chloroplasts, and it involved in photosynthesis and melatonin biosynthesis. However, its mechanism of action was still unknowns so far. Therefore, in this study, we constructed AtHDA14 protein model using homology modeling method, validated using PROCHECK and presented using Ramachandran plots...
May 6, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29775966/an-enigmatic-case-presentation-of-budd-chiari-syndrome-with-pulmonary-embolism-an-unusual-syndrome-with-an-uncommon-complication
#7
A M Al-Sharydah, A H Al-Abdulwahhab, H A Abu AlOla
INTRODUCTION: In patients with a hypercoagulable state, such as patients with pulmonary embolism and/or Budd-Chiari syndrome, the complications from multiple gene mutations are more numerous than those from a single mutation. The authors present a woman with no major prior medical history who presented with pulmonary embolism and Budd-Chiari syndrome; this enigmatic co-occurrence has never been solely reported without underlying aetiology in a patient without prior medical conditions...
May 3, 2018: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/29775963/brain-ischemic-preconditioning-protects-against-ischemic-injury-and-preserves-the-blood-brain-barrier-via-oxidative-signaling-and-nrf2-activation
#8
Tuo Yang, Yang Sun, Leilei Mao, Meijuan Zhang, Qianqian Li, Lili Zhang, Yejie Shi, Rehana K Leak, Jun Chen, Feng Zhang
Brain ischemic preconditioning (IPC) with mild ischemic episodes is well known to protect the brain against subsequent ischemic challenges. However, the underlying mechanisms are poorly understood. Here we demonstrate the critical role of the master redox transcription factor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), in IPC-mediated neuroprotection and blood-brain barrier (BBB) preservation. We report that IPC causes generation of endogenous lipid electrophiles, including 4-hydroxy-2-nonenal (4-HNE), which release Nrf2 from inhibition by Keap1 (via Keap1-C288) and inhibition by glycogen synthase kinase 3β (via GSK3β-C199)...
May 6, 2018: Redox Biology
https://www.readbyqxmd.com/read/29775961/antioxidant-response-elements-discovery-classes-regulation-and-potential-applications
#9
REVIEW
Azhwar Raghunath, Kiruthika Sundarraj, Raju Nagarajan, Frank Arfuso, Jinsong Bian, Alan P Kumar, Gautam Sethi, Ekambaram Perumal
Exposure to antioxidants and xenobiotics triggers the expression of a myriad of genes encoding antioxidant proteins, detoxifying enzymes, and xenobiotic transporters to offer protection against oxidative stress. This articulated universal mechanism is regulated through the cis-acting elements in an array of Nrf2 target genes called antioxidant response elements (AREs), which play a critical role in redox homeostasis. Though the Keap1/Nrf2/ARE system involves many players, AREs hold the key in transcriptional regulation of cytoprotective genes...
May 7, 2018: Redox Biology
https://www.readbyqxmd.com/read/29775946/il-9-exhibits-elevated-expression-in-osteonecrosis-of-femoral-head-patients-and-promotes-cartilage-degradation-through-activation-of-jak-stat-signaling-in-vitro
#10
Wei Geng, Wen Zhang, Jinzhu Ma
Osteonecrosis of the femoral head (ONFH) often causes severe symptoms in young people and limits the mobility of the hip joint. Interleukin-9 (IL-9) is a multi-functional inflammatory factor that participates in lumbar disk herniation and arthritis and has been reported in many studies. However, the correlation between IL-9 and ONFH is unclear. The present study aimed to determine the role of IL-9 in the pathogenetic mechanism of osteonecrosis. To assess IL-9 expression in ONFH and femoral neck fracture patients, cartilage tissue was examined through western blot analysis and immunohistochemistry...
May 15, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29775928/tributyltin-impaired-reproductive-success-in-female-zebrafish-through-disrupting-oogenesis-reproductive-behaviors-and-serotonin-synthesis
#11
Wei-Yang Xiao, Ying-Wen Li, Qi-Liang Chen, Zhi-Hao Liu
Tributyltin (TBT), an organotin acting as aromatase (Cyp19a1) inhibitor, has been found to disrupt gametogenesis and reproductive behaviors in several fish species. However, few studies addressing the mechanisms underlying the impaired gametogenesis and reproduction have been reported. In this study, female adults of zebrafish (Danio rerio) were continuously exposed to two nominal concentrations of TBT (100 and 500 ng/L, actual concentrations: 90.8 ± 1.3 ng/L and 470.3 ± 2.7 ng/L, respectively) for 28 days...
May 12, 2018: Aquatic Toxicology
https://www.readbyqxmd.com/read/29775927/effects-of-microcystin-lr-on-the-tissue-growth-and-physiological-responses-of-the-aquatic-plant-iris-pseudacorus-l
#12
Naiyu Wang, Can Wang
The release of cyanobacterial toxins during algal bloom has adverse effects on aquatic plants and animals. This study aimed to understand the toxic effects and mechanism of microcystin-LR (MC-LR) on the seedling growth and physiological responses of Iris pseudacorus L. (calamus). After a one-month exposure experiment, the growth and development of the calamus leaves were significantly inhibited, and this inhibitory effect was verified to be concentration dependent. Furthermore, the cell membrane system was damaged, and the photosynthesis was also adversely affected by MC-LR...
April 27, 2018: Aquatic Toxicology
https://www.readbyqxmd.com/read/29775910/hip-and-patellofemoral-joint-loading-during-gait-are-increased-in-children-with-idiopathic-torsional-deformities
#13
Elyse Passmore, H Kerr Graham, Marcus G Pandy, Morgan Sangeux
BACKGROUND: Torsional deformities of the femur and tibia are associated with gait impairments and joint pain. Several studies have investigated these gait deviations in children with cerebral palsy. However, relatively little is known about gait deviations in children with idiopathic torsion and debate ensues about the management of these patients. RESEARCH QUESTION: What are the effects of idiopathic increased femoral neck anteversion and external tibial torsion on lower-limb kinematics, kinetics and joint loading during gait in children and adolescents...
May 9, 2018: Gait & Posture
https://www.readbyqxmd.com/read/29775902/type-1-diabetes-through-the-lens-of-human-genome-and-metagenome-interplay
#14
REVIEW
Sepideh Zununi Vahed, Hakimeh Moghaddas Sani, Yalda Rahbar Saadat, Abolfazl Barzegari, Yadollah Omidi
Diabetes is a genetic- and epigenetic-related disease from which a large population worldwide suffers. Some genetic factors along with various mutations related to the immune system for disease mechanism(s) have contrastively been determined. However, sometimes mechanisms have not been fully managed for the clarification of the initiation and/or progression of diseases to help patients. In the recent years, due to familiarity with the role of gut microbiota in the health, it has been found that the changes of the microbial balance in the industrialized societies can cause a battery of modern diseases, for which we have no specific definition of how they emerge...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29775900/hordenine-protects-against-hyperglycemia-associated-renal-complications-in-streptozotocin-induced-diabetic-mice
#15
Shuhao Su, Meng Cao, Guangyuan Wu, Zi Long, Xiaodong Cheng, Junshu Fan, Zhongrui Xu, Hongfei Su, Yiming Hao, Ge Li, Jie Peng, Shuang Li, Xin Wang
The worldwide prevalence of diabetes and associated metabolic diseases has dramatically increased. Pharmacological treatment of diabetes is still limited. Hordenine (HOR), a phenethylamine alkaloid, is a natural constituent in many plants. The present study was designed to explore the possible anti-diabetic effect of HOR in streptozotocin (STZ)-induced diabetic mice. Combined treatment of HOR and insulin significantly reduced fasting and postprandial blood glucose level in diabetic mice. HOR and insulin did not show evident protective effect against structural and functional injuries of pancreas...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29775899/hispidulin-alleviates-high-glucose-induced-podocyte-injury-by-regulating-protective-autophagy
#16
Fengbo Wu, Sijia Li, Nan Zhang, Wei Huang, Xiang Li, Manyi Wang, Ding Bai, Bo Han
OBJECTIVES: Diabetic nephropathy (DN) is one of the most common complications in patients with diabetes, and the discovery of novel targeted therapeutic approaches for DN treatment still faces severe challenges. In the current study, we aimed to discover a novel natural product for potential DN treatment and determine its molecular mechanisms. MATERIALS AND METHODS: Methylthiazoltetrazolium (MTT) assay was employed to evaluate cell viability. Transmission electron microscopy, GFP-LC3 fluorescence fusion plasmid, and Annexin V/PI apoptosis assay were carried out to determine cellular autophagy and apoptosis...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29775897/the-gastric-mucosal-protective-effects-of-astragaloside-iv-in-mnng-induced-gpl-rats
#17
Tiantian Cai, Chengzhe Zhang, Ziming Zhao, Siyi Li, Haobin Cai, Xiaodong Chen, Dake Cai, Wei Liu, Yan Yan, Kaifeng Xie, Huafeng Pan, Xiaohui Zeng
Gastric Cancer is one of the most common types of cancer. And the occurrence of gastric carcinoma is an evolutionary histopathological stage. As a result, further research of GPL, which is a borderline of gastric cancer, is indispensable for preventing the formation and development of gastric carcinoma. Several studies have demonstrated a correlation between the expression of autophagy, apoptosis and Gastric cancer (GC). However, the effects of autophagy and apoptosis on human gastric cancer progression, particularly on gastric precancerous lesions (GPL), have not totally been investigated...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29775895/ozone-therapy-prevents-the-onset-of-dysplasia-in-hpv16-transgenic-mice-a-pre-clinical-efficacy-and-safety-analysis
#18
C Peirone, V F Mestre, B Medeiros-Fonseca, B Colaço, M J Pires, T Martins, R M Gil da Costa, M J Neuparth, R Medeiros, M M S M Bastos, J A Marques-Magallanes, P A Oliveira
Infection with high-risk human papillomavirus (HPV), most often HPV16, is associated with the development of anogenital and oropharyngeal cancers. Recently, ozone therapy was reported to have considerable efficacy against rabbit VX2 tumors, induced by the cottontail rabbit papillomavirus. The present study aims to determine whether similar results can be obtained in HPV16-transgenic mice, possibly paving the way for new therapeutic options against HPV-induced cancers. HPV16-transgenic and wild-type, female, 20 weeks-old mice were injected intraperitoneally with medical O3 /O2 (80░mL/kg, at O3 50░μg/mL), once a day, for 5 consecutive days...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29775894/positive-effects-of-antitumor-drugs-in-combination-with-propolis-on-canine-osteosarcoma-cells-spos-2-and-mesenchymal-stem-cells
#19
Pedro Negri Bernardino, Paulo Ricardo Oliveira Bersano, João Ferreira Lima Neto, José Maurício Sforcin
The combination of lower concentrations of antitumor drugs (carboplatin - CARB, doxorubicin - DOX, and methotrexate - MET) with propolis was investigated against canine osteosarcoma (spOS-2) and mesenchymal stem cells (MSC) in vitro. The mechanism of action in the combinations was analyzed. spOS-2 cells were incubated up to 72 h with propolis (50 μg/ml) alone or in combination with CARB (10-400 μmol/l), DOX (0.5-2 μmol/l) or MET (50-200 μmol/l). Cell viability was assessed by MTT assay, apoptosis/necrosis by flow cytometry, and MSC was incubated with the optimum combination...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29775893/puerarin-prevents-vascular-endothelial-injury-through-suppression-of-nf-%C3%AE%C2%BAb-activation-in-lps-challenged-human-umbilical-vein-endothelial-cells
#20
Hua-Fei Deng, Sha Wang, Lian Li, Qin Zhou, Wan-Bei Guo, Xiao-Li Wang, Mei-Dong Liu, Ke Liu, Xian-Zhong Xiao
OBJECTIVE: In the present study, we aimed to explore the effects of puerarin on vascular endothelial cell injury induced by lipopolysaccharide (LPS) and its underlying mechanisms. METHODS: The cell viability and morphological changes were assessed using the cell counting kit-8 (CCK-8) assay and 4´,6-diamidino-2-phenylindole (DAPI) staining, respectively. The levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), monocyte/macrophage chemotactic protein-1 (MCP-1), IL-8, intercellular cell adhesion molecule-1 (ICAM-1), thrombomodulin (TM) and plasminogen activator inhibitor-1 (PAI-1) in cell culture supernatant were determined by the enzyme-linked immunosorbent assay (ELISA)...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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