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https://www.readbyqxmd.com/read/28821161/britannin-induces-apoptosis-through-akt-foxo1-pathway-in-human-pancreatic-cancer-cells
#1
Marzieh Moeinifard, Zuhair Mohammad Hassan, Faranak Fallahian, Maryam Hamzeloo-Moghadam, Mohammad Taghikhani
Induction of apoptosis in cancerous cells is considered as a promising treatment option for cancer therapy. The present study was designed to evaluate the anticancer properties of Britannin and its possible mechanisms of action in human pancreatic cancer cells. Apoptosis induction by Britannin was confirmed by annexin V-FITC/PI staining, Hoechst 33258 staining and caspase-3 activity assay in both AsPC-1 and Panc-1 cells. Additionally, by using western blot and Real-time PCR, we observed that Britannin induced apoptosis by decreasing the expression of BCL-2 and increasing the expression of BAX...
August 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28820388/blockade-of-the-lrp16-pkr-nf-%C3%AE%C2%BAb-signaling-axis-sensitizes-colorectal-carcinoma-cells-to-dna-damaging-cytotoxic-therapy
#2
Xiaolei Li, Zhiqiang Wu, Xiaojing An, Qian Mei, Miaomiao Bai, Leena Hanski, Xiang Li, Tero Ahola, Weidong Han
Acquired therapeutic resistance by tumors is a substantial impediment to reducing the morbidity and mortality that are attributable to human malignancies. The mechanisms responsible for the dramatic shift between chemosensitivity and chemoresistance in colorectal carcinoma have not been defined. Here, we report that LRP16 selectively interacts and activates double-stranded RNA-dependent kinase (PKR), and also acts as scaffolds to assist the formation of a ternary complex of PKR and IKKβ, prolonging the polymers of ADP-ribose (PAR)-dependent nuclear factor kappa B (NF-κB) transactivation caused by DNA-damaging agents and confers acquired chemoresistance...
August 18, 2017: ELife
https://www.readbyqxmd.com/read/28820061/renin-angiotensin-system-and-cytokines-in-chronic-kidney-disease-clinical-and-experimental-evidence
#3
Ariadna Andrade Saldanha Silva, Beranardo Bahia Finotti, Amanda Oliveira Lauar, Thiago Ruiz Rodrigues Prestes, Ana Cristina Simões E Silva
Chronic kidney disease (CKD) has become a major public health problem in Brazil and worldwide. There are many causes of CKD, being the congenital anomalies of the kidney and urinary tract and the glomerular diseases very common in pediatric patients, while diabetic nephropathy, CKD due to chronic arterial hypertension and glomerular diseases are predominant in adult patients. Many endogenous mediators have been related to the pathophysiology of CKD, being relevant the effects of the renin-angiotensin system (RAS) and the immune-inflammatory mediators including cytokines...
August 18, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28820053/neurobiological-mechanisms-of-stress-resilience-and-implications-for-the-aged-population
#4
Charlène Faye, Josephine C Mcgowan, Christine A Denny, Denis J David
Stress is a common reaction to an environmental adversity, but a dysregulation of the stress response can lead to psychiatric illnesses such as major depressive disorder (MDD), post-traumatic stress disorder (PTSD), and anxiety disorders. Yet, not all individuals exposed to stress will develop psychiatric disorders; those with enhanced stress resilience mechanisms have the ability to adapt successfully to stress without developing persistent psychopathology. Notably, the potential to enhance stress resilience in at-risk populations may prevent the onset of stress-induced psychiatric disorders...
August 17, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28819168/resistance-training-regulates-gene-expression-of-molecules-associated-with-intramyocellular-lipids-glucose-signaling-and-fiber-size-in-old-rats
#5
Manoel Benício Teixeira Ribeiro, Vinicius Guzzoni, Jeffrey M Hord, Gisele Nunes Lopes, Rita de Cássia Marqueti, Rosângela Vieira de Andrade, Heloisa Sobreiro Selistre-de-Araujo, João Luiz Q Durigan
Sarcopenia is a complex multifactorial process, some of which involves fat infiltration. Intramyocellular lipid (IMCL) accumulation is postulated to play a role on sarcopenia during aging, which is believed to be due alterations in glucose homeostasis in the skeletal muscle. Sarcopenia, along with intramuscular lipids, is associated with physical inactivity. Resistance training (RT) has been indicated to minimize the age-induced muscle skeletal adaptations. Thus, we aimed to investigate the effects of RT on mRNA levels of regulatory components related to intramyocellular lipid, glucose metabolism and fiber size in soleus and gastrocnemius muscles of aged rats...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818859/renal-denervation-suppresses-coronary-hyperconstricting-responses-after-drug-eluting-stent-implantation-in-pigs-in-vivo-through-the-kidney-brain-heart-axis
#6
Hironori Uzuka, Yasuharu Matsumoto, Kensuke Nishimiya, Kazuma Ohyama, Hideaki Suzuki, Hirokazu Amamizu, Susumu Morosawa, Michinori Hirano, Tomohiko Shindo, Yoku Kikuchi, Kiyotaka Hao, Takashi Shiroto, Kenta Ito, Jun Takahashi, Koji Fukuda, Satoshi Miyata, Yoshihito Funaki, Hatsue Ishibashi-Ueda, Satoshi Yasuda, Hiroaki Shimokawa
OBJECTIVE: Drug-eluting stent-induced coronary hyperconstricting responses remain an important issue. The adventitia harbors a variety of components that potently modulate vascular tone, including sympathetic nerve fibers (SNF) and vasa vasorum. Catheter-based renal denervation (RDN) inhibits sympathetic nerve activity. We, thus, examined whether RDN suppresses drug-eluting stent-induced coronary hyperconstricting responses, and if so, what mechanisms are involved. APPROACH AND RESULTS: Protocol 1: pigs implanted with everolimus-eluting stents into the left coronary arteries underwent coronary angiography at 1 month after implantation for assessment of coronary vasomotion and adventitial SNF formation...
August 17, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28818773/adversity-driven-changes-in-hypothalamic-pituitary-adrenal-axis-functioning-during-adolescence-the-trails-study
#7
Odilia M Laceulle, Esther Nederhof, Marcel A G van Aken, Johan Ormel
The hypothalamic-pituitary-adrenal (HPA) axis has been proposed to be a key mechanism underlying the link between adversity and mental health, but longitudinal studies on adversity and HPA-axis functioning are scarce. Here, we studied adversity-driven changes in HPA-axis functioning during adolescence (N=141). HPA-axis functioning (basal cortisol, cortisol awakening response, anticipation of, reaction to and recovery after a stress task) was measured twice, at age 16 and 19. Adversity (i.e., social defeat and loss/illness) since age 16 was measured extensively with the Life Stress Interview at age 19...
August 4, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28817980/pathways-to-pulmonary-hypertension-in-sickle-cell-disease-the-search-for-prevention-and-early-intervention
#8
Natalie R Shilo, Claudia R Morris
Pulmonary hypertension (PH) develops in a significant number of patients with sickle cell disease (SCD), resulting in increased morbidity and mortality. This review focuses on PH pathophysiology, risk stratification, and new recommendations for screening and treatment for patients with SCD. Areas covered: An extensive PubMed literature search was performed. While the pathophysiology of PH in SCD is yet to be fully deciphered, it is known that the etiology is multifactorial; hemolysis, hypercoagulability, hypoxemia, ischemic-reperfusion injury, oxidative stress, and genetic susceptibility all contribute in varying degrees to endothelial dysfunction...
August 18, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28817691/rac2-is-required-for-alternative-macrophage-activation-and-bleomycin-induced-pulmonary-fibrosis-a-macrophage-autonomous-phenotype
#9
Shweta Joshi, Alok R Singh, Simon S Wong, Muamera Zulcic, Min Jiang, Annie Pardo, Moises Selman, James S Hagood, Donald L Durden
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by cellular phenotype alterations and deposition of extracellular matrix proteins. The alternative activation of macrophages in the lungs has been associated as a major factor promoting pulmonary fibrosis, however the mechanisms underlying this phenomenon are poorly understood. In the present study, we have defined a molecular mechanism by which signals transmitted from the extracellular matrix via the α4β1 integrin lead to the activation of Rac2 which regulates alternative macrophage differentiation, a signaling axis within the pulmonary macrophage compartment required for bleomycin induced pulmonary fibrosis...
2017: PloS One
https://www.readbyqxmd.com/read/28815409/insulin-like-growth-factor-igf-pathway-targeting-in-cancer-role-of-the-igf-axis-and-opportunities-for-future-combination-studies
#10
Aaron Simpson, Wilfride Petnga, Valentine M Macaulay, Ulrike Weyer-Czernilofsky, Thomas Bogenrieder
Despite a strong preclinical rationale for targeting the insulin-like growth factor (IGF) axis in cancer, clinical studies of IGF-1 receptor (IGF-1R)-targeted monotherapies have been largely disappointing, and any potential success has been limited by the lack of validated predictive biomarkers for patient enrichment. A large body of preclinical evidence suggests that the key role of the IGF axis in cancer is in driving treatment resistance, via general proliferative/survival mechanisms, interactions with other mitogenic signaling networks, and class-specific mechanisms such as DNA damage repair...
August 16, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28815046/response-to-single-agent-pd-1-inhibitor-after-progression-on-previous-pd-1-pd-l1-inhibitors-a-case-series
#11
Dylan J Martini, Aly-Khan A Lalani, Dominick Bossé, John A Steinharter, Lauren C Harshman, F Stephen Hodi, Patrick A Ott, Toni K Choueiri
BACKGROUND: Monoclonal antibodies targeting the PD-1/PD-L1 axis have gained increasing attention across many solid tumors and hematologic malignancies due to their efficacy and favorable toxicity profile. With more than 1 agent now FDA-approved in a wide variety of tumor types, and with others in clinical trials, it is becoming more common that patients present to clinic for potential treatment with a second PD-1/PD-L1 inhibitor. CASE PRESENTATION: In this report, we present two patients with renal cell carcinoma and one with melanoma who received PD-1/PD-L1 inhibitors...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28814605/adam10-mediated-icos-ligand-shedding-on-b-cells-is-necessary-for-proper-t-cell-icos-regulation-and-t-follicular-helper-responses
#12
Joseph C Lownik, Andrea J Luker, Sheela R Damle, Lauren Folgosa Cooley, Riham El Sayed, Andreas Hutloff, Costantino Pitzalis, Rebecca K Martin, Mohey Eldin M El Shikh, Daniel H Conrad
The proper regulation of ICOS and ICOS ligand (ICOSL) has been shown to be essential for maintaining proper immune homeostasis. Loss of either protein results in defective humoral immunity, and overexpression of ICOS results in aberrant Ab production resembling lupus. How ICOSL is regulated in response to ICOS interaction is still unclear. We demonstrate that a disintegrin and metalloproteinase (ADAM)10 is the primary physiological sheddase of ICOSL in mice and humans. Using an in vivo system in which ADAM10 is deleted only on B cells, elevated levels of ICOSL were seen...
August 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28814434/combined-cdk4-6-and-mtor-inhibition-is-synergistic-against-glioblastoma-via-multiple-mechanisms
#13
Inan Olmez, Breanna Brenneman, Aizhen Xiao, Vlad Serbulea, Mouadh Benamar, Ying Zhang, Laryssa Manigat, Tarek Abbas, Jeongwu Lee, Ichiro Nakano, Jakub Godlewski, Agnieszka Bronisz, Roger Abounader, Norbert Leitinger, Benjamin Purow
PURPOSE: Glioblastoma (GBM) is a deadly brain tumor marked by dysregulated signaling and aberrant cell cycle control. Molecular analyses have identified that the CDK4/6-Rb-E2F axis is dysregulated in about 80% of GBMs. Single-agent CDK4/6 inhibitors have failed to provide durable responses in GBM, suggesting a need to combine them with other agents. We investigate the efficacy of the combination of CDK4/6 inhibition and mTOR inhibition against GBM. EXPERIMENTAL DESIGN: Preclinical in vitro and in vivo assays using primary GBM cell lines were performed...
August 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28813947/exploiting-kinematic-constraints-to-compensate-magnetic-disturbances-when-calculating-joint-angles-of-approximate-hinge-joints-from-orientation-estimates-of-inertial-sensors
#14
Daniel Laidig, Thomas Schauer, Thomas Seel
Inertial Measurement Units (IMUs) have become a widely used tool for rehabilitation and other application domains in which human motion is analyzed using an ambulatory or wearable setup. Since the magnetic field is inhomogeneous in indoor environments and in the proximity of ferromagnetic material, standard orientation estimation and joint angle calculation algorithms often lead to inaccurate or even completely wrong results. One approach to circumvent this is to exploit the kinematic constraint that is induced by mechanical hinge joints and also by approximate hinge joints such as the knee joint and the finger (interphalangeal) joints of the human body...
July 2017: IEEE ... International Conference on Rehabilitation Robotics: [proceedings]
https://www.readbyqxmd.com/read/28813880/series-elastic-actuation-of-an-elbow-rehabilitation-exoskeleton-with-axis-misalignment-adaptation
#15
Kuan-Yi Wu, Yin-Yu Su, Ying-Lung Yu, Kuei-You Lin, Chao-Chieh Lan
Powered exoskeletons can facilitate rehabilitation of patients with upper limb disabilities. Designs using rotary motors usually result in bulky exoskeletons to reduce the problem of moving inertia. This paper presents a new linearly actuated elbow exoskeleton that consists of a slider crank mechanism and a linear motor. The linear motor is placed beside the upper arm and closer to shoulder joint. Thus better inertia properties can be achieved while lightweight and compactness are maintained. A passive joint is introduced to compensate for the exoskeleton-elbow misalignment and intersubject size variation...
July 2017: IEEE ... International Conference on Rehabilitation Robotics: [proceedings]
https://www.readbyqxmd.com/read/28813705/the-lncrna-tug1-ezh2-axis-promotes-pancreatic-cancer-cell-proliferation-migration-and-emt-phenotype-formation-through-sponging-mir-382
#16
Liang Zhao, Hongwei Sun, Hongru Kong, Zongjing Chen, Bicheng Chen, Mengtao Zhou
BACKGROUND/AIMS: Pancreatic carcinoma (PC) is the one of the most common and malignant cancers worldwide. LncRNA taurine upregulated gene 1 (TUG1) was initially identified as a transcript upregulated by taurine, and the abnormal expression of TUG1 has been reported in many cancers. However, the biological role and molecular mechanism of TUG1 in PC still needs further investigation. METHODS: Quantitative real-time PCR (qRT-PCR) was performed to measure the expression of TUG1 in PC cell lines and tissues...
August 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28813465/long-term-persistent-infection-of-hpv-16-e6-up-regulate-sp1-and-htert-by-inhibiting-lkb1-in-lung-cancer-cells
#17
Jing-Hua Yang, Xiao-Yan Li, Xin Wang, Wei-Jian Hou, Xue-Shan Qiu, En-Hua Wang, Guang-Ping Wu
HPV 16 E6 upregulates hTERT expression in lung cancer cells. However, the underlying molecular mechanism is unclear. In this paper, E6, LKB1, SP1, and hTERT mRNA expression levels were detected in brushing cells of patients with lung cancer (n = 106) and with benign lung disease (n = 68) by qRT-PCR. The mRNA expression levels of E6, SP1, and hTERT were significantly increased in the malignant group compared with the benign group (P < 0.01). Conversely, the mRNA expression level of LKB1 was significantly decreased in the malignant group (P < 0...
2017: PloS One
https://www.readbyqxmd.com/read/28812343/xanthohumol-suppresses-mylip-idol-gene-expression-and-modulates-ldlr-abundance-and-activity-in-hepg2-cells
#18
Shih-Fen Chen, Pei-Yi Chen, Hao-Jen Hsu, Ming-Jiuan Wu, Jui-Hung Yen
Xanthohumol, a prenylated flavonoid found in hops (Humulus lupulus L.), exhibits multiple biological activities such as anti-atherosclerosis and hypolipidemic activities. In this study, we aim to investigate the hypocholesterolemic effects and molecular mechanisms of xanthohumol in hepatic cells. We found that xanthohumol (10 and 20 μM) increased the amount of cell-surface low-density lipoprotein receptor (LDLR) from 100.0 ± 2.1% to 115.0±1.3% and 135.2±2.7%, and enhanced the LDL uptake activity from 100...
August 16, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28811739/a-fem-experimental-approach-for-the-development-of-a-conceptual-linear-actuator-based-on-tendril-s-free-coiling
#19
Luca Cortese, Selena Milanovic, Renato Vidoni
Within the vastness of the plant species, certain living systems show tendril structures whose motion is of particular interest for biomimetic engineers. Tendrils sense and coil around suitable grips, and by shortening in length, they erect the remaining plant body. To achieve contraction, tendrils rotate along their main axis and shift from a linear to a double-spring geometry. This phenomenon is denoted as the free-coiling phase. In this work, with the aim of understanding the fundamentals of the mechanics behind the free coiling, a reverse-engineering approach based on the finite element method was firstly applied...
2017: Applied Bionics and Biomechanics
https://www.readbyqxmd.com/read/28811467/the-mtorc1-4e-bp-eif4e-axis-controls-de-novo-bcl6-protein-synthesis-in-t-cells-and-systemic-autoimmunity
#20
Woelsung Yi, Sanjay Gupta, Edd Ricker, Michela Manni, Rolf Jessberger, Yurii Chinenov, Henrik Molina, Alessandra B Pernis
Post-transcriptional modifications can control protein abundance, but the extent to which these alterations contribute to the expression of T helper (TH) lineage-defining factors is unknown. Tight regulation of Bcl6 expression, an essential transcription factor for T follicular helper (TFH) cells, is critical as aberrant TFH cell expansion is associated with autoimmune diseases, such as systemic lupus erythematosus (SLE). Here we show that lack of the SLE risk variant Def6 results in deregulation of Bcl6 protein synthesis in T cells as a result of enhanced activation of the mTORC1-4E-BP-eIF4E axis, secondary to aberrant assembly of a raptor-p62-TRAF6 complex...
August 15, 2017: Nature Communications
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