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https://www.readbyqxmd.com/read/29670085/a-trib2-p38-axis-controls-myeloid-leukaemia-cell-cycle-and-stress-response-signalling
#1
Mara Salomé, Aoife Magee, Krisha Yalla, Shahzya Chaudhury, Evgenia Sarrou, Ruaidhrí J Carmody, Karen Keeshan
Trib2 pseudokinase is involved in the etiology of a number of cancers including leukaemia, melanoma, ovarian, lung and liver cancer. Both high and low Trib2 expression levels correlate with different types of cancer. Elevated Trib2 expression has oncogenic properties in both leukaemia and lung cancer dependent on interactions with proteasome machinery proteins and degradation of transcription factors. Here, we demonstrated that Trib2 deficiency conferred a growth and survival advantage both at steady state and in stress conditions in leukaemia cells...
April 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29667660/a-new-functional-membrane-protein-microarray-based-on-tethered-phospholipid-bilayers
#2
Meriem Chadli, Ofelia Maniti, Christophe Marquette, Bruno Tillier, Sandra Cortès, Agnès Girard-Egrot
A new prototype of a membrane protein biochip is presented in this article. This biochip was created by the combination of novel technologies of peptide-tethered bilayer lipid membrane (pep-tBLM) formation and solid support micropatterning. Pep-tBLMs integrating a membrane protein were obtained in the form of microarrays on a gold chip. The formation of the microspots was visualized in real-time by surface plasmon resonance imaging (SPRi) and the functionality of a GPCR (CXCR4), reinserted locally into microwells, was assessed by ligand binding studies...
April 18, 2018: Analyst
https://www.readbyqxmd.com/read/29661835/sexual-differentiation-of-contextual-fear-responses
#3
Lorianna Colon, Natalie Odynocki, Anthony Santarelli, Andrew M Poulos
Development and sex differentiation impart an organizational influence on the neuroanatomy and behavior of mammalian species. Prior studies suggest that brain regions associated with fear motivated defensive behavior undergo a protracted and sex-dependent development. Outside of adult animals, evidence for developmental sex differences in conditioned fear is sparse. Here, we examined in male and female Long-Evans rats how developmental age and sex affect the long-term retention and generalization of Pavlovian fear responses...
May 2018: Learning & Memory
https://www.readbyqxmd.com/read/29643043/-shaoyangzhugu-formula-regulates-p19-arf-p53-p21-cip1-signaling-pathway-to-ameliorate-cartilage-degeneration-in-aged-cynomolgus-monkeys-with-knee-osteoarthritis
#4
Xin Zhou, Lei Zhang, Shi-Jie Fu, Gang Liu, Xiao-Guang Guo, Gang Yi, Yang Liu, Guo-You Wang
OBJECTIVE: To study the effect of Shaoyangzhugu (SYZG) Formula (a formula consisting of 9 traditional Chinese drugs) in delaying the degeneration of articular cartilage and the role p19Arf -p53-p21Cip1 signaling pathway in mediating this effect. METHOD: Thirteen aged cynomolgus monkeys with degenerative knee joints were selected based on X-ray findings, and one of them was randomly selected for pathological observation. The other monkeys were randomized equally into SYZG Formula group (treated with SYZG decoction), ammonia moxime group and saline group...
March 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/29569324/distinct-gene-expression-pathways-in-islets-from-individuals-with-short-and-long-duration-type-1-diabetes
#5
Teresa L Mastracci, Jean-Valery Turatsinze, Benita K Book, Ivan A Restrepo, Michael J Pugia, Eric A Wiebke, Mark D Pescovitz, Decio L Eizirik, Raghavendra G Mirmira
AIMS: Our current understanding of the pathogenesis of type 1 diabetes (T1D) arose in large part from studies using the non-obese diabetic (NOD) mouse model. In the present study, we chose a human-focused method to investigate T1D disease mechanisms and potential targets for therapeutic intervention by directly analyzing human donor pancreatic islets from individuals with T1D. MATERIALS AND METHODS: We obtained islets from a young individual with T1D for three years and an older individual with T1D for 27 years and performed unbiased functional genomic analysis by high-depth RNA sequencing; the T1D islets were compared with islets isolated from three non-diabetic donors...
March 22, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29559852/-bmi1-deficient-mice-exhibit-male-infertility
#6
Xiuliang Dai, Qian Zhang, Zhenzhen Yu, Weiwei Sun, Rong Wang, Dengshun Miao
Previous studies have demonstrated that the polycomb repressor Bmi1 is universally expressed in all types of testicular cells and might regulate the spermatogonia proliferation, however, it is unclear whether Bmi1 plays a critical role in maintaining normal male fertility in vivo. To answer this question, we first confirmed that Bmi1 is universally expressed in all types of testicular cells and found that the gene relative expression levels of Bmi1 in testis were the highest relative to other organs. Then we investigated the role of Bmi1 in maintaining normal male fertility using Bmi1 knockout male mouse model...
2018: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29557200/new-therapies-versus-first-generation-biologic-drugs-in-psoriasis-a-review-of-adverse-events-and-their-management
#7
J M Carrascosa, E Del-Alcazar
Biologic drugs have revolutionized the treatment of moderate to severe psoriasis in recent years because of their high efficacy and low risk of toxicity. However, even within the group of biologic therapies, there are differences related to the different mechanisms of action. Areas covered: We review the main adverse events associated with the biologic agents currently available for the treatment of psoriasis and the new inhibitors targeting the p19 subunit of interleukin (IL) 23 and the IL-17A receptor. This review covers injection site reactions, infections, cardiovascular events, demyelinating disorders, tumours, class effects secondary adverse events, immunogenicity, safety in pregnancy and vaccines efficacy...
March 20, 2018: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/29556726/new-treatment-options-for-inflammatory-bowel-diseases
#8
REVIEW
Bram Verstockt, Marc Ferrante, Séverine Vermeire, Gert Van Assche
The advent of anti-TNF agents has dramatically changed the treatment algorithms for IBD in the last 15 years, but primarily and more importantly secondary loss of response is often observed. Fortunately , new treatment options have been actively explored and some have already entered our clinical practice. In the class of anti-cytokine agents, the anti-IL12/IL23 monoclonal antibodies (mAbs) have entered clinical practice with the anti-p40 mAb ustekinumab in Crohn's disease (CD). Also, more selective anti-IL23 agents (anti-p19) have shown efficacy and are being further developed, in contrast to agents inhibiting IL-17 downstream which have failed in clinical trials despite their clear efficacy in psoriasis (Verstockt et al...
March 19, 2018: Journal of Gastroenterology
https://www.readbyqxmd.com/read/29541669/dataset-on-characterization-of-recombinant-interleukin-23%C3%AE-il-12p40-and-il-23-complex-protein-which-activates-jak-stat-signaling-pathway-in-chicken-cell-lines-using-immunocytochemical-staining
#9
Anh Duc Truong, Cong Thanh Hoang, Yeojin Hong, Janggeun Lee, Kyungbaek Lee, Hyun S Lillehoj, Yeong Ho Hong
The data herein is related to the research article entitled "Functional analyses of the interaction of chicken interleukin 23 subunit p19 with IL-12 subunit p40 to form the IL-23 complex" [1] where we demonstrated that the chicken interleukin (IL)-23α, IL-12p40, and IL-23 complex regulates Th1, Th17, and Treg cytokine production through heterodimer receptors as well as a homodimer receptor consisting of IL-12Rβ1 and IL-23R, and activates the JAK/STAT signaling pathways. Here, we evaluated the effects of the recombinant chicken IL-23α, IL-12p40, and IL-23 complex protein on cell proliferation and nitric oxide (NO) production in chicken macrophage (HD11) and CU91 T cell lines...
February 2018: Data in Brief
https://www.readbyqxmd.com/read/29531090/phosphorylation-induced-unfolding-regulates-p19-ink4d-during-the-human-cell-cycle
#10
Amit Kumar, Mohanraj Gopalswamy, Annika Wolf, David J Brockwell, Mechthild Hatzfeld, Jochen Balbach
Cell cycle progression is tightly regulated by cyclin-dependent kinases (CDKs). The ankyrin-repeat protein p19INK4d functions as a key regulator of G1/S transition; however, its molecular mode of action is unknown. Here, we combine cell and structural biology methods to unravel the mechanism by which p19INK4d controls cell cycle progression. We delineate how the stepwise phosphorylation of p19INK4d Ser66 and Ser76 by cell cycle-independent (p38) and -dependent protein kinases (CDK1), respectively, leads to local unfolding of the three N-terminal ankyrin repeats of p19INK4d This dissociates the CDK6-p19INK4d inhibitory complex and, thereby, activates CDK6...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29512726/ginsenoside-rg1-ameliorates-testicular-senescence-changes-in-d%C3%A2-gal%C3%A2-induced-aging-mice-via-anti%C3%A2-inflammatory-and-antioxidative-mechanisms
#11
Zi-Ling Wang, Lin-Bo Chen, Zhu Qiu, Xiong-Bin Chen, Ying Liu, Jing Li, Lu Wang, Ya-Ping Wang
With the growing population, aging, extended lifespans and anti-aging have become popular areas of research in the life and social sciences. With increasing age, the structure and function of the testes, the spermatogenetic and androgen‑producing organ in the male reproductive system, gradually declines. Ginsenoside Rg1 is an extract of Panax ginseng in traditional Chinese medicine. The extract facilitates anti‑aging through its anti‑inflammatory and antioxidant properties. However, it has not been reported whether ginsenoside Rg1 delays testicular aging...
March 1, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29510001/pharmacokinetics-of-tildrakizumab-mk-3222-an-anti-il-23-monoclonal-antibody-following-intravenous-or-subcutaneous-administration-in-healthy-subjects
#12
Sauzanne Khalilieh, Peter Hodsman, Christine Xu, Anjela Tzontcheva, Shirley Glasgow, Diana Montgomery
Tildrakizumab, a high-affinity humanized IgG1k antibody that selectively binds interleukin (IL)-23 p19 subunit of cytokine IL-23 and neutralizes its function, is under investigation for treatment of moderate-to-severe chronic plaque psoriasis. The objective of this analysis was to assess the pharmacokinetics (PK), bioavailability and safety/tolerability of single ascending doses of tildrakizumab following intravenous (IV) and subcutaneous (SC) dosing in healthy subjects. P05661 was a phase 1, single dose, randomized, placebo-controlled study of tildrakizumab IV doses of 0...
March 6, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29507063/spread-of-plasmid-encoded-ndm-1-and-ges-5-carbapenemases-among-extensively-drug-resistant-and-pandrug-resistant-clinical-enterobacteriaceae-in-durban-south-africa
#13
Torunn Pedersen, John Osei Sekyere, Usha Govinden, Krishnee Moodley, Audun Sivertsen, Ørjan Samuelsen, Sabiha Yusuf Essack, Arnfinn Sundsfjord
Whole-genome sequence analyses revealed the presence of bla NDM-1 ( n =31), bla GES-5 ( n =8), bla OXA-232 ( n =1), or bla NDM-5 ( n =1) in extensively drug-resistant and pandrug-resistant Enterobacteriaceae isolated from in-patients in 10 private hospitals (2012-2013) in Durban, South Africa. Two novel NDM-1 encoding plasmids from Klebsiella pneumoniae were closed by PacBio sequencing. In p19-10_01 (IncFIB(K), 223.434 bp) bla NDM-1 was part of a Tn 1548 -like structure (16.276 bp) delineated by IS 26 The multireplicon plasmid p18-43_01 (IncR_1/IncFIB(pB171)/IncFII(Yp); 212...
March 5, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29504607/the-long-non-coding-rna-uc-4-influences-cell-differentiation-through-the-tgf-beta-signaling-pathway
#14
Zijie Cheng, Qijun Zhang, Anwen Yin, Mengwen Feng, Hua Li, Hailang Liu, Yun Li, Lingmei Qian
In a previous study, we screened thousands of long non-coding RNAs (lncRNAs) to assess their potential relationship with congenital heart disease (CHD). In this study, uc.4 attracted our attention because of its high level of evolutionary conservation and its antisense orientation to the CASZ1 gene, which is vital for heart development. We explored the function of uc.4 in cells and in zebrafish, and describe a potential mechanism of action. P19 cells were used to investigate the function of uc.4. We studied the effect of uc...
February 16, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29501420/c-type-natriuretic-peptide-functions-as-an-innate-neuroprotectant-in-neonatal-hypoxic-ischemic-brain-injury-in-mouse-via-natriuretic-peptide-receptor-2
#15
Qingyi Ma, Lubo Zhang
Neonatal hypoxia-ischemia (HI) is the most common cause of brain injury in neonates, which leads to high neonatal mortality and severe neurological morbidity in later life (Vannucci, 2000; Volpe, 2001). Yet the molecular mechanisms of neuronal death and brain damage induced by neonatal HI remain largely elusive. Herein, using both in vivo and in vitro models, we determine an endogenous neuroprotectant role of c-type natriuretic peptide (CNP) in preserving neuronal survival after HI brain injury in mouse pups...
March 5, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29499194/hdac8-regulates-neural-differentiation-through-embryoid-body-formation-in-p19-cells
#16
Syouichi Katayama, Atsushi Morii, Juliet O Makanga, Takayoshi Suzuki, Naoki Miyata, Tetsuya Inazu
Histone acetylation and deacetylation correlate with diverse biological phenomena through gene transcription. Histone deacetylases (HDACs) regulate deacetylation of histones and other proteins. However, as a member of the HDAC family, HDAC8 function during neurodevelopment is currently unknown. Therefore, we investigated HDAC8 function during neurodevelopment by examining embryoid body (EB) formation in P19 cells. HDAC8-selective inhibitor (NCC-149) (HDAC8i)-treated cells showed smaller EBs than non-treated cells, as well as reduced expression levels of the neuronal marker, NeuN...
February 27, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29491403/electrochemical-sensor-for-detection-of-mirs-based-on-the-differential-effect-of-competitive-structures-in-the-p19-function
#17
E Ghazizadeh, R K Oskuee, M R Jaafari, S Hosseinkhani
The present study aim to design a liposomal electrochemical sensor using 1, 2-dioleoyl-3-trimethylammoniumpropane (DOTAP) and dioleoylphosphatidylethanolamine(DOPE), chimeric probes and p19, it has been considered as a caliper molecule as well. Also the competitor structural hybrid (RNA) was used to detect three types of miRs in one screen printed electrode modified by gold nanoparticle (SCPE/GNP). In this purpose, the sensor signal stabilized when the cationic DOTAP-DOPE with hybrids of the chimeric probes (Stem, M-linear) sandwiched in order to detect 221-124a miRs...
February 28, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29486614/molecular-mechanism-of-amygdalin-action-in-vitro-review-of-the-latest-research
#18
Przemysław Liczbiński, Bożena Bukowska
Amygdalin, named as 'laetrile' and 'vitamin B-17' was initially supposed to be a safe drug for cancer treatment and was recognized by followers of natural medicine since it has been considered to be hydrolyzed only in cancer cells releasing toxic hydrogen cyanide (HCN), and thus destroying them. Unfortunately, current studies have shown that HCN is also released in normal cells, therefore it may not be safe for human organism. However, there have still been research works conducted on anti-cancer properties of this compound...
February 28, 2018: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/29484736/pharmacological-or-transcriptional-inhibition-of-both-hdac1-and-2-leads-to-cell-cycle-blockage-and-apoptosis-via-p21-waf1-cip1-and-p19-ink4d-upregulation-in-hepatocellular-carcinoma
#19
Hengyu Zhou, Ying Cai, Dina Liu, Menghui Li, Yu Sha, Wenlu Zhang, Kai Wang, Jianping Gong, Ni Tang, Ailong Huang, Jie Xia
OBJECTIVES: Histone deacetylases (HDACs) are commonly dysregulated in cancer and represent promising therapeutic targets. However, global HDAC inhibitors have shown limited efficacy in the treatment of solid tumours, including hepatocellular carcinoma (HCC). In this study, we investigated the therapeutic effect of selectively inhibiting HDAC1 and 2 in HCC. METHODS: HDAC1 inhibitor Tacedinaline (CI994), HDAC2 inhibitor Santacruzamate A (CAY10683), HDAC1/2 common inhibitor Romidepsin (FK228) and global HDAC inhibitor Vorinostat (SAHA) were used to treat HCC cells...
February 27, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/29482382/guselkumab-for-the-treatment-of-psoriasis
#20
Matteo Megna, Anna Balato, Annunziata Raimondo, Nicola Balato
Psoriasis is a chronic immune mediated disease in which the interplay of T cells and keratinocytes seems to play a key role. In this context, the interleukin (IL)-23/IL-17 axis is currently considered to be crucial in the pathogenesis of psoriasis and the selective inhibition of IL-23 may be viewed as an improvement of treatments blocking both IL-23 and IL-12, since its upstream actions. Areas covered: The authors performed a thorough and updated review on guselkumab, a fully human IgG1λ monoclonal antibody that blocks the p19 subunit of IL-23, analyzing efficacy and safety data from phase I, II and III trials...
April 2018: Expert Opinion on Biological Therapy
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