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https://www.readbyqxmd.com/read/28429995/new-insights-into-the-role-of-dietary-spermine-on-inflammation-immune-function-and-related-signalling-molecules-in-the-thymus-and-spleen-of-piglets
#1
Wei Cao, Xianjian Wu, Gang Jia, Hua Zhao, Xiaoling Chen, Caimei Wu, Jiayong Tang, Jing Wang, Jingyi Cai, Guangmang Liu
This study aimed to determine the effects of dietary spermine supplementation on the inflammatory response and immune function of the thymus and spleen in piglets. Eighty suckling piglets were randomly assigned to receive adequate nutrients supplemented with spermine (0.4 mmol/kg body weight) or restricted nutrient intake supplemented with normal saline for 7 h or 3, 6 and 9 days in pairs. Regardless of treatment time, spermine supplementation decreased (p < 0.05, compared with the controls) the following: (1) tumour necrosis factor α (TNF-α), interleukin (IL)-1β, 2 and 6, and interferon (IFN)-γ levels in serum; (2) gene expression of cluster of differentiation 8 and integrin beta-2 in the thymus and spleen and the lymphocyte function-associated antigen 1 in the thymus; (3) mRNA levels of TNF-α, IL 1β, 2, 6, and 12, IFN-γ and inducible nitric oxide synthase in the thymus and spleen, as well as IL-8 in the spleen; and (4) eukaryotic IF4E-binding protein 1, Janus kinase 2, signal transducer and activator of transcription 3, and nuclear factor-kappa B P65 gene transcriptions in the thymus and spleen...
June 2017: Archives of Animal Nutrition
https://www.readbyqxmd.com/read/28427901/the-20kda-and-22kda-forms-of-human-growth-hormone-hgh-exhibit-different-intracellular-signalling-profiles-and-properties
#2
Liu Yao-Xia, Chen Jing-Yan, Tang Xia-Lian, Chen Ping, Zhang Min
Human Growth Hormone (hGH) includes two main variants. The first is 22 kilodalton GH (22K-GH), which is predominant in the blood circulation. The second most abundant variant is 20K-GH, which makes up 5-10% of the blood circulation. Both bind and activate the same receptor, called the human growth hormone receptor (GHR). However, the reason why 22K-GH and 20K-GH exhibit similar, but not identical physiological activities remains poorly understood. In this article, the intracellular signalling profiles between these two hormones were examined...
April 17, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28425456/salt-suppresses-ifn%C3%AE-inducible-chemokines-through-the-ifn%C3%AE-jak1-stat1-signaling-pathway-in-proximal-tubular-cells
#3
Yohei Arai, Daiei Takahashi, Kenichi Asano, Masato Tanaka, Mayumi Oda, Shigeru B H Ko, Minoru S H Ko, Shintaro Mandai, Naohiro Nomura, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
The mechanisms of immunoactivation by salt are now becoming clearer. However, those of immunosuppression remain unknown. Since clinical evidence indicates that salt protects proximal tubules from injury, we investigated mechanisms responsible for salt causing immunosuppression in proximal tubules. We focused on cytokine-related gene expression profiles in kidneys of mice fed a high salt diet using microarray analysis and found that both an interferon gamma (IFNγ) inducible chemokine, chemokine (C-X-C motif) ligand 9 (CXCL9), and receptor, CXCR3, were suppressed...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424277/janus-kinase-2-regulates-transcription-factor-eb-expression-and-autophagy-completion-in-glomerular-podocytes
#4
Tamadher A Alghamdi, Syamantak Majumder, Karina Thieme, Sri N Batchu, Kathryn E White, Youan Liu, Angela S Brijmohan, Bridgit B Bowskill, Suzanne L Advani, Minna Woo, Andrew Advani
The nonreceptor kinase Janus kinase 2 (JAK2) has garnered attention as a promising therapeutic target for the treatment of CKD. However, being ubiquitously expressed in the adult, JAK2 is also likely to be necessary for normal organ function. Here, we investigated the phenotypic effects of JAK2 deficiency. Mice in which JAK2 had been deleted from podocytes exhibited an elevation in urine albumin excretion that was accompanied by increased podocyte autophagosome fractional volume and p62 aggregation, which are indicative of impaired autophagy completion...
April 19, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28424262/magnesium-reduces-hepatic-lipid-accumulation-in-yellow-catfish-pelteobagrus-fulvidraco-and-modulates-lipogenesis-and-lipolysis-via-ppara-jak-stat-and-ampk-pathways-in-hepatocytes
#5
Chuan-Chuan Wei, Kun Wu, Yan Gao, Li-Han Zhang, Dan-Dan Li, Zhi Luo
Background: Magnesium influences hepatic lipid deposition in vertebrates, but the underlying mechanism is unknown.Objective: We used yellow catfish and their isolated hepatocytes to test the hypothesis that magnesium influences lipid deposition by modulating lipogenesis and lipolysis.Methods: Juvenile yellow catfish (mean ± SEM weight: 3.43 ± 0.02 g, 3 mo old, mixed sex) were fed a 0.14- (low), 0.87- (intermediate) or 2.11- (high) g Mg/kg diet for 56 d. Primary hepatocytes were incubated for 48 h in control or MgSO4-containing medium with or without 2-h pretreatment with an inhibitor (AG490, GW6471, or Compound C)...
April 19, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28423239/a-novel-jak-inhibitor-jte-052-reduces-skin-inflammation-and-ameliorates-chronic-dermatitis-in-rodent-models-comparison-with-conventional-therapeutic-agents
#6
Atsuo Tanimoto, Yuichi Shinozaki, Yasuo Yamamoto, Yoshiaki Katsuda, Eriko Riya, Kaoru Toyoda, Kochi Kakimoto, Yukari Kimoto, Wataru Amano, Noriko Konishi, Mikio Hayashi
Janus kinases (JAKs) are required for several inflammatory cytokine signaling pathways and are implicated in the pathogenesis of chronic dermatitis, including atopic dermatitis and psoriasis. JAK inhibitors are therefore promising therapeutic candidates for chronic dermatitis. In this study, we evaluated the effects of the novel JAK inhibitor JTE-052 on inflammatory responses associated with chronic dermatitis, and compared its profile with those of conventional therapeutic agents in rodent models of chronic dermatitis...
April 19, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28415825/recombinant-human-erythropoietin-stimulates-melanoma-tumor-growth-through-activation-of-initiation-factor-eif4e
#7
Annabelle Julius, Anjali Desai, Raymond L Yung
Recombinant human erythropoietin (EPO) is standard treatment for anemia in cancer patients. Recent clinical trials suggest that EPO may accelerate tumor progression and increase mortality. However, the evidence supporting a growth-promoting effect of EPO has remained controversial. Employing an in vivo model of B16 murine melanoma, we observed that administration of EPO to tumor bearing C57BL/6 mice resulted in pronounced acceleration of melanoma growth. Our in vitro studies demonstrate that B16 murine melanoma cells express EPOR, both at the protein and mRNA levels...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413047/a-homolog-of-teleostean-signal-transducer-and-activator-of-transcription-3-stat3-from-rock-bream-oplegnathus-fasciatus-structural-insights-transcriptional-modulation-and-subcellular-localization
#8
S D N K Bathige, William Shanthakumar Thulasitha, Navaneethaiyer Umasuthan, J D H E Jayasinghe, Qiang Wan, Bo-Hye Nam, Jehee Lee
Signal transducer and activator of transcription 3 (STAT3) is one of the crucial transcription factors in the Janus kinase (JAK)/STAT signaling pathway, and it was previously considered as acute phase response factor. A number of interleukins (ILs) such as IL-5, IL-6, IL-9, IL-10, IL-12, and IL-22 are known to be involved in activation of STAT3. In addition, various growth factors and pathogenic or oxidative stresses mediate the activation of a wide range of functions via STAT3. In this study, a STAT3 homolog was identified and functionally characterized from rock bream (RbSTAT3), Oplegnathus fasciatus...
April 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28411440/tweak-fn14-promotes-pro-inflammatory-cytokine-secretion-in-hepatic-stellate-cells-via-nf-%C3%AE%C2%BAb-stat3-pathways
#9
Aixiu Wang, Feng Zhang, Hui Xu, Mingcui Xu, Yu Cao, Chen Wang, Yuanyuan Xu, Min Su, Ming Zhang, Yuzheng Zhuge
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) have been associated with liver disease. Hepatic stellate cells (HSCs) play a critical role in the hepatic wound-healing response after liver injury, but there is little information available on the role of the TWEAK/Fn14 pathway in human HSCs. In this study, we explored the role of TWEAK/Fn14 in activated human HSCs. The LX-2 cells were treated with TWEAK, and the expression of pro-inflammatory cytokines was assayed by enzyme-linked immunosorbent assay (ELISA) and real-time PCR (RT-PCR)...
April 12, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28408900/the-thrombopoietin-receptor-structural-basis-of-traffic-and-activation-by-ligand-mutations-agonists-and-mutated-calreticulin
#10
REVIEW
Leila N Varghese, Jean-Philippe Defour, Christian Pecquet, Stefan N Constantinescu
A well-functioning hematopoietic system requires a certain robustness and flexibility to maintain appropriate quantities of functional mature blood cells, such as red blood cells and platelets. This review focuses on the cytokine receptor that plays a significant role in thrombopoiesis: the receptor for thrombopoietin (TPO-R; also known as MPL). Here, we survey the work to date to understand how this receptor functions at a molecular level throughout its lifecycle, from traffic to the cell surface, dimerization and binding cognate cytokine via its extracellular domain, through to its subsequent activation of associated Janus kinases and initiation of downstream signaling pathways, as well as the regulation of these processes...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28404878/activation-of-liver-x-receptor-delayed-the-retinal-degeneration-of-rd1-mice-through-modulation-of-the-immunological-function-of-glia
#11
Xiao He, Dayu Sun, Siyu Chen, Haiwei Xu
Retinal degeneration (RD), including retinitis pigmentosa (RP), is an inherited eye disease characterized by progressive degeneration of photoreceptors. Recently, immune cells, including microglia, Müller cells and astrocytes, in degenerative retina are demonstrated to play key roles in the development of RD and can be used as potential therapeutic targets. Liver X receptors (LXRs) are important immuno-inflammatory response transcription factors that have been reported to be a new potential therapeutic drug target for neurodegenerative diseases...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402164/hijaking-the-epigenome-in-leukemia-and-lymphoma
#12
Amanda C Drennan, Lixin Rui
The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is central to signaling by receptors of diverse cytokines, growth factors, and other related molecules. Many of these receptors transmit anti-apoptosis, proliferation, and differentiation signals that are critical for normal hematopoiesis and immune response. However, the JAK/STAT signaling pathway is deregulated in many hematologic malignancies, and as such is co-opted by malignant cells to promote their survival and proliferation...
April 12, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28399940/baseline-jak-phosphorylation-profile-of-peripheral-blood-leukocytes-studied-by-whole-blood-phosphospecific-flow-cytometry-is-associated-with-1-year-treatment-response-in-early-rheumatoid-arthritis
#13
Krista Kuuliala, Antti Kuuliala, Riitta Koivuniemi, Hannu Kautiainen, Heikki Repo, Marjatta Leirisalo-Repo
BACKGROUND: We found recently that baseline signal transducer and activator of transcription 3 phosphorylation in peripheral blood CD4(+) T cells of patients with early rheumatoid arthritis (RA) is associated with treatment response to synthetic disease-modifying antirheumatic drugs (DMARDs). This prompted us to study the baseline phosphorylation profiles of Janus kinases (JAKs) in blood leukocytes with respect to treatment response in early RA. METHODS: Thirty-five DMARD-naïve patients with early RA provided blood samples for whole blood flow cytometric determination of phosphorylation of JAKs in CD4(+) and CD8(+) T cells, CD19(+) B cells, and CD14(+) monocytes...
April 11, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28398275/natural-killer-t-cell-lymphomas-in-pediatric-and-adolescent-patients
#14
REVIEW
Amanda M Termuhlen
Natural killer/T-cell (NK/T-cell) lymphomas are rare in children and adolescents and consist predominantly of nasal-type extranodal NK/T-cell lymphomas. More than half of pediatric/adolescent patients with NK/T-cell lymphomas present with localized nasal/sinus involvement, but the disease may involve many organs. NK/T-cell lymphoma cells are cytotoxic and associated with necrosis and angioinvasion; they express CD56, CD2, cytoplasmic CD3 epsilon, and to a variable degree CD30. The cells contain Epstein-Barr virus (EBV)-encoded RNA...
March 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/28396102/efficacy-of-tofacitinib-for-the-treatment-of-nail-psoriasis-two-52-week-randomized-controlled-phase-3-studies-in-patients-with-moderate-to-severe-plaque-psoriasis
#15
Joseph F Merola, Boni Elewski, Svitlana Tatulych, Shuping Lan, Anna Tallman, Mandeep Kaur
BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor. Efficacy and safety of tofacitinib in patients with moderate-to-severe plaque psoriasis have been demonstrated. OBJECTIVE: We sought to assess the efficacy of tofacitinib for the treatment of nail psoriasis over a period of 52 weeks. METHODS: In 2 identical phase 3 studies (OPT Pivotal 1 and 2), patients were randomized 2:2:1 to receive tofacitinib 5 mg, tofacitinib 10 mg, or placebo, twice daily...
April 7, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28394822/janus-kinase-signal-transducer-and-activator-of-transcription-pathways-in-spondyloarthritis
#16
Smriti K Raychaudhuri, Siba P Raychaudhuri
PURPOSE OF REVIEW: Cytokines are major drivers of autoimmunity, and biologic agents targeting cytokines have revolutionized the treatment of immune-mediated diseases. Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway represents a group of several intracellular molecules with a key role in signal pathways activated by growth factors and cytokines. These kinase proteins are associated with the signaling process of multiple key cytokines, which regulates various T-cell subpopulations and their effector cytokines...
April 7, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28392989/sevoflurane-postconditioning-protects-the-myocardium-against-ischemia-reperfusion-injury-via-activation-of-the-jak2-stat3-pathway
#17
Jianjiang Wu, Jin Yu, Peng Xie, Yiliyaer Maimaitili, Jiang Wang, Long Yang, Haiping Ma, Xing Zhang, Yining Yang, Hong Zheng
BACKGROUND: Sevoflurane postconditioning (S-post) has similar cardioprotective effects as ischemic preconditioning. However, the underlying mechanism of S-post has not been fully elucidated. Janus kinase signaling transduction/transcription activator (JAK2-STAT3) plays an important role in cardioprotection. The purpose of this study was to determine whether the cardioprotective effects of S-post are associated with activation of the JAK2-STAT3 signal pathway. METHODS: An adult male Sprague-Dawley (SD) rat model of myocardial ischemia/reperfusion (I/R) injury was established using the Langendorff isolated heart perfusion apparatus...
2017: PeerJ
https://www.readbyqxmd.com/read/28391340/targeting-the-tyrosine-kinase-signalling-pathways-for-treatment-of-immune-mediated-glomerulonephritis-from-bench-to-bedside-and-beyond
#18
Terry King-Wing Ma, Stephen P McAdoo, Frederick Wai Keung Tam
Glomerulonephritis (GN) affects patients of all ages and is an important cause of morbidity and mortality. Non-selective immunosuppressive drugs have been used in immune-mediated GN but often result in systemic side effects and occasionally fatal infective complications. There is increasing evidence from both preclinical and clinical studies that abnormal activation of receptor and non-receptor tyrosine kinase signalling pathways are implicated in the pathogenesis of immune-mediated GN. Activation of spleen tyrosine kinase (SYK), Bruton's tyrosine kinase (BTK), platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR) and discoidin domain receptor 1 (DDR1) have been demonstrated in anti-GBM disease...
January 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28390737/treatment-of-vitiligo-with-the-topical-janus-kinase-inhibitor-ruxolitinib
#19
Brooke Rothstein, Deep Joshipura, Ami Saraiya, Rana Abdat, Huda Ashkar, Yana Turkowski, Vaneeta Sheth, Victor Huang, Shiu Chung Au, Courtney Kachuk, Nicole Dumont, Alice B Gottlieb, David Rosmarin
BACKGROUND: Existing therapies for vitiligo are limited in efficacy and can be associated with undesirable side effects. Topical Janus kinase inhibitors may offer a new therapeutic option for vitiligo. OBJECTIVE: We sought to assess the role of topical ruxolitinib 1.5% cream, a Janus kinase inhibitor, in vitiligo treatment. METHODS: This 20-week, open-label, proof-of-concept trial of twice-daily topical ruxolitinib 1.5% cream was conducted in 12 patients with a minimum of 1% affected body surface area of vitiligo...
April 5, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28387906/facilitation-of-liver-cancer-smcc7721-cell-aging-by-sirtuin-4-via-inhibiting-jak2-stat3-signal-pathway
#20
X-H Xia, C-J Xiao, H Shan
OBJECTIVE: Liver cancer severely threatens public health. Molecular targeted treatment is the further of cancer treatment. The functional role of Sir-related enzymes 4 (sirtuin 4) in treating liver cancer still requires further investigation. This study aimed to elucidate the effect of sirtuin 4 on aging of SMCC7721 liver cancer cell line, to underlying molecular mechanism and potential application in clinics. MATERIALS AND METHODS: Adriamycin-induced aging model was established on SMCC7721 liver cancer cell line...
March 2017: European Review for Medical and Pharmacological Sciences
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