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https://www.readbyqxmd.com/read/27913527/myelofibrosis-to-transplant-or-not-to-transplant
#1
Rebecca Devlin, Vikas Gupta
Hematopoietic cell transplantation (HCT) is the only curative therapeutic modality for myelofibrosis (MF) at present. The optimal timing of HCT is not known in the presence of wider availability of less risky nontransplant therapies such as JAK 1/2 inhibitors. Careful review of patient, disease, and transplant-related factors is required in the appropriate selection of HCT vs the best available nontransplant therapies. We highlight some of the relevant issues and positioning of HCT in light of evolving data on JAK 1/2 inhibitors...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27906090/muscle-specific-deletion-of-socs3-increases-the-early-inflammatory-response-but-does-not-affect-regeneration-after-myotoxic-injury
#2
Kristy Swiderski, Savant S Thakur, Timur Naim, Jennifer Trieu, Annabel Chee, David I Stapleton, René Koopman, Gordon S Lynch
BACKGROUND: Muscles of old animals are injured more easily and regenerate poorly, attributed in part to increased levels of circulating pro-inflammatory cytokines. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling cascade is a key mediator of inflammatory cytokine action, and signaling via this pathway is increased in muscles with aging. As a negative regulator of JAK/STAT signaling, a key mediator of myogenic proliferation and differentiation, altered expression of suppressor of cytokine signaling (SOCS3) is likely to have important consequences for muscle regeneration...
October 24, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27905994/the-role-of-il-10-in-mycobacterium-avium-subsp-paratuberculosis-infection
#3
REVIEW
Tariq Hussain, Syed Zahid Ali Shah, Deming Zhao, Srinand Sreevatsan, Xiangmei Zhou
Mycobacterium avium subsp. paratuberculosis (MAP) is an intracellular pathogen and is the causative agent of Johne's disease of domestic and wild ruminants. Johne's disease is characterized by chronic granulomatous enteritis leading to substantial economic losses to the livestock sector across the world. MAP persistently survives in phagocytic cells, most commonly in macrophages by disrupting its early antibacterial activity. MAP triggers several signaling pathways after attachment to pathogen recognition receptors (PRRs) of phagocytic cells...
December 1, 2016: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/27901106/the-role-of-pim1-pim2-kinases-in-tumors-of-the-male-reproductive-system
#4
Manuel Pedro Jiménez-García, Antonio Lucena-Cacace, María José Robles-Frías, Maja Narlik-Grassow, Carmen Blanco-Aparicio, Amancio Carnero
The PIM family of serine/threonine kinases has three highly conserved isoforms (PIM1, PIM2 and PIM3). PIM proteins are regulated through transcription and stability by JAK/STAT pathways and are overexpressed in hematological malignancies and solid tumors. The PIM kinases possess weak oncogenic abilities, but enhance other genes or chemical carcinogens to induce tumors. We generated conditional transgenic mice that overexpress PIM1 or PIM2 in male reproductive organs and analyzed their contribution to tumorigenesis...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895317/il-4-a-direct-target-of-mir-340-429-is-involved-in-radiation-induced-aggressive-tumor-behavior-in-human-carcinoma-cells
#5
Eun Sook Kim, Young Eun Choi, Su Jin Hwang, Young-Hoon Han, Myung-Jin Park, In Hwa Bae
Radiotherapy induces the production of cytokines, thereby increasing aggressive tumor behavior. This radiation effect results in the failure of radiotherapy and increases the mortality rate in patients. We found that interleukin-4 (IL-4) and IL-4Rα (IL-4 receptor) are highly expressed in various human cancer cells subsequent to radiation treatment. In addition, IL-4 is highly overexpressed in metastatic carcinoma tissues compared with infiltrating carcinoma tissues. High expression of IL-4 in patients with cancer is strongly correlated with poor survival...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27894402/hsp90-inhibitor-enhances-anti-proliferative-and-apoptotic-effects-of-celecoxib-on-ht-29-colorectal-cancer-cells-via-increasing-bax-bcl-2-ratio
#6
A Mohammadi, M M Yaghoobi, A GholamhoseynianNajar, B Kalantari-Khandani, H Sharifi, M Saravani
Due to the high prevalence and mortality rate of colorectal cancer (CRC), new treatment approaches like combination therapy seem to be necessary. The relationship between chronic inflammation and colorectal cancer development and progression has been shown to be important. Celecoxib, a selective COX-2 inhibitor, is the only non-steroidal anti-inflammatory drug (NSAID) that has been approved for cancer therapy and prevention. Because of cardiovascular side effects of COX-2 inhibitors, combination therapy may improve the therapeutic profile...
October 31, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/27892610/beside-to-bench-jak-inhibitor-ruxolitinib-inhibits-the-expression-of-cytokines-characteristic-of-cutaneous-lupus-erythematosus
#7
Anna Sophie Klaeschen, Dominik Wolf, Peter Brossart, Thomas Bieber, Joerg Wenzel
This study was stimulated by the clinical observation of a rapid response of a chilblain lupus patient to treatment with JAK1/2-kinase inhibitor ruxolitinib. We investigated the in-vivo expression of phospho-JAK2 in CLE skin samples as well as the immunomodulatory in-vitro effect of ruxolitinib in cultured immortalized keratinocytes and in a 3D human epidermis model (epiCS). Our results demonstrate that ruxolitinib significantly decreases the production of CLE-typical cytokines (CXCL10, CXCL9, MxA) and might be a promising drug for future clinical studies in patients with CLE and related autoimmune skin diseases...
November 28, 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27888751/remote-ischemic-preconditioning-attenuates-egr-1-expression-following-myocardial-ischemia-reperfusion-injury-through-activation-of-the-jak-stat-pathway
#8
H Mudaliar, B Rayner, M Billah, N Kapoor, W Lay, A Dona, R Bhindi
BACKGROUND/OBJECTIVES: Remote ischemic preconditioning (RIPC) protects the myocardium from ischemia/reperfusion (I/R) injury however the molecular pathways involved in cardioprotection are yet to be fully delineated. Transcription factor Early growth response-1 (Egr-1) is a key upstream activator in a variety of cardiovascular diseases. In this study, we elucidated the role of RIPC in modulating the regulation of Egr-1. METHODS: This study subjected rats to transient blockade of the left anterior descending (LAD) coronary artery with or without prior RIPC of the hind-limb muscle and thereafter excised the heart 24h following surgical intervention...
November 10, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27881658/porcine-reproductive-and-respiratory-syndrome-virus-antagonizes-jak-stat3-signaling-via-nsp5-by-inducing-stat3-degradation
#9
Liping Yang, Rong Wang, Zexu Ma, Yueqiang Xiao, Yuchen Nan, Yu Wang, Shaoli Lin, Yan-Jin Zhang
: Signal transducer and activator of transcription 3 (STAT3) is a pleiotropic signaling mediator of many cytokines including interleukin-6 (IL-6) and IL-10. STAT3 is known to play critical roles in cell growth, proliferation, differentiation, immunity and inflammatory responses. The objective of this study was to determine the effect of porcine reproductive and respiratory syndrome virus (PRRSV) infection on the STAT3 signaling since PRRSV induces a weak protective immune response in host animals...
November 23, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27879577/potential-involvement-of-the-il-6-jak-stat3-pathway-in-the-pathogenesis-of-intervertebral-disc-degeneration
#10
Satoshi Suzuki, Nobuyuki Fujita, Takeshi Fujii, Kota Watanabe, Mitsuru Yagi, Takashi Tsuji, Ken Ishii, Takeshi Miyamoto, Keisuke Horiuchi, Masaya Nakamura, Morio Matsumoto
STUDY DESIGN: Laboratory study. OBJECTIVE: To elucidate the potential involvement of the Interleukin-6 (IL-6) / Janus kinase (JAK) / Signal Transducers and Activator of Transcription (STAT3) pathway in the development of intervertebral disc (IVD) degeneration. SUMMARY OF BACKGROUND DATA: IL-6 plays a crucial role in IVD degeneration; however, the downstream intracellular signaling of IL-6 in the IVD is not fully understood. METHODS: The expression levels of IL-6 and Suppressors of Cytokine Signaling 3 (SOCS3), a target gene of the IL-6/JAK/STAT3 pathway, were evaluated in rat and human degenerated IVD samples...
November 22, 2016: Spine
https://www.readbyqxmd.com/read/27872730/diagnosis-of-del-5q-mds-14-years-after-jak-2-positive-pv-appearance-complete-remission-of-both-diseases-with-lenalidomide-monotherapy
#11
Antonella Vaccarino, Irene Dogliotti, Fabio Marletto, Andrea Demarchi, Mario Bazzan
This is the report of the clinical case of a patient who presents the association of a JAK-2 positive chronic myeloproliferative neoplasia to a subsequent 5q- myelodysplastic syndrome, developed after about 14 years from the first diagnosis. Patient's symptoms had rapidly worsened, and she became transfusion-dependent. Therapy with low-dose Lenalidomide quickly reduced the splenomegaly and completely brought white cells counts, haemoglobin, and platelets back to normal. After more than one year from the start, blood cell count is still normal...
2016: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/27860076/incoming-human-papillomavirus-16-genome-is-lost-in-pml-protein-deficient-hacat-keratinocytes
#12
Malgorzata Bienkowska-Haba, Wioleta Luszczek, Timothy R Keiffer, Lucile G M Guion, Stephen DiGiuseppe, Rona S Scott, Martin Sapp
Human papillomaviruses (HPVs) target PML nuclear bodies (NBs) during infectious entry and PML protein is important for efficient transcription of incoming viral genome. However, the transcriptional down regulation was shown to be promoter-independent in that heterologous promoters delivered by papillomavirus particles were also affected. To further investigate the role of PML protein in HPV entry, we used shRNA to knockdown PML protein in HaCaT keratinocytes. Confirming previous findings, PML knockdown in HaCaT cells reduced HPV16 transcript levels significantly following infectious entry without impairing binding and trafficking...
November 17, 2016: Cellular Microbiology
https://www.readbyqxmd.com/read/27856937/allylpyrocatechol-attenuates-collagen-induced-arthritis-via-attenuation-of-oxidative-stress-secondary-to-modulation-of-the-mapk-jak-stat-and-nrf2-ho-1-pathways
#13
Soumita De, Alak Manna, Sunanda Kundu, Sritama De Sarkar, Uttara Chatterjee, Tuhinadri Sen, Subrata Chattopadhyay, Mitali Chatterjee
Rheumatoid arthritis (RA), an inflammatory autoimmune disorder is characterized by synovial hyperplasia and bony destruction. The pathogenesis of RA includes redox dysregulation, concomitant with increased levels of pro-inflammatory mediators. As the ability of Allylpyrocatechol (APC), a phytoconstituent of Piper betle leaves to alleviate oxidative stress has been demonstrated in patients with RA, its anti-arthritic activity was evaluated in an animal model of arthritis, along with establishment of the underlying mechanism(s) of action...
November 17, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27855377/inhibition-of-stat-pathway-impairs-anti-hepatitis-c-virus-effect-of-interferon-alpha
#14
Lan-Juan Zhao, Sheng-Fei He, Yuan Liu, Ping Zhao, Zhong-Qi Bian, Zhong-Tian Qi
BACKGROUND/AIMS: Signal transducer and activator of transcription (STAT) pathway plays an important role in antiviral efficacy of interferon alpha (IFN-α). IFN-α is the main therapeutic against hepatitis C virus (HCV) infection. We explored effects of IFN-α on HCV replication and antiviral gene expression by targeting STAT. METHODS: In response to IFN-α, STAT status, HCV replication, and antiviral gene expression were analyzed in human hepatoma Huh7.5.1 cells before and after cell culture-derived HCV infection...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27847245/celastrol-inhibits-dengue-virus-replication-via-up-regulating-type-i-interferon-and-downstream-interferon-stimulated-responses
#15
Jung-Sheng Yu, Chin-Kai Tseng, Chun-Kuang Lin, Yao-Chin Hsu, Yu-Hsuan Wu, Ching-Liang Hsieh, Jin-Ching Lee
ETHNOPHARMACOLOGICAL RELEVANCE AND AIM OF THE STUDY: Tripterygium wilfordii (lei gong teng; Thunder of God Vine), a member of the Celastraceae family, is a medicinal plant used to treat a range of illnesses. Celastrol is a quinone methide triterpene and the most abundant bioactive constituent isolated from the root extracts of T. wilfordii. Previous studies have shown that celastrol exhibits antiviral activity against HIV and SARS-CoV. To date, no investigations of the anti-DENV activity of celastrol have been reported...
November 12, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27844252/effect-of-puerarin-on-transcriptome-of-astrocyte-during-oxygen-glucose-deprivation-reoxygenation-injury
#16
Shuyong Wei, Jie Tong, Qiang Xue, Yang Liu, Xiaoyu Xu
Stroke is a serious disease with complex pathomechanism and limited therapeutic effect in clinic. Our previous research has found obvious therapeutic effect of Puerarin (Pur) on stroke injury of rat. The aim of this study is to investigate the transcriptome changes of oxygen-glucose deprivation/reoxygenation (OGD/R)-injured astrocytes before and after the intervention of Pur. Cells activity and apoptosis detection indicated that the activity of OGD/R-injured astrocytes was improved, and the apoptosis was ameliorated by Pur...
November 14, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27827939/effects-of-di-2-ethylhexyl-phthalate-on-lipid-metabolism-by-the-jak-stat-pathway-in-rats
#17
Yiyang Jia, Te Liu, Liting Zhou, Jian Zhu, Juan Wu, Di Sun, Jin Xu, Qi Wang, Huaiji Chen, Feng Xu, Yuezhu Zhang, Tianrong Zhang, Hongbo Liu, Lin Ye
The most widely used plasticizer, di-(2-ethylhexyl) phthalate (DEHP), is known to affect lipid metabolism and adipogenesis. We studied the effects of dietary DEHP exposure on metabolism in rats as well as the role of the JAK/STAT pathway in this process. Eighty rats were exposed to DEHP (0, 5, 50 and 500 mg/kg/d) through dietary intake for 4 weeks. We then collected blood samples, liver, and adipose tissues to detect modifications in the levels of serum lipids, leptin, adiponectin and insulin. JAK3, STAT5a and PPARγ expression were detected at both the gene and protein levels...
November 4, 2016: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/27826299/leishmania-donovani-induced-increase-in-macrophage-bcl-2-favors-parasite-survival
#18
Rajeev Kumar Pandey, Sanjana Mehrotra, Smriti Sharma, Ramachandra Subbaraya Gudde, Shyam Sundar, Chandrima Shaha
Members of the Bcl-2 family are major regulators of apoptosis in mammalian cells, and hence infection-induced perturbations in their expression could result into elimination of the parasites or creation of a niche favoring survival. In this investigation, we uncover a novel role of host Bcl-2 in sustaining Leishmania donovani infection. A rapid twofold increase in Bcl-2 expression occurred in response to parasite challenge. Downregulation of post infection Bcl-2 increase using siRNA or functional inhibition using Bcl-2 small molecule inhibitors interfered with intracellular parasite survival confirming the necessity of elevated Bcl-2 during infection...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27825048/the-effect-of-the-tlr9-ligand-cpg-oligodeoxynucleotide-on-the-protective-immune-response-to-radiation-induced-lung-fibrosis-in-mice
#19
Jing Chen, Xiaoli Tian, Zijie Mei, Yacheng Wang, Ye Yao, Shimin Zhang, Xin Li, Hui Wang, Junhong Zhang, Conghua Xie
CpG-oligodeoxynucleotide (CpG-ODN) is not only reported to protect against airway hyper responsiveness but is also known as a potent vaccine adjuvant for anti-tumor therapy. Little is known about the effect of CpG-ODN in mice with radiation-induced lung fibrosis (RILF), a common late stage form of tissue damage that occurs after thorax radiotherapy (RT). Here, we evaluated the immunomodulatory effects of CpG-ODN on the development of RILF. Mice were divided into four groups: (1) RT, single dose of 12Gy to the whole thorax; (2) CpG, only intraperitoneal injection of CpG-ODN for total 5 weeks; (3) RT+CpG, irradiation plus CpG-ODN treatment before and after irradiation for total 5 weeks; and (4) control (CTL): No RT or CpG-ODN treatment...
November 5, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27824951/epigenetic-signatures-at-aqp3-and-socs3-engage-in-low-grade-inflammation-across-different-tissues
#20
Carola Marzi, Lesca M Holdt, Giovanni Fiorito, Pei-Chien Tsai, Anja Kretschmer, Simone Wahl, Simonetta Guarrera, Daniel Teupser, Tim D Spector, Licia Iacoviello, Carlotta Sacerdote, Konstantin Strauch, Serene Lee, Wolfgang E Thasler, Annette Peters, Barbara Thorand, Petra Wolf, Holger Prokisch, Rosario Tumino, Christian Gieger, Vittorio Krogh, Salvatore Panico, Jordana T Bell, Giuseppe Matullo, Melanie Waldenberger, Harald Grallert, Wolfgang Koenig
BACKGROUND: Elevated levels of C-reactive protein (CRP, determined by a high-sensitivity assay) indicate low-grade inflammation which is implicated in many age-related disorders. Epigenetic studies on CRP might discover molecular mechanisms underlying CRP regulation. We aimed to identify DNA methylation sites related to CRP concentrations in cells and tissues regulating low-grade inflammation. RESULTS: Genome-wide DNA methylation was measured in peripheral blood in 1,741 participants of the KORA F4 study using Illumina HumanMethylation450 BeadChip arrays...
2016: PloS One
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