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https://www.readbyqxmd.com/read/28944901/effect-of-modified-xiaochaihu-decoction%C3%A2-containing-serum-on-hepg2-2-15-cells-via-the-jak2-stat3-signaling-pathway
#1
Shaofang Chen, Zhanglin Wang, Shichuan Wan, Hai Huang, Huiqing Liang
The present study aimed to investigate the possible mechanisms underlying the effect of modified Xiaochaihu decoction (mXCHD) in the treatment of chronic hepatitis B (CHB). Patients with CHB, in addition to liver stagnation and spleen deficiency syndrome were randomly assigned to receive either Chinese (mXCHD) or western (entecavir) treatment, with 30 cases in each group. Serum was collected following treatment with mXCHD or entecavir for 7 days. A healthy group of 30 individuals was also included. HepG2...
September 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28942146/leptin-positively-regulates-muc5ac-production-and-secretion-induced-by-interleukin-13-in-human-bronchial-epithelial-cells
#2
Wanming Hao, Jing Wang, Yu Zhang, Yunying Wang, Lixin Sun, Wei Han
Mucus hypersecretion and plugging of lower respiratory tract airways due to mucus plugs have long been recognized as the leading cause of the morbidity and mortality in asthma. MUC5AC protein is a major component of airway mucus. Here, we showed that interleukin (IL)-13 induced MUC5AC production and secretion, and leptin expression in the human bronchial epithelial cell line-16 (HBE16) cells in a concentration-dependent manner. Leptin knockdown suppressed MUC5AC production and secretion induced by IL-13. We further investigated the molecular mechanism by which leptin functioned, and found that leptin regulated IL-13-induced MUC5AC production and secretion via the JAK2-STAT3 pathway...
September 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28939023/vascular-protective-effects-of-aqueous-extracts-of-tribulus-terrestris-on-hypertensive-endothelial-injury
#3
Yue-Hua Jiang, Jin-Hao Guo, Sai Wu, Chuan-Hua Yang
Angiotensin II (Ang II) is involved in endothelium injury during the development of hypertension. Tribulus terrestris (TT) is used to treat hypertension, arteriosclerosis, and post-stroke syndrome in China. The present study aimed to determine the effects of aqueous TT extracts on endothelial injury in spontaneously hypertensive rats (SHRs) and its protective effects against Ang II-induced injury in human umbilical vein endothelial cells (HUVECs). SHRs were administered intragastrically with TT (17.2 or 8.6 g·kg(-1)·d(-1)) for 6 weeks, using valsartan (13...
August 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/28935989/fibrotic-progression-in-polycythemia-vera-is-associated-with-early-concomitant-driver-mutations-besides-jak2
#4
S Bartels, M Faisal, G Büsche, J Schlue, H Kreipe, U Lehmann
Leukemia accepted article preview online, 22 September 2017. doi:10.1038/leu.2017.298.
September 22, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28934680/a-phase-1-study-of-the-janus-kinase-2-jak2-v617f-inhibitor-gandotinib-ly2784544-in-patients-with-primary-myelofibrosis-polycythemia-vera-and-essential-thrombocythemia
#5
Srdan Verstovsek, Ruben A Mesa, Mohamed E Salama, Li Li, Celine Pitou, Fabio P Nunes, Gregory L Price, Jennifer L Giles, Deborah N D'Souza, Richard A Walgren, Josef T Prchal
Mutations in Janus kinase 2 (JAK2) are implicated in the pathogenesis of Philadelphia-chromosome negative myeloproliferative neoplasms, including primary myelofibrosis, polycythemia vera, and essential thrombocythemia. Gandotinib (LY2784544), a potent inhibitor of JAK2 activity, shows increased potency for the JAK2(V617F) mutation. The study had a standard 3+3 dose-escalation design to define the maximum-tolerated dose. Primary objectives were to determine safety, tolerability, and recommended oral daily dose of gandotinib for patients with JAK2(V617F)-positive myelofibrosis, essential thrombocythemia, or polycythemia vera...
August 31, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28931526/cellubrevin-vesicle-associated-membrane-protein-3-vamp-3-mediated-endocytosis-and-trafficking-regulate-platelet-functions
#6
Meenakshi Banerjee, Smita Joshi, Jinchao Zhang, Carole L Moncman, Shilpi Yadav, Beth A Bouchard, Brian Storrie, Sidney W Whiteheart
Endocytosis is key to fibrinogen (Fg) uptake, trafficking of integrins (αIIbβ3, αvβ3) and purinergic receptors (P2Y1, P2Y12), and thus for normal platelet function. However, the molecular machinery required and possible trafficking routes are still ill-defined. To further identify elements of the platelet endocytic machinery, we examined the role of a vesicle-residing, Soluble N-ethylmaleimide Factor Attachment Protein Receptor (v-SNARE) called Cellubrevin/Vesicle-Associated Membrane Protein-3 (VAMP-3) in platelet function...
September 20, 2017: Blood
https://www.readbyqxmd.com/read/28923882/mutational-profiling-of-acute-myeloid-leukemia-with-normal-cytogenetics-in-brazilian-patients-the-value-of-next-generation-sequencing-for-genomic-classification
#7
Thiago Rodrigo de Noronha, Miguel Mitne-Neto, Maria de Lourdes Chauffaille
Karyotype (KT) aberrations are important prognostic factors for acute myeloid leukemia (AML); however, around 50% of cases present normal results. Single nucleotide polymorphism array can detect chromosomal gains, losses or uniparental disomy that are invisible to KT, thus improving patients' risk assessment. However, when both tests are normal, important driver mutations can be detected by the use of next-generation sequencing (NGS). Fourteen adult patients with AML with normal cytogenetics were investigated by NGS for 19 AML-related genes...
September 18, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28923114/homocysteine-exaggerates-microglia-activation-and-neuroinflammation-through-microglia-localized-stat3-overactivation-following-ischemic-stroke
#8
Shuang Chen, Zhiping Dong, Man Cheng, Yaqian Zhao, Mengying Wang, Na Sai, Xuan Wang, Huan Liu, Guowei Huang, Xumei Zhang
BACKGROUND: Elevated plasma homocysteine (Hcy) levels have been indicated as a strong and modifiable risk factor of ischemic stroke; the previous studies have shown that exposure to Hcy activates cultured microglia. However, whether neurotoxicity of Hcy involves microglia activation following brain ischemia and the underlying mechanisms remains incompletely understood. METHODS: The cerebral damage was evaluated by staining with 2,3,5-triphenyltetrazolium chloride, hematoxylin-eosin, and Fluoro Jade B...
September 18, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28922406/loss-of-liver-specific-and-sexually-dimorphic-gene-expression-by-aryl-hydrocarbon-receptor-activation-in-c57bl-6-mice
#9
Rance Nault, Kelly A Fader, Jack R Harkema, Tim Zacharewski
The aryl hydrocarbon receptor (AhR) is a highly conserved transcription factor that mediates a broad spectrum of species-, strain-, sex-, age-, tissue-, and cell-specific responses elicited by structurally diverse ligands including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Dose-dependent effects on liver-specific and sexually dimorphic gene expression were examined in male and female mice gavaged with TCDD every 4 days for 28 or 92 days. RNA-seq data revealed the coordinated repression of 181 genes predominately expressed in the liver including albumin (3...
2017: PloS One
https://www.readbyqxmd.com/read/28919782/inhibitory-effects-of-a-selective-jak2-inhibitor-on-adrenocorticotropic-hormone-production-and-proliferation-of-corticotroph-tumor-att20-cells
#10
Yuko Asari, Kazunori Kageyama, Yuki Nakada, Mizuki Tasso, Shinobu Takayasu, Kanako Niioka, Noriko Ishigame, Makoto Daimon
PURPOSE: The primary cause of Cushing's disease is adrenocorticotropic hormone (ACTH)-producing pituitary adenomas. EGFR signaling induces POMC mRNA-transcript levels and ACTH secretion from corticotroph tumors. The Jak-STAT pathway is located downstream of EGFR signaling; therefore, a Jak2 inhibitor could be an effective therapy for EGFR-related tumors. In this study, we determined the effect of a potent and selective Jak2 inhibitor, SD1029, on ACTH production and proliferation in mouse AtT20 corticotroph tumor cells...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28913408/hepatocyte-specific-deletion-of-mouse-lamin-a-c-leads-to-male-selective-steatohepatitis
#11
Raymond Kwan, Graham F Brady, Maria Brzozowski, Sujith V Weerasinghe, Hope Martin, Min-Jung Park, Makayla J Brunt, Ram K Menon, Xin Tong, Lei Yin, Colin L Stewart, M Bishr Omary
BACKGROUND & AIMS: Lamins are nuclear intermediate filament proteins that comprise the major components of the nuclear lamina. Mutations in LMNA, which encodes lamins A/C, cause laminopathies, including lipodystrophy, cardiomyopathy, and premature aging syndromes. However, the role of lamins in the liver is unknown, and it is unclear whether laminopathy-associated liver disease is caused by primary hepatocyte defects or systemic alterations. METHODS: To address these questions, we generated mice carrying a hepatocyte-specific deletion of Lmna (knockout [KO] mice) and characterized the KO liver and primary hepatocyte phenotypes by immunoblotting, immunohistochemistry, microarray analysis, quantitative real-time polymerase chain reaction, and Oil Red O and Picrosirius red staining...
November 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28912580/ptprj-inhibits-leptin-signaling-and-induction-of-ptprj-in-the-hypothalamus-is-a-cause-of-the-development-of-leptin-resistance
#12
Takafumi Shintani, Satoru Higashi, Ryoko Suzuki, Yasushi Takeuchi, Reina Ikaga, Tomomi Yamazaki, Kenta Kobayashi, Masaharu Noda
Leptin signaling in the hypothalamus plays a crucial role in the regulation of body weight. Leptin resistance, in which leptin signaling is disrupted, is a major obstacle to the improvement of obesity. We herein demonstrated that protein tyrosine phosphatase receptor type J (Ptprj) is expressed in hypothalamic neurons together with leptin receptors, and that PTPRJ negatively regulates leptin signaling by inhibiting the activation of JAK2, the primary tyrosine kinase in leptin signaling, through the dephosphorylation of Y813 and Y868 in JAK2 autophosphorylation sites...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28905990/the-mtor-kinase-inhibitor-everolimus-synergistically-enhances-the-anti-tumor-effect-of-the-bruton-s-tyrosine-kinase-btk-inhibitor-pls-123-on-mantle-cell-lymphoma
#13
Jiao Li, Xiaogan Wang, Yan Xie, Zhitao Ying, Weiping Liu, Lingyan Ping, Chen Zhang, Zhengying Pan, Ning Ding, Yuqin Song, Jun Zhu
Mantle cell lymphoma (MCL) is an aggressive and incurable malignant disease. Despite of general chemotherapy, relapse and mortality are common, highlighting the need for the development of novel targeted drugs or combination of therapeutic regimens. Recently, several drugs that target the B-cell receptor (BCR) signaling pathway, especially the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, have demonstrated notable therapeutic effects in relapsed/refractory patients, which indicate that pharmacological inhibition of BCR pathway holds promise in MCL treatment...
September 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28904065/angptl1-interacts-with-integrin-%C3%AE-1%C3%AE-1-to-suppress-hcc-angiogenesis-and-metastasis-by-inhibiting-jak2-stat3-signaling
#14
Qian Yan, Lingxi Jiang, Ming Liu, Dandan Yu, Yu Zhang, Yan Li, Shuo Fang, Yan Li, Ying-Hui Zhu, Yunfei Yuan, Xin Yuan Guan
Downregulation of tumor suppressor signaling plays an important role in the pathogenesis of hepatocellular carcinoma (HCC). Here we report that downregulation of the angiopoietin-like protein ANGPTL1 is associated with vascular invasion, tumor thrombus, metastasis and poor prognosis in HCC. Ectopic expression of ANGPTL1 in HCC cells effectively decreased their in vitro and in vivo tumorigenicity, cell motility and angiogenesis. shRNA-mediated depletion of ANGPTL1 exerted opposing effects. ANGPTL1 promoted apoptosis via inhibition of the STAT3/Bcl-2 mediated anti-apoptotic pathway and decreased cell migration and invasion via downregulation of transcription factors SNAIL and SLUG...
September 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28903325/cxcl12-cxcr4-pathway-is-activated-by-oncogenic-jak2-in-a-pi3k-dependent-manner
#15
Hadjer Abdelouahab, Yanyan Zhang, Monika Wittner, Shinya Oishi, Nobutaka Fujii, Rodolphe Besancenot, Isabelle Plo, Vincent Ribrag, Eric Solary, William Vainchenker, Giovanni Barosi, Fawzia Louache
JAK2 activation is the driver mechanism in BCR-ABL-negative myeloproliferative neoplasms (MPN). These diseases are characterized by an abnormal retention of hematopoietic stem cells within the bone marrow microenvironment and their increased trafficking to extramedullary sites. The CXCL12/CXCR4 axis plays a central role in hematopoietic stem cell/ progenitor trafficking and retention in hematopoietic sites. The present study explores the crosstalk between JAK2 and CXCL12/CXCR4 signaling pathways in MPN. We show that JAK2, activated by either MPL-W515L expression or cytokine stimulation, cooperates with CXCL12/CXCR4 signaling to increase the chemotactic response of human cell lines and primary CD34(+) cells through an increased phosphatidylinositol-3-kinase (PI3K) signaling...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901902/simian-varicella-virus-inhibits-the-interferon-gamma-signalling-pathway
#16
Werner J D Ouwendijk, Suzanne van Veen, Ravi Mahalingam, Georges M G M Verjans
The alphaherpesvirus simian varicella virus (SVV) causes varicella and zoster in nonhuman primates. Herpesviruses evolved elaborate mechanisms to escape host immunity, but the immune evasion strategies employed by SVV remain ill-defined. We analysed whether SVV impairs the cellular response to key antiviral cytokine interferon-γ (IFNγ). SVV infection inhibited the expression of IFNγ-induced genes like C-X-C motif chemokine 10 and interferon regulatory factor 1. Phosphorylation and nuclear translocation of the signal transducer and activator of transcription 1 (STAT1) was blocked in SVV-infected cells, which did not involve cellular and viral phosphatases...
September 13, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28901507/%C3%AE-7-nicotinic-acetylcholine-receptor-in-tumor-associated-macrophages-inhibits-colorectal-cancer-metastasis-through-the-jak2-stat3-signaling-pathway
#17
Rushan Fei, Yuanwei Zhang, Saisai Wang, Tao Xiang, Wenbin Chen
Considerable evidence has implied that α7 nicotinic receptor subtypes play an important role in chronic inflammatory and neuropathic pain signaling. The aim of the present study was to determine the role of endogenous α7nAChR signaling in tumor-associated macrophages (TAMs) in human colorectal cancer (CRC) metastasis and prognosis. α7nAChR expression in primary tumor cells and adjacent stroma cells especially in TAMs in 51 CRC patients was observed. Using a human monocyte THP-derived macrophages (TMs) with α7nAChR-siRNA knockdown (TMα7-/-) and a CRC cell Transwell co-culture model, the migration and invasion of two CRC cells, LoVo and SW620, were determined...
September 4, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28901435/differential-regulation-by-ifn%C3%A2-%C3%AE-on-tnf%C3%A2-%C3%AE-%C3%A2-induced-chemokine-expression-in-synovial-fibroblasts-from-temporomandibular-joint
#18
Kouji Ohta, Takako Naruse, Hiroki Kato, Yoko Ishida, Takayuki Nakagawa, Shigehiro Ono, Hideo Shigeishi, Masaaki Takechi
Tumor necrosis factor (TNF)‑α and interferon (IFN)‑γ, are inflammatory cytokines in the synovial fluid of patients with temporomandibular joint disorder (TMD). However, it remains unknown whether they participate in the regulation of various chemokine expression levels associated with TMD. The effects of TNF‑α and IFN‑γ on the expression of several different inflammatory chemokines, including interleukin (IL)‑8, C‑X‑C motif chemokine ligand (CXCL)1, C‑C motif chemokine ligand (CCL)20, CXCL9, CXCL10, and CXCL11 in synovial fibroblasts obtained from the temporomandibular joint (TMJ) were examined...
September 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28886309/the-correlation-between-pax5-deletion-and-patients-survival-in-iranian-children-with-precursor-b-cell-acute-lymphocytic-leukemia
#19
A Moafi, A Zojaji, R Salehi, S Najafi Dorcheh, S Rahgozar
Despite advances in treatment, children with acute lymphoblastic leukemia (ALL) still experience drug resistance and relapse. Several gene mutations are involved in the onset of this disease and resistance to therapy. The present study examines the incidence of IKZF1, CDKN2A/B, PAX5, EBF1, ETV6, BTG1, RB1, JAK2, and Xp22.33 gene deletions/duplications associated with pediatric ALL in Iran and investigates the possible effect of these mutations on drug resistance. Three-year disease-free survival (3DFS) was evaluated for children diagnosed with Philadelphia negative precursor-B-cell ALL hospitalized at Sayed-al-Shohada Hospital, Isfahan-Iran, from January 2009 until December 2012...
August 30, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28883791/proteasome-inhibitor-ysy01a-abrogates-constitutive-stat3-signaling-via-down-regulation-of-gp130-and-jak2-in-human-a549-lung-cancer-cells
#20
Wei Huang, Xia Yuan, Ting Sun, Shujie Fan, Jun Wang, Quan Zhou, Wei Guo, Fuxiang Ran, Zemei Ge, Huayu Yang, Runtao Li, Jingrong Cui
Proteasome inhibition interfering with many cell signaling pathways has been extensively explored as a therapeutic strategy for cancers. Proteasome inhibitor YSY01A is a novel agent that has shown remarkable anti-tumor effects; however, its mechanisms of action are not fully understood. Here we report that YSY01A is capable of suppressing cancer cell survival by induction of apoptosis. Paradoxically, we find that YSY01A abrogates constitutive activation of STAT3 via proteasome-independent degradation of gp130 and JAK2, but not transcriptional regulation, in human A549 non-small cell lung cancer cells...
2017: Frontiers in Pharmacology
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