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https://www.readbyqxmd.com/read/29775946/il-9-exhibits-elevated-expression-in-osteonecrosis-of-femoral-head-patients-and-promotes-cartilage-degradation-through-activation-of-jak-stat-signaling-in-vitro
#1
Wei Geng, Wen Zhang, Jinzhu Ma
Osteonecrosis of the femoral head (ONFH) often causes severe symptoms in young people and limits the mobility of the hip joint. Interleukin-9 (IL-9) is a multi-functional inflammatory factor that participates in lumbar disk herniation and arthritis and has been reported in many studies. However, the correlation between IL-9 and ONFH is unclear. The present study aimed to determine the role of IL-9 in the pathogenetic mechanism of osteonecrosis. To assess IL-9 expression in ONFH and femoral neck fracture patients, cartilage tissue was examined through western blot analysis and immunohistochemistry...
May 15, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29773813/amelioration-of-experimental-autoimmune-encephalomyelitis-and-dss-induced-colitis-by-ntg-a-009-through-the-inhibition-of-th1-and-th17-cells-differentiation
#2
Suman Acharya, Maheshwor Timilshina, Liyuan Jiang, Sabita Neupane, Dong-Young Choi, Sang Won Park, Sang Yeul Lee, Byeong-Seon Jeong, Jung-Ae Kim, Tae-Gyu Nam, Jae-Hoon Chang
CD4+ T cells are the central for the mammalian adaptive immune system. Naïve CD4+ T cells mainly differentiate in to pro-inflammatory Th1, Th2 and Th17 cells upon antigenic stimulation. IFN-γ secreting Th1 cells and IL-17 secreting Th17 cells are found to play key roles in autoimmune diseases like multiple sclerosis (MS) and ulcerative colitis (UC). In this study we found NTG-A-009, 6-aminopyridin-3-ol, has great inhibitory effect on in vitro differentiation of Th1 and Th17 cells without affecting regulatory T cells...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29772037/a-review-of-fabry-disease
#3
A Cinats, E Heck
The class of medications known as Janus kinase inhibitors block cytokine-mediated signaling via the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, which plays an important role in immunoregulation and normal cell growth. This class includes the drugs tofacitinib, approved for the treatment of rheumatoid arthritis, and ruxolitinib, approved for the treatment of myelofibrosis and polycythemia rubra vera. The most common adverse events (AEs) reported in patients taking tofacitinib are infections, whereas the most common AEs in patients taking ruxolitinib are anemia and thrombocytopenia...
May 2018: Skin Therapy Letter
https://www.readbyqxmd.com/read/29771047/-effect-of-shrna-targeting-silencing-of-vtcn1-gene-on-nasopharyngeal-carcinoma-cells
#4
J Dong, T Peng, P Song, S C Yin, X H Zhou
Objective: The aim of this study is to investigate the expression of VTCN1 in nasopharyngeal carcinoma cells and targeting silencing of VTCN1 gene by infected with lentiviral vector to inhibit the proliferation and invasion in nasopharyngeal carcinoma cells. Method: The VTCN1 expression level of different nasopharyngeal carcinoma cells was detected by RT-PCR and Western blotting, the cell lines of the most expression level were seleted to conduct the Subsequent experiments; The lentiviral vector of silenced VTCN1 was transfected into HNE2 cells with VTCN1 expression by lipofectamine 2000, and stable cell lines were screened...
May 20, 2017: Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery
https://www.readbyqxmd.com/read/29766731/-current-and-prospective-biologics-and-small-molecules-in-the-treatment-of-inflammatory-bowel-diseases
#5
Milan Buc
Crohns disease (CD) and ulcerative colitis (UC) belong to chronic inflammatory bowel diseases, which are induced by autoimmune processes. While CD is characterized by over-activity of Th1, ILC1, and MAIT cells, UC is mediated by exaggerated activities of Th2 and ILC2 cells and cytokines they produce. Knowledge of the pathogenesis enabled a rational therapy based mostly on biologics and small molecules. TNF is the principal proinflammatory cytokine in both diseases. Anti-TNF monoclonal antibodies, mostly infliximab or adalimumab were therefore introduced to their treatment...
2018: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/29765973/complete-regrowth-of-beard-hair-with-ruxolitinib-in-an-alopecia-universalis-patient
#6
Yuval Ramot, Abraham Zlotogorski
While most alopecia areata (AA) cases resolve spontaneously, the more severe types of AA, alopecia totalis (AT) and alopecia universalis (AU), can be highly resistant to therapy. We report on a 33-year-old ultraorthodox Jewish man with an 11-year history of AA that resulted in complete loss of the scalp and body hair 7 years ago. Previous treatments with intralesional and systemic corticosteroids had only partial and temporary effects. The patient was treated with ruxolitinib, 20 mg twice daily, resulting in complete growth of the beard after 4 months of treatment...
April 2018: Skin Appendage Disorders
https://www.readbyqxmd.com/read/29765906/epstein-barr-virus-and-human-papillomaviruses-interactions-and-their-roles-in-the-initiation-of-epithelial-mesenchymal-transition-and-cancer-progression
#7
REVIEW
Farhan S Cyprian, Halema F Al-Farsi, Semir Vranic, Saghir Akhtar, Ala-Eddin Al Moustafa
Oncoviruses are implicated in around 20% of all human cancers including both solid and non-solid malignancies. Epstein-Barr virus (EBV) and human papillomaviruses (HPVs) are the most common oncoviruses worldwide. Currently, it is well established that onco-proteins of EBV (LMP1, LMP2A, and EBNA1) and high-risk HPVs (E5 and E6/E7) play an important role in the initiation and/or progression of several human carcinomas, including cervical, oral, and breast. More significantly, it has been recently pointed out that viral onco-proteins of EBV and high-risk HPVs can be co-present and consequently cooperate to initiate and/or amplify epithelial-mesenchymal transition (EMT), which is the hallmark of cancer progression and metastasis...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29765155/genetic-transcriptional-and-post-translational-regulation-of-the-programmed-death-protein-ligand-1-in-cancer-biology-and-clinical-correlations
#8
REVIEW
Ioannis Zerdes, Alexios Matikas, Jonas Bergh, George Z Rassidakis, Theodoros Foukakis
The programmed death protein 1 (PD-1) and its ligand (PD-L1) represent a well-characterized immune checkpoint in cancer, effectively targeted by monoclonal antibodies that are approved for routine clinical use. The regulation of PD-L1 expression is complex, varies between different tumor types and occurs at the genetic, transcriptional and post-transcriptional levels. Copy number alterations of PD-L1 locus have been reported with varying frequency in several tumor types. At the transcriptional level, a number of transcriptional factors seem to regulate PD-L1 expression including HIF-1, STAT3, NF-κΒ, and AP-1...
May 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29765118/ifn-%C3%AE-s-inhibit-hantaan-virus-infection-through-the-jak-stat-pathway-and-expression-of-mx2-protein
#9
Ning Li, Fan Luo, Qingzhou Chen, Ni Zhu, Hui Wang, Linlin Xie, Hairong Xiong, Ming Yue, Yun Zhang, Yong Feng, Wei Hou
Hantaan virus (HTNV), member of the newly defined Hantaviridae family, within the order Bunyavirales, can cause a hemorrhagic fever with renal syndrome with high fatality rates in humans. However, no specific antiviral agents are currently available for HTNV infection approved by the US Food and Drug Administration. Although interferon lambdas (IFN-λs) have been shown to induce an antiviral state against HTNV, the molecular mechanisms remain to be determined. In this study, we found that IFN-λs exerted its anti-HTNV effect by activating Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway-mediated antiviral immunity in A549 cells...
May 15, 2018: Genes and Immunity
https://www.readbyqxmd.com/read/29763909/cardiac-ablation-of-socs3-aggravates-doca-salt-induced-hypertrophic-remodeling-by-activation-of-gp130-dependent-signaling-in-mice
#10
Shuang Liu, Li-Xin Liu, Yun-Long Zhang, Song Lai, Yun-Peng Xie, Nan-Nan Li, Hong-Xia Wang, Yun-Long Xia, Ying Liu, Hui-Hua Li
BACKGROUND/AIMS: Cardiac remodeling is a critical pathogenetic process leading to heart failure. Suppressor of cytokine signaling-3 (SOCS3) is demonstrated as a key negative regulator of the gp130 receptor to inhibit cardiac hypertrophy. However, the role of SOCS3 in deoxycorticosterone-acetate (DOCA)-salt-induced cardiac remodeling remains unclear. METHODS: Cardiac-specific SOCS3 knockout (SOCS3cKO) and wild-type (WT) C57BL/6J mice were subjected to uninephrectomy and DOCA-salt for 3 weeks...
May 10, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29762824/long-noncoding-rna-uca1-promotes-cell-proliferation-migration-and-invasion-of-human-leukemia-cells-via-sponging-mir-126
#11
M-D Sun, Y-Q Zheng, L-P Wang, H-T Zhao, S Yang
OBJECTIVE: Acute myeloid leukemia (AML) is a bone marrow malignancy. Long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) plays an important role in several cancers. However, the role of lncRNA UCA1 in AML remained unclear. MATERIALS AND METHODS: LncRNA UCA1 expressions in different cell lines were determined by RT-PCR. In human myelogenous leukemia (ML) cell lines K562 and HL60, effects of lncRNA UCA1 knockdown on cell viability, migration, invasion, and apoptosis were assessed, respectively...
April 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29761158/phase-ii-study-of-ruxolitinib-a-selective-jak1-2-inhibitor-in-patients-with-metastatic-triple-negative-breast-cancer
#12
Daniel G Stover, Carlos R Gil Del Alcazar, Jane Brock, Hao Guo, Beth Overmoyer, Justin Balko, Qiong Xu, Aditya Bardia, Sara M Tolaney, Rebecca Gelman, Maxwell Lloyd, Yu Wang, Yaomin Xu, Franziska Michor, Vivian Wang, Eric P Winer, Kornelia Polyak, Nancy U Lin
Preclinical data support a role for the IL-6/JAK2/STAT3 signaling pathway in breast cancer. Ruxolitinib is an orally bioavailable receptor tyrosine inhibitor targeting JAK1 and JAK2. We evaluated the safety and efficacy of ruxolitinib in patients with metastatic breast cancer. This was a non-randomized phase II study enrolling patients with refractory, metastatic triple-negative breast cancer. The primary endpoint was objective response by RECIST 1.1. The study was designed to enroll patients whose archival tumor tissue was pSTAT3-positive ( T -score >5) by central immunohistochemistry...
2018: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29757976/fatty-acid-%C3%AE-oxidation-is-essential-in-leptin-mediated-oocytes-maturation-of-yellow-catfish-pelteobagrus-fulvidraco
#13
Yu-Feng Song, Xiao-Ying Tan, Ya-Xiong Pan, Li-Han Zhang, Qi-Liang Chen
Although several studies have been conducted to study leptin function, information is very scarce on the molecular mechanism of leptin in fatty acid β-oxidation and oocytes maturation in fish. In this study, we investigated the potential role of fatty acid β-oxidation in leptin-mediated oocytes maturation in Pelteobagrus fulvidraco . Exp. 1 investigated the transcriptomic profiles of ovary and the differential expression of genes involved in β-oxidation and oocytes maturation following rt-hLEP injection; rt-hLEP injection was associated with significant changes in the expression of genes, including twenty-five up-regulated genes ( CPT1 , Acsl , Acadl , Acadm , Hadhb , Echsl , Hsd17b4 , Acca , PPARα , CYP8B1 , ACOX1 , ACBP , MAPK , RINGO , Cdc2 , MEK1 , IGF-1R , APC/C, Cdk2 , GnRHR, STAG3 , SMC1 , FSHβ and C-Myc ) and ten down-regulated gene ( PPARγ , FATCD36 , UBC , PDK1 , Acads , Raf , Fizzy , C3H-4 , Raf and PKC ), involved in fatty acid β-oxidation and oocytes maturation...
May 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29755657/regulatory-effect-of-anti-gp130-functional-mab-on-il-6-mediated-rankl-and-wnt5a-expression-through-jak-stat3-signaling-pathway-in-fls
#14
Ping Miao, Xiao Wei Zhou, Ping Wang, Rong Zhao, Ninan Chen, Chao Ying Hu, Xue Hua Chen, Liu Qian, Qi Wen Yu, Ji Ying Zhang, Rong Xu, Dong Yi He, Lian Bo Xiao, Pu Li, Mason Lu, Dong Qing Zhang
We investigated the effect on rheumatoid arthritis (RA) of an anti-gp130 monoclonal antibody (mAb) and its mechanism using RA fibroblast-like synoviocytes (FLS) and a collagen antibody-induced arthritis (CAIA) mouse model. We determined the interleukin 6 (IL-6), IL-6 receptor α (IL-6Rα), gp130, receptor activator of nuclear factor κB ligand (RANKL), matrix metalloproteinase 3 (MMP3), TIMP metallopeptidase inhibitor 1 (TIMP1), and Bcl-2 levels in RA and osteoarthritis (OA) serum and synovial fluid. RA FLS were cultured with or without IL-6/IL-6Rα; WNT5A and RANKL levels were detected...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29752723/mimetics-of-suppressor-of-cytokine-signalling-3-novel-potential-therapeutics-in-triple-breast-cancer
#15
Sara La Manna, Eunmi Lee, Maria Ouzounova, Concetta Di Natale, Ettore Novellino, Antonello Merlino, Hasan Korkaya, Daniela Marasco
Suppressor of cytokine signaling (SOCS) family of proteins plays critical role in the regulation of immune responses controlling JAK/STAT mediated inflammatory cytokines. Among the members, SOCS1 and SOCS3 contain a kinase inhibitory region (KIR) and SOCS3 binds to JAK/STAT/gp130 complex by inhibiting the downstream signaling and suppressing inflammatory cytokines. Loss or reduced levels of SOCS3 have been linked to cancer-associated inflammation and suppressive immunity leading to enhanced tumour growth and metastasis...
May 11, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29752314/ifnar1-controls-autocrine-type-i-ifn-regulation-of-pd-l1-expression-in-myeloid-derived-suppressor-cells
#16
Wei Xiao, John D Klement, Chunwan Lu, Mohammed L Ibrahim, Kebin Liu
Tumor cells respond to IFN-γ of activated T cells to upregulate programmed death-ligand 1 (PD-L1) in the tumor microenvironment as an adaptive immune resistance mechanism. Tumor cells also express oncogene-driven PD-L1. PD-L1 is also expressed on myeloid-derived suppressor cells (MDSCs). It is known that both type I and II IFNs upregulate PD-L1 expression in MDSCs. However, the molecular mechanism underlying PD-L1 expression in MDSCs is still largely unknown. We report in this article that MDSCs exhibit constitutive STAT1 phosphorylation in vitro without exogenous IFNs, indicating a constitutive active JAK-STAT signaling pathway in mouse MDSCs in vitro...
May 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29752146/a-novel-topical-nonsteroidal-trpv1-antagonist-pac-14028-cream-improves-skin-barrier-function-and-exerts-anti-inflammatory-action-through-modulating-epidermal-differentiation-markers-and-suppressing-th2-cytokines-in-atopic-dermatitis
#17
Ji-Hae Lee, Chang Soon Choi, Il-Hong Bae, Jin Kyu Choi, Young-Ho Park, Miyoung Park
BACKGROUND: Although it is established that epidermal barrier disturbance and immune dysfunction resulting in IgE sensitization are critical factors in the development of cutaneous inflammation, the pathogenesis and targeted therapy of atopic dermatitis (AD)-specific pathways have still been unknown. OBJECTIVE: Taking into account the fact that Th2 cytokines in AD have both unique and overlapping functions including increased epidermal thickening, inflammation, and decreased expressing of the barrier proteins keratinocyte differentiation, we sought to clarify our hypothesis that TRPV1 antagonist plays a critical role in skin barrier function and can be a therapeutic target for AD...
April 30, 2018: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29751177/activation-of-the-il-6-jak2-stat3-pathway-induces-plasma-cell-mastitis-in-mice
#18
Yang Liu, Jian Zhang, Yu-Hui Zhou, Hui-Min Zhang, Ke Wang, Yu Ren, Yi-Na Jiang, Shui-Ping Han, Jian-Jun He, Xiao-Jiang Tang
Plasma cell mastitis (PCM) is a chronic mastitis with limited treatment options and common recurrence. A histopathological hallmark of PCM is the infiltration of numerous plasma cells surrounding the mammary duct. Our previous study showed that the activity of the IL-6/STAT3 signaling pathway was elevated in patients with PCM. However, the etiology of PCM remains largely unclear. In this study, we sought to explore the effects of IL-6/JAK2/STAT3 signaling pathway in the pathogenesis of PCM. Histological analysis showed that the mammary glands of mice that received human breast tissue homogenates, followed by an injection of IL-6, exhibited features of PCM similar to human PCM...
May 8, 2018: Cytokine
https://www.readbyqxmd.com/read/29750040/a-phase-ib-study-of-ruxolitinib-gemcitabine-%C3%A2-nab-paclitaxel-in-patients-with-advanced-solid-tumors
#19
Todd M Bauer, Manish R Patel, Andres Forero-Torres, Thomas J George, Albert Assad, Yining Du, Herbert Hurwitz
Purpose: Aberrant activation of the Janus-associated kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is associated with increased malignant cell proliferation and survival. This Phase Ib study evaluated ruxolitinib, a potent JAK1/2 inhibitor, in combination with gemcitabine with or without nab-paclitaxel in patients with advanced solid tumors. Patients and methods: Patients received ruxolitinib + gemcitabine (regimen A) or ruxolitinib + gemcitabine + nab-paclitaxel (regimen B)...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29749494/downregulation-of-rpn2-induces-apoptosis-and-inhibits-migration-and-invasion-in-colon-carcinoma
#20
Chongyao Bi, Baofei Jiang
The morbidity of colorectal cancer (CRC) increases annualy, which accounts to higher mortality worldwide. Therefore, it is important to study the pathogenesis of colon cancer. Ribophorin II (RPN2), part of the N-oligosaccharyltransferase complex, is highly expressed in CRC. In the present study, we investigated whether RPN2 can regulate apoptosis, migration and invasion by RNA interference in CRC and sought to clarify the molecular mechanism involved. Based on previous research, an abnormal high expression of RPN2 was observed in CRC tissues and cell lines by real-time (RT)-PCR, immunohistochemistry (IHC) and western blot analysis...
May 10, 2018: Oncology Reports
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