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https://www.readbyqxmd.com/read/29778097/hyperprolactinemia-inducing-antipsychotics-increase-breast-cancer-risk-by-activating-jak-stat5-in-precancerous-lesions
#1
A N Johnston, W Bu, S Hein, S Garcia, L Camacho, L Xue, L Qin, C Nagi, S G Hilsenbeck, J Kapali, K Podsypanina, J Nangia, Y Li
BACKGROUND: Psychiatric medications are widely prescribed in the USA. Many antipsychotics cause serum hyperprolactinemia as an adverse side effect; prolactin-Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) signaling both induces cell differentiation and suppresses apoptosis. It is controversial whether these antipsychotics increase breast cancer risk. METHODS: We investigated the impact of several antipsychotics on mammary tumorigenesis initiated by retrovirus-mediated delivery of either ErbB2 or HRas or by transgenic expression of Wnt-1...
May 19, 2018: Breast Cancer Research: BCR
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
#2
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/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/29765991/immune-response-and-evasion-mechanisms-of-plasmodium-falciparum-parasites
#4
REVIEW
Esmael Besufikad Belachew
Malaria causes approximately 212 million cases and 429 thousand deaths annually. Plasmodium falciparum is responsible for the vast majority of deaths (99%) than others. The virulence of P. falciparum is mostly associated with immune response-evading ability. It has different mechanisms to evade both Anopheles mosquito and human host immune responses. Immune-evading mechanisms in mosquito depend mainly on the Pfs47 gene that inhibits Janus kinase-mediated activation. Host complement factor also protects human complement immune attack of extracellular gametes in Anopheles mosquito midgut...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29765973/complete-regrowth-of-beard-hair-with-ruxolitinib-in-an-alopecia-universalis-patient
#5
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/29765446/inhibitory-effect-of-pdgf-bb-and-serum-stimulated-responses-in-vascular-smooth-muscle-cell-proliferation-by-hinokitiol-via-up-regulation-of-p21-and-p53
#6
Jiun-Yi Li, Chun-Ping Liu, Wei-Cheng Shiao, Thanasekaran Jayakumar, Yi-Shin Li, Nen-Chung Chang, Shih-Yi Huang, Cheng-Ying Hsieh
Introduction: Vascular smooth muscle cell (VSMC) proliferation plays a major role in the progression of vascular diseases. In the present study, we established the efficacy and the mechanisms of action of hinokitiol, a tropolone derivative found in Chamaecyparis taiwanensis , Cupressaceae, in relation to platelet-derived growth factor-BB (PDGF-BB) and serum-dependent VSMC proliferation. Material and methods: Primary cultured rat VSMCs were pre-treated with hinokitiol and then stimulated by PDGF-BB (10 ng/ml) or serum (10% fetal bovine serum)...
April 2018: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/29765118/ifn-%C3%AE-s-inhibit-hantaan-virus-infection-through-the-jak-stat-pathway-and-expression-of-mx2-protein
#7
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/29763638/effects-of-sc99-on-cerebral-ischemia-perfusion-injury-in-rats-selective-modulation-of-microglia-polarization-to-m2-phenotype-via-inhibiting-jak2-stat3-pathway
#8
Yiping Ding, Jinhong Qian, Haiying Li, Haitao Shen, Xiang Li, Yan Kong, Zhuan Xu, Gang Chen
Inhibition of Janus kinases 2-Signal transducers and activators of transcription3 (JAK2-STAT3) pathway has been shown to exert anti-inflammatory actions. SC99, a novel specific inhibitor targeting JAK2-STAT3 pathway, has been verified to negatively modulate platelet activation and aggregation in vitro. In current study, a middle cerebral artery occlusion and reperfusion (MCAO/R) model was established in Sprague Dawley rats and primary cultured microglia was exposed to oxygen and glucose deprivation (OGD/R) in vitro...
May 12, 2018: Neuroscience Research
https://www.readbyqxmd.com/read/29761420/long-term-radiographic-and-patient-reported-outcomes-in-patients-with-rheumatoid-arthritis-treated-with-tofacitinib-oral-start-and-oral-scan-post-hoc-analyses
#9
Vibeke Strand, Arthur Kavanaugh, Alan J Kivitz, Désirée van der Heijde, Kenneth Kwok, Ermeg Akylbekova, Arif Soonasra, Mark Snyder, Carol Connell, Eustratios Bananis, Josef S Smolen
INTRODUCTION: Here we examine the relationship between achieving different levels of disease activity with tofacitinib (an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis), long-term structural progression, and patient-reported physical function. METHODS: This was a post hoc analysis of two 24-month, phase III randomized controlled trials in methotrexate (MTX)-naïve (ORAL Start [NCT01039688]) or MTX-inadequate responder (IR) patients (ORAL Scan [NCT00847613]) receiving tofacitinib 5 or 10 mg twice daily as either monotherapy or with background MTX...
May 14, 2018: Rheumatology and Therapy
https://www.readbyqxmd.com/read/29761313/genomewide-dna-methylation-responses-in-patients-with-%C3%AE-thalassemia-treated-with-yisui-shengxue-granules
#10
Yan-Ling Cheng, Xin-Hua Zhang, Yu-Wen Sun, Wen-Juan Wang, Jie Huang, Na-Li Chu, Su-Ping Fang, Zhi-Kui Wu
OBJECTIVE: To examine the clinical effects of Yisui Shengxue Granules () in the treatment of β-thalassemia and explore its mechanism on DNA methylation levels. METHODS: A randomized placebo-controlled double-blinded trial was conducted. Forty patients with β-thalassemia were recruited and distributed randomly by envelope method into an experimental group and a control group, 20 patients in each group. The patients were given Yisui Shengxue Granules in the experimental group and placebo in the control group (12 g/bag three times a day) during a 3-month intervention...
May 3, 2018: Chinese Journal of Integrative Medicine
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
#11
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/29751003/special-at-rich-binding1-protein-satb1-in-malignant-t-cells
#12
Simon Fredholm, Andreas Willerslev-Olsen, Özcan Met, Linda Kubat, Maria Gluud, Sarah L Mathiasen, Christina Friese, Edda Blümel, David L Petersen, Tengpeng Hu, Claudia Nastasi, Lise M Lindahl, Terkild B Buus, Thorbjørn Krejsgaard, Mariusz A Wasik, Katharina L Kopp, Sergei B Koralov, Jenny L Persson, Charlotte M Bonefeld, Carsten Geisler, Anders Woetmann, Lars Iversen, Jurgen C Becker, Niels Odum
Deficient expression of Suppressor Special AT-rich Binding-1 (SATB1) hampers thymocyte development and results in inept T cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides (MF), the most frequent variant of cutaneous T cell lymphoma (CTCL). Here we report on a disease-stage-associated decrease of SATB1 expression and an inverse expression of STAT5 and SATB1 in situ. Importantly, STAT5 inhibited SATB1 expression through induction of miR-155. Decreased SATB1 expression triggered enhanced expression of IL-5 and IL-9 (but not IL-6 and IL-32) whereas increased SATB1 expression had the opposite effect indicating that the mir-155 target SATB1 is a repressor of IL-5 and IL-9 in malignant T cells...
May 8, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29750040/a-phase-ib-study-of-ruxolitinib-gemcitabine-%C3%A2-nab-paclitaxel-in-patients-with-advanced-solid-tumors
#13
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
#14
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
https://www.readbyqxmd.com/read/29749443/trim24-sirna-induced-cell-apoptosis-and-reduced-cell-viability-in-human-nasopharyngeal-carcinoma-cells
#15
Peng Wang, Na Shen, Danzheng Liu, Xianhui Ning, Daquan Wu, Xinsheng Huang
Nasopharyngeal carcinoma (NPC) is a common cancer occurring primarily in East Asia and Africa. The high rate of recurrence and metastasis of NPC continuously endangers the health of patients. The present study aimed to identify the underlying mechanisms involved in the progression of NPC and provide experimental basis to develop a novel and efficient agent against NPC. The present study measured the expression level of tripartite motif containing 24 (TRIM24) in tumor tissues from NPC patients using reverse transcription quantitative polymerase chain reaction...
May 2, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29748971/association-between-serum-interleukin-17a-and-clinical-response-to-tofacitinib-and-etanercept-in-moderate-to-severe-psoriasis
#16
L Fitz, W Zhang, C Soderstrom, S Fraser, J Lee, A Quazi, R Wolk, C A Mebus, H Valdez, G Berstein
BACKGROUND: Psoriasis is a systemic inflammatory disease with a pathophysiology involving interleukin (IL)-17. Tofacitinib is an oral Janus kinase inhibitor. Etanercept is a tumour necrosis factor-α inhibitor used in the treatment of psoriasis. Neither agent inhibits IL-17 directly. AIM: To evaluate correlations between circulating IL-17A and clinical efficacy in patients with psoriasis treated with tofacitinib or etanercept. METHODS: Serum concentrations of IL-17A homodimer and IL-17A/F heterodimer were determined by immunoassays at weeks 0, 4 and 12 in patients with moderate to severe psoriasis treated with placebo (n = 60), tofacitinib 5 mg twice daily (n = 184), tofacitinib 10 mg twice daily (n = 190), or etanercept 50 mg subcutaneously twice weekly (n = 190)...
May 10, 2018: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/29748919/severe-atopic-dermatitis-in-children
#17
REVIEW
Evie Huang, Peck Y Ong
PURPOSE OF REVIEW: Severe atopic dermatitis (AD) in childhood leads to significant morbidity including psychosocial problems and infectious complications. There are only a few approved treatment options for these patients. These include topical corticosteroids and tacrolimus ointment, which are associated with potential side effects. RECENT FINDINGS: In order to find better and safer treatments, further understanding of AD mechanisms is needed. Primary skin barrier defects play an important role in the pathogenesis of AD...
May 10, 2018: Current Allergy and Asthma Reports
https://www.readbyqxmd.com/read/29748515/growth-hormone-receptor-mutations-related-to-individual-dwarfism
#18
REVIEW
Shudai Lin, Congjun Li, Charles Li, Xiquan Zhang
Growth hormone (GH) promotes body growth by binding with two GH receptors (GHRs) at the cell surface. GHRs interact with Janus kinase, signal transducers, and transcription activators to stimulate metabolic effects and insulin-like growth factor (IGF) synthesis. However, process dysfunctions in the GH⁻GHR⁻IGF-1 axis cause animal dwarfism. If, during the GH process, GHR is not successfully recognized and/or bound, or GHR fails to transmit the GH signal to IGF-1, the GH dysfunction occurs. The goal of this review was to focus on the GHR mutations that lead to failures in the GH⁻GHR⁻IGF-1 signal transaction process in the dwarf phenotype...
May 10, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29746867/mir-26a-5p-potentiates-metastasis-of-human-lung-cancer-cells-by-regulating-itg%C3%AE-8-jak2-stat3-axis
#19
Qianqian Song, Boning Liu, Xueqin Li, Qicheng Zhang, Limin Cao, Meilin Xu, Zhaowei Meng, Xiang Wu, Ke Xu
Most lung cancer patients die of metastasis. Recent studies have indicated that dysregulated microRNAs (miRNAs) are involved not only in tumorigenesis, but also in metastasis. In the present study, we found that over-expression of miR-26a-5p potentiated the migration and invasion of lung cancer cells evidenced by wound healing assay and transwell assay, and metastasis-related genes MMP-9 and CD44 were up-regulated. We identified integrin-beta8 (ITGβ8) as a novel target of miR-26a, and ITGβ8 expression was negatively correlated with miR-26a-5p expression in lung cancer specimens...
May 7, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29745885/explorative-analyses-of-protein-biomarkers-in-patients-with-early-rheumatoid-arthritis-achieving-sustained-drug-free-remission-after-treatment-with-tocilizumab-or-methotrexate-based-strategies-from-transcriptomics-to-proteomics
#20
Xavier M Teitsma, Johannes W G Jacobs, Arno N Concepcion, Attila Pethö-Schramm, Michelle E A Borm, Jacob M van Laar, Johannes W J Bijlsma, Floris P J G Lafeber
OBJECTIVES: Previously, we identified networks of co-expressed genes related to achieving sustained drug-free remission (sDFR). The aim of the present exploratory analysis was to identify inflammatory proteins associated with achieving sDFR and their enriched biological pathways, and compare these pathways with those found in the previous transcriptomic analyses. METHODS: Serum samples were used from 60 patients who participated in the U-Act-Early trial and were treated-to-target with tocilizumab plus methotrexate, or tocilizumab or methotrexate; 37 achieved sDFR (≥3 months drug-free) and 23 did not (controls)...
May 8, 2018: Clinical and Experimental Rheumatology
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