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Yalin Chen, Li Bian, Yingmei Zhang
OBJECTIVE: To investigate the relationship between miR-505 and RASSF8 as well as the effect of miR-505 on methotrexate (MTX) resistance of human colorectal cancer (CRC). METHODS: Microarray was used to select differentially expressed miRNAs. QRT-PCR and western blot were performed to assess miR-505 and RASSF8 mRNA levels in MTX-sensitive and MTX-resistant CRC tissues and cells. Cell viability, propagation and apoptosis were confirmed by MTT, colony formation assays and flow cytometry...
May 3, 2018: Journal of Pharmacy and Pharmacology
D Y Saad, M M Soliman, A A Mohamed, G B Youssef
The current study was aimed to evaluate the protective effect of Holothurian atra (HA) extract; naturally occurring marine resource, against methotrexate (MTX) induced testicular dysfunction. Mature rats received either MTX (20 mg/kg, intraperitoneally) or saline on the 7th day of experiment al design. Seven days prior and after MTX-injection, rats received HA at dose of 300 mg/kg intragastrically (HA + MTX group; HA group alone). Serum was extracted and testicular tissues were examined for the changes in serum biochemistry (liver & kidney biomarkers, testicular hormones and antioxidants), molecular and histopthological alterations using RT-PCR and immunohistochemistry...
April 23, 2018: Andrologia
Naoki Shinojima, Kenji Fujimoto, Keishi Makino, Kohei Todaka, Kazumichi Yamada, Yoshiki Mikami, Kazutaka Oda, Kazumi Nakamura, Hirofumi Jono, Jun-Ichi Kuratsu, Hideo Nakamura, Shigetoshi Yano, Akitake Mukasa
The therapeutic response to high-dose methotrexate (HD-MTX) therapy for primary central nervous system lymphoma (PCNSL) varies. Polyglutamylation is a reversible protein modification with a high occurrence rate in tumor cells. MTX incorporated into cells is polyglutamylated and strongly binds to dihydrofolate reductase without competitive inhibition by leucovorin (LV). Tumor cells with high polyglutamylation levels are selectively killed, whereas normal cells with lower polyglutamylation are rescued by LV. We hypothesized that the extent of polyglutamylation in tumor cells determines treatment resistance...
February 23, 2018: Acta Neuropathologica Communications
Qiao Tang, Xin Ma, Yi Zhang, Xiang Cai, Wei Xue, Dong Ma
Polymeric prodrugs are of immense interest as anticancer drug-delivery system owing to their superior drug stability during circulation and satisfactory drug loading capacity. However, they are usually less effective than free drugs due to imperfect degradable characteristics or active sites blockage. A polymeric prodrug (HPAA-MTX) with chemotherapeutic self-sensibilization effect consisting of glutathione (GSH)-triggered hyperbranched poly(amido amine) (HPAA) and methotrexate (MTX) was designed and synthesized in this work...
March 15, 2018: Acta Biomaterialia
Can Qian, Mei Kuang, Yong Wang
QianghuoErhuang Decoction (QED) is an effective recipe in treating rheumatoid arthritis. The present study aimed to explore the effects of QED on Treg and Th17 in adjuvant arthritis (AA) model. The study included 6 group rats: normal control group, AA group, AA + methotrexate (MTX) group, AA + high, moderate, and low dose QED groups. The arthritis score was significantly decreased in the MTX and high-dose QED groups compared with the AA group on days 24 and 28 (P < 0.01), respectively. The synovial tissue inflammation was attenuated by histological observation, and the proliferation of splenocytes was significantly inhibited in MTX and high-dose QED groups (P < 0...
December 8, 2017: Scientific Reports
Hadis Yousefzadeh, Farahzad Jabbari Azad, Maryam Rastin, Mahnaz Banihashemi, Mahmoud Mahmoudi
BACKGROUND: Psoriasis is a T cell-mediated autoimmune disease in patients with elevated levels of proinflammatory cytokines belonging mainly to the Th1 pathway. We investigated whether treatment of psoriasis patients with methotrexate (MTX), along with micronutrients, modulated mRNA expression of Th1 and Th2 components and whether expression of these components correlated with psoriasis severity. METHODS: Thirty plaque-type psoriasis patients with Psoriasis Area and Severity Index (PASI) scores greater than 10 were recruited; these were 15 non-micronutrients taking- (NMT) patients treated with MTX daily (0...
October 2017: Reports of Biochemistry & Molecular Biology
Jingchao Hao, Xiaodong Wu, Sarra Setrerrahmane, Kun Qian, Yueying Hou, Liting Yu, Chenyu Lin, Qianqian Wu, Hanmei Xu
At present, the early phenomenon of inflammatory angiogenesis is rarely studied in Rheumatoid arthritis (RA). Previous research found that PEG-HM-3, an integrin inhibitor, possessed anti-angiogenesis and anti-rheumatic activity. In this study, the advantages of inhibiting angiogenesis and immune cell adhesion and migration, as well as the benefits of anti-arthritis effects, were evaluated using a combination of PEG-HM-3 and methotrexate (MTX). In vitro, spleen cell proliferation and the levels of tumor necrosis factor α (TNF-α) in macrophage supernatant were assessed...
July 21, 2017: International Journal of Molecular Sciences
Gabriele De Marco, Philip Helliwell, Dennis McGonagle, Paul Emery, Laura C Coates, Elizabeth M A Hensor, Helena Marzo-Ortega
BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis which impacts significantly on the quality of life and work capacity of affected individuals. Recent evidence has shown that early control of inflammation in PsA leads to improved long-term outcomes. It is postulated that prompt intervention after diagnosis using a remission-induction treatment strategy will lead to improved outcomes and optimal disease control of PsA. The aim of the present study was to compare the clinical efficacy of a treatment strategy in newly diagnosed, treatment naïve PsA subjects, using the combination of golimumab (GOL), methotrexate (MTX) and steroids versus standard care (MTX monotherapy plus steroids)...
July 18, 2017: BMC Musculoskeletal Disorders
Ayman M Mahmoud, Omnia E Hussein, Walaa G Hozayen, Sanaa M Abd El-Twab
18β-glycyrrhetinic acid (18β-GA) is a bioactive component of licorice with promising hepatoprotective activity. However, its protective mechanism on methotrexate (MTX) hepatotoxicity in not well defined. We investigated the hepatoprotective effect of 18β-GA, pointing to the role of peroxisome proliferator activated receptor gamma (PPARγ) and the redox-sensitive nuclear factor erythroid 2-related factor 2 (Nrf2). Wistar rats were orally administered 18β-GA (50 and 100 mg/kg) 7 days either before or after MTX injection...
May 25, 2017: Chemico-biological Interactions
Hany M Abo-Haded, Mohamed A Elkablawy, Zeyad Al-Johani, Osama Al-Ahmadi, Dina S El-Agamy
Sitagliptin is selective dipeptidyl peptidase-4 inhibitor (DPP4-I), used clinically as a new oral anti-diabetic agent. This study explored the underlying mechanisms of the hepatoprotective role of sitagliptin pretreatment against methotrexate (MTX) induced hepatotoxicity in mice. Forty mice were divided into four groups (10 mice each); control, MTX, and two sitagliptin groups (pretreated with sitagliptin 10 and 20 mg/kg/day, respectively) for five consecutive days prior to MTX injection. Results showed that MTX induced marked hepatic injury in the form of cloudy swelling, hydropic degeneration, apoptosis and focal necrosis in all hepatic zones...
2017: PloS One
S Sithamparanathan, L Thirugnanasothy, K E Morley, A J Fisher, J L Lordan, G Meachery, G Parry, P A Corris
BACKGROUND: Methotrexate (MTX) is potential change in immunosuppression after lung transplantation that may help to slow down the decline in lung function in bronchiolitis obliterans syndrome (BOS). METHODS: We sought to analyze the safety and efficacy of MTX in patients with BOS, by retrospective case review. RESULTS: Thirty lung allograft patients were treated with MTX for BOS after one bilateral lower lobe, nine single, 16 bilateral, and four heart-lung transplants...
December 2016: Transplantation Proceedings
Sanam Arami, Majid Mahdavi, Mohammad Reza Rashidi, Marziyeh Fathi, Mohammad Saeid Hejazi, Nasser Samadi
BACKGROUND: Targeted delivery of small interfering RNA (siRNA) to the specific tumor tissues and cells is the key challenge in the development of RNA interference as a therapeutic application. METHODS: To target breast cancer, we developed a cationic nanoparticle as a therapeutic delivery system. The successful synthesis of the magnetic nanoparticles modified by polyaspartate (PAA) and polyethyleneimine (PEI) was confirmed using fourier transform infrared (FT-IR) measurements...
2017: Current Pharmaceutical Design
S García-Rodríguez, S Arias-Santiago, G Blasco-Morente, J Orgaz-Molina, A Rosal-Vela, P Navarro, C Magro-Checa, A Martínez-López, J-C Ruiz, E Raya, R Naranjo-Sintes, J Sancho, M Zubiaur
BACKGROUND: MicroRNAs (miRNAs) gene expression regulators are altered in psoriasis suggesting their role in the pathogenesis. OBJECTIVE: To study expression changes of inflammation and toll-like receptor (TLR)-related miRNAs, miRNA-155, let-7i, miRNA-21, miRNA-146a and miRNA-223 in peripheral mononuclear cells (PBMCs) and miRNA-21, miRNA-146a and miRNA-223 in plasma, from chronic plaque-type psoriasis patients who were treatment-naive or had undergone a washout period (n = 11)...
February 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
Patrick Verschueren, Diederik De Cock, Luk Corluy, Rik Joos, Christine Langenaken, Veerle Taelman, Frank Raeman, Isabelle Ravelingien, Klaas Vandevyvere, Jan Lenaerts, Elke Geens, Piet Geusens, Johan Vanhoof, Anne Durnez, Jan Remans, Bert Vander Cruyssen, Els Van Essche, An Sileghem, Griet De Brabanter, Johan Joly, Sabrina Meyfroidt, Kristien Van der Elst, Rene Westhovens
OBJECTIVES: Combining disease-modifying antirheumatic drugs (DMARDs) with glucocorticoids (GCs) is an effective treatment strategy for early rheumatoid arthritis (ERA), yet the ideal schedule and feasibility in daily practice are debated. We evaluated different DMARD combinations and GC remission induction schemes in poor prognosis patients; and methotrexate (MTX) with or without GC remission induction in good prognosis patients, during the first treatment year. METHODS: The Care in ERA (CareRA) trial is a 2-year investigator-initiated randomised pragmatic open-label superiority trial comparing remission induction regimens in a treat-to-target approach...
March 2017: Annals of the Rheumatic Diseases
Nicole P C Konijn, Lilian H D van Tuyl, Maarten Boers, Peter M van de Ven, Debby den Uyl, Marieke M Ter Wee, Pit Kerstens, Alexandre E Voskuyl, Dirkjan van Schaardenburg, Willem F Lems, Michael T Nurmohamed
OBJECTIVE: To investigate the effect of two different high-dose, step-down prednisolone regimens on body composition in early RA patients after 26 weeks of treatment. METHODS: Prednisolone-naive patients with recent-onset RA (n = 108) were randomized to either COBRA (prednisolone 60 mg/day, tapered to 7.5 mg/day in 6 weeks; MTX and SSZ) or COBRA-light therapy (prednisolone 30 mg/day, tapered to 7.5 mg/day in 8 weeks and MTX). Body composition was assessed at baseline (before or soon after start of treatment) and after 26 weeks with DXA, and recorded as total body mass (TBM), total fat mass (FM), total lean mass (LM) and trunk/peripheral fat ratio...
September 2016: Rheumatology
Jingyu Chen, Qingtong Wang, Huaxun Wu, Kangkang Liu, Yujing Wu, Yan Chang, Wei Wei
CONTEXT: Compound K (CK, 20-O-d-glucopyranosyl-20(S)-protopanaxadiol), a novel ginsenoside metabolite, is structurally a member of the dammarane-type triterpene saponins. Several studies have identified the anti-inflammatory activity of CK. Our previous study demonstrated that CK exerted its anti-inflammatory effect via inhibition of abnormal activation and differentiation of T cells. However, its mechanism of action on B cells remains unclear. OBJECTIVE: The objective of this study is to investigate the effect and underlying mechanisms of CK's effects on memory B cells in the setting of adjuvant-arthritis (AA)...
July 2016: Pharmaceutical Biology
Tamás Fodor, Magdolna Szántó, Omar Abdul-Rahman, Lilla Nagy, Ádám Dér, Borbála Kiss, Peter Bai
Cancer cells are characterized by metabolic alterations, namely, depressed mitochondrial oxidation, enhanced glycolysis and pentose phosphate shunt flux to support rapid cell growth, which is called the Warburg effect. In our study we assessed the metabolic consequences of a joint treatment of MCF-7 breast cancer cells with AICAR, an inducer of AMP-activated kinase (AMPK) jointly with methotrexate (MTX), a folate-analog antimetabolite that blunts de novo nucleotide synthesis. MCF7 cells, a model of breast cancer cells, were resistant to the individual application of AICAR or MTX, however combined treatment of AICAR and MTX reduced cell proliferation...
2016: PloS One
Huaxun Wu, Shangxue Yan, Jingyu Chen, Xuexia Luo, Peipei Li, Xiaoyi Jia, Xing Dai, Chun Wang, Qiong Huang, Lihua Liu, Yunfang Zhang, Aiwu Zhou, Yan Chang, LingLing Zhang, Wei Wei
OBJECTIVE: To investigate the effects of JAK inhibitor (SHR0302) on adjuvant-induced arthritis (AA) rats and the partial mechanisms focused on T, B lymphocyte subsets through JAK1-STAT3 pathway, including Th17, Treg, total B cells and memory B cells. METHODS: Animals were divided randomly into normal control, AA, SHR0302 (0.3,1.0, 3.0mg/kg) and MTX. The effects of SHR0302 on AA rats by evaluating arthritis index, arthritis global assessment and paw swelling degree, histopathology of joint and spleen...
October 2016: Joint, Bone, Spine: Revue du Rhumatisme
Hitoshi Imamura, Sawako Yoshina, Katsunori Ikari, Keiji Miyazawa, Shigeki Momohara, Shohei Mitani
OBJECTIVE: A non-synonymous single nucleotide polymorphism (nsSNP, rs2233434, Val194Ala) in the NFKBIE (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon) gene is known to be a rheumatoid arthritis (RA) susceptibility polymorphism in the Japanese RA population and could be closely associated with nuclear factor kappaB (NF-κB) activity. Inflammation caused by RA is sometimes associated with changes in expression levels of MTX (methotrexate) pathway-related genes...
July 2016: Modern Rheumatology
Xiao-Rong Yang, Yan Xiong, Hong Duan, Ren-Rong Gong
BACKGROUND: This study aimed to better understand the mechanisms underlying methotrexate (MTX)-resistance in osteosarcoma. METHODS: The raw transcription microarray data GSE16089 collected from three MTX-sensitive osteosarcoma (Saos-2) cell samples and three MTX-resistant osteosarcoma (Saos-2) cell samples were downloaded from Gene Expression Omnibus. After data processing, the differentially expressed genes (DEGs) were identified. Next, DEGs were submitted to DAVID for functional annotation based on the GO (Gene Ontology) database, as well as pathway enrichment analysis based on the KEGG (Kyoto Encyclopedia of Genes and Genomes) database...
2015: Journal of Orthopaedic Surgery and Research
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