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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)...
August 17, 2016: 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...
July 18, 2016: 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
Yu Wei, Xiaoxun Sun, Minhui Hua, Wenfeng Tan, Fang Wang, Miaojia Zhang
T-614 (also named as iguratimod), a novel antirheumatic drug, could attenuate joint inflammation and articular damage in rheumatoid arthritis (RA) patients, providing a new therapy for RA. Here, we tested the role T-614 on the IL-6-induced receptor activator of nuclear factor κB ligand (RANKL)/osteoprotegerin (OPG), IL-17, and MMP-3 expression in synovial fibroblasts from rheumatoid arthritis (RASFs) patients. T-614 decreased RANKL expression and RANKL/OPG ratio in IL-6-induced RASFs. We confirmed this effect by a decrease of the mRNA and protein RANKL and mRNA RANKL/OPG in RASFs exposed in vitro to T-614 or MTX...
2015: BioMed Research International
Shin-Young Kang, Yeon-Gu Kim, Hong Weon Lee, Eun Gyo Lee
Gene amplification using dihydrofolate reductase gene (dhfr) and methotrexate (MTX) is widely used for recombinant protein production in mammalian cells and is typically conducted in DHFR-deficient Chinese hamster ovary (CHO) cell lines. Generation of DHFR-deficient cells can be achieved by an expression vector incorporating short hairpin RNA (shRNA) that targets the 3'-untranslated region (UTR) of endogenous dhfr. Thus, shRNAs were designed to target the 3'-UTR of endogenous dhfr, and shRNA-2 efficiently down-regulated dhfr expression in CHO-K1 cells...
December 2015: Applied Microbiology and Biotechnology
Michael B Cammarata, Ross Thyer, Jake Rosenberg, Andrew Ellington, Jennifer S Brodbelt
The stepwise reduction of dihydrofolate to tetrahydrofolate entails significant conformational changes of dihydrofolate reductase (DHFR). Binary and ternary complexes of DHFR containing cofactor NADPH, inhibitor methotrexate (MTX), or both NADPH and MTX were characterized by 193 nm ultraviolet photodissociation (UVPD) mass spectrometry. UVPD yielded over 80% sequence coverage of DHFR and resulted in production of fragment ions that revealed the interactions between DHFR and each ligand. UVPD of the binary DHFR·NADPH and DHFR·MTX complexes led to an unprecedented number of fragment ions containing either an N- or C-terminal protein fragment still bound to the ligand via retention of noncovalent interactions...
July 22, 2015: Journal of the American Chemical Society
Tahereh Komeili-Movahhed, Shamileh Fouladdel, Elmira Barzegar, Shekoufeh Atashpour, Mohammad Hossein Ghahremani, Seyed Nasser Ostad, Zahra Madjd, Ebrahim Azizi
OBJECTIVES: Multidrug resistance (MDR) of cancer cells is a major obstacle to successful chemotherapy. Overexpression of breast cancer resistance protein (BCRP) is one of the major causes of MDR. In addition, it has been shown that PI3K/Akt signaling pathway involves in drug resistance. Therefore, we evaluated the effects of novel approaches including siRNA directed against BCRP and targeted therapy against PI3K/Akt signaling pathway using LY294002 (LY) to re-sensitize breast cancer MCF7 cell line to mitoxantrone (MTX) chemotherapy...
May 2015: Iranian Journal of Basic Medical Sciences
Mohamed G Ewees, Tamer M Abdelghany, Abdel-Aziz H Abdel-Aziz, Mohamed S Abdel-Bakky
Methotrexate (MTX) is a widely used drug for treatment of rheumatic and autoimmune diseases as well as different types of cancer. One of the major side effects of MTX is hepatotoxicity. Retinoid receptors, including retinoid X receptor (RXR), and retinoic acid receptor (RAR) are vitamin A receptors that are highly expressed in the liver and regulate important physiological processes through regulation of different genes. In this study, we investigated the effect of MTX on RXR-α and RAR-α expression in the liver and the potential protective effects of all-trans retinoic acid (ATRA) in MTX-induced hepatotoxicity...
September 2015: Naunyn-Schmiedeberg's Archives of Pharmacology
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, Kristien Van der Elst, Sabrina Meyfroidt, Rene Westhovens
INTRODUCTION: Considering a lack of efficacy data in patients with early rheumatoid arthritis (eRA) presenting without classical markers of poor prognosis, we compared methotrexate (MTX) with or without step-down glucocorticoids in the CareRA trial. METHODS: Disease-modifying antirheumatic drug-naïve patients with eRA were stratified into a low-risk group based on prognostic markers that included non-erosiveness, anti-citrullinated protein antibodies and rheumatoid factor negativity and low disease activity (Disease Activity Score in 28 joints based on C-reactive protein (DAS28(CRP)) ≤3...
2015: Arthritis Research & Therapy
Jaleh Barar, Vala Kafil, Mostafa Heidari Majd, Abolfazl Barzegari, Sajjad Khani, Mohammad Johari-Ahar, Davoud Asgari, George Coukos, George Cokous, Yadollah Omidi
BACKGROUND: Targeted delivery of anticancer chemotherapeutics such as mitoxantrone (MTX) can significantly intensify their cytotoxic effects selectively in solid tumors such as breast cancer. In the current study, folic acid (FA)-armed and MTX-conjugated magnetic nanoparticles (MNPs) were engineered for targeted eradication of folate receptor (FR)-positive cancerous cells. Polyethylene glycol (PEG), FA and MTX were covalently conjugated onto the MNPs to engineer the PEGylated FA-MTX-MNPs...
2015: Journal of Nanobiotechnology
Mehran Mesgari Abbasi, Rana Jahanban-Esfahlan, Amir Monfaredan, Khaled Seidi, Hamed Hamishehkar, Monir Moradzadeh Khiavi
Oral cancer is one of the most common and lethal cancers in the world. Combination chemotherapy coupled with nanoparticle drug delivery holds substantial promise in cancer therapy. This study aimed to evaluate the efficacy and safety of two dosages of our novel pH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NPs) with attention to the MMP-2 mRNA profile in a 4-nitroquinoline-1-oxide induced oral squamous cell carcinoma (OSCC) model in the rat. Our results showed that both IV and oral dosages of DOX-MTX NP caused significant decrease in mRNA levels of MMP-2 compared to the untreated group (p<0...
2014: Asian Pacific Journal of Cancer Prevention: APJCP
Raimundo Fernandes de Araújo, Maria Patrícia Oliveira da Silva Reinaldo, Gerly Anne de Castro Brito, Pedro de França Cavalcanti, Marco Aurélio Freire, Marco Aurélio de Moura Freire, Caroline Addison Xavier de Medeiros, Aurigena Antunes de Araújo
Methotrexate (MTX) is a pro-oxidant compound that depletes dihydrofolate pools and is widely used in the treatment of leukaemia and other malignancies. The efficacy of methotrexate is often limited by mucositis and intestinal injury, which are major causes of morbidity in children and adults. The aim of this study was to evaluate the effect of olmesartan (OLM), an angiotensin II receptor antagonist, on an Intestinal Mucositis Model (IMM) induced by MTX in Wistar rats. IMM was induced via intraperitoneal (i...
2014: PloS One
Mehran Mesgari Abbasi, Amir Monfaredan, Hamed Hamishehkar, Rana Jahanban-Esfahlan
BACKGROUND: Oral squamous cell carcinoma (OSCC) remains as one of the most difficult malignancies to control because of its high propensity for local invasion and cervical lymph node dissemination. In this study, we evaluate the efficacy of our novel pH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in affecting HER2 expression profile in OSCC model in rat. RESULTS: DOX-MTX- nanoparticle complexes caused significant decrease in mRNA level of HER2 compared to untreated cancers (p<0...
2014: Asian Pacific Journal of Cancer Prevention: APJCP
Neda Alidadiyani, Roya Salehi, Shahrooz Ghaderi, Nasser Samadi, Soodabeh Davaran
In this study, the ability of methotrexate (MTX)-loaded stimuli-responsive novel silica nanocomposites (MSNs) (with mean diameter of ± 60 nm) in the induction of apoptosis, and change in the Bax/Bcl-2 mRNA levels, were investigated. MTT assay and RT -PCR analysis were performed on MDA-MB-231 breast cancer cells, to evaluate their anti-proliferative, apoptotic and anti-apoptotic effects. MTX-loaded MSNs caused marked decrease in the percentage of viable cells, with a significant down-regulation in the level of expression of the anti-apoptotic gene (Bcl-2), and up-regulation in the apoptotic gene (Bax)...
2016: Artificial Cells, Nanomedicine, and Biotechnology
P Verschueren, D De Cock, L Corluy, R Joos, C Langenaken, V Taelman, F Raeman, I Ravelingien, K Vandevyvere, J Lenaerts, E Geens, P Geusens, J Vanhoof, A Durnez, J Remans, B Vander Cruyssen, E Van Essche, A Sileghem, G De Brabanter, J Joly, S Meyfroidt, K Van der Elst, R Westhovens
OBJECTIVES: To compare the efficacy and safety of intensive combination strategies with glucocorticoids (GCs) in the first 16 weeks (W) of early rheumatoid arthritis (eRA) treatment, focusing on high-risk patients, in the Care in early RA trial. METHODS: 400 disease-modifying antirheumatic drugs (DMARD)-naive patients with eRA were recruited and stratified into high risk or low risk according to classical prognostic markers. High-risk patients (n=290) were randomised to 1/3 treatment strategies: combination therapy for early rheumatoid arthritis (COBRA) Classic (methotrexate (MTX)+ sulfasalazine+60 mg prednisone tapered to 7...
January 2015: Annals of the Rheumatic Diseases
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