MTX&down

PURPOSE: Methotrexate (MTX) induces hepatotoxicity, limiting its clinical efficacy as a widely known chemotherapy drug. In the current study, we examined the protective effect of human placenta extract (HPE) against MTX-induced liver damage in rats, as well as its ability to regulate antioxidative and anti-inflammatory liver responses. METHODS: Male rats were orally administered MTX at a daily dose of 5 mg/kg-body-weight in the presence or absence of HPE (10.08 mg/kg) for 2 weeks...

Glycyrrhiza glabra root (licorice) is a widely used herb for its beneficial effects on health. This study explored the protective effects of licorice extract against oxidative stress and testicular dysfunction caused by methotrexate (MTX). Mice were allocated into (i) negative control group that received saline; (ii) licorice extract group, orally administered with 200 mg/kg body weight (bw) licorice extract for 12 days; (iii) positive MTX-intoxicated group, injected with a single intraperitoneal dose of MTX (20 mg/kg bw) on day 7; and (iv) a protective group that received licorice extract for 12 days and then MTX on day 7 as in groups 2 and 3...

AIM: Male reproductive toxicity is becoming of growing significance due to clinical chemotherapy usage. Methotrexate (MTX) is an anti-folate used on a large scale for different tumors and autoimmune conditions. Despite its wide clinical use, MTX is associated with severe testicular intoxication. The exact underlying mechanism is unclear. METHODS: Our study was conducted to explore the pathogenesis mechanism of MTX-induced testicular damage and the potential testicular protective effects of apocynin (APO) on testicular injury induced by single i...

Rheumatoid arthritis (RA) is an inflammatory disease with challenging therapeutic potential due to the implication of cross-talking intracellular pathways in the pathogenesis of the disease. This study aimed to evaluate the effects of the combination therapy of atorvastatin and quercetin on glycogen synthase kinase-3 beta/ nuclear factor kappa-B/ nucleotide-binding oligomerization domain-like receptor family pyrin domain containing-3 or inflammasome (GSK-3β/NF-KB/NLRP-3) pathway as well as on microRNAs 26b and 20a (miR-26b, miR-20a) and to investigate the possible beneficial outcomes of the combination to offer a better treatment option than methotrexate (MTX) in adjuvant-induced arthritis (AIA)...

Sinomenine (SIN) is a clinical drug for treating rheumatoid arthritis (RA) in China. Our previous study found SIN inhibited inflammation via alpha7 nicotinic acetylcholine receptor (α7nAChR) in macrophages in vitro. Adenosine receptor A2A has anti-inflammatory and immunosuppressive function. However, the mechanisms of SIN acting on α7nAChR and the effect on adenosine A2A receptor (A2A R) in RA are not clear. In the present study, the effects of SIN on adjuvant-induced-arthritis (AIA) rats in vivo and on fibroblast-like synoviocytes (FLSs) in vitro were investigated...

BACKGROUND: Imbalance between apoptosis and autophagy in fibroblast-like synoviocytes (FLS) is one of the pathogenic mechanisms responsible for their abnormal proliferation in rheumatoid arthritis (RA). Methotrexate (MTX) demonstrated limited efficacy in amending this imbalance in fluid-derived (fd)-FLS. The active compound of black tea Theaflavin 3,3'-digallate (TF3) may be effective in restoring apoptosis-autophagy imbalance in (fd)-FLS. The combined effect of MTX + TF3 upon the same is yet to be elucidated...

AIM: The present study was undertaken to elucidate the potential protective mechanism of berberine (BBR) and/or zinc (Zn) against methotrexate (MTX)-induced intestinal injury. METHODS: Five groups of rats were assigned; normal group (received vehicle), MTX group (20 mg/kg; i.p. single dose), and the other three groups received a single daily oral dose of BBR (50 mg/kg), Zn (5 mg/kg), and BBR plus Zn respectively, for 5 days before MTX and 5 days after...

BACKGROUND: Methotrexate (MTX) is used potently for a wide range of diseases. However, hepatic intoxication by MTX hinders its clinical use. OBJECTIVES: The present study was conducted to investigate the diallyl disulfide (DADS) ability to ameliorate MTX-induced hepatotoxicity. METHODS: Thirty-two rats were randomly divided into four groups: normal control, DADS (50 mg/kg/day, orally), MTX (single i.p. injection of 20 mg/kg) and DADS+MTX. Liver function biomarkers, histopathological examinations, oxidative stress, inflammation, and apoptosis biomarkers were investigated...

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease which causes disability and threatens the health of humans. Therefore, it is of great significance to seek novel effective drugs for RA. It has been reported that various ginsenoside monomers are able to treat RA. However, it is still unclear which ginsenoside is the most effective and has the potential to be developed into an anti-RA drug. METHODS: The ginsenosides, including Rg1, Rg3, Rg5, Rb1, Rh2 and CK, were evaluated and compared for their therapeutic effect on RA...

OBJECTIVE: To explore non-steroidal anti-inflammatory drug (NSAID) and analgesic use in early rheumatoid arthritis (eRA) patients with a favourable risk profile initiating methotrexate (MTX) with or without glucocorticoid (GC) bridging. METHODS: Patients with eRA (≤1 year) and favourable risk profile (no erosions, negative rheumatoid factor and anticitrullinated protein antibodiesor low disease activity) in the 2-year CareRA trial were randomised to MTX 15 mg with a step-down GC scheme (COBRA Slim), or MTX without oral GCs, Tight-Step-Up (TSU)...

Methotrexate (MTX) is a promising chemotherapeutic agent. Its medical use is limited by induced nephropathy. Our study was designed to explore the reno-protective effect of diallyl disulfide (DADS), an organosulfur compound of garlic oil, on MTX-induced nephropathy. Adult rats were randomly divided into 4 groups; normal control, DADS (50 mg kg-1  day-1 , p.o.), MTX (20 mg/kg, i.p.) and DADS+MTX. DADS significantly decreased serum creatinine, urea, uric acid, and albumin levels with an improvement of final body weight...

Cholangiocarcinoma (CCA) is a type of solid tumor derived from the bile duct epithelium that features universal gemcitabine resistance. Here, we utilized a gene-encoded ROS biosensor probe (HyPer3 probe) to sort subpopulations with different redox statuses from CCA cells. The isolated HyPer-low subpopulation CCA cells, which exhibited relatively lower cellular ROS levels, exhibited higher chemoresistance to gemcitabine than HyPer-high subpopulation CCA cells in vitro and in vivo. Mechanistically, increased expression of MTHFD1 was found in HyPer-low cells...

Methotrexate (MTX) is known antagonist of folic acid and widely used as an anti-cancer drug. The folate receptor (FR) and reduced folate carrier are mostly responsible for internalization of methotrexate in tumor cells. Mutation in reduced folate carrier (RFC) leads to resistance against MTX in various tumor cell lines including MDA-MB-231 breast cancer cells. To overcome the resistance of MTX, folate receptor targeted nanoparticles have been commonly used for targeting breast tumors. The aim of the study is to determine the ability of methotrexate gold nanoparticles (MTX-GNPs) in the induction of apoptosis and to explore the molecular changes at genomics and proteomics level...

Objective To investigate the therapeutic effect of Bushentongluo recipe (BSTL) on bone destruction and its inhibiting effect on NF-κB/RANK/RANKL pathway in collagen-induced arthritis (CIA) rats. Methods SD rats were randomly divided into blank control group, CIA model group, methotrexate (MTX, 1 mg/kg) group, BSTL 0.5 g/kg and 2 g/kg groups, with 10 rats in each. Except the control group, the other rats were injected subcutaneously with type 2 collagen(Col2) at the base of the tail to establish CIA models...

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is a chronic inflammatory skin disease mediated by immunity. Our pre-clinical studies have proved that QZLX mixture can improve patients' clinical symptoms with psoriasis without noticeable adverse reactions. In a psoriasis-like mouse model induced by imiquimod, QZLX mixture has been shown to alleviate epidermal inflammation and inhibit the hyperproliferation of keratinocytes. However, its related molecular mechanism remains to be elucidated. AIM OF THE STUDY: To assess the mechanism of QZLX mixture against psoriasis...

OBJECTIVES: To assess current practices around the use of combination immunosuppression in paediatric inflammatory bowel disease (PIBD) with a focus on the subsequent withdrawal process. METHODS: A web-based, 43-question survey. RESULTS: Surveys were completed by 70 paediatric gastroenterologists (PGs) from 27 nations across Europe, North America, Oceania and Asia from 62 centres covering approximately 15,000 PIBD patients (median of 200 patients [interquartile range (IQR) 130-300] per centre)...

Background: The bark of Securidaca inappendiculata Hassk. is traditionally used for treating inflammatory diseases and bone fractures in China. We have previously validated the xanthone-enriched fraction (XRF) of S. inappendiculata with anti-rheumatic potentials, but mechanism underlying the joints protective effects is still largely unknown. Materials and Methods: The male rats with collagen-induced arthritis (CIA) were treated with XRF. The therapeutic efficacy of XRF was evaluated by arthritis score changes, morphological observation of paws, histological examinations and serological analyses...

MicroRNA-24-3p (miR-24-3p) has been implicated as a key promoter of chemotherapy resistance in numerous cancers. Meanwhile, cancer-associated fibroblasts (CAFs) can secret exosomes to transfer miRNAs, which mediate tumour development. However, little is known regarding the molecular mechanism of CAF-derived exosomal miR-24-3p in colon cancer (CC). Hence, this study intended to characterize the functional relevance of CAF-derived exosomal miR-24-3p in CC cell resistance to methotrexate (MTX). We identified differentially expressed HEPH, CDX2 and miR-24-3p in CC through bioinformatics analyses, and validated their expression in CC tissues and cells...

The aim is to evaluate the published evidence on whether methotrexate (MTX) use causes progressive fibrotic interstitial lung disease (fILD). This PRISMA-compliant systematic review has been registered electronically with PROSPERO 2018 ID CRD42018087838, Centre of review and dissemination at the University of York. A total of 29 articles met the inclusion criteria. Thirteen articles were found to support the claim that MTX causes fILD. They all had a low Downs and Black quality score (< 6/27). Their 'risk of bias' assessment scores indicated serious to critical risk of bias...

OBJECTIVES: Treatment with golimumab monotherapy in early peripheral Spondyloarthritis (pSpA) results in higher rates of clinical remission compared to treatment in more longstanding disease. When reaching remission, treat-to-target recommendations suggest tapering of treatment. We therefore explored whether addition of methotrexate would permit discontinuation of golimumab in patients with pSpA in sustained clinical remission. METHODS: After a 2-year extension phase with golimumab treatment, patients with pSpA reaching clinical remission in the CRESPA-trial were offered a tapering strategy leading to discontinuation of golimumab and replacement by methotrexate monotherapy...