The level of cytokines and expression of caspase genes in rheumatoid arthritis

Malysheva, I. E.; Топчиева, Л. В.; Barysheva, O. Yu; Kurbatova, I. V.; Vasykova, O. A.; Везикова, Н. Н.; Марусенко, И. М.; Немова, Н. Н.

doi:10.1134/s1607672916030194

Cited by 9 publications

(6 citation statements)

References 11 publications

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“…Therefore, it is possible that the discrepancy between the findings in this in vivo study and the previous in vitro study may be due to the differences in IL‐6 and TNF‐α concentrations. According to Malysheva et al ., 24 plasma IL‐6 and TNF‐α concentrations in patients with RA under methotrexate treatment were 8.89 ± 1.34 pg/mL and 3.62 ± 0.99 pg/mL, respectively, which did not differ greatly from our findings. Hence, inflammatory cytokines may have little effect on OATP1B activity at plasma concentrations of patients with RA.…”

Section: Discussioncontrasting

confidence: 57%

Factors Influencing Plasma Coproporphyrin‐I Concentration as Biomarker of OATP1B Activity in Patients With Rheumatoid Arthritis

Ono

Tanaka

Suzuki

et al. 2021

Clin Pharma and Therapeutics

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Organic anion transporting polypeptides (OATPs) 1B are drug transporters mainly expressed in the sinusoidal membrane. In previous reports, genetic factor, 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid (CMPF), which is one of the uremic toxins, inflammatory cytokines such as tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) decreased OATP1B1 activity in vitro, but in vivo effects of these factors have not been elucidated. Plasma coproporphyrin‐I (CP‐I) is spotlighted as a highly accurate endogenous substrate of OATP1B. This study focused on patients with rheumatoid arthritis (RA) and evaluated the influence of several factors comprising gene polymorphisms, uremic toxins, and inflammatory cytokines on OATP1B activity using plasma CP‐I concentration. Thirty‐seven outpatients with RA who satisfied the selection criteria were analyzed at the time of recruitment (baseline) and at the next visit. OATP1B1*15 carriers tended to have higher CP‐I concentration compared with noncarriers. Plasma CP‐I correlated positively with CMPF concentration, but did not correlate with IL‐6 or TNF‐α concentration. Multiple logistic regression analysis by stepwise selection identified plasma CMPF concentration and OATP1B1*15 allele as significant factors independently affecting plasma CP‐I concentration at baseline and at the next visit, respectively. In conclusion, the present results suggest that inflammatory cytokines do not have clinically significant effects on OATP1B activity, whereas the effects of genetic polymorphisms and uremic toxins should be considered.

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Section: Discussioncontrasting

confidence: 57%

Factors Influencing Plasma Coproporphyrin‐I Concentration as Biomarker of OATP1B Activity in Patients With Rheumatoid Arthritis

Ono

Tanaka

Suzuki

et al. 2021

Clin Pharma and Therapeutics

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“…Caspase-3 (CASP-3) is known to cause apoptosis in cells. The expression of caspase-3 mRNA in PBLs was significantly higher in MT-treated RA patients than in patients without MT [48]. Our study showed that CASP3 can be directly affected by MOL000422 and MOL003187 compounds and the gene was enriched in the three pathways of IL-17 signaling pathway, MAPK signaling pathway, and TNF signaling pathway.…”

Section: Resultsmentioning

confidence: 82%

A Network Pharmacology Study on the Active Ingredients and Potential Targets ofTripterygium wilfordiiHook for Treatment of Rheumatoid Arthritis

Wei

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Traditional Chinese medicine has specific effect on some chronic diseases in clinic, especially in rheumatic diseases. Tripterygium wilfordii Hook (TWH) is a traditional Chinese medicine commonly used in the treatment of rheumatoid arthritis (RA); the unique therapeutic effect has been confirmed by a large number of research papers. TWH has many compounds that lead to its active compounds. However, the potential targets and pharmacological and molecular mechanism of its action treatment of rheumatic diseases are not entirely clear. Therefore, the network pharmacology approach is needed to further study and explore its treatment mechanism. We have successfully set up 10 networks, including four major networks and other networks. Four major networks include rheumatoid arthritis disease network, compound-compound target network of TWH, TWH compound target-rheumatoid arthritis disease network, and TWH-rheumatoid arthritis disease-mechanism network. Other networks consist of RA disease and TWH related targets clusters, biological processes, and pathways network. Our study successfully predicted, explained, and confirmed the TWH of RA disease molecular synergy and found the potential of RA related targets, cluster, biological process, and pathways. This study not only provides prompts to the researcher who explores pharmacological and biological molecular mechanism of TWH applying to RA disease, but also proves a feasible method for discovering potential activated compounds from Chinese herbs.

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“…For several decades apoptosis has been known to be an important vital biological process that occurs in living cells during tissue development, immune responses [ 39 , 40 ], and homeostasis [ 41 ]. Anti-apoptotic mediators can be abrogated in pathological states, as in cancer [ 42 ] and autoimmunity [ 43 ], or exacerbated, as in stroke [ 44 ], neurodegeneration [ 45 ], retinal cell death [ 46 ], rheumatoid arthritis [ 47 ], myocardial and liver ischemia [ 48 , 49 ], and inflammatory diseases such as sepsis [ 50 ], osteoarthritis (OA) [ 51 ], and asthma [ 52 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, and In Vivo Study of Some Novel 3,4,5-Trimethoxybenzylidene-hydrazinecarbothioamides and Thiadiazoles as Anti-Apoptotic Caspase-3 Inhibitors

et al. 2022

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The present study aims to discover novel derivatives as antiapoptotic agents and their protective effects against renal ischemia/reperfusion. Therefore, a series of new thiadiazole analogues 2a–g was designed and synthesized through cyclization of the corresponding opened hydrazinecarbothioamides 1a–g, followed by confirmation of the structure via spectroscopic tools (NMR, IR and mass spectra) and elemental analyses. The antiapoptotic activity showed alongside decreasing of tissue damage induced by I/R in the kidneys of rats using N-acetylcysteine (NAC) as an antiapoptotic reference. Most of the cyclized thiadiazoles are better antiapoptotic agents than their corresponding opened precursors. Particularly, compounds 2c and 2g were the most active antiapoptotic compounds with significant biomarkers. A preliminary mechanistic study was performed through caspase-3 inhibition. Compound 2c was selected along with its corresponding opened precursor 1c. An assay of cytochrome C revealed that there is an attenuation of cytochrome C level of about 5.5-fold, which was better than 1c with a level of 4.1-fold. In caspases-3, 8 and 9 assays, compound 2c showed more potency and selectivity toward caspase-3 and 9 compared with 1c. The renal histopathological investigation indicated normal renal tissue for most of the compounds, especially 2c and 2g, relative to the control. Finally, a molecular docking study was conducted at the caspase-3 active site to suggest possible binding modes.

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The level of cytokines and expression of caspase genes in rheumatoid arthritis

Cited by 9 publications

References 11 publications

Factors Influencing Plasma Coproporphyrin‐I Concentration as Biomarker of OATP1B Activity in Patients With Rheumatoid Arthritis

Factors Influencing Plasma Coproporphyrin‐I Concentration as Biomarker of OATP1B Activity in Patients With Rheumatoid Arthritis

A Network Pharmacology Study on the Active Ingredients and Potential Targets ofTripterygium wilfordiiHook for Treatment of Rheumatoid Arthritis

Synthesis, Characterization, and In Vivo Study of Some Novel 3,4,5-Trimethoxybenzylidene-hydrazinecarbothioamides and Thiadiazoles as Anti-Apoptotic Caspase-3 Inhibitors

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