Astaxanthin, Compared to Other Carotenoids, Increases the Efficacy of Methotrexate in Rat Adjuvant Arthritis.

This in vivo study performed in rat adjuvant arthritis aims to advance the understanding of astaxanthin's therapeutic properties for the possible treatment of rheumatoid arthritis (RA) in monotherapy and along with the standard RA treatment, methotrexate (MTX), in combination therapy. The main goal was to elucidate astaxanthin's full therapeutic potential, evaluate its dose dependency, and compare its effects in monotherapy with other carotenoids such as ß-carotene and ß-cryptoxanthin (KXAN). Moreover, potential differences in therapeutic activity caused by using different sources of astaxanthin, synthetic (ASYN) versus isolated from Blakeslea trispora (ASTAP), were evaluated using one-way ANOVA (Tukey-Kramer post hoc test). KXAN was the most effective in reducing plasma MMP-9 levels in monotherapy, significantly better than MTX, and in reducing hind paw swelling. The differences in the action of ASTAP and ASYN have been observed across various biometric, anti-inflammatory, and antioxidative parameters. In combined therapy with MTX, the ASYN + MTX combination proved to be better. These findings, especially the significant anti-arthritic effect of KXAN and ASYN + MTX, could be the basis for further preclinical studies.

Impact of culture medium on the interpretation of qRT-PCR data in HepG2 incubated with lactobacilli.

Recently, an increasing number of studies have investigated the mechanism of action of lactobacilli in the treatment of non-alcoholic fatty liver disease. Using four computational tools (NormFinder, geNorm, Delta Ct, and BestKeeper), six potential reference genes (RGs) were analyzed in the human liver cell line HepG2 cultivated 24 h in the presence of two strains of heat-killed lactobacilli, Limosilactobacillus reuteri E and Lactiplantibacillus plantarum KG4, respectively, in different cultivation media [Dulbecco´s Modified Eagle´s Medium (DMEM) high glucose or Roswell Park Memorial Institute (RPMI)]. The analysis revealed that the suitability of RG was similar between the two lactobacilli but quite different between the two media. The commonly used RGs, 18S rRNA and glyceraldehyde-3-phosphate dehydrogenase were the most unstable in DMEM high glucose. Normalization of the mRNA expression of the target gene encoding sterol regulatory element-binding protein 1c (SREBP-1c) to different RGs resulted in different expression profiles. This demonstrates that validation of candidate RGs under specific experimental conditions is crucial for the correct interpretation of quantitative polymerase chain reaction data. In addition, the choice of media has a profound impact on the effect of lactobacilli on lipogenesis at the gene expression level, as shown by the transcription factor SREBP-1c.

Combination Therapy of Carnosic Acid and Methotrexate Effectively Suppressed the Inflammatory Markers and Oxidative Stress in Experimental Arthritis.

BACKGROUND: Combination therapy with methotrexate (MTX) is the most common therapeutic strategy used for the treatment of patients with rheumatoid arthritis (RA). In this study, we combined the natural compound carnosic acid (CA) with MTX to reduce inflammation and oxidative stress in adjuvant arthritis (AA). METHODS: AA was induced in 6-8 rats per group. MTX was administrated twice a week at a dose of 0.3 mg/kg b.w., while CA was administered daily at a dose of 100 mg/kg both in monotherapy and in combination with MTX. Plasma samples were collected on the 14th, 21st, and 28th day. Body weight and hind paw volume were measured once a week. RESULTS: We found that, mainly, the CA + MTX combination significantly reduced the hind paw swelling, the levels of IL-17A, MMP-9, and MCP-1 in plasma, and GGT activity in joint homogenates. The mRNA expression of HO-1, catalase, and IL-1ß in the liver were significantly improved by CA + MTX only. Our results indicate that adding CA to MTX treatment could be a good therapeutic option for patients suffering from RA. CONCLUSIONS: The addition of CA to methotrexate treatment significantly improved its efficacy in decreasing the development of AA by inhibiting the markers of inflammation and oxidative stress.

Alterations of HDL's to piHDL's Proteome in Patients with Chronic Inflammatory Diseases, and HDL-Targeted Therapies.

Chronic inflammatory diseases, such as rheumatoid arthritis, steatohepatitis, periodontitis, chronic kidney disease, and others are associated with an increased risk of atherosclerotic cardiovascular disease, which persists even after accounting for traditional cardiac risk factors. The common factor linking these diseases to accelerated atherosclerosis is chronic systemic low-grade inflammation triggering changes in lipoprotein structure and metabolism. HDL, an independent marker of cardiovascular risk, is a lipoprotein particle with numerous important anti-atherogenic properties. Besides the essential role in reverse cholesterol transport, HDL possesses antioxidative, anti-inflammatory, antiapoptotic, and antithrombotic properties. Inflammation and inflammation-associated pathologies can cause modifications in HDL's proteome and lipidome, transforming HDL from atheroprotective into a pro-atherosclerotic lipoprotein. Therefore, a simple increase in HDL concentration in patients with inflammatory diseases has not led to the desired anti-atherogenic outcome. In this review, the functions of individual protein components of HDL, rendering them either anti-inflammatory or pro-inflammatory are described in detail. Alterations of HDL proteome (such as replacing atheroprotective proteins by pro-inflammatory proteins, or posttranslational modifications) in patients with chronic inflammatory diseases and their impact on cardiovascular health are discussed. Finally, molecular, and clinical aspects of HDL-targeted therapies, including those used in therapeutical practice, drugs in clinical trials, and experimental drugs are comprehensively summarised.