Exploring the supplementary potential of all-trans retinoic acid with methotrexate in rheumatoid arthritis: modulation of synovial cell apoptosis and autophagy.

OBJECTIVES: The imbalance between apoptosis and proliferation in fibroblast-like synoviocytes (FLSs) plays a key role in the pathogenesis of rheumatoid arthritis (RA). This study aims to investigate the potential of all-trans retinoic acid (ATRA) as a supplementary therapeutic agent alongside methotrexate (MTX) for RA, by examining its ability to inhibit synovial cell proliferation and enhance apoptosis through the ROS-JNK signalling pathway. METHODS: The viability, apoptosis, and autophagy levels of human rheumatoid arthritis fibroblast-like synovial cells (HFLS-RA) were evaluated, while ROS generation was measured through the DCFH-DA fluorescence microplate assay. Western blotting was used to analyse the expression levels of JNK signalling pathway-related proteins. To assess therapeutic potential in vivo, a collagen-induced arthritis (CIA) model was established in Wistar rats. RESULTS: Small doses of MTX did not significantly affect the viability of HFLS-RAs or induce apoptosis. However, when ATRA was added to the treatment, the therapy markedly inhibited cell proliferation and induced apoptosis and excessive autophagy. Mechanistically, ATRA activated the ROS/JNK signalling pathway in HFLS-RAs. ROS scavengers and JNK inhibitors significantly attenuated ATRA-induced apoptosis and autophagy. In vivo, the combination therapy demonstrated a remarkable enhancement of the anti-arthritic efficacy in CIA rats. CONCLUSIONS: The ability of ATRA to inhibit proliferation in RA FLSs through autophagy and apoptosis underscores its potential as a supplementary therapeutic agent alongside MTX for RA, particularly when compared to the limited impact of MTX on these processes. This combined strategy holds promise for enhancing therapeutic outcomes and warrants further investigation in the management of RA.

Experience of undergraduate nursing students participating in artificial intelligence + project task driven learning at different stages: a qualitative study.

BACKGROUND: Artificial intelligence is a growing phenomenon that will soon facilitate wide-scale changes in many professions, and is expected to play an important role in the field of medical education. This study explored the realistic feelings and experiences of nursing undergraduates participating in different stages of artificial intelligence + project task driven learning, and provide a basis for artificial intelligence participation in nursing teaching. METHODS: We conducted face-to-face semi-structured interviews with nursing undergraduates participating in Nursing Research Course which adopts artificial intelligence + project task driven learning from a medical university in Ningxia from September to November 2023, to understand their experience of using artificial intelligence for learning and the emotional changes at different stages. The interview guide included items about their personal experience and feelings of completing project tasks through dialogue with artificial intelligence, and suggestions for course content. Thematic analysis was used to analyze interview data. This study followed the COREQ checklist. RESULTS: According to the interview data, three themes were summarized. Undergraduate nursing students have different experiences in participating in artificial intelligence + project task driven learning at different stages, mainly manifested as diverse emotional experiences under initial knowledge deficiency, the individual growth supported by external forces during the adaptation period, and the expectations and suggestions after the birth of the results in the end period. CONCLUSIONS: Nursing undergraduates can actively adapt to the integration of artificial intelligence into nursing teaching, dynamically observe students' learning experience, strengthen positive guidance, and provide support for personalized teaching models, better leveraging the advantages of artificial intelligence participation in teaching.

Dietary diversity, diet quality, and oxidative stress in older adults.

This cross-sectional study aimed to explore the relationship between diet quality, dietary diversity, and oxidative stress levels in older adults in parts of the Ningxia Hui Autonomous Region in northwestern China. A total of 335 participants voluntarily participated in the study from April to July 2021. Laboratory tests and questionnaires were used to obtain general characteristics, dietary conditions, and indicators of oxidative stress. The dietary diversity scores of the participants were 5.20±1.39, the diet quality indices were 56.91±11.14, and most had poor diet quality. The levels of the oxidative stress markers malondialdehyde, superoxide dismutase, 8-iso-prostaglandin F2α, and total antioxidant capacity were 4.77±1.77, 40.33±9.85, 763.10±245.41, and 1.02±0.14, respectively. The results showed that the diet quality scores of participants were related to dietary diversity and whether the scores passed or not was significantly related to total antioxidant capacity.

[Effects of Genistein on Whole Genome Expression Profiles of Mice Testes Tissue Cultured in vitro].

OBJECTIVE: To investigate the effects of Genistein (Gen) on the whole expression profiles of testes in mice by using the gene chip technology,and analyze the mechanism how Gen exerts testis on gene level. METHODS: The testicular tissues of suckling mice were cultured in vitro,and separated into control group and Gen group with the dose of 5 µmol/L. After 72 h of culture,we extracted the total RNA and purified it,then detected the gene expression by using Agilent gene array. RESULTS: Compared with the control,there were 84 genes expressed differently in Gen group,including 47 upregulated genes and 37 downregulated genes. We classified these genes as 14 categories in Gen group by GO ( P<0.05),including cell proliferation,cell death,the immune system and reproductive development. CONCLUSION: The whole gene chip test found that Gen can mainly affect the functions of testes by regulating the expression of gene related to cell development,proliferation and cell cycle function, which can influence the spermatogenesis and change the testis cell proliferation and apoptosis.

[The Effects of All-trans Retinoic Acid on the Expression of Inflammatory Cytokines and Cartilage Damage Related Protease in Rats with Collagen Induced Arthritis].

OBJECTIVES: To investigate the effects of all-trans retinoic acid (ATRA) on arthritis and the expressions of inflammatory cytokines and cartilage damage related proteases of the collagen-induced arthritis model (CIA) rats in vivo. METHODS: The CIA model of rheumatoid arthritis was induced with C2 and incomplete Freund's adjuvant. The rats were randomly divided into control group, CIA model group and two ATRA dose groups (ATRA 0.50 mg/kg group and ATRA 1.00 mg/kg group). ATRA were given three times per week for six weeks in ATRA groups. Morphological changes, arthritis index (AI) scores, the semi-quantitative scores of pathology damage, the protein expressions of cartilage damage related proteases and the serum levels of TNF-α, IL-17A, IFN-γ, IL-4, IL-10 were observed. RESULTS: The AI scores of ATRA groups were similar to CIA model group ( P<0.05). Apparent morphological disorders in knee and ankle joints were observed in the CIA model group and ATRA 1.00 mg/kg group. The structure of knee joint was improved slightly in ATRA 0.50 mg/kg group. The serum levels of TNF-α, IFN-γ and IL-17A were decreased in both ATRA groups; ATRA also can increase the serum level of IL-4. Compared to CIA model group, the protein expressions of ADAMTS-4, MMP3, MMP1 were decreased in both ATRA groups ( P<0.05). CONCLUSIONS: ATRA, which was able to inhibit pro-inflammatory cytokines secretion, could correct the imbalance of Th1/Th2 and Th17/Treg. ATRA also can reduce the expressions of cartilage damage related proteases, which proved that ATRA may have a beneficial effect on rheumatoid arthritis.

Effects of All-Trans Retinoic Acid on Lipopolysaccharide-Induced Synovial Explant.

The present study was conducted to assess the effect of all-trans retinoic acid (ATRA) on synovial explants from rats with rheumatoid arthritis (RA) induced by lipopolysaccharides (LPS). In our study, synovial membranes were excised from the knees of healthy adult Wistar female rats under sterile conditions. We first investigated the synoviums incubated in a control medium or in a medium containing 10 µg/mL LPS, each for 24, 48, and 72 h (LPS-experiment). The changes in inflammatory response from the synoviums were observed at different culture times. Then, we assessed the synoviums exposed to different ATRA concentrations for 24 h (ATRA-experiment). The controls (blank, model group, and solvent groups) were set up. The effects of ATRA on synovitis were evaluated by measuring the production of cytokines, and nitric oxide (NO) and the expression of cartilage damage related proteases. In the LPS-experiment, LPS contributed to the release of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and matrix metalloproteinase-9 (MMP-9) in synovial explants. Importantly, LPS did not cause a significant pathological damage. The inflammatory response observed in this model was significant for 24 h, suggesting that LPS-induced synovial explants were successfully established. In the ATRA-experiment, ATRA suppressed the expression of IL-6, TNF-α, NO, a disintegrin and metalloprotease with thrombospondin motifs-4 (ADAMTS-4), MMP-3, and MMP-9. Taken together, ATRA exhibited inhibitory effects on LPS-induced synovial immune inflammatory response stimulated by the regulation of inflammatory mediators and cartilage damage related proteases in synovial explants, demonstrating a potential protective effect on synovitis and joint destruction in the patients with RA.

The quality of evidence on nutrition intervention published in Chinese journals: an assessment of meta-analyses on vitamin interventions.

BACKGROUND AND OBJECTIVES: The quality of meta-analyses (MAs) on nutrition intervention in mainland China remains uninvestigated. To assess the quality of the evidence regarding nutrition intervention in mainland China, we used vitamin intervention as an example to assess the overall methodological and reporting qualities of MAs on nutrition interventions published in Chinese journals. METHODS AND STUDY DESIGN: A cross-sectional study on MAs of vitamin interventions was performed. Four Chinese databases were searched from inception through September 2016 for all MAs of vitamin intervention. A Measurement Tool to Assess Systematic Reviews (AMSTAR) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements were used to assess methodological and reporting qualities, respectively. RESULTS: A total of 43 MAs of vitamin interventions were included, but none of the studies had been updated. These reviews mainly focused on the effects of interventions involving vitamin D, B vitamins and vitamin E, and the most studied condition was "Endocrine, Nutritional and Metabolic diseases," such as diabetes, obesity, and nutritional rickets. The median AMSTAR score was 6 (0-7), and median PRISMA score was 18 (3-24). No study provided an 'a priori' design, a list of excluded studies, or a statement on conflict of interest, and less than 50.0% of included MAs stated the publication status and performed an adequate structure summary. CONCLUSIONS: The quality of the included MAs was disappointing regarding some items, and some lower quality reviews should be updated. Future MAs should improve on reporting conflicts of interest, harm, and publication bias.

[Prophylactic administration of all-trans retinoic acid alleviates inflammation in rats with collagen-induced arthritis].

OBJECTIVE: To investigate the effects of prophylactic administration of all-trans retinoic acid (ATRA) in relieving inflammation in a rat model of collagen-induced arthritis (CIA). METHODS: Female Wistar rats (6 to 8 weeks old) were randomly divided into normal control group, solvent control group, and prophylactic ATRA treatment (0.05, 0.5, and 5 mg/kg) groups. All the rats except for those in normal control group were subjected to subcutaneous injection of type II collagen and incomplete Freund adjuvant in the tails to induce CIA, followed by injection on the following day with saline, corn oil or different doses of ATRA 3 times a week. The arthritis index (AI) scores, histological scores, serum levels of TNF-α, IL-17A, and IL-10, and expressions of proteases related with cartilage damage were evaluated. RESULTS: On the 15th day after the primary immunization, the AI scores increased significantly in all but the normal control groups; the scores increased progressively in all the 3 ATRA groups but remained lower than that in the solvent control group, which was stable over time. The rats in the 3 ATRA groups showed obvious pathologies in the knee and ankle joints, but the semi-quantitative scores of pathology damage showed no significance among them. Compared with those in solvent control group, the serum IL-17A and TNF-α levels decreased, serum IL-10 level increased, and the expressions of ADAMT-4 and MMP-3 proteins decreased significantly in the knees in the 3 ATRA groups. CONCLUSION: ATRA can reduce the production of TNF-α and IL-17A and increase the production of IL-10 to alleviate the inflammation in rats with CIA. ATRA may delay the progression of RA by correcting the imbalance of Th1/Th2 and Th17/Treg.