Resveratrol attenuates inflammation and fibrosis in rheumatoid arthritis-associated interstitial lung disease via the AKT/TMEM175 pathway.

BACKGROUND AND PURPOSE: Interstitial lung disease (ILD) represents a significant complication of rheumatoid arthritis (RA) that lacks effective treatment options. This study aimed to investigate the intrinsic mechanism by which resveratrol attenuates rheumatoid arthritis complicated with interstitial lung disease through the AKT/TMEM175 pathway. METHODS: We established an arthritis model by combining chicken type II collagen and complete Freund's adjuvant. Resveratrol treatment was administered via tube feeding for 10 days. Pathological changes in both the joints and lungs were evaluated using HE and Masson staining techniques. Protein expression of TGF-ß1, AKT, and TMEM175 was examined in lung tissue. MRC-5 cells were stimulated using IL-1ß in combination with TGF-ß1 as an in vitro model of RA-ILD, and agonists of AKT, metabolic inhibitors, and SiRNA of TMEM175 were used to explore the regulation and mechanism of action of resveratrol RA-ILD. RESULTS: Resveratrol mitigates fibrosis in rheumatoid arthritis-associated interstitial lung disease and reduces oxidative stress and inflammation in RA-ILD. Furthermore, resveratrol restored cellular autophagy. When combined with the in vitro model, it was further demonstrated that resveratrol could suppress TGF-ß1 expression, and reduce AKT metamorphic activation, consequently inhibiting the opening of AKT/MEM175 ion channels. This, in turn, lowers lysosomal pH and enhances the fusion of autophagosomes with lysosomes, ultimately ameliorating the progression of RA-ILD. CONCLUSION: In this study, we demonstrated that resveratrol restores autophagic flux through the AKT/MEM175 pathway to attenuate inflammation as well as fibrosis in RA-ILD by combining in vivo and in vitro experiments. It further provides a theoretical basis for the selection of therapeutic targets for RA-ILD.

Sleep disturbance and suicidal ideation among youth with depression.

BACKGROUND: Sleep disturbance may exacerbate the risk of suicide among youth with depression, but whether this association is independent of psychopathology requires further study. METHODS: This cross-sectional study included 576 youths (13-25 years old) recruited from January 2022 to May 2023. The patients were first divided into two groups by the presence of suicidal ideation according to the Columbia-Suicide Severity Scale (C-SSRS). Sleep quality was assessed by the Athens Insomnia Scale (AIS) and mental health with the Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA). Logistic regression was conducted to analyze the association between sleep disturbance and suicidal ideation, adjusted for depressive symptoms severity. RESULTS: The suicidal ideation group exhibited more severe sleep disturbances, anxiety symptoms, and depressive symptoms than the non-suicidal ideation group. Pearson correlation showed that sleep disturbance (AIS) was significantly correlated with the severity of anxiety symptoms, depressive symptoms, and suicidal ideation. Logistic regression analysis revealed that the AIS factor "daytime dysfunction" (ß = 0.145; OR = 1.156, 95 % CI: 1.02, 1.309; p = 0.023) was significantly associated with suicidal ideation after adjusting for demographic characteristics and depressive symptoms severity. LIMITATIONS: Due to the cross-sectional nature of the data, no causal inference can be made regarding the observed associations between sleep disturbance and suicidal ideation. CONCLUSION: Sleep disturbance, particularly in the realm of daytime dysfunction, is associated with increased suicidal ideation among depressed youth. Clinicians need to assess and manage sleep disturbance in the context of suicidal ideation for young depression patients.

Development of in situ Li isotope analysis using laser ablation quadrupole inductively coupled plasma mass spectrometry.

RATIONALE: Lithium isotope geochemistry is an important tool in the studies of Earth and planetary materials. In situ Li isotope analyses are typically performed using secondary ion mass spectrometry (SIMS) or laser ablation multicollector inductively coupled plasma mass spectrometry (LA-MC-ICPMS), but these instruments are not widely accessible. Here, the capability of laser ablation quadrupole ICPMS for conducting Li isotopic analyses is evaluated. METHODS: An array of MPI-DING and USGS silicate glass reference materials was analyzed repeatedly over the course of 6 months. These materials range from komatiite to rhyolite in terms of silica content (45.5-75.6 wt%) with 9-45 ppm Li. Their Li isotope compositions have been previously characterized so that matrix effects could be tested with these reference materials. Analyses were conducted using an NWR193 laser ablation system coupled to an Agilent 7900 ICPMS system. RESULTS: Analytical precision is primarily limited by Li concentration in the samples. For samples with ~9 ppm Li, the internal precision is 6‰ (2 SD, 150 µm spot diameter), whereas that for a sample with ~45 ppm Li is 4‰ (2 SD, 120 µm spot diameter). The technique is somewhat sensitive to sample matrix: samples with SiO2 content that deviates from the bracketing standard display fractionated δ7 Li, necessitating correction using a session-specific matrix correction curve. CONCLUSION: Lithium isotope analysis by ns-LA-QICPMS is worthwhile for samples with high Li concentrations and when a matrix-matched standard can be obtained. Although the precision of this method is not as high as those achievable with SIMS and LA-MC-ICPMS, it remains adequate for resolving large isotope fractionations found in natural and laboratory settings.

Factors associated with balance impairments in the community-dwelling elderly in urban China.

BACKGROUND: Identification of factors relevant to balance performance impairments in the elderly population was critical for developing effective interventions and preventions. However, there have been very limited data available based on large scale studies. The present study identified factors that independently contributed to performance impairments in overall balance, domains of static balance, postural stability, and dynamic balance, and individual items. METHODS: A total of 1984 community-dwelling Chinese elderly from urban areas of Shanghai were recruited. Information on demographic characteristic, exercise, and health status were collected with a face-to-face interview. Balance performances were assessed on site by trained investigators based on the X16 balance testing scale. To identify the effectors, ordinal logistic regression analysis was applied for overall balance, static balance, postural stability, and dynamic balance. Binary logistic regression analysis was used for 16 items. RESULTS: The community-dwelling elderly residents were aged from 60 to 97 years old. With increases of age, risks of impairments in overall balance increased gradually (ORs from 1.26 to 3.20, all P < 0.01). In the elderly with overweight and obesity, there was higher proportion of balance impairments compared to the elderly with normal BMI (OR = 1.26, P < 0.001). Regular exercise every week was associated with reduced risks of balance impairments (ORs from 0.63 to 0.73, all P < 0.001). Presences with vision lesion (ORs from 1.28 to 1.59, all P < 0.001), moderate hearing impairment (OR = 1.54, P < 0.001), somesthesis dysfunction (ORs from 1.59 to 13.26, all P < 0.001), and cerebrovascular disease (OR = 1.45, P = 0.001) were related to increased risks of balance impairments. Likewise, age, exercise, vision, hearing, somesthesis, and cerebrovascular disease were significantly associated with static balance, postural stability, and dynamic balance. Both overweight and obesity and underweight were associated with higher proportions of dynamic balance impairments. Regular exercise was significantly related to reduced risks of impairments in 15 out of the 16 items. CONCLUSIONS: In the elderly, age, overweight and obesity, exercise, vision, hearing, somesthesia, and cerebrovascular disease were dominant factors associated with impairments in overall balance, domains of static balance, postural stability, and dynamic balance, and most individual items. TRIAL REGISTRATION: Not applicable.

The regulatory role and mechanism of lncTUG1 on cartilage apoptosis and inflammation in osteoarthritis.

BACKGROUND: Long-stranded non-coding RNA TUG1 is lowly expressed in osteoarthritic chondrocytes. This study aimed to elucidate the role of TUG1 in osteoarthritic cartilage damage and the underlying mechanisms. METHODS: Combined database analysis, using primary chondrocytes as well as the C28/I2 cell line, was performed by qRT-PCR, Western blotting, and immunofluorescence to determine the expression of TUG1, miR-144-3p, DUSP1, and other target proteins. Dual luciferase reporter gene and RIP to verify direct interaction of TUG1 with miR-144-3-p and miR-144-3-p with DUSP1, Annexin V-FITC/PI double staining to detect apoptosis. CCK-8 to detect cell proliferation. The biological significance of TUG1, miR-144-3p, and DUSP1 was assessed in vitro experiments using siRNA for TUG1, mimic and repressor for miR-144-3p, and overexpression plasmid for DUSP1. In this study, all data were subjected to a t-test or one-way analysis of variance with a p-value < 0.05 as the cutoff. RESULTS: TUG1 expression was closely associated with osteoarthritic chondrocyte damage, and knockdown of TUG1 significantly promoted chondrocyte apoptosis and inflammation. In the present study, we found that TUG1 inhibited chondrocyte apoptosis and inflammation by competitively binding miR-144-3p, deregulating the negative regulatory effect of miR-144-3p on DUSP1, promoting DUSP1 expression, and inhibiting the p38 MAPK signaling pathway. CONCLUSIONS: In conclusion, our study clarifies the role of the ceRNA regulatory network of TUG1/miR-144-3p/DUSP1/P38 MAPK in OA cartilage injury and provides an experimental and theoretical basis for genetic engineering tools to promote articular cartilage repair.

Resveratrol Ameliorates Fibrosis in Rheumatoid Arthritis-Associated Interstitial Lung Disease via the Autophagy-Lysosome Pathway.

Interstitial lung disease associated with rheumatoid arthritis (RA-ILD) can lead to interstitial fibrosis and even lung failure as a complication of rheumatoid arthritis (RA), and there is currently no effective treatment and related basic research. Studies have found that resveratrol (Res) can improve the progression of RA by regulating autophagy, and increasing evidence supports the connection between autophagy and common interstitial lung disease (ILD). We explored changes in autophagy levels in fibrotic lungs in RA-ILD and found that the level of autophagy is enhanced in the early stage but inhibited in the late stage. However, resveratrol treatment improved the level of autophagy and reversed the inhibition of autophagy, and attenuated fibrosis. We created corresponding cell models that exhibited the same phenotypic changes as animal models; under the effect of resveratrol, the level of fibrosis changed accordingly, and the fusion process of lysosomes and autophagosomes in autophagy was liberated from the inhibition state. Resveratrol effects were reversed by the addition of the late autophagy inhibitor chloroquine. These results suggest that resveratrol attenuates pulmonary fibrosis, increases autophagic flux, and modulates the autophagy-lysosome pathway, and particularly it may work by improving the formation of autophagic lysosomes, which may be an effective treatment for induced RA-ILD.