All-trans retinoic acid pretreatment of mesenchymal stem cells enhances the therapeutic effect on acute kidney injury.

A promising new therapy option for acute kidney injury (AKI) is mesenchymal stem cells (MSCs). However, there are several limitations to the use of MSCs, such as low rates of survival, limited homing capacity, and unclear differentiation. In search of better therapeutic strategies, we explored all-trans retinoic acid (ATRA) pretreatment of MSCs to observe whether it could improve the therapeutic efficacy of AKI. We established a renal ischemia/reperfusion injury model and treated mice with ATRA-pretreated MSCs via tail vein injection. We found that AKI mice treated with ATRA-MSCs significantly improved renal function compared with DMSO-MSCs treatment. RNA sequencing screened that hyaluronic acid (HA) production from MSCs promoted by ATRA. Further validation by chromatin immunoprecipitation experiments verified that retinoic acid receptor RARα/RXRγ was a potential transcription factor for hyaluronic acid synthase 2. Additionally, an in vitro hypoxia/reoxygenation model was established using human proximal tubular epithelial cells (HK-2). After co-culturing HK-2 cells with ATRA-pretreated MSCs, we observed that HA binds to cluster determinant 44 (CD44) and activates the PI3K/AKT pathway, which enhances the anti-inflammatory, anti-apoptotic, and proliferative repair effects of MSCs in AKI. Inhibition of the HA/CD44 axis effectively reverses the renal repair effect of ATRA-pretreated MSCs. Taken together, our study suggests that ATRA pretreatment promotes HA production by MSCs and activates the PI3K/AKT pathway in renal tubular epithelial cells, thereby enhancing the efficacy of MSCs against AKI.

Evaluation of the reliability and validity of the health regulatory focus scale in Chinese samples.

This study sought to validate the psychometric properties of the Health Regulatory Focus Scale (HRFS), emphasizing its manifestation and association with personality traits in a Chinese context. Originally developed by Ferrer, the HRFS gauges individuals' inclinations either to avoid negative health outcomes (prevention focus) or achieve positive health outcomes (promotion focus). Our cross-sectional analysis involved a diverse sample of 652 Chinese participants, averaging 39.6 years in age (SD = 9.39). Data were analyzed using SPSS and AMOS, and both exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were employed to assess the HRFS's factor structure. Additionally, we evaluated convergent and discriminant validity, criterion-related validity, internal consistency reliability, and test-retest reliability. The CFA results (CFI = 0.985, TLI = 0.971, RMSEA = 0.059, and SRMR = 0.047), combined with McDonald's omega value (0.916) and the test-retest correlation coefficient (0.78) for the HRFS, underscore its robust construct validity and reliability. Furthermore, the promotion dimension of the HRFS exhibited significant positive correlations with all dimensions of the Chinese Adjectives Short Scale of Big-Five Factor Personality (BFFP-CAS-S). In conclusion, the HRFS's Chinese adaptation offers a reliable and valid instrument for assessing health regulatory focus.

Neutrophil gelatinase-associated lipocalin protects renal tubular epithelial cells in hypoxia-reperfusion by reducing apoptosis.

PURPOSE: The aim of this study was to elucidate the role of neutrophil gelatinase-associated lipocalin (NGAL) in regulating apoptosis of tubular epithelial cells in a hypoxia-reperfusion model. METHODS: A hypoxia-reperfusion model was established with NRK-52E cells to assess apoptosis and cell cycle progression after the addition of NGAL. We investigated the expression of four apoptosis factors, Bcl-2, Bax, Fas and FasL, as well as the expression level of two NGAL receptors, 24p3R and megalin, by both Western blot and real-time PCR. RESULTS: NGAL induced cell proliferation and reduced apoptosis by regulating four apoptosis factors Bcl-2, Bax, Fas and FasL. Western blot demonstrated that the two NGAL receptors, 24p3R and megalin, were increased after hypoxia-reperfusion, which was reduced by exogenous NGAL. Moreover, overexpression of the two receptors induced the expression of the anti-apoptotic factor Bcl-2 and reduced the expression of pro-apoptotic Bax, Fas and FasL. CONCLUSIONS: These findings indicate that NGAL reduces apoptosis by regulating the four apoptosis factors Bcl-2, Bax, Fas and FasL through its two receptors 24p3R and megalin. These results also suggest that ectopic expression of NGAL in renal cells might provide a therapeutic strategy in ischemia-reperfusion by reducing apoptosis and promoting renal cell proliferation.