Hepatic aldose reductase (AR) expression is known to be induced in liver diseases, including hepatitis and hepatocellular carcinoma. However, the role of AR in the development of these diseases remains unclear. We performed this current study to determine whether and how AR might be involved in the development of diet-induced nonalcoholic steatohepatitis. Our results showed that the level of AR protein expression was significantly higher in db/db mice fed the methionine-choline-deficient (MCD) diet than in mice fed the control diet. In parallel with the elevation in AR, steatohepatitis was observed in MCD diet-fed mice, and this diet-induced steatohepatitis was significantly attenuated by lentiviral-mediated knock-down of the AR gene. This suppressive effect of AR knock-down was associated with repressed levels of serum alanine aminotransferase and hepatic lipoperoxides, reduced mRNA and protein expression of hepatic cytochrome P450 2E1 (CYP2E1), and decreased mRNA expression of pro-inflammatory tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Moreover, AR-induced elevations on the level of CYP2E1 expression, reactive oxygen species, mRNA expression of TNF-α and IL-6 were confirmed in AML12 hepatocytes. Further, lentiviral-mediated knock-down of AR ameliorated MCD diet-induced collagen deposition in the livers of db/db mice. With the improvement in liver fibrosis, the mRNA levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metalloproteinase-2 (MMP-2), two genes involved in hepatic fibrogenesis, were found to be significantly suppressed, while TIMP-2 and MMP-13 were unaffected. Together these data indicate that inhibition of AR alleviates the MCD diet-induced liver inflammation and fibrosis in db/db mice, probably through dampening CYP2E1 mediated-oxidative stress and ameliorating the expression of pro-inflammatory cytokines.

Purpose This study aimed to identify the heterogeneity of dyadic quality of life (QoL) profiles, determine whether these profiles differ in terms of demographic and medical factors, neuroticism, resilience, and family functioning, and explore the combined effect of patient and caregiver neuroticism, resilience, and family functioning on dyadic QoL profiles. Methods A cross-sectional study was conducted with 304 advanced lung cancer patient-caregiver dyads enrolled from radiotherapy and chemotherapy departments at three tertiary hospitals. Self-report questionnaires were administered to patient-caregiver dyads to assess demographic and medical characteristics, neuroticism, resilience, family functioning and QoL. Results The latent profile analysis identified four subgroups of dyadic QoL: patient low-caregiver high profile (38.82%), patient high-caregiver high profile (22.37%), patient high-caregiver low profile (19.74%), and patient low-caregiver low profile (19.08%). Additionally, when both patients and their caregivers had a high level of neuroticism or low level of resilience, and low family functioning, compared with only member having them, there was a higher risk of poorer dyadic QoL. Conclusions Our study identified the four heterogeneities of dyadic QoL profiles among advanced lung cancer patient-caregiver dyads. Future dyadic interventions should consider the heterogeneity of dyadic QoL in this population and prioritize patient-caregiver dyads who are at risk of poor dyadic QoL. Furthermore, when high neuroticism, low resilience, or family functioning coexist between patients and their caregivers, both parties exhibit much lower dyadic QoL.