PSMD12 promotes non-small cell lung cancer progression through activating the Nrf2/TrxR1 pathway.

BACKGROUND: Non-small cell lung cancer (NSCLC) contributes to the vast majority of cancer-related deaths. Proteasome 26S subunit, non-ATPase 12 (PSMD12), a subunit of 26S proteasome complex, is known to play the tumor-promoting role in several types of cancer but its function in NSCLC remains elusive. OBJECTIVE: To explore the role and underlying mechanisms of PSMD12 in NSCLC. METHODS: The PSMD12 expression in human normal lung epithelial cell line (BEAS-2B) and four NSCLC cell lines (A549, NCI-H1299, NCI-H1975, Calu-1) were determined by qRT-PCR and western blot. Malignant phenotypes of NSCLC cells were detected by CCK-8, EdU staining, immunofluorescence staining for E-cadherin, flow cytometry, and Transwell assays to assess cell viability, proliferation, epithelial-mesenchymal transition (EMT), apoptosis, migration and invasion. Dual luciferase assay was used to verify the regulatory role of transcription factor on the promoter. RESULTS: We identified the upregulation of PSMD12 in NSCLC tissues based on the GEO datasets, which further verified in NSCLC and BEAS-2B cell lines. PSMD12 knockdown significantly suppressed malignant behaviors of NSCLC cells, including cell growth, invasion, and migration, while PSMD12 overexpression presented the opposite effects. Interestingly, we found that PSMD12 upregulated the tumor-promoting factor TrxR1 mRNA expression. For its potential mechanisms, we demonstrated that PSMD12 elevated transcription factor Nrf2 protein level and promoted Nrf2 nuclear translocation. And Nrf2 further increased TrxR1 promoter activity and enhanced TrxR1 transcription. Meanwhile, we proved that TrxR1 overexpression erased the inhibitory effect of PSMD12 knockdown. CONCLUSION: PSMD12 promotes NSCLC progression by activating the Nrf2/TrxR1 pathway, providing a novel prognostic and therapeutic target for NSCLC treatment.

Association between living arrangements and cognitive decline in older adults: A nationally representative longitudinal study in China.

BACKGROUND: Living arrangements are critical to the survival and well-being of older people, especially in China where the filial piety culture demands adult children care for and serve their parents. The study aimed to explore the association between living arrangements and cognitive decline among older people in China. METHODS: Participants included 6,074 older adults over 60 years old (49.65% male, mean age 67.2 years [range 60-98]) from four waves (2011-2018) of the China Health and Retirement Longitudinal Study. Two to four assessments were conducted over a follow-up of an average of 5.3 years (range, 2-7). Cognitive function was assessed using an adapted Chinese version of Mini-Mental State Examination (MMSE). Living arrangements were classified as follows: living alone, living with spouse, living with adult children, living with spouse and adult children and living with others. Multilevel models were used to investigate the relationship between living arrangements and cognitive decline, as well as the gender difference. RESULTS: As the main type of living arrangements of the study participants (44.91%), living with spouse was taken as the reference group. Compared to the reference group, living alone (ß=-0.126, P < 0.001), living with adult children (ß=-0.136, P < 0.001), living with spouse and adult children (ß=-0.040, P < 0.05) and living with others (ß=-0.155, P < 0.05) were all related to a faster rate of cognitive decline. Further, the association between living arrangements and cognitive decline varied by gender. Living alone (ß=-0.192, P < 0.001) was associated with a faster cognitive decline only in older men. Living with spouse and adult children (ß=-0.053, P < 0.05) and living with others (ß=-0.179, P < 0.05) were associated with faster cognitive decline only in older women. CONCLUSION: This study suggests that living arrangements in older people in China were associated with cognitive decline, and these associations varied by gender. Greater attention to living arrangements might yield practical implications for preserving the cognitive function of the older population.

Role of physical performance measures for identifying functional disability among Chinese older adults: Data from the China Health and Retirement Longitudinal Study.

BACKGROUND: Functional disability is a common health burden in older adults and follows a hierarchical pattern. Physical performance measures are useful for the objective estimation of functional disability. This study primarily aimed to compare the validity of handgrip strength and gait speed, alone and in combination, for recognizing the functional disability among Chinese older adults. This study also aimed to stratify the functional disability according to the criterion-referenced values of handgrip strength and gait speed. METHODS: We selected 6127 respondents from the 2011 wave of the China Health and Retirement Longitudinal Study. Here, we defined functional disability as needing any help in any items of activities of daily living (ADL) and instrumental activities of daily living (IADL). To assess the validity of physical performance measures alone and in combination for the recognition of functional disability, we conducted the receiver operating characteristic analysis. RESULTS: Compared with handgrip strength, the gait speed could better discriminate ADL disability and showed a satisfactory discriminant validity (area under the curve ≥ 0.7) in men. However, this finding was not found in the recognition of IADL disability. When combining these two measures, the parallel test showed a high sensitivity with a poor specificity, whereas the serial test showed a perfect specificity with a poor sensitivity. CONCLUSION: We developed the hierarchical cut-off values of handgrip strength and gait speed for identifying and stratifying the functional disability among Chinese adults over 60 years old. The speed test was superior to handgrip strength in identifying ADL disability. The parallel tests of those with high sensitivity perhaps could help identify the functional disability. Further work on cost-utility analysis is warranted.