ABSTRACT
Evidences have shown a strong link between particulate matter (PM) and increased risk in human mortality and morbidity, including asthma, chronic obstructive pulmonary disease (COPD), respiratory infection, and lung cancer. However, the underlying toxicologic mechanisms remain largely unknown. Utilizing PM-treated human pulmonary fibroblasts (HPF) models, we analyzed gene expression microarray data and Ingenuity Pathway Analysis (IPA) to identify that the transcription factor sterol regulatory element-binding protein 1 (SREBP1) was the main downstream regulator of Sirtuin1 (SIRT1). Quantitative PCR and western blot results showed that SIRT1 inhibited SREBP1 and further downregulated Pirin (PIR) and Nod-like receptor protein 3 (NLRP3) inflammasome after PM exposure. Inhibitors of SIRT1, SREBP1, and PIR could reverse PM-induced inflammation. An in silico analysis revealed that PIR correlated with smoke exposure and early COPD. Immunohistochemical analysis of tissue microarrays from PM-fed mouse models was used to determine the association of PIR with PM. These data demonstrate that the SIRT1-SREBP1-PIR/ NLRP3 inflammasome axis may be associated with PM-induced adverse health issues. SIRT1 functions as a protector from PM exposure, whereas PIR acts as a predictor of PM-induced pulmonary disease. The SIRT1-SREBP1-PIR/ NLRP3 inflammasome axis may present several potential therapeutic targets for PM-related adverse health events.
Subject(s)
Dioxygenases/metabolism , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Particulate Matter/adverse effects , Pneumonia/metabolism , Sirtuin 1/metabolism , Sterol Regulatory Element Binding Protein 1/metabolism , Animals , Cellular Microenvironment , Humans , Male , Mice , Mice, Inbred NOD , Mice, SCID , Pneumonia/complications , Pulmonary Disease, Chronic Obstructive/etiology , Signal TransductionABSTRACT
The aldolase family members involved in metabolism and glycolysis are present in three isoforms: ALDOA, ALDOB, and ALDOC. Aldolases are differentially expressed in human tissues, and aberrant expression has been observed in several human diseases and cancer types. However, non-enzymatic functions through protein-protein interactions or epigenetic modifications have been reported in recent years. Using high-throughput screening and -omics database integration, aldolase has been validated as an independent clinical prognostic marker of human cancers. Therefore, the aim of this review was to provide potential clinical value from in silico predictions and also summarize well-known signaling axes or phenotypes in various cancer types. Finally, we discuss the role of aldolase in the treatment of human diseases and cancers.
Subject(s)
Aldehyde-Lyases/metabolism , Biomarkers, Tumor/metabolism , Neoplasms/diagnosis , Neoplasms/metabolism , HumansABSTRACT
OBJECTIVE: To investigate the association between mid-upper arm circumference (MUAC), calf circumference (CC) and all-cause mortality in a Chinese population. DESIGN: Prospective cohort study. SETTING: Eight long-term care facilities in central Taiwan. PARTICIPANTS: A total of 329 residents age 60 years and older (median 79.0 years, range 60-101; 139 men, 190 women) were enrolled. METHODS: Anthropometrics and metabolic parameters were measured at the time of enrolment to the study. Mean MUAC and CC were 24.2±3.4 cm and 27.5±4.3 cm, respectively. Mortality data were obtained from the Department of Health in Taiwan. MAIN OUTCOME MEASURE: To identify the association between all-cause mortality and MUAC or CC. RESULTS: There were 255 deaths during the 7-year follow-up period. After adjusting for age, sex, cigarette smoking, betel nut chewing, alcohol use, Karnofsky Performance Status Scale score, serum albumin level, hypertension and diabetes mellitus, subjects in the highest tertile of MUAC (27.8±2.2 cm) and CC (32.1±2.6 cm) had a significantly lower mortality rate than did subjects in the lowest tertile (MUAC 20.6±1.7 cm; CC 22.8±1.9 cm). The adjusted HR for all-cause mortality in the highest versus lowest MUAC tertile was 0.64 (95% CI 0.45 to 0.90). The adjusted HR for all-cause mortality in the highest versus lowest CC tertile was 0.51 (95% CI 0.35 to 0.74). CONCLUSIONS: MUAC and CC are negative predictors for all-cause mortality in older Chinese adults living in long-term care facilities. Participants with higher MUAC and CC had lower all-cause mortality.
