Hepatocellular carcinoma cells downregulate NADH:Ubiquinone Oxidoreductase Subunit B3 to maintain reactive oxygen species homeostasis.

BACKGROUND: HCC is a leading cause of cancer-related death. The role of reactive oxygen species (ROS) in HCC remains elusive. Since a primary ROS source is the mitochondrial electron transport chain complex Ι and the NADH:ubiquinone Oxidoreductase Subunit B3 (NDUFB3), a complex I subunit, is critical for complex I assembly and regulates the associated ROS production, we hypothesize that some HCCs progress by hijacking NDUFB3 to maintain ROS homeostasis. METHODS: NDUFB3 in human HCC lines was either knocked down or overexpressed. The cells were then analyzed in vitro for proliferation, migration, invasiveness, colony formation, complex I activity, ROS production, oxygen consumption, apoptosis, and cell cycle. In addition, the in vivo growth of the cells was evaluated in nude mice. Moreover, the role of ROS in the NDUFB3-mediated changes in the HCC lines was determined using cellular and mitochondrion-targeted ROS scavengers. RESULTS: HCC tissues showed reduced NDUFB3 protein expression compared to adjacent healthy tissues. In addition, NDUFB3 knockdown promoted, while its overexpression suppressed, HCC cells' growth, migration, and invasiveness. Moreover, NDUFB3 knockdown significantly decreased, whereas its overexpression increased complex I activity. Further studies revealed that NDUFB3 overexpression elevated mitochondrial ROS production, causing cell apoptosis, as manifested by the enhanced expressions of proapoptotic molecules and the suppressed expression of the antiapoptotic molecule B cell lymphoma 2. Finally, our data demonstrated that the apoptosis was due to the activation of the c-Jun N-terminal kinase (JNK) signaling pathway and cell cycle arrest at G0/G1 phase. CONCLUSIONS: Because ROS plays essential roles in many biological processes, such as aging and cancers, our findings suggest that NDFUB3 can be targeted for treating HCC and other human diseases.

[Effectiveness of combined anteversion angle technique in total hip arthroplasty for treatment of ankylosing spondylitis affecting hip joint].

Objective: To explore the effectiveness of the combined anteversion angle technique in total hip arthroplasty (THA) for treating ankylosing spondylitis (AS) affecting the hip joint. Methods: A retrospective analysis was conducted on the clinical data of 73 patients with AS affecting the hip joint who underwent THA between August 2018 and August 2021. According to whether the combined anteversion angle technique was used in THA, the patients were divided into study group (37 cases, combined anteversion angle technique was used in THA) and control group (36 cases, traditional THA). There was no significant difference in baseline data such as gender, age, body mass index, disease duration, preoperative Harris score, range of motion (ROM), acetabular anteversion angle, acetabular abduction angle, femoral anteversion angle, and combined anteversion angle between the two groups ( P>0.05). The operation time, hospital stay, and complications of the two groups were recorded and compared. The Harris score and hip ROM were compared between the two groups before operation, at 1, 3, 6, 12 months after operation, and at last follow-up. The acetabular component anteversion angle, femoral component anteversion angle, acetabular component abduction angle, and component combined anteversion angle were measured postoperatively. Results: The operation time in the study group was significantly shorter than that in the control group ( P<0.05), and there was no significant difference in hospital stay between the two groups ( P>0.05). There was no intraoperative complication such as acetabular and proximal femoral fractures, neurovascular injuries in both groups, and the incisions healed by first intention. All patients were followed up 2-3 years, with an average of 2.4 years; there was no significant difference in the follow-up time between the two groups ( P>0.05). During the follow-up period, there was no complication such as hip dislocation, wound infection, delayed wound healing, deep venous thrombosis, and hip dislocation in both groups. The hip Harris score and ROM of the two groups gradually increased with time after operation, and the differences were significant when compared with those before operation ( P<0.05); the above two indicators of the study group were significantly better than those of the control group at each time point after operation ( P<0.05). Extensive bone ingrowth on the surface of the components could be observed in the anteroposterior X-ray films of the hip joint of the two groups at 12 months after operation, and the acetabular components was stable without femoral stem subsidence, osteolysis around the components, and heterotopic ossification. At last follow-up, the acetabular component anteversion angle, femoral component anteversion angle, and component combined anteversion angle in the study group were significantly superior to those in the control group ( P<0.05), except that there was no significant difference in the acetabular component abduction angle between the two groups ( P>0.05). Conclusion: For patients with AS affecting the hip joint, the use of the combined anteversion angle technique during THA effectively promotes the recovery of hip joint function and enhances the postoperative quality of life of patients when compared to traditional THA.

Exploration and comparison of the relationship between PAHs and ROS in PM2.5 emitted from multiple anthropogenic sources in the Guanzhong Plain, China.

Anthropogenic emissions have emerged as an important source of urban atmospheric PM2.5, exacerbating air pollution and the associated health implications. This study analyses PM2.5, originating from major anthropogenic sources (industries, motor vehicles, and solid-fuel combustion for domestic applications) in the Guanzhong Plain in China, along with the parent- (p-), alkylated- (a-), and oxygenated- (o-) polycyclic aromatic hydrocarbons (PAHs) and reactive oxygen species (ROS) levels in PM2.5. Industrial emissions are mainly characterised by high abundances of benzo[b]fluoranthene (BbF), benzo[k]fluoranthene (BkF), and benz[a]fluoranthene (BaF). The 4-ring p-PAHs, such as fluoranthene (FLA), pyrene (PYR), benzo[a]anthracene (BaA), and chrysene (CHR) proportions and the diagnostic ratios of indeno[1,2,3-cd]pyrene (IcdP)/[IcdP + benzo[ghi]perylene (BghiP)] and 1-acenaphthenone (1ACO)/[1ACO + 9-fluorenone (9FO)] in motor vehicle emission PM2.5 were higher than the other sources. Household solid fuel combustion features high proportions of methylnaphthalene (M-NAP), i.e., 2 M-NAP and 1 M-NAP and 3-ring p-PAHs. Acenaphthylene (ACY), acenaphthene (ACE), anthracene (ANT), 1,4-chrysenequinone (1,4CHRQ), and reactive oxygen species (ROS) were positively correlated among the three anthropogenic sources. Moreover, the correlations between other PAHs and ROS varied significantly among the three sources. As mixed and compound organic pollutants, 2- and 3-ring p-PAHs were more positively correlated with the ROS activity of household solid fuel combustion sources compared with industrial and motor vehicle sources. Based on the relative contribution of these three sources to PAHs in PM2.5, we estimated the cancer risks of males and females in the Guanzhong area to be 2.95 × 10-6 and 2.87 × 10-6, respectively, exceeding the safety threshold of 1 × 10-6. This study provides a basic dataset for conducting a refined source apportionment of PM2.5 and a scientific basis for further understanding the relationship between PM2.5, PAHs, and ROS in northern China.

GLUD1 inhibits hepatocellular carcinoma progression via ROS-mediated p38/JNK MAPK pathway activation and mitochondrial apoptosis.

Glutamate dehydrogenase 1 (GLUD1) is an important enzyme in glutamine metabolism. Previously, we found GLUD1 was down-regulated in tumor tissues of hepatocellular carcinoma (HCC) patients by proteomics study. To explore its role in the progression of HCC, the expressional level of GLUD1 was firstly examined and presented as that both the protein and mRNA levels were down-regulated in tumor tissues compared to the normal liver tissues. GLUD1 overexpression significantly inhibited HCC cells proliferation, migration, invasion and tumor growth both in vitro and in vivo, while GLUD1 knocking-down promoted HCC progression. Metabolomics study of GLUD1 overexpressing and control HCC cells showed that 129 differentially expressed metabolites were identified, which mainly included amino acids, bases, and phospholipids. Moreover, metabolites in mitochondrial oxidative phosphorylation system (OXPHOS) were differentially expressed in GLUD1 overexpressing cells. Mechanistic studies showed that GLUD1 overexpression enhanced mitochondrial respiration activity and reactive oxygen species (ROS) production. Excessive ROS lead to mitochondrial apoptosis that was characterized by increased expression levels of p53, Cytochrome C, Bax, Caspase 3 and decreased expression level of Bcl-2. Furthermore, we found that the p38/JNK MAPK pathway was activated in GLUD1 overexpressing cells. N-acetylcysteine (NAC) treatment eliminated cellular ROS and blocked p38/JNK MAPK pathway activation, as well as cell apoptosis induced by GLUD1 overexpression. Taken together, our findings suggest that GLUD1 inhibits HCC progression through regulating cellular metabolism and oxidative stress state, and provide that ROS generation and p38/JNK MAPK pathway activation as promising methods for HCC treatment.

Associations of personal exposure to domestic heating and cooking fuel emissions and epidemiological effects on rural residents in the Fenwei Plain, China.

Solid fuel combustion for domestic heating in northern China in the wintertime is of great environmental and health concern. This study assesses personal exposure to particulate matter with different aerodynamic diameters and multiple gaseous pollutants from 123 rural residents in Yuncheng, the Fenwei Plain. The subjects are divided into groups based on the unique energy source applied, including biomass, coal, and electricity/no heating activities. The health effects of the exposures are expressed with four urinary biomarkers. The personal exposure levels to three different aerodynamic particle sizes (i.e., PM10, PM2.5, and PM1) of the electricity/no heating group are 5.1 % -12 % lower than those of the coal group. In addition, the exposure levels are 25 %-40 % lower for carbon monoxide (CO) and 10.8 %-20.3 % lower for ozone (O3) in the electricity/no heating group than the other two fuel groups. C-reactive protein (CRP) in the urine of the participants in biomass and coal groups is significantly higher than that in the electricity/no heating group, consistent with the observations on other biomarkers. Increases in 8-hydroxy-2 deoxyguanosine (8-OHdG), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) are observed for the exposures to higher concentrations of air pollutants. For instance, PMs and nitrogen dioxide (NO2) show significant impacts on positive correlations with 8-OHdG and IL-8, while O3 positively correlates with CRP. PM1 exhibits higher effects on the biomarkers than the gaseous pollutants, especially on VEGF and IL-8. The study indicates that excessive use of traditional domestic solid fuels could pose severe health effects on rural residents. The promotion of using clean energy is urgently needed in the rural areas of northern China.

Prognostic value of a microRNA-pair signature in laryngeal squamous cell carcinoma patients.

PURPOSE: Predicting the prognosis in laryngeal squamous cell carcinoma (LSCC) patients will improve clinical decision-making. Here, we aimed to identify a qualitative signature based on the within-sample relative expression orderings (REOs) of microRNA (miRNA) pairs to predict the overall survival (OS) of LSCC patients. METHODS: First, we constructed non-repeating miRNA pairs based on differentially expressed miRNAs (DEmiRNAs) between LSCC and normal tissues. Then, we applied a bootstrap-based feature selection method to identify a robust miRNA-pair signature. The bootstrap-based feature selection improved the stability of feature selection by an ensemble based on the data perturbation. Furthermore, a series of bioinformatics analyses were carried out to explore the potential mechanisms of the signature and potential drug targets for LSCC. RESULTS: Based on the REOs of miRNA pairs, we identified a qualitative signature that consisted of 12 miRNA pairs. The constructed signature has good performance in predicting the OS of LSCC patients. It is robust against batch effects and more suitable for individual clinical applications. Furthermore, we identified several hub genes that may be potential drug targets for LSCC. CONCLUSION: Overall, our findings provided a promising signature for predicting the OS of LSCC patients.

Environmental and health risks of VOCs in the longest inner-city tunnel in Xi'an, Northwest China: Implication of impact from new energy vehicles.

Traffic source-dominated volatile organic compound (VOC) samples were collected during four time-intervals in a day (Ⅰ: 7:30-10:30, Ⅱ: 11:00-14:00, Ⅲ: 16:30-19:30, and Ⅳ: 20:00-23:00) in a tunnel in summer, 2019, in Xi'an, China. The total measured VOC (TVOC) in periods Ⅰ and Ⅲ (rush hours, 107.2 ± 8.2 parts per billion by volume [ppbv]) was 1.8 times that in periods Ⅱ and Ⅳ (non-rush hours, 58.6 ± 13.8 ppbv), consistent with the variation in vehicle numbers in the tunnel. The considerably elevated ethane and ethylbenzene levels could have been attributed to emissions from compressed natural gas vehicles and the rapid development of methanol-fueled taxis in Xi'an in 2019. The mixing ratios of benzene, toluene, ethylbenzene, and xylenes (BTEX) contributed 9.4%-12.7% to TVOCs, and the contributions were nearly 40% higher in periods Ⅰ and Ⅲ than in Ⅱ and Ⅳ, indicating that BTEX levels were strongly affected by vehicle emissions. The indicators of motor vehicle emission, namely ethylene, propylene, toluene, m/p-xylenes, o-xylene, and propane, contributed to more than half of the ozone formation potential in this study. The noncarcinogenic risks of VOCs in this study were within the international safety standard, whereas the carcinogenic risks exceeded the standard by 2.3-4.6 times, suggesting that carcinogenic risks were more serious than noncarcinogenic risks. VOCs presented 2.2 and 1.4 times noncarcinogenic and carcinogenic risks during rush hours than during non-rush hours, respectively. Notably, the carcinogenic risk in period Ⅳ was comparable with that in period Ⅲ; however, the vehicle numbers and VOC mixing ratios were the lowest at night, which may have attributed to the increasing number and proportion of methanol M100-fueled vehicles in the tunnel. Therefore, VOCs emitted by new energy vehicles should also be seriously considered while evaluating fossil fuel vehicle emissions.

Effects of domestic solid fuel combustion emissions on the biomarkers of homemakers in rural areas of the Fenwei Plain, China.

BACKGROUND: The health effects of heavy solid fuel use in winter in rural China are of concern. The effects of air pollution resulting from domestic solid fuel combustion in rural households on rural homemakers' biomarkers were revealed in this study. METHODS: In total, 75 female homemakers from rural areas of Guanzhong Basin, the Fenwei Plain, People's Republic of China, were randomly selected and divided into three groups (biomass users, coal users, and nonusers of solid fuel user [control group]). The differences in biological indicators, including 8-hydrox-2'-deoxyguanosine (8-OHdG), interlukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in urine samples as well as blood pressure (BP, including systolic BP [SBP] and diastolic BP [DBP]) and heart rate (HR) among the groups in winter and summer were investigated using statistical analysis. RESULTS: IL-6, 8-OHdG, HR, SBP, and DBP were significantly higher in winter than in summer (P < 0.05) owing to the poor air quality resulted from the excessive use of solid fuels in winter. Significant seasonal differences in 8-OHdG were observed for both coal and biomass users. After the influence of confounders was removed, only IL-6 levels in the urine of solid fuel users were significantly higher than that of the control group. CONCLUSIONS: IL-6 is a sensitive biomarker representing inflammatory responses to particulate matter emitted through household solid fuel combustion. Locally, excessive use of solid fuels in winter posed serious PM2.5 pollution in this area and adverse effects on inflammatory biomarkers in these rural homemakers and induced DNA damage related to oxidative stress.