Low expression of Lnc-ENST00000535078 inhibits the migration, invasion, and enhances apoptosis of CTPE-induced malignantly transformed BEAS-2B cells.

Long non-coding RNA (LncRNA) plays an important role in malignant transformation of cells. This study aimed to explore the role of Lnc-ENST00000535078 in the malignant transformation of immortalized human bronchial epithelial cells (BEAS-2B) induced by coal tar pitch extract (CTPE). The malignant transformation model of BEAS-2B cells exposed to CTPE. Cell proliferation was examined by Cell counting kit-8 (CCK-8) assay. Colony formation assay was used to assess the colony of cells. Cell migration and invasion were detected by Transwell analysis. Cell cycle progression and apoptotic status were assessed by flow cytometry. Differentially expressed genes were screened by RNA sequencing. The results showed that Lnc-ENST00000535078 expression was highest in malignantly transformed BEAS-2B cells passaged to the 30th generation. Knockdown of Lnc-ENST00000535078 inhibited the migration, invasion and anti-apoptotic abilities of malignantly transformed BEAS-2B cells. Transcriptome analysis found 608 differential genes. CCND1 and FOS genes were screened out because of their levels were positive correlation with the expression of Lnc-ENST00000535078, which were consistent with the RNA sequencing results. In conclusion, Low expression of Lnc-ENST00000535078 inhibits the migration and invasion of malignant transformed BEAS-2B cells and promotes apoptosis in these cells. Lnc-ENST00000556926 might affect the malignant transformation of cells through the regulation of CCND1 and FOS. This study may provide a potential target for intervention in CTPE-induced lung cancer.

Role of TRIM59 in regulating PPM1A in the pathogenesis of silicosis and the intervention effect of tanshinone IIA.

This study examines the involvement of TRIM59 in silica-induced pulmonary fibrosis and explores the therapeutic efficacy of Tanshinone IIA (Tan IIA). In vivo experiments conducted on rats with silica-induced pulmonary fibrosis unveiled an increase in TRIM59 levels and a decrease in PPM1A levels. Subsequent investigations using in vitro silicosis cell models demonstrated that modulation of TRIM59 expression significantly impacts silicosis fibrosis, influencing the levels of PPM1A and activation of the Smad2/3 signaling pathway. Immunofluorescence and co-immunoprecipitation assays confirmed the interaction between TRIM59 and PPM1A in fibroblasts, wherein TRIM59 facilitated the degradation of PPM1A protein via proteasomal and ubiquitin-mediated pathways. Furthermore, employing a rat model of silica-induced pulmonary fibrosis, Tan IIA exhibited efficacy in mitigating lung tissue damage and fibrosis. Immunohistochemical analysis validated the upregulation of TRIM59 and downregulation of PPM1A in silica-induced pulmonary fibrosis, which Tan IIA alleviated. In vitro studies elucidated the mechanism by which Tan IIA regulates the Smad2/3 signaling pathway through TRIM59-mediated modulation of PPM1A. Treatment with Tan IIA in silica-induced fibrosis cell models resulted in concentration-dependent reductions in fibrotic markers and attenuation of relevant protein expressions. Tan IIA intervention in silica-induced fibrosis cell models mitigated the TRIM59-induced upregulation of fibrotic markers and enhanced PPM1A expression, thereby partially reversing Smad2/3 activation. Overall, the findings indicate that while overexpression of TRIM59 may activate the Smads pathway by suppressing PPM1A expression, treatment with Tan IIA holds promise in counteracting these effects by inhibiting TRIM59 expression.

Fatty acids metabolism in ozone-induced pulmonary inflammatory injury: Evidence, mechanism and prevention.

Ozone (O3) is a major air pollutant that directly threatens the respiratory system, lung fatty acid metabolism disorder is an important molecular event in pulmonary inflammatory diseases. Liver kinase B1 (LKB1) and nucleotide-binding domain leucine-rich repeat-containing protein 3 (NLRP3) inflammasome not only regulate inflammation, but also have close relationship with fatty acid metabolism. However, the role and mechanism of LKB1 and NLRP3 inflammasome in lung fatty acid metabolism, which may contribute to ozone-induced lung inflammation, remain unclear, and effective strategy for preventing O3-induced pulmonary inflammatory injury is lacking. To explore these, mice were exposed to 1.00 ppm O3 (3 h/d, 5 days), and pulmonary inflammation was determined by airway hyperresponsiveness, histopathological examination, total cells and cytokines in bronchoalveolar lavage fluid (BALF). Targeted fatty acids metabolomics was used to detect medium and long fatty acid in lung tissue. Then, using LKB1-overexpressing adenovirus and NLRP3 knockout (NLRP3-/-) mice to explore the mechanism of O3-induced lung fatty acid metabolism disorder. Results demonstrated that O3 exposure caused pulmonary inflammatory injury and lung medium and long chain fatty acids metabolism disorder, especially decreased dihomo-γ-linolenic acid (DGLA). Meanwhile, LKB1 expression was decreased, and NLRP3 inflammasome was activated in lung of mice after O3 exposure. Additionally, LKB1 overexpression alleviated O3-induced lung inflammation and inhibited the activation of NLRP3 inflammasome. And we found that pulmonary fatty acid metabolism disorder was ameliorated of NLRP3 -/- mice compared with those in wide type mice after O3 exposure. Furthermore, administrating DGLA intratracheally prior to O3 exposure significantly attenuated O3-induced pulmonary inflammatory injury. Taken together, these findings suggest that fatty acids metabolism disorder is involved in O3-induced pulmonary inflammation, which is regulated by LKB1-mediated NLRP3 pathway, DGLA supplement could be a useful preventive strategy to ameliorate ozone-associated lung inflammatory injury.

RDFC-GAN: RGB-Depth Fusion CycleGAN for Indoor Depth Completion.

Raw depth images captured in indoor scenarios frequently exhibit extensive missing values due to the inherent limitations of the sensors and environments. For example, transparent materials frequently elude detection by depth sensors; surfaces may introduce measurement inaccuracies due to their polished textures, extended distances, and oblique incidence angles from the sensor. The presence of incomplete depth maps imposes significant challenges for subsequent vision applications, prompting the development of numerous depth completion techniques to mitigate this problem. Numerous methods excel at reconstructing dense depth maps from sparse samples, but they often falter when faced with extensive contiguous regions of missing depth values, a prevalent and critical challenge in indoor environments. To overcome these challenges, we design a novel two-branch end-to-end fusion network named RDFC-GAN, which takes a pair of RGB and incomplete depth images as input to predict a dense and completed depth map. The first branch employs an encoder-decoder structure, by adhering to the Manhattan world assumption and utilizing normal maps from RGB-D information as guidance, to regress the local dense depth values from the raw depth map. The other branch applies an RGB-depth fusion CycleGAN, adept at translating RGB imagery into detailed, textured depth maps while ensuring high fidelity through cycle consistency. We fuse the two branches via adaptive fusion modules named W-AdaIN and train the model with the help of pseudo depth maps. Comprehensive evaluations on NYU-Depth V2 and SUN RGB-D datasets show that our method significantly enhances depth completion performance particularly in realistic indoor settings.

Dose Prediction and Pharmacokinetic Simulation of XZP-5610, a Small Molecule for NASH Therapy, Using Allometric Scaling and Physiologically Based Pharmacokinetic Models.

The objectives of this study were to support dose selection of a novel FXR agonist XZP-5610 in first-in-human (FIH) trials and to predict its liver concentrations in Chinese healthy adults. Key parameters for extrapolation were measured using in vitro and in vivo models. Allometric scaling methods were employed to predict human pharmacokinetics (PK) parameters and doses for FIH clinical trials. To simulate the PK profiles, a physiologically based pharmacokinetic (PBPK) model was developed using animal data and subsequently validated with clinical data. The PBPK model was employed to simulate XZP-5610 concentrations in the human liver across different dose groups. XZP-5610 exhibited high permeability, poor solubility, and extensive binding to plasma proteins. After a single intravenous or oral administration of XZP-5610, the PK parameters obtained from rats and beagle dogs were used to extrapolate human parameters, resulting in a clearance of 138 mL/min and an apparent volume of distribution of 41.8 L. The predicted maximum recommended starting dose (MRSD), minimal anticipated biological effect level (MABEL), and maximum tolerated dose (MTD) were 0.15, 2, and 3 mg, respectively. The PK profiles and parameters of XZP-5610, predicted using the PBPK model, demonstrated good consistency with the clinical data. By using allometric scaling and PBPK models, the doses, PK profile, and especially the liver concentrations were successfully predicted in the FIH study.

Sulforaphane inhibits the migration and invasion of BPDE-induced lung adenocarcinoma cells by regulating NLRP12.

This study aims to explore the impact and underlying mechanism of sulforaphane (SFN) intervention on the migration and invasion of lung adenocarcinoma induced by 7, 8-dihydroxy-9, 10-epoxy-benzo (a) pyrene (BPDE). Human lung adenocarcinoma A549 cells were exposed to varying concentrations of BPDE (0.25, 0.50, and 1.00 µM) and subsequently treated with 5 µM SFN. Cell viability was determined using CCK8 assay, while migration and invasion were assessed using Transwell assays. Lentivirus transfection was employed to establish NLRP12 overexpressing A549 cells. ELISA was utilized to quantify IL-33, CXCL12, and CXCL13 levels in the supernatant, while quantitative real-time PCR (qRT-PCR) and Western Blot were used to analyze the expression of NLRP12 and key factors associated with canonical and non-canonical NF-κB pathways. Results indicated an increase in migratory and invasive capabilities, concurrent with heightened expression of IL-33, CXCL12, CXCL13, and factors associated with both canonical and non-canonical NF-κB pathways. Moreover, mRNA and protein levels of NLRP12 were decreased in BPDE-stimulated A549 cells. Subsequent SFN intervention attenuated BPDE-induced migration and invasion of A549 cells. Lentivirus-mediated NLRP12 overexpression not only reversed the observed phenotype in BPDE-induced cells but also led to a reduction in the expression of critical factors associated with both canonical and non-canonical NF-κB pathways. Collectively, we found that SFN could inhibit BPDE-induced migration and invasion of A549 cells by upregulating NLRP12, thereby influencing both canonical and non-canonical NF-κB pathways.

PM2.5 induces a senescent state in mouse AT2 cells.

PM2.5 is known to induce lung injury, but its toxic effects on lung regenerative machinery and the underlying mechanisms remain unknown. In this study, primary mouse alveolar type 2 (AT2) cells, considered stem cells in the gas-exchange barrier, were sorted using fluorescence-activated cell sorting. By developing microfluidic technology with constricted microchannels, we observed that both passage time and impedance opacities of mouse AT2 cells were reduced after PM2.5, indicating that PM2.5 induced a more deformable mechanical property and a higher membrane permeability. In vitro organoid cultures of primary mouse AT2 cells indicated that PM2.5 is able to impair the proliferative potential and self-renewal capacity of AT2 cells but does not affect AT1 differentiation. Furthermore, cell senescence biomarkers, p53 and γ-H2A.X at protein levels, P16ink4a and P21 at mRNA levels were increased in primary mouse AT2 cells after PM2.5 stimulations as shown by immunofluorescent staining and quantitative PCR analysis. Using several advanced single-cell technologies, this study sheds light on new mechanisms of the cytotoxic effects of atmospheric fine particulate matter on lung stem cell behavior.

Evaluation of the effectiveness of using flipped classroom in puncture skills teaching.

BACKGROUND: The effectiveness of flipped classroom (FC) on puncture skills in medical education is still uncertain. This study aimed to assess the role of the FC model in puncture skills and investigate the acceptance and approval of FC among medical students and instructors. METHODS: A mixed research approach of quasi-experimental research design and descriptive qualitative research was conducted in September 2022 for one month, using an FC teaching method that combined instructional videos and group learning. The study participants were 71 fifth-year medical students from two classes at a Chinese medical school and four instructors. The medical students were randomly divided into two groups: the traditional classroom (TC) group (Group A) and the FC group (Group B). For teaching, Group B used FC, and Group A used PowerPoint-based TC. The effectiveness of the two teaching models was assessed with Objective Structured Clinical Examination (OSCE), and questionnaires were distributed to the medical students and instructors after the assessment. Two independent sample t-tests were used to analyse the differences in demographic data and the OSCE scores of the two groups of medical students. RESULTS: Group B scored higher in puncture skills than Group A, especially regarding abdominal puncture (p = 0.03), thoracentesis (p < 0.001), bone marrow puncture (p < 0.001) and average performance of puncture skills (p < 0.001). For lumbar puncture, no difference in skill scores was observed between groups A and B (p > 0.409). The medical students thought that the FC improved their self-learning ability and helped them acquire knowledge. Regarding the OSCE of their skills, most medical students thought that it was more innovative and objective than traditional examinations and that it was better for assessing their overall abilities. Both the FC and OSCE were supported by the medical students. The instructors were also satisfied with the students' performance in the FC and supported the teaching model, agreeing to continue using it. CONCLUSIONS: This study shows that FC teaching that combines instructional videos and group learning is a reliable and well-received teaching method for puncture skills, which supplements and expands existing teaching methods in the medical field.

Alzheimer's disease diagnostic accuracy by fluid and neuroimaging ATN framework.

OBJECTIVES: The ATN's different modalities (fluids and neuroimaging) for each of the Aß (A), tau (T), and neurodegeneration (N) elements are used for the biological diagnosis of Alzheimer's disease (AD). We aim to identify which ATN category achieves the highest potential for diagnosis and predictive accuracy of longitudinal cognitive decline. METHODS: Based on the availability of plasma ATN biomarkers (plasma-derived Aß42/40 , p-tau181, NFL, respectively), CSF ATN biomarkers (CSF-derived Aß42 /Aß40 , p-tau181, NFL), and neuroimaging ATN biomarkers (18F-florbetapir (FBP) amyloid-PET, 18F-flortaucipir (FTP) tau-PET, and fluorodeoxyglucose (FDG)-PET), a total of 2340 participants were selected from ADNI. RESULTS: Our data analysis indicates that the area under curves (AUCs) of CSF-A, neuroimaging-T, and neuroimaging-N were ranked the top three ATN candidates for accurate diagnosis of AD. Moreover, neuroimaging ATN biomarkers display the best predictive ability for longitudinal cognitive decline among the three categories. To note, neuroimaging-T correlates well with cognitive performances in a negative correlation manner. Meanwhile, participants in the "N" element positive group, especially the CSF-N positive group, experience the fastest cognitive decline compared with other groups defined by ATN biomarkers. In addition, the voxel-wise analysis showed that CSF-A related to tau accumulation and FDG-PET indexes more strongly in subjects with MCI stage. According to our analysis of the data, the best three ATN candidates for a precise diagnosis of AD are CSF-A, neuroimaging-T, and neuroimaging-N. CONCLUSIONS: Collectively, our findings suggest that plasma, CSF, and neuroimaging biomarkers differ considerably within the ATN framework; the most accurate target biomarkers for diagnosing AD were the CSF-A, neuroimaging-T, and neuroimaging-N within each ATN modality. Moreover, neuroimaging-T and CSF-N both show excellent ability in the prediction of cognitive decline in two different dimensions.

Relationship between homocysteine and chronic total coronary occlusion: a cross-sectional study from southwest China.

BACKGROUND: Chronic total coronary occlusion is among the most complex coronary artery diseases. Elevated homocysteine is a risk factor for coronary artery diseases. However, few studies have assessed the relationship between homocysteine and chronic total coronary occlusion. METHODS: 1295 individuals from Southwest China were enrolled in the study. Chronic total coronary occlusion was defined as complete occlusion of coronary artery for more than three months. Homocysteine was divided into quartiles according to its level. Univariate and multivariate logistic regression models, receiver operating characteristic curves, and subgroup analysis were applied to assess the relationship between homocysteine and chronic total coronary occlusion. RESULTS: Subjects in the higher homocysteine quartile had a higher rate of chronic total coronary occlusion (P < 0.001). After adjustment, the odds ratio for chronic total coronary occlusion in the highest quartile of homocysteine compared with the lowest was 1.918 (95% confidence interval 1.237-2.972). Homocysteine ≥ 15.2 µmol/L was considered an independent indicator of chronic total coronary occlusion (odds ratio 1.53, 95% confidence interval 1.05-2.23; P = 0.0265). The area under the receiver operating characteristic curve was 0.659 (95% confidence interval, 0.618-0.701; P < 0.001). Stronger associations were observed in elderly and in those with hypertension and diabetes. CONCLUSIONS: Elevated homocysteine is significantly associated with chronic total coronary occlusion, particularly in elderly and those with hypertension and diabetes.

Cigarette smoking and air pollution exposure and their effects on cardiovascular diseases.

Cardiovascular disease (CVD) has no socioeconomic, topographical, or sex limitations as reported by the World Health Organization (WHO). The significant drivers of CVD are cardio-metabolic, behavioral, environmental, and social risk factors. However, some significant risk factors for CVD (e.g., a pitiable diet, tobacco smoking, and a lack of physical activities), have also been linked to an elevated risk of cardiovascular disease. Lifestyles and environmental factors are known key variables in cardiovascular disease. The familiarity with smoke goes along with the contact with the environment: air pollution is considered a source of toxins that contribute to the CVD burden. The incidence of myocardial infarction increases in males and females and may lead to fatal coronary artery disease, as confirmed by epidemiological studies. Lipid modification, inflammation, and vasomotor dysfunction are integral components of atherosclerosis development and advancement. These aspects are essential for the identification of atherosclerosis in clinical investigations. This article aims to show the findings on the influence of CVD on the health of individuals and human populations, as well as possible pathology and their involvement in smoking-related cardiovascular diseases. This review also explains lifestyle and environmental factors that are known to contribute to CVD, with indications suggesting an affiliation between cigarette smoking, air pollution, and CVD.

Exercise for prevention of falls and fall-related injuries in neurodegenerative diseases and aging-related risk conditions: a meta-analysis.

Introduction: Neurodegenerative diseases often cause motor and cognitive deterioration that leads to postural instability and motor impairment, while aging-associated frailty frequently results in reduced muscle mass, balance, and mobility. These conditions increase the risk of falls and injuries in these populations. This study aimed to determine the effects of exercise on falls and consequent injuries among individuals with neurodegenerative diseases and frail aging people. Methods: Electronic database searches were conducted in PubMed, Cochrane Library, SportDiscus, and Web of Science up to 1 January 2023. Randomized controlled trials that reported the effects of exercise on falls and fall-related injuries in neurodegenerative disease and frail aging people were eligible for inclusion. The intervention effects for falls, fractures, and injuries were evaluated by calculating the rate ratio (RaR) or risk ratio (RR) with 95% confidence interval (CI). Results: Sixty-four studies with 13,241 participants met the inclusion criteria. Exercise is effective in reducing falls for frail aging people (RaR, 0.75; 95% CI, 0.68-0.82) and participants with ND (0.53, 0.43-0.65) [dementia (0.64, 0.51-0.82), Parkinson's disease (0.49, 0.39-0.69), and stroke survivors (0.40, 0.27-0.57)]. Exercise also reduced fall-related injuries in ND patients (RR, 0.66; 95% CI, 0.48-0.90) and decreased fractures (0.63, 0.41-0.95) and fall-related injuries (0.89, 0.84-0.95) among frail aging people. For fall prevention, balance and combined exercise protocols are both effective, and either short-, moderate-, or long-term intervention duration is beneficial. More importantly, exercise only induced a very low injury rate per participant year (0.007%; 95% CI, 0-0.016) and show relatively good compliance with exercise (74.8; 95% CI, 69.7%-79.9%). Discussion: Exercise is effective in reducing neurodegenerative disease- and aging-associated falls and consequent injuries, suggesting that exercise is an effective and feasible strategy for the prevention of falls.

NLRP12 attenuates ozone-induced pulmonary inflammation by regulating canonical NF-κB Pathway.

Ozone (O3) is an important urban air pollutant having strong correlations with respiratory diseases. Several lines of evidence suggest that O3 exposure causes airway hyperresponsiveness (AHR) and pulmonary inflammation. Inhibitory innate immune receptors, such as NLRP12, have been demonstrated to alleviate inflammation, but the functional role for NLRP12 in O3-induced lung inflammatory inflammation remains to be reported. Here, we determined whether NLRP12 took a protective role in O3-induced AHR and pulmonary inflammation via the suppression of canonical NF-κB. C57BL/6 J mice were exposed to filtered air (FA) or 0.25, 0.50 and 1.00 ppm (3 h/day for 5 consecutive days) followed by detection of airway resistance, white blood cells, total proteins, and cytokines. Meanwhile, NLRP12 in lung tissue were detected by real time PCR. Moreover, we also examined protein expression of NLRP12 and key biomarkers of NF-κB pathway. It was shown that 24 h post O3 exposure, AHR as wells as total cells, proteins, and cytokines contents in BALF of mice were increased compare to those of FA controls in a dose-dependent manner. Notably, O3-induced AHR and lung inflammation were associated with significant decrease in pulmonary NLRP12 and upregulation of phosphorylated IRAK1, p65 and IκBα in canonical NF-κB pathway. Intratracheal administration of NLRP12-overexpresing adenovirus 4 days prior to O3 exposure alleviated AHR and lung inflammation, and inhibited canonical NF-κB pathway activation. The findings from this study indicate that NLRP12 attenuates O3-induced AHR and pulmonary inflammation, possibly through regulating canonical NF-κB pathway. This provides a novel target for the prevention and treatment of lung diseases induced by O3 exposure.

Lung proteomics combined with metabolomics reveals molecular characteristics of inflammation-related lung tumorigenesis induced by B(a)P and LPS.

Inflammatory microenvironment may take a promoting role in lung tumorigenesis. However, the molecular characteristics underlying inflammation-related lung cancer remains unknown. In this work, the inflammation-related lung tumorigenesis mouse model was established by treated with B(a)P (1 mg/mouse, once a week for 4 weeks), followed by LPS (2.5 µg/mouse, once every 3 weeks for five times), the mice were sacrificed 30 weeks after exposure. TMT-labeled quantitative proteomics and untargeted metabolomics were used to interrogate differentially expressed proteins and metabolites in different mouse cancer tissues, followed by integrated crosstalk between proteomics and metabolomics through Spearman's correlation analysis. The result showed that compared with the control group, 103 proteins and 37 metabolites in B(a)P/LPS group were identified as significantly altered. By searching KEGG pathway database, proteomics pathways such as Leishmaniasis, Asthma and Intestinal immune network for IgA production, metabolomics pathways such as Vascular smooth muscle contraction, Linoleic acid metabolism and cGMP-PKG signaling pathway were enriched. A total of 22 pathways were enriched after conjoint analysis of the proteomic and metabolomics, and purine metabolism pathway, the unique metabolism-related pathway, which included significantly altered protein (adenylate cyclase 4, ADCY4) and metabolites (L-Glutamine, guanosine monophosphate (GMP), adenosine and guanosine) was found. Results suggested purine metabolism may contribute to the inflammation-related lung tumorigenesis, which may provide novel clues for the therapeutic strategies of inflammation-related lung cancer.

The activation of SIRT1 ameliorates BPDE-induced inflammatory damage in BEAS-2B cells via HMGB1/TLR4/NF-κB pathway.

Benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), the metabolite of environmental pollutant benzo(a)pyrene (B(a)P) could induce pulmonary toxicity and inflammation. SIRT1, an NAD+ -dependent histone deacetylase, is known to regulate inflammation in the occurrence and development of various diseases, but its effects on BPDE-induced acute lung injury are still unknown. The present study aimed to explore the role of SIRT1 in BPDE-induced acute lung injury. Here, human bronchial epithelial (HBE) cells (BEAS-2B) cells were stimulated with BPDE at different concentrations (0.50, 0.75, and 1.00 µmol/L) for 24 h, we found that the levels of cytokines in the supernatant were increased and the expression of SIRT1 in cells was down-regulated, at the same time, BPDE stimulation up-regulated the protein expression of HMGB1, TLR4, and p-NF-κBp65 in BEAS-2B cells. Then the activator and inhibitor of SIRT1 were used before BPDE exposure, it was shown that the activation of SIRT1 significantly attenuated the levels of inflammatory cytokines and HMGB1, and reduced the expression of HMGB1, AC-HMGB1, TLR4, and p-NF-κBp65 protein; while these results were reversed by the inhibition of SIRT1. This study revealed that the SIRT1 activation may protect against BPDE-induced inflammatory damage in BEAS-2B cells by regulating the HMGB1/TLR4/NF-κB pathway.

Screening of the differentially expressed proteins in malignant transformation of BEAS-2B cells induced by coal tar pitch extract.

Coal tar pitch extract (CTPE) was carcinogenic and could cause occupational lung cancer. Hence, we explored the changes of protein molecules during CTPE-induced malignant transformation (MT) of immortalized human bronchial epithelial (BEAS-2B) cells and provided clues for screening early biomarkers of CTPE-associated occupational lung cancer. The MT model of BEAS-2B cells induced by CTPE with 15.0 µg/mL. Subsequently, the MT of the BEAS-2B cells was verified by morphological observation, cell proliferation test, plate colony formation assay, and cell cycle assay. At the end of the experiment, we explored the differentially expressed proteins (DEPs) by total protein tandem mass tags quantitative proteomics technique between DMSO40 cells and CTPE40 cells. It was found that the proliferation ability, and colony formation rate were enhanced, and the cell cycle was changed. Then, bioinformatics analysis showed that a total of 107 DEPs were screened between CTPE40 and DMSO40 cells, of which 74 were up-regulated and 33 were down-regulated. As a result, 6 hub proteins were screened by protein-protein interaction network analysis. The expression levels of COX7A2, COX7C, MT-CO2, NDUFB4, and NDUFB7 were up-regulated as well as the expression of RPS29 protein was down-regulated. In summary, we established an MT model in vitro and explored the changes in protein molecules. As a result, this study suggested that changes of protein molecules, including COX7A2, COX7C, NDUFB7, MT-CO2, NDUFB4, and RPS29, occurred at the stage of BEAS-2B cell malignancy following CTPE exposure, which provided key information for screening biomarkers for CTPE-related occupational lung cancer.

The promising roles of exosomal microRNAs in osteosarcoma: A new insight into the clinical therapy.

Osteosarcoma is the most common malignant bone sarcoma in children. Chemotherapy drugs resistance significantly hinders the overall survival of patients. Due to high biocompatibility and immunocompatibility, exosomes have been explored extensively. Multiple parent cells can actively secrete numerous exosomes, and the membrane structure of exosomes can protect miRNAs from degradation. Based on these characteristics, exosomal miRNAs play an important role in the occurrence, development, drug resistance. Therefore, in-depth exploration of exosome biogenesis and role of exosomal miRNAs will provide new strategies and targets for understanding the pathogenesis of osteosarcoma and overcoming chemotherapy drug resistance. Moreover, advancing evidences have showed that engineering modification could attribute stronger targeting to exosomes to deliver cargos to recipient cells more effectively. In this review, we focus on the mechanisms of exosomal miRNAs on the occurrence and development of osteosarcoma and the potential to function as tumor biomarkers for diagnosis and prognosis prediction. In addition, we also summarize recent advances in the clinical application values of engineering exosomes to provide novel ideas and directions for overcoming the chemotherapy resistance in osteosarcoma.

Polyphyllin I induces apoptosis and autophagy in temozolomide-resistant glioma via modulation of NRF2 and MAPK-signaling activation.

Glioma is the most prevailing main malignant neoplasm of the central nervous system with a miserable prognosis. Temozolomide is the first-line chemotherapy drug for glioma, but its drug resistance reduces temozolomide's clinical efficacy and becomes the principal cause of the failure of glioma chemotherapy. Polyphyllin I (PPI), an active component in Rhizoma Paridis, demonstrates favorable therapeutic actions in diverse malignant neoplasms. Its effect on temozolomide-resistant glioma, however, has not yet been characterized. Here, we demonstrated that polyphyllin I inhibited the proliferation of temozolomide-resistant glioma cell in a concentration-dependent manner. Further, we found that polyphyllin I had a direct effect on temozolomide-resistant glioma tumor cells and promote reactive oxygen species (ROS)-dependent apoptosis and autophagy via mitogen-activated protein kinase (MAPK)-signaling (p38-JNK) pathway. Mechanistically, we showed that polyphyllin I downregulate the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway, indicating that polyphyllin I may be an expected therapeutic strategy for patients with temozolomide-resistant gliomas.

The association between urinary polycyclic aromatic hydrocarbon metabolites and liver function among US population: a cross-sectional study.

Most studies have focused on the pulmonary toxicity of inhaled PAHs to date; therefore, their hepatotoxic consequences are yet unknown. The main aim of this study is to examine the association between urinary polycyclic aromatic hydrocarbons (PAHs) and liver function parameters among the US population. The data included in this study were from the National Health and Nutritional Examination Survey (NHANES) 2003-2016. Finally, we included 2515 participants from seven cycles of the NHANES. Logistic regression was performed to calculate the association between each PAH and liver function parameters (elevated vs. normal) with odds ratio (OR) and 95% confidence intervals (CIs), along with adjustment for confounding variables. P < 0.05 was considered to indicate a statistically significant difference. All analyses were performed using R software 4.0.1. In the present study, all 2515 individuals were aged ≥ 18 years, 1211 males, and 1304 females. The average age normal was 45.56 ± 20.20, and the elevated was 46.04 ± 19.73 years, respectively. The results of logistic regression indicated that increased 9-hydroxyfluorene (OR = 2.11, 95% CI = [1.52, 2.95], P < 0.001), 2-hydroxyfluorene (OR = 1.61, 95% CI = [1.23, 2.11], P < 0.001), and 3-hydroxyfluorene (OR = 1.54, 95% CI = [1.21, 1.95], P < 0.001) were associated with elevated GGT. In conclusion, 9-hydroxyfluorene is associated with elevated GGT level, and the effect of 9-hydroxyfluorene on GGT is modified by other PAHs, which means that 9-hydroxyfluorene has a greater influence on GGT when other PAHs are increased.

Core genes in lung adenocarcinoma identified by integrated bioinformatic analysis.

This study aims to identify potential core genes of lung adenocarcinoma (LUAD). Three datasets (GSE32863, GSE43458, and GSE116959) were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between LUAD and normal tissues were filtrated by GEO2R tool. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed via Metascape database. The protein-protein interaction (PPI) network was constructed and core genes were identified using STRING and Cytoscape. Core genes expressions and their relevant clinical characteristics were performed via Oncomine and UALCAN databases respectively. The correlation between core genes and immune infiltrates was investigated by TIMER database. Kaplan-Meier plotter was performed for survival analysis. The signal pathway network of core genes was mapped by KEGG Mapper analysis tool. In this study, ten core genes were significantly related to overall survival (OS) of LUAD patients, which can provide clues for prognosis of LUAD.