MicroRNA-503-5p protects streptozotocin-induced erectile dysfunction in diabetic rats by downregulating SYDE2.

Plentiful studies have clarified miRNAs take on a key role in the sexual dysfunction of diabetic rats. This study aimed to figure out microRNA (miR)-503-5p/SYDE2 axis' latent mechanisms in streptozotocin-induced diabetic rat sexual dysfunction. A model of erectile dysfunction (ED) in diabetic rats was established by injecting streptozotocin. MiR-503-5p and SYDE2 in ED rats were altered by injection of miR-503-5p mimic or si/oe-SYDE2. The targeting link between miR-503-5p and SYDE2 was testified. ICP/MAP value was tested by pressure sensor; Penile capillary abundance was assessed; Penile cGMP and AGEs were detected; penile smooth muscle cell apoptosis was assessed; MiR-503-5p and SYDE2 were tested. In streptozotocin-induced ED rats, miR-503-5p was reduced and SYDE2 was elevated. Elevating miR-503-5p or silencing of SYDE2 can enhance penile erection rate, ICP/MAP value, capillary abundance, and cGMP but reduce AGEs and penile smooth muscle cell apoptosis rate in ED rats. Strengthening SYDE2 with elevating miR-503-5p turned around the accelerating effect of elevated miR-503-5p on penile erection in ED rats. SYDE2 was a downstream target gene of miR-503-5p. MiR-503-5p protects streptozotocin-induced sexual dysfunction in diabetic rats by targeting SYDE2.

Particulate matter deposition and its impact on tuberculosis severity: A cross-sectional study in Taipei.

The objective of this study was to examine the association between the lung lobe-deposited dose of inhaled fine particulate matter (PM2.5) and chest X-ray abnormalities in different lung lobes of pulmonary tuberculosis (TB), multidrug-resistant tuberculosis (MDR-TB), and non-tuberculosis mycobacteria infections (NTM). A cross-sectional study was conducted between 2014 and 2022, comprising 1073 patients who were recruited from chest department clinic in a tertial refer hospital in Taipei City, Taiwan. Ambient 1-, 7-, and 30-day PM2.5 exposure and the deposition of PM2.5 in different lung lobes were estimated in each subject. The ß coefficient for PM2.5 and deposited PM2.5 in lungs with the outcome variables (pulmonary TB, MDR-TB, and NTM infection) was derived through regression analysis and adjusted for age, gender, BMI, smoking status, and family income. We observed that a 1 µg/m3 increase in ambient PM2.5 was associated with an increase of MDR-TB infections of 0.004 times (95%CI: 0.001-0.007). A 1 µg/m3 increase in 1-day and 7-day PM2.5 deposition in left upper lobe and left lower lobe was associated with an increase in chest X-ray abnormalities of 9.19 % and 1.18 % (95%CI: 0.87-17.51 and 95%CI: 0.08-2.28), and 4.52 % and 5.20 % (95%CI: 0.66-8.38 and 95%CI: 0.51-9.89) in left lung of TB patients, respectively. A 1 µg/m3 increase in 30-day PM2.5 deposition in alveolar region was associated with an increase in percent abnormality of 2.50 % (95%CI: 0.65-4.35) in left upper lobe and 3.33 % (95%CI: 0.65-6.01) in right middle lobe, while in total lung was 0.63 % (95%CI: 0.01-1.27) in right upper lobe and 0.37 % (95%CI, 0.06-0.81) in right lung of MDR-TB patients. Inhaled PM2.5 deposition in lungs was associated with an exacerbation of the radiographic severity of pulmonary TB, particularly in pulmonary MDR-TB patients in upper and middle lobes. Particulate air pollution may potentially exacerbate the radiographic severity and treatment resistance in individuals with pulmonary TB.

Alveolar deposition of inhaled fine particulate matter increased risk of severity of pulmonary tuberculosis in the upper and middle lobes.

Inhaled PM2.5 associated with pulmonary tuberculosis https://bit.ly/3VXAKfq.

Ambient relative humidity-dependent obstructive sleep apnea severity in cold season: A case-control study.

BACKGROUND: The objective of this study was to examine associations of daily averages and daily variations in ambient relative humidity (RH), temperature, and PM2.5 on the obstructive sleep apnea (OSA) severity. METHODS: A case-control study was conducted to retrospectively recruit 8628 subjects in a sleep center between January 2015 and December 2021, including 1307 control (apnea-hypopnea index (AHI) < 5 events/h), 3661 mild-to-moderate OSA (AHI of 5-30 events/h), and 3597 severe OSA subjects (AHI > 30 events/h). A logistic regression was used to examine the odds ratio (OR) of outcome variables (daily mean or difference in RH, temperature, and PM2.5 for 1, 7, and 30 days) with OSA severity (by the groups). Two-factor logistic regression models were conducted to examine the OR of RH with the daily mean or difference in temperature or PM2.5 with OSA severity. An exposure-response relationship analysis was conducted to examine the outcome variables with OSA severity in all, cold and warm seasons. RESULTS: We observed associations of mean PM2.5 and RH with respective increases of 0.04-0.08 and 0.01-0.03 events/h for the AHI in OSA patients. An increase in the daily difference of 1 % RH increased the AHI by 0.02-0.03 events/h in OSA patients. A daily PM2.5 decrease of 1 µg/m3 reduced the AHI by 0.03 events/h, whereas a daily decrease in the RH of 1 % reduced the AHI by 0.03-0.04 events/h. The two-factor model confirmed the most robust associations of ambient RH with AHI in OSA patients. The exposure-response relationship in temperature and RH showed obviously seasonal patterns with OSA severity. CONCLUSION: Short-term ambient variations in RH and PM2.5 were associated with changes in the AHI in OSA patients, especially RH in cold season. Reducing exposure to high ambient RH and PM2.5 levels may have protective effects on the AHI in OSA patients.

How platinum-induced nephrotoxicity occurs? Machine learning prediction in non-small cell lung cancer patients.

BACKGROUND AND OBJECTIVE: Platinum-induced nephrotoxicity is a severe and unexpected adverse drug reaction that could lead to treatment failure in non-small cell lung cancer patients. Better prediction and management of this nephrotoxicity can increase patient survival. Our study aimed to build up and compare the best machine learning models with clinical and genomic features to predict platinum-induced nephrotoxicity in non-small cell lung cancer patients. METHODS: Clinical and genomic data of patients undergoing platinum chemotherapy at Wan Fang Hospital were collected after they were recruited. Twelve models were established by artificial neural network, logistic regression, random forest, and support vector machine with integrated, clinical, and genomic modes. Grid search and genetic algorithm were applied to construct the fine-tuned model with the best combination of predictive hyperparameters and features. Accuracy, precision, recall, F1 score, and area under the receiver operating characteristic curve were calculated to compare the performance of the 12 models. RESULTS: In total, 118 patients were recruited for this study, among which 28 (23.73%) were experiencing nephrotoxicity. Machine learning models with clinical and genomic features achieved better prediction performances than clinical or genomic features alone. Artificial neural network with clinical and genomic features demonstrated the best predictive outcomes among all 12 models. The average accuracy, precision, recall, F1 score and area under the receiver operating characteristic curve of the artificial neural network with integrated mode were 0.923, 0.950, 0.713, 0.808 and 0.900, respectively. CONCLUSIONS: Machine learning models with clinical and genomic features can be a preliminary tool for oncologists to predict platinum-induced nephrotoxicity and provide preventive strategies in advance.

Associations between lung-deposited dose of particulate matter and culture-positive pulmonary tuberculosis pleurisy.

Epidemiological studies identified the relationship between air pollution and pulmonary tuberculosis. Effects of lung-deposited dose of particulate matter (PM) on culture-positive pulmonary tuberculosis remain unclear. This study investigates the association between lung-deposited dose of PM and pulmonary tuberculosis pleurisy. A case-control study of subjects undergoing pleural effusion drainage of pulmonary tuberculosis (case) and chronic heart failure (control) was conducted. Metals and biomarkers were quantified in the pleural effusion. The air pollution exposure was measured and PM deposition in the head, tracheobronchial, alveolar region, and total lung region was estimated by Multiple-path Particle Dosimetry (MPPD) Model. We performed multiple logistic regression to examine the associations of these factors with the risk of tuberculosis. We observed that 1-µg/m3 increase in PM10 was associated with 1.226-fold increased crude odds ratio (OR) of tuberculosis (95% confidence interval (CI): 1.023-1.469, p<0.05), 1-µg/m3 increase in PM2.5-10 was associated with 1.482-fold increased crude OR of tuberculosis (95% CI: 1.048-2.097, p < 0.05), 1-ppb increase in NO2 was associated with 1.218-fold increased crude OR of tuberculosis (95% CI: 1.025-1.447, p < 0.05), and 1-ppb increase in O3 was associated with 0.735-fold decreased crude OR of tuberculosis (95% CI: 0.542 0.995). We observed 1-µg/m3 increase in PM deposition in head and nasal region was associated with 1.699-fold increased crude OR of tuberculosis (95% CI: 1.065-2.711, p < 0.05), 1-µg/m3 increase in PM deposition in tracheobronchial region was associated with 1.592-fold increased crude OR of tuberculosis (95% CI: 1.095-2.313, p < 0.05), 1-µg/m3 increase in PM deposition in alveolar region was associated with 3.981-fold increased crude OR of tuberculosis (95% CI: 1.280-12.386, p < 0.05), and 1-µg/m3 increase in PM deposition in total lung was associated with 1.511-fold increased crude OR of tuberculosis (95% CI: 1.050-2.173, p < 0.05). The results indicate that particle deposition in alveolar region could cause higher risk of pulmonary tuberculosis pleurisy than deposition in other lung regions.

Erratum: Barsasella et al. Sleep Quality among Breast and Prostate Cancer Patients: A Comparison between Subjective and Objective Measurements. Healthcare 2021, 9, 785.

The authors wish to make the following erratum to this paper [...].

Correction: Artificial Intelligence-Based Prediction of Lung Cancer Risk Using Nonimaging Electronic Medical Records: Deep Learning Approach.

[This corrects the article DOI: 10.2196/26256.].

Artificial Intelligence-Based Prediction of Lung Cancer Risk Using Nonimaging Electronic Medical Records: Deep Learning Approach.

BACKGROUND: Artificial intelligence approaches can integrate complex features and can be used to predict a patient's risk of developing lung cancer, thereby decreasing the need for unnecessary and expensive diagnostic interventions. OBJECTIVE: The aim of this study was to use electronic medical records to prescreen patients who are at risk of developing lung cancer. METHODS: We randomly selected 2 million participants from the Taiwan National Health Insurance Research Database who received care between 1999 and 2013. We built a predictive lung cancer screening model with neural networks that were trained and validated using pre-2012 data, and we tested the model prospectively on post-2012 data. An age- and gender-matched subgroup that was 10 times larger than the original lung cancer group was used to assess the predictive power of the electronic medical record. Discrimination (area under the receiver operating characteristic curve [AUC]) and calibration analyses were performed. RESULTS: The analysis included 11,617 patients with lung cancer and 1,423,154 control patients. The model achieved AUCs of 0.90 for the overall population and 0.87 in patients ≥55 years of age. The AUC in the matched subgroup was 0.82. The positive predictive value was highest (14.3%) among people aged ≥55 years with a pre-existing history of lung disease. CONCLUSIONS: Our model achieved excellent performance in predicting lung cancer within 1 year and has potential to be deployed for digital patient screening. Convolution neural networks facilitate the effective use of EMRs to identify individuals at high risk for developing lung cancer.

Sleep Quality among Breast and Prostate Cancer Patients: A Comparison between Subjective and Objective Measurements.

Breast and prostate cancer patients may experience physical and psychological distress, and a possible decrease in sleep quality. Subjective and objective methods measure different aspects of sleep quality. Our study attempted to determine differences between objective and subjective measurements of sleep quality using bivariate and Pearson's correlation data analysis. Forty breast (n = 20) and prostate (n = 20) cancer patients were recruited in this observational study. Participants were given an actigraphy device (ACT) and asked to continuously wear it for seven consecutive days, for objective data collection. Following this period, they filled out the Pittsburgh Sleep Quality Index Questionnaire (PSQI) to collect subjective data on sleep quality. The correlation results showed that, for breast cancer patients, PSQI sleep duration was moderately correlated with ACT total sleeping time (TST) (r = -0.534, p < 0.05), and PSQI daytime dysfunction was related to ACT efficiency (r = 0.521, p < 0.05). For prostate cancer patients, PSQI sleep disturbances were related to ACT TST (r = 0.626, p < 0.05). Both objective and subjective measurements are important in validating and determining details of sleep quality, with combined results being more insightful, and can also help in personalized care to further improve quality of life among cancer patients.

Evaluation of association between methylenetetrahydrofolate reductase and azoospermia: A meta-analysis.

BACKGROUND: Infertility affects childbearing age couples all over the world. One of the important reasons for infertility is genetic factors. Our study evaluated the association between methylenetetrahydrofolate reductase (MTHFR) and azoospermia. METHODS: Multiple databases like MEDLINE, EMBASE, Cochrane library, and China journal full-text database were used to search for relevant studies, and full-text articles involved in the evaluation of MTHFR and azoospermia. The results were evaluated using STATA 12.0. Heterogeneity analysis, sensitivity analysis, and bias analysis were also performed on the data. RESULTS: Thirteen related studies eventually met the inclusion criteria. Significant association between C677T polymorphism and azoospermia (relative risk [RR] = 0.94 [0.90, 0.99], I2 = 60.9%, P = .002), and between A1298C polymorphism and azoospermia (RR = 0.98 [0.94, 1.02], I2 = 56.3%, P = .011) was observed. Meanwhile, in subgroup analysis, Caucasians had higher risk than Mongolians in association between MTHFR and azoospermia. CONCLUSION: There was association between MTHFR polymorphism and azoospermia. Caucasian populations had higher risk than Mongolian populations in association between MTHFR and azoospermia.

Exposure to PM2.5 is associated with malignant pleural effusion in lung cancer patients.

Air pollution has been recognized to be a risk factor for lung cancer. The objective of this study was to investigate the effects of air pollution on heavy metal alterations in the pleural effusion of lung cancer patients. Pleural effusion was collected from patients with lung cancer and congestive heart failure (CHF). One-year average levels of particulate matter with an aerodynamic diameter of < 10 µm (PM10), PM2.5, NO2, and SO2 were linked to the exposure of these subjects. Traffic-related metals, included Al, Fe, Cu, Zn, and Pb, were determined in the pleural effusion. Logistic regression models were used to examine their associations. There were 63 lung cancer patients and 31 CHF patients enrolled in the current study. We found that PM10, PM2.5, and NO2 were negatively correlated with Al in the pleural effusion, whereas PM2.5 was positively correlated with Zn in the pleural effusion. Increases in 1 µg/m3 of PM2.5 and 1 ng/mL of Zn were associated with lung cancer (adjusted OR=2.394, 95% CI= 1.446-3.964 for PM2.5; adjusted OR=1.003, 95% CI=1.000-1.005 for Zn). Increases in PM2.5 and Zn in the pleural effusion increased the risk of malignant pleural effusion in lung cancer patients (adjusted OR=1.517; 95% CI=1.082-2.127 for PM2.5; adjusted OR=1.002, 95% CI=1.000-1.005 for Zn). Furthermore, we observed that adenocarcinomas increased in association with a 1-µg/m3 increase in PM2.5 (crude OR=1.683; 95% CI=1.006-2.817) in lung cancer patients. In conclusion, PM2.5 exposure and the possible resultant Zn in the pleural effusion associated with the development of malignant pleural effusion in lung cancer.

TGF-ß Induced CTGF Expression in Human Lung Epithelial Cells through ERK, ADAM17, RSK1, and C/EBPß Pathways.

BACKGROUND: Lung epithelial cells play critical roles in idiopathic pulmonary fibrosis. METHODS: In the present study, we investigated whether transforming growth factor-ß (TGF-ß)-induced expression of connective tissue growth factor (CTGF) was regulated by the extracellular signal-regulated kinase (ERK)/a disintegrin and metalloproteinase 17 (ADAM17)/ribosomal S6 kinases 1 (RSK1)/CCAAT/enhancer-binding protein ß (C/EBPß) signaling pathway in human lung epithelial cells (A549). RESULTS: Our results revealed that TGF-ß-induced CTGF expression was weakened by ADAM17 small interfering RNA (ADAM17 siRNA), TNF-α processing inhibitor-0 (TAPI-0, an ADAM17 inhibitor), U0126 (an ERK inhibitor), RSK1 siRNA, and C/EBPß siRNA. TGF-ß-induced ERK phosphorylation as well as ADAM17 phosphorylation was attenuated by U0126. The TGF-ß-induced increase in RSK1 phosphorylation was inhibited by TAPI-0 and U0126. TGF-ß-induced C/EBPß phosphorylation was weakened by U0126, ADAM17 siRNA, and RSK1 siRNA. In addition, TGF-ß increased the recruitment of C/EBPß to the CTGF promoter. Furthermore, TGF-ß enhanced fibronectin (FN), an epithelial-mesenchymal transition (EMT) marker, and CTGF mRNA levels and reduced E-cadherin mRNA levels. Moreover, TGF-ß-stimulated FN protein expression was reduced by ADAM17 siRNA and CTGF siRNA. CONCLUSION: The results suggested that TGF-ß induces CTGF expression through the ERK/ADAM17/RSK1/C/EBPß signaling pathway. Moreover, ADAM17 and CTGF participate in TGF-ß-induced FN expression in human lung epithelial cells.

ESTAT3 Inhibitor AG-490 Inhibits the Growth of Prostate Cancer by miR-503-5p Both In Vivo and In Vitro.

OBJECTIVE: To explore the effect and the related mechanism of STAT3 inhibitor AG-490 on inhibiting the proliferation of prostate cancer cells. METHODS: PC3 cells and DU145 cells were cultured stably and treated with AG-490 to detect the changes in the activity of PC3 cells and DU145 cells. Thirty 6-8 weeks male BALB/c nude mouse were randomly divided into a control group, a DMSO group, and an AG-490 group to detect differences in various indexes . RESULTS: The overexpression of miR-503-5p depends on the activation of STAT3. After treatment with AG-490, The proliferation and invasion of PC3 cells and DU145 cells and the expression of miR-503-5p were all reduced. Luciferase reporter assay demonstrated that the target proteins of miR-503-5p include PDCD4, TIMP-3, and PTEN. After treatment with AG-490, the expression of PDCD4, TIMP-3, and PTEN in cells was significantly up-regulated. IL-6-induced overexpression of miR-503-5p and restored the expression of STAT3, demonstrating the correlation between STAT3 and miR-503-5p. AG-490 can inhibit tumor growth and induce tumor cell apoptosis in the PC3 BALB/c nude mouse xenograft model. Western blotting and immunohistochemical staining showed that the expression levels of STAT3, Ki67, Bcl-2 and MMP-2 in the AG-490 group were significantly reduced, and the expression of PDCD4, TIMP-3 and PTEN increased. CONCLUSION: AG-490 can inhibit the growth of prostate cancer cells in a miR-503-5p-dependent manner by targeting STAT3. AG-490 is expected to become a new candidate drug for the treatment of prostate cancer.

Microglial activation and inflammation caused by traffic-related particulate matter.

Neurotoxicity caused by particulate matter (PM) has been highlighted as being a potential risk factor for neurodegenerative diseases. However, the effects of brain inflammation in response to traffic-related PM remain unclear. The objective of this study was to investigate the effects of traffic-related PM on microglial responses. We determined the cytotoxicity, oxidative stress, lipid peroxidation, inflammation, activation, autophagy, and apoptosis due to exposure to carbon black (CB) and diesel exhaust particles (DEPs) in Bv2 microglial cells. Additionally, cells were pretreated with corticosteroid to determine alterations in microglial activation and inflammation. For in vivo confirmation, Sprague Dawley (SD) rats were whole-body exposed to traffic-related PM1 (PM with an aerodynamic diameter of <1 µm) for 3 and 6 months. We observed that a decrease in cell viability and increases in dichlorodihydrofluorescein (DCFH), lactate dehydrogenase (LDH), and thiobarbituric acid-reactive substances (TBARSs) occurred due to CB and DEP. Production of interleukin (IL)-6 and soluble tumor necrosis factor (TNF)-α was significantly stimulated by CB and DEP, whereas production of cellular TNF-α was significantly stimulated by CB. Iba1 and prostaglandin E2 (PGE2) significantly increased due to CB and DEP. Consistently, we observed significant increases in Iba1 in the hippocampus of rats after 3 and 6 months of exposure to traffic-related PM1. We found that the light chain 3II (LC3II)/LC3I ratio and caspase-3 activity increased due to CB and DEP exposure. Subsequently, LDH, TBARS, LC3II/I, and caspase-3 activities did not clearly respond to corticosteroid pretreatment followed by DEP exposure in BV2 cells. Results of the present study suggested that traffic-related PM induced cytotoxicity, lipid peroxidation, microglial activation, and inflammation as well as autophagy and caspase-3 regulation in microglia. We demonstrated that microglial activation and inflammation may play important roles in the response of the brain to traffic-related PM.

Circulating sphingosine-1-phosphate as a prognostic biomarker for community-acquired pneumonia.

Early determination of the severity of Community-Acquired Pneumonia (CAP) is essential for better disease prognosis. Current predictors are suboptimal, and their clinical utility remains to be defined, highlighting the need for developing biomarkers with efficacious prognostic value. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid with a documented regulatory role in immune defense and maintenance of endothelial barrier integrity. For early diagnose of CAP and recognition of severe CAP patients, we conduct this pilot study to access the potential utility of the circulating S1P in an Emergency department setting. In the prospective study, plasma S1P levels were quantified in healthy controls and patients with CAP. Also, their discriminating power was assessed by receiver operating characteristic analysis. The association between S1P levels and disease severity indices was assessed by Spearman correlation and logistic regression tests. Patients with CAP had significantly higher plasma S1P levels than healthy individuals (CAP: 27.54 ng/ml, IQR = 14.37-49.99 ng/ml; Controls: 10.58 ng/ml, IQR = 4.781-18.91 ng/ml; p < 0.0001). S1P levels were inversely correlated with disease severity in patients with CAP. Based on multivariate logistic regression analysis, the plasma S1P concentrations showed significant predicting power for mortality (OR: 0.909; CI: 0.801-0.985; p < 0.05), intensive care unit admission (OR: 0.89; CI: 0.812-0.953; p < 0.005) and long hospital stay (OR: 0.978; CI: 0.961-0.992; p < 0.005). Interestingly, significantly elevated levels of S1P were noted in patients who received methylprednisolone treatment during hospitalization. These results suggest that S1P may be associated with the pathogenesis of CAP and may have prognostic utility in CAP and its therapy, especially in the Emergency Department setting.

Alterations by Air Pollution in Inflammation and Metals in Pleural Effusion of Pneumonia Patients.

Air pollution is known to increase the risk of pneumonia. However, the effects of air pollution on the pleural effusion of patients with pneumonia are unclear. The objective of this study was to investigate alterations in inflammatory⁻immune biomarkers by air pollution in patients with pneumonia by analyzing their pleural effusion. Patients who had undergone thoracentesis to drain their pleural effusion in a hospital were recruited for this study. Patients with pneumonia and those with congestive heart failure respectively served as the case and control groups. We observed that an increase of 1 ppb in one-year NO2 was associated with a decrease of 0.105 ng/mL in cluster of differentiation 62 (CD62) (95% confidence interval (CI) = -0.085, -0.004, p < 0.05) in the pleural effusion. Furthermore, we observed that an increase in one-year 1 ppb of NO2 was associated with a decrease of 0.026 ng/mL in molybdenum (Mo) (95% CI = -0.138, -0.020, p < 0.05). An increase in one-year 1 ppb of SO2 was associated with a decrease of 0.531 ng/mL in zinc (95% CI = -0.164, -0.006, p < 0.05). Also, an increase in one-year 1 ppb of O3 was associated with a decrease of 0.025 ng/mL in Mo (95% CI = -0.372, -0.053, p < 0.05). In conclusion, air pollution exposure, especially gaseous pollution, may be associated with the regulation of immune responses and changes in metal levels in the pleural effusion of pneumonia patients.

Hyperoside protects the blood-brain barrier from neurotoxicity of amyloid beta 1-42.

Mounting evidence indicates that amyloid ß protein (Aß) exerts neurotoxicity by disrupting the blood-brain barrier (BBB) in Alzheimer's disease. Hyperoside has neuroprotective effects both in vitro and in vivo against Aß. Our previous study found that hyperoside suppressed Aß1-42-induced leakage of the BBB, however, the mechanism remains unclear. In this study, bEnd.3 cells were pretreated with 50, 200, or 500 µM hyperoside for 2 hours, and then exposed to Aß1-42 for 24 hours. Cell viability was determined using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay were used to analyze cell apoptosis. Western blot assay was carried out to analyze expression levels of Bax, Bcl-2, cytochrome c, caspase-3, caspse-8, caspase-9, caspase-12, occludin, claudin-5, zonula occludens-1, matrix metalloproteinase-2 (MMP-2), and MMP-9. Exposure to Aß1-42 alone remarkably induced bEnd.3 cell apoptosis; increased ratios of cleaved caspase-9/caspase-9, Bax/Bcl-2, cleaved caspase-8/caspase-8, and cleaved caspase-12/caspase-12; increased expression of cytochrome c and activity of caspase-3; diminished levels of zonula occludens-1, claudin-5, and occludin; and increased levels of MMP-2 and MMP-9. However, hyperoside pretreatment reversed these changes in a dose-dependent manner. Our findings confirm that hyperoside alleviates fibrillar Aß1-42-induced BBB disruption, thus offering a feasible therapeutic application in Alzheimer's disease.

Effects of diesel exhaust particles on the expression of tau and autophagy proteins in human neuroblastoma cells.

Particulate air pollution is recognized as a potential risk factor for neurological disorders; however, the underlying mechanisms of neurodegenerative diseases that occur due to particulate air pollution remain unclear. The objective of the present study was to evaluate the neurotoxic effects caused by diesel exhaust particles (DEPs). We determined the ability of DEPs and carbon black (CB) to induce neurotoxicity, oxidative stress and inflammation, and to disrupt the expression of tau and autophagy proteins in human neuroblastoma IMR-32 cells. Spherical CB (dominated by C, N, and S) and DEPs (dominated by C, N, and O) in aggregates were observed using a field emission-scanning electron microscope (FE-SEM) equipped with energy-dispersive x-ray (EDX) microanalysis. Cell viability was significantly decreased by CB and DEPs in IMR-32 cells, but neither particle altered malondialdehyde (MDA) production. We observed that exposure to DEPs significantly increased 8-isoprostane and tumor necrosis factor (TNF)-α levels. Significantly increased expression of tau was induced in IMR-32 cells by DEPs but not by CB. Expression of beclin 1 was increased by DEPs, whereas the light chain 3II (LC3II)/LC3I ratio was increased by CB. Results of the present study suggested that DEPs induced neuroinflammation, oxidative stress, and neurodegenerative-related tau overexpression and regulation by autophagy in IMR-32 cells. We demonstrated that DEPs are able to induce neurotoxicity, which could be associated with the development of neurodegenerative diseases.

Prognostic value of localization of epidermal growth factor receptor in lung adenocarcinoma.

BACKGROUND: The nuclear translocation of epidermal growth factor receptor (EGFR) has been considered to play a role in carcinogenesis. However, the relevance of differentially located EGFR proteins in lung cancer remains unclear. METHODS: We examined 161 patients with primary lung adenocarcinoma to detect EGFR expression in lung cancer cells using immunohistochemistry and determined the correlations of EGFR expression with clinical characteristics, EGFR mutations, and survival time. Moreover, we graded complete membranous staining with strong intensity as high membranous EGFR (mEGFR) expression, and nuclear EGFR staining with strong intensity as high nuclear (nEGFR) expression. RESULTS: The prevalence of high mEGFR and nEGFR expression in lung adenocarcinoma was 42.86 and 39.13%, respectively. After multivariate analyses, high mEGFR expression was associated with a significantly reduced mortality risk in older patients, those with a history of smoking, and those without brain metastasis (hazard ratio[95% confidential interval], HR[95% CI] = 0.55[0.32~ 0.92]; 0.51[0.26~ 0.98] and 0.56[0.33~ 0.94], in overall survival, respectively). An association between high nEGFR expression and early recurrence was observed in patients with metastasis (HR[95% CI] =1.68[1.05~ 2.68], in progression-free survival). Notably, patients with low mEGFR and low nEGFR expression had the lowest survival rate in cases without brain metastasis (p = 0.018) and with a history of smoking (p = 0.062) and total EGFR (any high mEGFR or nEGFR) expression indicated a more favorable response to platinum-based chemotherapy regardless of EGFR mutations (HR[95% CI] =0.33[0.12-0.92]; adjusted HR[95% CI] = 0.36[0.13~ 1.02] with the use of tyrosine kinase inhibitor). CONCLUSIONS: EGFR proteins at different cellular locations in lung adenocarcinoma might influence the biology of cancer cells and are an independent indicator of more favorable prognosis and treatment response.