Development and validation of a 3D-convolutional neural network model based on chest CT for differentiating active pulmonary tuberculosis from community-acquired pneumonia.

PURPOSE: To develop and validate a 3D-convolutional neural network (3D-CNN) model based on chest CT for differentiating active pulmonary tuberculosis (APTB) from community-acquired pneumonia (CAP). MATERIALS AND METHODS: Chest CT images of APTB and CAP patients diagnosed in two imaging centers (n = 432 in center A and n = 61 in center B) were collected retrospectively. The data in center A were divided into training, validation and internal test sets, and the data in center B were used as an external test set. A 3D-CNN was built using Keras deep learning framework. After the training, the 3D-CNN selected the model with the highest accuracy in the validation set as the optimal model, which was applied to the two test sets in centers A and B. In addition, the two test sets were independently diagnosed by two radiologists. The 3D-CNN optimal model was compared with the discrimination, calibration and net benefit of the two radiologists in differentiating APTB from CAP using chest CT images. RESULTS: The accuracy of the 3D-CNN optimal model was 0.989 and 0.934 with the internal and external test set, respectively. The area-under-the-curve values with the 3D-CNN model in the two test sets were statistically higher than that of the two radiologists (all P < 0.05), and there was a high calibration degree. The decision curve analysis showed that the 3D-CNN optimal model had significantly higher net benefit for patients than the two radiologists. CONCLUSIONS: 3D-CNN has high classification performance in differentiating APTB from CAP using chest CT images. The application of 3D-CNN provides a new automatic and rapid diagnosis method for identifying patients with APTB from CAP using chest CT images.

Seropositive Reaction Rates of 9 B-Cell Epitopes of the SARS-CoV-2 Spike Protein and the Relationship between the Epitopes and Neutralizing Antibody.

OBJECTIVE: The aim of the study was to analyze the relationship between serum antibody and neutralizing antibody titers in convalescent coronavirus disease 2019 (COVID-19) patients with different disease severities, and the seropositive reaction rates of 9 reported B-cell epitopes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Serum IgG and total antibody titers of 165 convalescent COVID-19 patients were determined by chemiluminescence, the serum neutralization antibody titers were determined by microneutralization assay, and the S/CO values of 9 peptides were detected by indirect enzyme-linked immunosorbent assay. Correlations between the aforementioned indexes were statistically analyzed, and differences in patients with different diseases severities were evaluated. RESULTS: IgG, total antibody, and neutralizing antibody titers increased with disease severity. The positive rate of the receptor-binding region (RBD) was 100%, and the average positive rate for all the 9 peptides was above 50% in 165 patients. IDf showed the highest rate of positivity (86.06%), with a rate of 95% for the (IDf + IDa) pattern. Moreover, S/CO values of RBD and mix (IDh) were significantly correlated with IgG, total antibody titers, and neutralizing antibody titers (p < 0.001), whereas the S/CO values for other 8 peptides showed no obvious correlation. CONCLUSION: In this study, a large sample was used to confirm that the peptide IDf had a high positive reaction rate for all patients (86.06%) and also had the highest detection rate in asymptomatic patients (86.67%). Only long peptide and mixed peptide showed correlation with neutralizing antibody titers, suggesting that the ability of SARS-CoV-2 antibody to neutralize virus infectivity may require the interaction of multiple sites.

Performance of CT radiomics in predicting the overall survival of patients with stage III clear cell renal carcinoma after radical nephrectomy.

PURPOSE: To investigate the performance of CT radiomics in predicting the overall survival (OS) of patients with stage III clear cell renal carcinoma (ccRCC) after radical nephrectomy. MATERIALS AND METHODS: The 132 patients with stage III ccRCC undergoing radical nephrectomy were collected, and the patients were divided into training set (n = 79) and validation set (n = 53). The ccRCC was segmented and 396 radiomics features were extracted. After dimensionality reduction, radiomics score (RS) was obtained. COX regression was used to construct Model 1 (clinical variables + CT findings) and Model 2 (clinical variables + CT findings + RS) in the training set to predict the OS of patients, and then, the performance of the two models in the two data sets was compared. RESULTS: In the training set, Akaike information criterion, C-index, and corrected C-index were 295.51, 0.744, and 0.728 for Model 1, and 271.78, 0.805, and 0.799 for Model 2, respectively. In the validation set, the corresponding values were 185.68, 0.701, and 0.699 for Model 1, and 175.99, 0.768, and 0.768 for Model 2. The calibration curves showed that both models had good calibration degrees in the validation set. Compared with Model 1, the continuous net reclassification index and integrated discrimination improvement index of Model 2 in the two data sets were positively improved. CONCLUSION: The two prediction models showed high performance in the evaluation of OS of stage III ccRCC patients after radical nephrectomy, among which Model 2 based on ISUP grade and RS was more concise and efficient.

The Bioavailability and Biological Activities of Phytosterols as Modulators of Cholesterol Metabolism.

Phytosterols are natural sterols widely found in plants that have a variety of physiological functions, and their role in reducing cholesterol absorption has garnered much attention. Although the bioavailability of phytosterols is only 0.5-2%, they can still promote cholesterol balance in the body. A mechanism of phytosterols for lowering cholesterol has now been proposed. They not only reduce the uptake of cholesterol in the intestinal lumen and affect its transport, but also regulate the metabolism of cholesterol in the liver. In addition, phytosterols can significantly reduce the plasma concentration of total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C), with a dose-response relationship. Ingestion of 3 g of phytosterols per day can reach the platform period, and this dose can reduce LDL-C by about 10.7%. On the other hand, phytosterols can also activate the liver X receptor α-CPY7A1 mediated bile acids excretion pathway and accelerate the transformation and metabolism of cholesterol. This article reviews the research progress of phytosterols as a molecular regulator of cholesterol and the mechanism of action for this pharmacological effect.

Computed Tomography Imaging Characteristics: Potential Indicators of Epidermal Growth Factor Receptor Mutation in Lung Adenocarcinoma.

PURPOSE: The purpose of this study was to investigate the correlation between computed tomography imaging characteristics in lung adenocarcinoma and epidermal growth factor receptor (EGFR) mutations. METHODS: A total of 124 patients with lung adenocarcinoma and known EGFR mutation status were collected in this retrospective study. Computed tomography quantitative parameters of each tumor, including total volume, total surface, surface-to-volume ratio (SVR), average diameter, maximum diameter, and average density, were determined using computer-aided detection software. The correlation between the EGFR mutation status and imaging characteristics was assessed. The predictive value of these imaging characteristics for EGFR mutation was calculated using the area under the receiver operating characteristic curve. RESULT: Fifty-eight of 124 patients showed EGFR mutations. Patients who are female (P < 0.001) and nonsmokers (P < 0.001) and those with serum carcinoembryonic antigen (CEA) level of ≥5 (P = 0.035) were likely to have EGFR mutation. Computed tomography features including air bronchogram (P = 0.035), absence of cavitation (P = 0.010), and absence of pulmonary emphysema (P = 0.002) and quantitative parameters, such as smaller total surface (P = 0.002), smaller total volume (P = 0.001), higher SVR (P = 0.003), and smaller average diameter (P = 0.001), were associated with EGFR mutation. Logistic regression analysis revealed that the most significant independent prognostic factors of EGFR mutation for the model were nonsmoking (P = 0.035), CEA level of ≥5 (P = 0.004), presence of air bronchogram (P = 0.040), absence of cavitation (P = 0.021), and high SVR (P = 0.014). The area under the receiver operating characteristic curve, sensitivity, and specificity of the model for predicting EGFR mutation were 0.827, 75.8%, and 82.8%, respectively. CONCLUSIONS: EGFR-mutated adenocarcinoma showed significantly increased CEA level, presence of air bronchogram, absence of cavitation, and higher quantitative parameter SVR than those with wild-type EGFR.

Effect of New Model-Based Iterative Reconstruction on Quantitative Analysis of Airway Tree by Computer-Aided Detection Software in Chest Computed Tomography.

OBJECTIVE: Compared the performance of computer-aided detection (CAD) software for quantitative analysis of airway using computed tomography (CT) images reconstructed with versions of model-based iterative reconstruction (MBIR) that either balances spatial and density resolution (MBIRSTND) or prefers spatial resolution (MBIRRP20), and adaptive statistical iterative reconstruction (ASIR) with lung kernel. METHODS: Thirty patients were included who were scanned for pulmonary disease using a routine dose multidetector CT system. Data were reconstructed with ASIR, MBIRSTND, and MBIRRP20. Airway dimensions from the 3 reconstructions were measured using an automated, quantitative CAD software designed to segment and quantify the bronchial tree automatically using a skeletonization algorithm. For each patient and reconstruction algorithm, the right middle lobe bronchus was selected as a representative for measuring the bronchial length of the matched airways. Two radiologists used a semiquantitative 5-point scale to rate the subjective image quality of MBIRSTND and MBIRRP20 reconstructions on airway trees analysis. RESULTS: Algorithm impacts the measurement variability of bronchus length in chest CT, MBIRRP20 were the best, whereas ASIR were the worst (P < 0.05). In addition, the optimal reconstruction algorithm was found to be MBIRSTND for the airway trees being assessed about subjective noise and MBIRRP20 about bronchial end shows, and there were no significant differences in the continuity and completeness of bronchial wall, whereas ASIR performed inferiorly compared with them (P < 0.05). CONCLUSIONS: Compared with ASIR, MBIRSTND, and MBIRRP20 from MBIRn algorithm potentially allow the desired airway quantification accuracy to be achieved on the performance of CAD, especially for MBIRRP20.

Reducing both radiation and contrast doses in coronary CT angiography in lean patients on a 16-cm wide-detector CT using 70 kVp and ASiR-V algorithm, in comparison with the conventional 100-kVp protocol.

OBJECTIVE: To investigate the value of prospectively ECG-triggered coronary CT angiography (CCTA) for lean patients with body mass index (BMI) ≤ 23 kg/m2 using 70 kVp and high-level volume-based adaptive statistical iterative reconstruction (ASiR-V) algorithm on a 16-cm wide-detector CT system for reducing both radiation and contrast doses in comparison with the conventional 100-kVp protocol. MATERIALS AND METHODS: Thirty patients (group A) were prospectively enrolled to undergo 70-kVp CCTA on a 16-cm wide-detector CT scanner with noise index (NI) of 36 HU and at weight-dependent contrast dose rate of 16 mg I/kg/s for 9-s injection. Images were reconstructed with 80% ASiR-V. Radiation dose, contrast dose, and image quality were statistically compared with 30 patients (group B) in database with matching BMI who underwent conventional 100-kVp CCTA with NI of 25 HU, and at 25 mg I/kg/s rate for 10-s injection and reconstructed with 60% ASiR-V. RESULTS: There was no significant difference in patient demographics between the two groups (all p > 0.05). The two groups also had similar mean CT values and contrast-noise ratio (CNR) and subjective image quality (all p > 0.05). However, group A with 70 kVp reduced the effective dose by 75.3% compared with group B (0.43 ± 0.20 mSv vs. 1.74 ± 1.01 mSv, p < 0.001), and required 42.4% less contrast dose than group B (22.46 ± 2.94 ml vs. 38.99 ± 5.10 ml, p < 0.001). CONCLUSIONS: Prospectively ECG-triggered CCTA using 70 kVp and high-level ASiR-V on a 16-cm wide-detector CT system provides diagnostic images with substantial reduction in both radiation and contrast doses for patients with BMI ≤ 23 kg/m2 compared to the conventional 100-kVp protocol. KEY POINTS: • 70-kVp CCTA produces excellent images at sub-millisievert radiation. • 70-kVp CCTA reduces both radiation and contrast doses over conventional protocol. • Achieving low-dose CCTA with combined low kVp and high-level ASIR-V.

Triple-rule-out CT angiography using two axial scans with 16 cm wide-detector for radiation dose reduction.

OBJECTIVE: To explore the use of two consecutive axial scans in triple-rule-out (TRO) examination on a 16 cm wide-detector CT for radiation dose reduction. MATERIALS AND METHODS: Sixty TRO patients were assigned to either study group (Group A, n = 30) or control group (Group B, n = 30). Group A used a two-phasic contrast injection: 25mgI/kg/s for 12 s in 1st and at 3.0 ml/s injection rate for 7 s in 2nd phase. The pulmonary artery, coronary artery and aorta were scanned in succession with two axial scans using smart-coverage technique. Group B used the conventional protocol of scanning pulmonary arteries first in helical, followed by coronary arteries in axial and aorta in helical mode with contrast injection of 25mgI/kg/s for 14 s. All images were reconstructed with 80% ASIR-V. The qualitative and quantitative image assessment and effective dose of the two groups were statistically compared. RESULTS: The demographic data and quantitative measurements and qualitative image scores between the two groups were statistically the same (p > 0.05). However, Group A reduced radiation dose by 52% (2.67 ± 0.98 mSv vs. 5.65 ± 1.37 mSv) (p < 0.001). CONCLUSION: Using two consecutive axial scans in triple-rule-out on a 16 cm wide-detector CT reduces radiation dose while maintaining image quality compared with the conventional TRO protocol. KEY POINTS: • Triple-rule-out can be performed with two-axial scans on a wide-detector CT system. • TRO with two-axial scans maintain image quality compared with conventional protocol. • TRO with two-axial scans reduces 52% radiation dose over conventional protocol.

The Value of 16-cm Wide-Detector Computed Tomography in Coronary Computed Tomography Angiography for Patients With High Heart Rate Variability.

OBJECTIVE: The aim of this study was to investigate radiation dose and image quality of coronary computed tomography (CT) angiography (CCTA) for patients with high heart rate variability (HRv) using 16-cm wide-detector CT scanner. METHODS: One hundred sixty-six patients with uncontrolled heart rate underwent CCTA on a 16-cm wide-detector CT system and were divided into 2 groups based on their HRv for analysis: group A (n = 95, HRv ≤10 beats/min [bpm]) and group B (n = 71, HRv >10 bpm). Images in both groups were reconstructed with motion correction algorithm. Subjective and objective image qualities were analyzed. RESULTS: There were no significant differences in age, body mass index, and heart rate (68.1 ± 11.4 vs 67.6 ± 12.3 bpm) between the 2 groups (P > 0.05). However, group B had significantly higher HRv than group A (33.5 ± 24.4 vs 7.8 ± 1.2 bpm, P < 0.001). All images were acceptable for clinical diagnosis. Compared with group A, image quality scores in group B decreased slightly (4.1 ± 0.5 vs 4.0 ± 0.6). However, the difference was not statistically significant. The mean effective doses were both relatively low at 2.2 ± 1.1 mSv in group A and 2.6 ± 1.4 mSv in group B. CONCLUSIONS: Single-heartbeat free-breathing CCTA can be performed for patients with high HRv using 16-cm wide-detector CT scanner to achieve diagnostic image quality with low radiation dose.

A three-dimensional approach for identifying small pulmonary vessels in smokers.

BACKGROUND: This study aims to develop a computerized scheme that utilizes a differential geometric approach to identify pulmonary vessels and then evaluate the performance of the scheme on the CT images of heavy smokers. METHODS: The scheme consists of two primary steps to segment entire lung vascular tree and identify the number of pulmonary vessels in a cross section. The scheme performance including accuracy, consistency, and efficiency was assessed using 102 chest CT scans. Further assessment was performed on the relationship between pulmonary vessels and the extent of emphysema as well as pulmonary artery alteration. RESULTS: The mean number of vessels in the cross section at the 5th generation was 17.84±4.74 and 17.23±4.85 assessed by computerized scheme and radiologists, respectively, which are significantly different (t = 2.12, p = 0.055). The results were consistent with those obtained by using a semi-automatic tool (r = 0.75, p = 0.01). In addition, in the 5th generation, the mean number of vessels was inversely related to the percentage of the low attenuation area (r = -0.704, p = 0.000), the mean lumen area of pulmonary vessel was inversely related to the mean value of main pulmonary artery diameter (r = -0.617, p = 0.000). The computational time of segmenting vessels was 6.50±0.02 seconds, which is much less than the average 8 minutes of the time spent by radiologists using the semi-automatic tool. CONCLUSION: Applying the computerized scheme yields reasonable performance on the segmentation of pulmonary vessels. The alteration of pulmonary vessels may reflect the presence of pulmonary hypertension, as well as the extent of emphysema.

The Structure-Activity Relationship of the Antioxidant Peptides from Natural Proteins.

Peptides derived from dietary proteins, have been reported to display significant antioxidant activity, which may exert notably beneficial effects in promoting human health and in food processing. Recently, much research has focused on the generation, separation, purification and identification of novel peptides from various protein sources. Some researchers have tried to discover the structural characteristics of antioxidant peptides in order to lessen or avoid the tedious and aimless work involving the ongoing generated peptide preparation schemes. This review aims to summarize the current knowledge on the relationship between the structural features of peptides and their antioxidant activities. The relationship between the structure of the precursor proteins and their abilities to release antioxidant fragments will also be summarized and inferred. The preparation methods and antioxidant capacity evaluation assays of peptides and a prediction scheme of quantitative structure-activity relationship (QSAR) will also be pointed out and discussed.

Association of heme oxygenase-1 polymorphisms with cancer risk: A systematic review and meta-analysis.

PURPOSE: Observational studies have recently focused on the association between heme oxygenase-1 (HMOX1) gene promoter polymorphisms and cancer risk. However, conflicting results have been obtained. To derive a precise estimate of the association, a systematic review and meta-analysis were conducted. METHODS: This study followed the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, Medline, Embase and Web of Knowledge were systematically searched for relevant studies. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for the allelic and genotypic comparisons according to the homozygous, heterozygous, dominant, and recessive genetic models. Between-study heterogeneity was quantified through I2 statistics, and publication bias was appraised by using funnel plots. Sensitivity analyses were conducted to evaluate the robustness of the meta-analysis findings. RESULTS: Meta-analysis of 9 studies involving 2491 cases and 3380 controls did not reveal any significant association of the HMOX-1 (GT)n and 413A>T polymorphisms with cancer risk. Stratified analysis by ethnicity showed a statistically significant association between (GT)n repeat length variant and susceptibility to cancer for the heterozygous genetic model among Asian populations (OR=1.42, 95% CI: 1.04-1.95, Pheterogeneity=0.218), which is a robust finding according to sensitivity analysis. Funnel plot inspection did not reveal any publication bias. CONCLUSION: In conclusion, this study comprehensively examined the available literature on the association of HMOX-1 (GT)n and 413A>T polymorphisms with cancer risk. Meta-analysis results suggest (GT)n repeat length polymorphism as a potential susceptibility variant for cancer in Asians. Additional large-scale and well-designed studies are needed to confirm these results.

Metastasis-associated protein 1 as a new prognostic marker for solid tumors: a meta-analysis of cohort studies.

Metastasis-associated protein 1 (MTA1) is a molecular marker in various solid tumors that has recently been investigated. The prognostic significance of MAT1 expression remains controversial. In this work, we aimed to determine the relationship between immunohistochemistry-detected MAT1 expression and survival of patients with solid tumors by conducting a meta-analysis of cohort studies. Relevant studies were identified via an electronic database search updated on October 28, 2013. We included cohort studies that reported hazard ratios (HRs) or odds ratios (ORs) with 95 % confidence intervals (CIs) to determine the association of high MTA1 expression with overall survival (OS) and clinicopathological characteristics. Heterogeneity was quantified using I (2) statistics, and publication bias was evaluated using funnel plots. Sensitivity analysis was conducted to evaluate the robustness of meta-analysis findings. We identified 16 cohort studies that focused on MTA1 overexpression and prognosis involving 2,253 cancer patients. Overall, the combined HR for OS was 1.85 (95 % CI: 1.55-2.28, P<0.001). Omission of any single study had no significant effect on the pooled HR estimate. When the studies were stratified by tumor type, similar results of poor prognosis were observed in non-small cell lung cancer (HR=2.05, 95 % CI: 1.14-3.68, P=0.016) and esophageal squamous cell carcinoma (HR=1.86, 95 % CI: 1.44-2.39, P<0.001). Moreover, multivariate survival analysis showed that MTA1 overexpression was an independent predictor of poor prognosis (HR=1.90, 95 % CI: 1.53-2.37, P<0.001). In addtional, MTA1 overexpression was significantly associated with tumor size (OR=2.72, 95 % CI=1.44-5.14, P=0.002), tumor stage (OR=2.44, 95 % CI=1.67-3.57, P<0.001), depth of invasion (OR=2.63, 95 % CI=1.74-3.97, P<0.001), and lymph node metastasis (OR=2.57, 95 % CI=1.57-4.19, P<0.001). However, when age, sex, and tumor differentiation were considered, no obvious association was observed. This study provides a comprehensive examination of the literature available on the association of MTA1 overexpression with OS and some clinicopathological features in solid tumors. Meta-analysis results provide evidence that MTA1 may be a new indicator of poor cancer prognosis. Considering the limitations of the eligible studies, other large-scale prospective trials must be conducted to clarify the prognostic value of MTA1 in predicting cancer survival.

Ultrasound-assisted extraction of Mangiferin from Mango (Mangifera indica L.) leaves using response surface methodology.

Mangiferin is a xanthone widely distributed in higher plants showing antioxidative, antiviral, anticancer, antidiabetic, immunomodulatory, hepatoprotective and analgesic effects. In the present study, an ultrasonic-assisted extraction method was developed for the effective extraction of mangiferin from mango leaves. Some parameters such as ethanol concentration, liquid-to-solid ratio, extraction temperature, and extraction time were optimized by single-factor experiment and response surface methodology. The optimal extraction conditions were 44% ethanol, the liquid-to-solid ratio was 38:1, and extraction for 19.2 min at 60 °C under ultrasound irradiation of 200 W. Under optimal conditions, the yield of mangiferin was 58.46 ± 1.27 mg/g. The results obtained are helpful for the full utilization of mango leaves, and also indicated that ultrasonic-assisted extraction is a very useful method for the extraction of mangiferin from plant materials.

Real-Time Detection of Ferulic Acid Effects on Rat Left Ventricle Using Pressure-Volume Conductivity Catheter.

Decreased cardiac function can have a negative impact on other organs. The left ventricular pressure-volume relationship is considered to be a valid method for evaluating cardiac function. Real-time monitoring of cardiac function is important for drug evaluation. Under closed-chest conditions, the miniature transducer, which is an important component of the pressure-volume catheter, enters the left ventricle of the rat through the right carotid artery. The device visualizes the changes in cardiac function during the experiment in the form of a pressure-volume loop. The actual volume of the ventricle is calculated by altering the conductivity of the blood by injecting 50 µL of a 20% sodium chloride solution into the rat's left jugular vein. The actual volume of the rat's ventricular cavity is calculated by measuring the conductivity of the blood in a known volume using a pressure-volume conductance catheter. This protocol allows for continuous observation of the effects of drugs on the heart and will promote the rationale for the use of specialty ethnic drugs in cardiovascular disease.

[Effect of Aloe emodin on invasion and metastasis of high metastatic breast cancer MDA-MB-231 cells].

OBJECTIVE: To investigate the effect of Aloe emodin (AE) on the invasive and metastatic abilities of human high metastatic breast cancer MDA-MB-231 cells. METHODS: MTT assay was used to evaluate the viability of MDA-MB-231 cells after treated with AE for 6 h and 24 h. The adhesive potential of MDA-MB-231 cells to FN and LN was tested by cell-matrix adhesion assay. The effect of AE on invasion of MDA-MB-231 cells was measured by Transwell chamber assay. Scratch wound healing assay was applied to determine the effect on migration of MDA-MB-231 cells. The effect of AE on MDA-MB-231 lung metastasis was determined on an experimental metastatic model. RESULTS: 80 micromol/L AE significantly inhibited the invasion, adhesion to FN, LN of MDA-MB-231 cells in vitro, the inhibitory rates were (52.98 +/- 5.46)%, (34.99 +/- 2.63)%, (28.73 +/- 7.00)%, respectively. After 24 h treatment, AE significantly inhibited the migration of MDA-MB-231 cells. The number and volume of lung metastatic nodules formed by MDA-MB-231 cells after 80 micromol/L AE 24 h treatment were decreased compared with control group. CONCLUSION: AE can suppress the metastasis of MDA-MB-231 cells. Their mechanisms may be related to the inhibition of the capabilities of invasion and migration of MDA-MB-231 cells.

Establishment of a non-alcoholic fatty liver disease model by high fat diet in adult zebrafish.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in recent years, but the pathogenesis is not fully understood. Therefore, it is important to establish an effective animal model for studying NAFLD. METHODS: Adult zebrafish were fed a normal diet or a high-fat diet combined with egg yolk powder for 30 days. Body mass index (BMI) was measured to determine overall obesity. Serum lipids were measured using triglyceride (TG) and total cholesterol (TC) kits. Liver lipid deposition was detected by Oil Red O staining. Liver injury was assessed by measuring glutathione aminotransferase (AST) and glutamic acid aminotransferase (ALT) levels. Reactive oxygen species (ROS) and malondialdehyde (MDA) were used to evaluate oxidative damage. The level of inflammation was assessed by qRT-PCR for pro-inflammatory factors. H&E staining was used for pathological histology. Caspase-3 immunofluorescence measured apoptosis. Physiological disruption was assessed via RNA-seq analysis of genes at the transcriptional level and validated by qRT-PCR. RESULTS: The high-fat diet led to significant obesity in zebrafish, with elevated BMI, hepatic TC, and TG. Severe lipid deposition in the liver was observed by ORO and H&E staining, accompanied by massive steatosis and ballooning. Serum AST and ALT levels were elevated, and significant liver damage was observed. The antioxidant system in the body was severely imbalanced. Hepatocytes showed massive apoptosis. RNA-seq results indicated that several physiological processes, including endoplasmic reticulum stress, and glucolipid metabolism, were disrupted. CONCLUSION: Additional feeding of egg yolk powder to adult zebrafish for 30 consecutive days can mimic the pathology of human nonalcoholic fatty liver disease.

Intermittent Fasting Alleviates Non-Alcoholic Steatohepatitis by Regulating Bile Acid Metabolism and Promoting Fecal Bile Acid Excretion in High-Fat and High-Cholesterol Diet Fed Mice.

SCOPE: Intermittent fasting (IF) has a protective role across a wide range of chronic disorders, including obesity, diabetes, and cardiovascular disease, but its protection against non-alcoholic steatohepatitis (NASH) is still lacking. This study seeks to investigate how IF alleviates NASH by regulating gut microbiota and bile acids (BAs) composition. METHODS AND RESULTS: Male C57BL/6 mice are fed a high-fat and high-cholesterol (HFHC) diet for 16 weeks to establish a NASH model. Mice then continued HFHC feeding and are treated with or without every other day fasting for 10 weeks. Hepatic pathology is assessed using hematoxylin-eosin staining. Gut microbiota of the cecum are profiled using 16S rDNA gene sequencing and the levels of BAs in serum, colon contents, and feces are measured using ultra-performance liquid chromatography-tandem mass spectrometry. Results indicate that IF significantly decreases murine body weight, insulin resistance, hepatic steatosis, ballooning, and lobular inflammation. IF reshapes the gut microbiota, reduces the accumulation of serum BAs, and increases total colonic and fecal BAs. Moreover, IF increases the expression of cholesterol 7α-hydroxylase 1 in liver, but decreases the expressions of both farnesoid-X-receptor and fibroblast growth factor 15 in the ileum. CONCLUSION: IF alleviates NASH by regulating bile acid metabolism and promoting fecal bile acid excretion.

Association of CYP1A1 polymorphisms with prostate cancer risk: an updated meta-analysis.

Epidemiological studies have evaluated the association between 3801T>C and 2455A>G polymorphisms of cytochrome P450 1A1 (CYP1A1) and prostate cancer risk. However, controversy exists regarding the role of these polymorphisms. In this work, a meta-analysis was performed to derive a more precise estimation of the relationship. PubMed and ISI Web databases were searched for all cases dated until March 2012. Crude odds ratios with 95 % confidence intervals were used to assess the strength of the association between CYP1A1 polymorphisms and prostate cancer risk. Sensitivity analysis, excluding the studies that deviated from the Hardy-Weinberg equilibrium (HWE), was performed. A total of 17 studies fulfilled our inclusion criteria in this meta-analysis, 12 of which were eligible (1,645 cases and 1,801 controls) for 3801T>C, and eleven (1,640 cases and 1,959 controls) were eligible for 2455A>G. Overall, the 2455A>G polymorphism resulted in a significantly increased susceptibility to prostate cancer. In addition, no significant associations between 3801T>C polymorphism and prostate cancer susceptibility were found in all genetic models. Only an elevated risk was observed for TC versus CC in Asian studies. However, no relationship was found in the Asian group for TC versus CC after excluding the studies that deviated from HWE. Thus, this meta-analysis finds the 2455A>G allele to be a risk factor for prostate cancer, whereas the 3801T>C status does not seem to be capable of modifying prostate cancer risk.

Coenzyme Q10 supplementation improves adipokine profile in dyslipidemic individuals: a randomized controlled trial.

BACKGROUND: In previous study, we found that coenzyme Q10 (CoQ10) improved glucolipid profile in dyslipidemic individuals, but the mechanism is not yet clear. Adipokines have been demonstrated to be vital targets of metabolic diseases. The hypothesis that adipokines mediate the association of CoQ10 on glucolipid metabolism needs to be further studied in human. METHODS: In this randomized, double-blinded, placebo-controlled trial, 101 dyslipidemic individuals were administrated to 120 mg CoQ10 or placebo for 24 weeks. Anthropometric parameters, glucolipid profile, serum total adiponectin, leptin, and resistin were evaluated at baseline, week 12 and week 24. RESULTS: CoQ10 treatment significantly increased serum adiponectin levels at week 12 (165 [0, 362] ng/mL, p < 0.001) and at week 24 (523 [0, 1056] ng/mL, p < 0.001]), which was significant different compared with placebo (p < 0.001). The increase of adiponectin was negative associated with decrease in index of homeostasis model assessment of insulin resistance (HOMA-IR, r = - 0.465, p = 0.001), triglyceride (TG, r = - 0.297, p = 0.047), and low-density lipoprotein cholesterol (LDL-c, r = - 0.440, p = 0.002) at week 24 only in CoQ10-treated group. Resistin was reduced by CoQ10 only at week 24 (- 1.19 [- 4.35, 0.00] ng/mL, p < 0.001), which was significant different compared with placebo (p < 0.001). Reduction of resistin was positively correlated with the change in HOMA-IR (r = 0.343, p = 0.021) and TG (r = 0.323, p = 0.030) at week 24 in CoQ10-treated group but not placebo group. Leptin was not influenced by CoQ10 treatment. Mediation analysis indicated that the improvement of HOMA-IR, TG and LDL-c by CoQ10 was mediated by adiponectin but not resistin. CONCLUSIONS: Our study shows that CoQ10 ameliorates glucolipid profile and adipokines dysfunction in dyslipidemic patients in 24 weeks' intervention. The beneficial effect of CoQ10 on glucolipid profile was mediated by adiponectin. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02407548. Registered on April 3, 2015, https://clinicaltrials.gov/ct2/show/NCT02407548 .