Alpha-Hederin induces incomplete autophagic injury in non-small cell lung cancer by interfering with the lysosomal acidification.

Lung cancer is the most common oncological disease worldwide, with non-small cell lung cancer accounting for approximately 85% of lung cancer cases. α-Hederin is a monodesmosidic triterpenoid saponin isolated from the leaves of Hedera helix L. or Nigella sativa and has been extensively studied for its antitumor activity against a variety of tumor cells. It has been suggested that α-Hederin is a potential regulator of autophagy and has high promise for application. However, the specific mechanism and characteristics of α-Hederin in regulating autophagy are not well understood. In this study, we confirmed the potential of α-Hederin application in lung cancer treatment and comprehensively explored the mechanism and characteristics of α-Hederin in regulating autophagy in lung cancer cells. Our results suggest that α-Hederin is an incomplete autophagy inducer that targets mTOR to activate the classical autophagic pathway, inhibits lysosomal acidification without significantly affecting the processes of autophagosome transport, lysosome biogenesis, autophagosome and lysosome fusion, and finally leads to impaired autophagic flux and triggers autophagic damage in NSCLC.

Investigation of damping coefficients for elastic collision particles utilizing the acoustic frequency sampling method.

The damping coefficient serves to quantify the energy dissipation in particle collisions and constitutes a crucial parameter in discrete element simulations. Nevertheless, the factors influencing the damping coefficient remain unclear, and the damping coefficients of the majority of materials have not been precisely determined. In this investigation, the damping coefficients of eight representative particles were studied using the acoustic frequency sampling method, and the correlations between these coefficients and collision velocity, material density, and elastic modulus were analyzed. The findings indicate that damping coefficients exhibit insensitivity to velocity in strongly elastic and moderately elastic material particles. Conversely, for weakly elastic material particles, damping coefficients demonstrate an increase with rising velocity. The damping coefficient of metallic particles exhibits a linear relationship with material density and elastic modulus.

Exploring causality in the association between gut microbiota and irritable bowel syndrome risk: a large Mendelian randomization study.

BACKGROUND: In the past, some observational studies have highlighted the correlation between gut microbiota and irritable bowel syndrome (IBS). However, it is still unknown if the composition of gut microbiota shows a causal effect on the risk of IBS. AIM: To conduct Mendelian randomization (MR) analysis of the samples to study the probable causal relationship between the gut microbiota, their taxonomic groups, and the risk of IBS. MATERIALS AND METHODS: In this study, the summarized data regarding 211 gut microbiota and their IBS genome-wide association studies (GWAS) were collected from public databases. The causal estimates were determined using five MR techniques, where Inverse Variance Weighted (IVW) regression was employed as the major MR technique. Herein, MR-PRESSO and MR-Egger intercept tests were conducted to prevent horizontal pleiotropy. Cochran's Q test was used to evaluate heterogeneity using the IVW and MR-Egger techniques. RESULTS: IVW results showed that gut microbes, belonging to Class Gammaproteobacteria (P = 0.04; OR = 1.45), Family XIII (P = 0.03; OR = 1.34), Family Prevotellaceae (P = 0.003; OR =1.24), and Lachnospiraceae UCG004 (P = 0.049; OR = 1.19) increased the risk of IBS, while Alcaligenaceae (P = 0.03; OR = 0.83, 95% CI: 0.69-0.98) and Coprobacter (P = 0.02; OR = 0.86, 95% CI: 0.76-0.98) decreased the risk of IBS. CONCLUSIONS: This study presented novel insights that highlighted the causal relationship between gut microbiota and IBS, and offered new treatment strategies for preventing or treating IBS.

Nomogram model predicting the overall survival for patients with primary gastric mucosa-associated lymphoid tissue lymphoma.

BACKGROUND: Increasingly extranodal marginal B-cell lymphoma of mucosa-associated lymphoid tissue, known as mucosa-associated lymphoid tissue (MALT) lymphoma, is a type of non-Hodgkin's lymphoma. The prognosis of primary gastric MALT (GML) patients can be affected by many factors. Clinical risk factors, including age, type of therapy, sex, stage and family hematologic malignancy history, also have significant effects on the development of the disease. The available data are mainly focused on epidemiology; in contrast, few studies have investigated the prognostic variables for overall survival (OS) in patients with primary GML. Based on the realities above, we searched a large amount of data on patients diagnosed with primary GML in the Surveillance, Epidemiology and End Results (SEER) database. The aim was to develop and verify a survival nomogram model that can predict the overall survival prognosis of primary GML by combining prognostic and determinant variables. AIM: To create an effective survival nomogram for patients with primary gastric GML. METHODS: All data of patients with primary GML from 2004 to 2015 were collected from the SEER database. The primary endpoint was OS. Based on the LASSO and COX regression, we created and further verified the accuracy and effectiveness of the survival nomogram model by the concordance index (C-index), calibration curve and time-dependent receiver operating characteristic (td-ROC) curves. RESULTS: A total of 2604 patients diagnosed with primary GML were selected for this study. A total of 1823 and 781 people were randomly distributed into the training and testing sets at a ratio of 7:3. The median follow-up of all patients was 71 mo, and the 3- and 5-year OS rates were 87.2% and 79.8%, respectively. Age, sex, race, Ann Arbor stage and radiation were independent risk factors for OS of primary GML (all P < 0.05). The C-index values of the nomogram were 0.751 (95%CI: 0.729-0.773) and 0.718 (95%CI: 0.680-0.757) in the training and testing cohorts, respectively, showing the good discrimination ability of the nomogram model. Td-ROC curves and calibration plots also indicated satisfactory predictive power and good agreement of the model. Overall, the nomogram shows favorable performance in discriminating and predicting the OS of patients with primary GML. CONCLUSION: A nomogram was developed and validated to have good survival predictive performance based on five clinical independent risk factors for OS for patients with primary GML. Nomograms are a low-cost and convenient clinical tool in assessing individualized prognosis and treatment for patients with primary GML.

The Ethyl acetate extract from Celastrus orbiculatus suppresses non-small-cell lung cancer by activating Hippo signaling and inhibiting YAP nuclear translocation.

BACKGROUND: Celastrus orbiculatus Thunb. is a medicinal plant that has been widely used for thousands of years in China, and the ethyl acetate extract (Celastrus orbiculatus Thunb. Extract, COE) from its stem was reported to exert antitumor and anti-inflammatory effects in various preclinical studies. However, the anti-non-small-cell lung cancer activity of COE and its potential mechanism are not yet fully understood. PURPOSE: To investigate the antitumor effects of COE on non-small-cell lung cancer (NSCLC) cells and explore its molecular mechanism from the perspective of Hippo signaling, YAP nuclear translocation, and reactive oxygen species (ROS) generation. METHODS: The effects of COE on proliferation, cell cycle arrest, apoptosis, stemness, and senescence in NSCLC cell lines were determined by CCK-8, clone formation, flow cytometry, and ß-galactosidase staining assays. The effects of COE on Hippo signaling were investigated by Western blotting. The intracellular expression and distribution of YAP were analyzed by immunofluorescence assay. DCFH-DA probe combined with flow cytometry was used to detect intracellular total ROS levels in NSCLC cells after COE treatment. Xenograft tumor model was established, and the animal living image system was employed to analyze the effects of COE on the Hippo-YAP signaling in vivo. RESULT: COE significantly inhibited NSCLC activity in vitro and in vivo, mainly by proliferation inhibition, cycle arrest, apoptosis promotion, senescence promotion, and stemness downregulation. COE strongly activated Hippo signaling and inhibited YAP expression and nuclear retention. Activation of Hippo signaling induced by COE was associated with ROS-mediated phosphorylation of MOB1. CONCLUSION: This study demonstrated that COE inhibited NSCLC through activating Hippo signaling and suppressing YAP nuclear translocation, in which ROS may play a role in the phosphorylation of the MOB1 protein.

WDR72 Enhances the Stemness of Lung Cancer Cells by Activating the AKT/HIF-1α Signaling Pathway.

Objectives: Lung cancer is a common malignant tumor with high morbidity and mortality rate. Lung cancer stem cells are crucial in the development of lung cancer. In this study, we investigate WD repeat-containing protein 72 (WDR72) on lung cancer cell stemness and explore its underlying mechanism. Methods: WDR72 expression was investigated in lung cancer tissues and lung cancer stem cells by Western blot and RT-qPCR. The stemness of lung cancer stem cells was verified by the sphere-forming experiment and the abundance of stem cell markers. For the purpose of determining lung cancer stem cell growth, metastasis, and apoptosis, the CCK-8 assay, colony formation, Transwell migration, and flow cytometry were carried out. The ability of tumorigenesis in vivo was explored by xenograft tumor mouse models. Results: Up-regulation of WDR72 was found in lung cancer tissues and lung cancer stem cells. WDR72 overexpression significantly activated the AKT/HIF-1α signaling pathway. Application of PI3K/AKT pathway inhibitor LY29004 was able to counteract the impacts of WDR72 upregulation on genes related to stemness, growth, migration, and apoptosis in lung cancer stem cells. The sphere formation of lung cancer stem cells was significantly diminished after inhibiting the AKT/HIF-1α pathway. The promotion of WDR72 overexpression on lung cancer stem cell proliferation and metastasis was also eliminated by LY29004 treatment. Conclusion: WDR72 activates the AKT/HIF-1α signaling pathway to enhance the stemness of lung cancer stem cells and promote the growth and metastasis of lung cancer.

Radiomics-based classification models for HBV-related cirrhotic patients with covert hepatic encephalopathy.

INTRODUCTION: The significant abnormalities of precuneus (PC), which are associated with brain dysfunction, have been identified in cirrhotic patients with covert hepatic encephalopathy (CHE). The present study aimed to apply radiomics analysis to identify the significant radiomic features in PC and their subregions, combine with clinical risk factors, then build and evaluate the classification models for CHE diagnosis. METHODS: 106 HBV-related cirrhotic patients (54 had current CHE and 52 had non-CHE) underwent the three-dimensional T1-weighted imaging. For each participant, PC and their subregions were segmented and extracted a large number of radiomic features and then identified the features with significant discriminative power as the radiomics signature. The logistic regression analysis was employed to develop and evaluate the classification models, which are constructed using the radiomics signature and clinical risk factors. RESULTS: The classification model (R-C model) achieved best diagnostic performance, which incorporated radiomics signature (4 radiomic features from right PC), venous blood ammonia, and the Child-Pugh stage. And the area under the receiver operating characteristic curve values (AUC), sensitivity, specificity, and accuracy values were 0.926, 1.000, 0.765, and 0.848, in the testing set. Application of the radiomics nomogram in the testing set still showed a good predictive accuracy. CONCLUSIONS: This study presented the radiomic features of the right PC, as a potential image marker of CHE. The radiomics nomogram that incorporates the radiomics signature and clinical risk factors may facilitate the individualized prediction of CHE.

Relationship between fatty pancreas and hypertriglyceridemic waist phenotype: a cross-sectional study.

Hypertriglyceridemic waist phenotype (HTWP) and its quantitative indicator, waist circumference-triglyceride index (WTI), are common quantitative indices of visceral obesity and are closely related to metabolic diseases. The purpose of this study was to investigate the relationship between fatty pancreas (FP) and HTWP in China. FP was diagnosed using trans-abdominal ultrasonography in all participants. According to the waist circumference and serum triglyceride levels, the participants were divided into four phenotype groups: normal waist circumference-normal triglyceride, normal waist circumference-elevated triglyceride, elevated waist circumference-normal triglyceride, and elevated waist circumference-elevated triglyceride (indicating HTWP). Clinical characteristics and biochemical indices were compared among the groups. Receiver operating characteristic (ROC) curves were used to evaluate the utility of WTI as a reference factor for FP screening. The HTWP group had a higher prevalence of metabolic syndrome (84.2%), FP (10.4%), fatty liver (64.5%), and hypertension (15.8%) than the other three phenotype groups. The occurrence rate of HTWP and the median WTI were significantly higher in participants with FP than in those without FP (54.7% vs 21.0%, 222 ± 135 vs 142 ± 141, p < 0.001). In the ROC curve analysis, when the maximum area under the curve was 0.746, the WTI was 107.09 and the corresponding sensitivity and specificity were 90.6% and 51.9%, respectively. HTWP is closely associated with FP and can be used as a reference factor for FP screening.

Tumor Location and Survival Outcomes in Lung Adenosquamous Carcinoma: A Propensity Score Matched Analysis.

BACKGROUND There is little information in the literature available on lung adenosquamous carcinoma (LASC). The association between tumor location and survival outcomes in LASC is poorly understood. Our study was designed to probe the effect of tumor location on survival outcomes of LASC. MATERIAL AND METHODS Patients with LASC between 2004 and 2015 were identified using the Surveillance, Epidemiology and End Results (SEER) databases. The patients were divided into 2 groups, a main bronchus group and a peripheral group, according to their primary sites. The Propensity Score Matching (PSM) method was used to reduce possible bias between groups. The primary endpoints were overall survival (OS) and cancer-specific survival (CSS). RESULTS A total of 3176 patients, afflicted with LASC between 2004 and 2015, were extracted from the SEER databases. Of these, 212 patients were found to be eligible for analysis after a propensity 1: 1 nearest neighbor matched analysis. After PSM, multivariate Cox regression analysis showed that primary site, American Joint Committee on Cancer (AJCC) stage, T stage and surgery were independent predictors of LASC in both OS and CSS. Kaplan-Meier survival analysis showed that patients with LASC located in a peripheral site had better survival outcomes than those with LASC located in the main bronchus. In subgroup analysis, the advantages of tumor located in a peripheral site were more pronounced in female patients and AJCC stage I patients. CONCLUSIONS Tumor location may have an impact on the survival outcomes of patients with LASC. Patients with LASC located in a peripheral site had better survival outcomes than patients with LASC located in the main bronchus, particularly in female patients and AJCC stage I patients.

Structural Brain Network Alteration and its Correlation With Structural Impairments in Patients With Depression in de novo and Drug-Naïve Parkinson's Disease.

Purpose: Depression is common in Parkinson's disease (PD) and is correlated with the severity of motor deficits and quality of life. The present study aimed to investigate alterations in the structural brain network related to depression in Parkinson's disease (d-PD) and their correlations with structural impairments of white matter (WM). Materials and Methods: Data were acquired from the Parkinson Progression Markers Initiative (PPMI) database. A total of 84 de novo and drug-naïve PD patients were screened and classified into two groups according to the 15-item Geriatric Depression Scale (GDS-15): d-PD (n = 28) and nondepression in PD (nd-PD, n = 56). Additionally, 37 healthy controls (HC) were screened. All subjects underwent DTI and 3D-T1WI on a 3.0 T MR scanner. Individual structural brain networks were constructed and analyses were performed using graph theory and network-based statistics (NBS) at both global and local levels. Differences in global topological properties were explored among the three groups. The association models between node and edge changes and the GDS-15 were constructed to detect regions that were specifically correlated with d-PD. Tract-based spatial statistics (TBSS) was used to detect structural impairments of WM between the d-PD and nd-PD groups. The correlations between altered global topological properties and structural impairments were analyzed in the d-PD group. Results: The global efficiency and characteristic path length of the structural brain network were impaired in the d-PD group compared with those in the nd-PD and HC groups. Thirteen nodes and 1 subnetwork with 10 nodes and 12 edges specifically correlated with d-PD were detected. The left hippocampus, left parahippocampal, left lingual, left middle occipital, left inferior occipital, left fusiform, left middle temporal, and left inferior temporal regions were all involved in the results of node and edge analysis. No WM microstructural impairments were identified in the d-PD group. Conclusion: Our study suggests that the integration of the structural brain network is impaired with disrupted connectivity of limbic system and visual system in the de novo and drug-naïve d-PD patients.The topological properties assessing integration of the structural brain network can serve as a potential objective neuroimaging marker for early diagnosis of d-PD.

In vivo and in vitro imaging tracing of dual-labeled bone mesenchymal stem cells transplanted into myocardium of F344 rats.

OBJECTIVE: To investigate the feasibility of in vitro and in vivo magnetic resonance imaging (MRI) and fluorescence imaging tracking of transplanted bone mesenchymal stem cells (BMSCs) dual-labeled with ultrasmall superparamagnetic iron oxide (USPIO) and red fluorescence protein (RFP). METHODS: BMSCs were incubated with culture medium containing USPIO for 24 hours. The Prussian-blue staining, transmission electron microscopy and trypan-blue staining were used to study the efficacy and safety of labeling. F344 rat model of acute myocardial infarction was established by ligating the left anterior descending coronary artery. The dual-labeled BMSCs were injected into the margin of the infraction myocardium. Then MRI and fluorescence imaging were performed to trace the cells both in vitro and in vivo. Postmortal study was carried out to observe the distribution of transplanted cells in myocardium. RESULTS: The percentage of dual-labeled BMSCs reached 99% after co-incubating with USPIO for 24 hours. USPIO particles were mainly located in lysosomes. As demonstrated by trypan-blue staining, there was no significant deference in viability between labeled and unlabeled groups (P>0.05). All dual-labeled transplanted BMSCs showed a significant decreasing signal on MRI, and the signal intensity changes had no significant difference over 4 weeks (P=0.66). In vitro cell tracing with fluorescence imaging of isolated heart from F344 rats was successful,while in vivo cell tracing with fluorescence imaging failed. Prussian blue staining showed that USPIO distributed near the infarcted myocardium, corresponding with the fluorescence imaging. CONCLUSION: MRI can be used to trace the dual-labeled BMSCs transplanted into F344 rat hearts in vivo, while fluorescence imaging and pathological fluorescence imaging can trace the transplanted cells in vitro.