Investigation of the pan-cancer property of FNDC1 and its molecular mechanism to promote lung adenocarcinoma metastasis.

BACKGROUND: Fibronectin type III domain containing 1 (FNDC1) has been associated with the metastasis of many tumors, but its function in lung cancer remains uncertain. METHODS: FNDC1 expression was analyzed in The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx), evaluate its prognostic value. Gene Set Enrichment Analysis (GSEA) enrichment analysis of differential expression of FNDC1 in lung cancer. The expression of FNDC1 was detected in five types of lung cancer cells, and screened to establish FNDC1 stable knockdown cell strains. To observe the migration and invasion ability of lung cancer cells after FNDC1 knockdown. Finally, we used rhIL-6 to interfere with the stable knockdown of FNDC1 in A549 cells and observed the recovery of migration and invasion. RESULT: Our results showed that FNDC1 expression was increased in 21 tumor tissues, including lung cancer, and was associated with poor prognosis in five cancers, including lung adenocarcinoma (LUAD) (P < 0.05). GSEA enrichment analysis showed that FNDC1 was related to the pathways involved the JAK-STAT signaling pathway. Stable knockdown of FNDC1 in A549 and H292 cells resulted in decreased migration and invasion ability of both cells, accompanied by decreased expression of MMP-2 and Snail, and a significant decline in the expression of p-JAK2 and p-STAT3. The suppressive effect of FNDC1 knockdown on lung cancer cell metastasis counteracted by the JAK-STAT agonist rhIL-6 were presented in the nude mouse metastatic tumor model. CONCLUSION: FNDC1 is implicated in poor prognosis of a diverse range of malignant tumors, which can promote metastasis and invasion of lung cancer through the JAK2-STAT3 signaling pathway.

Multiple ultrasonic parametric imaging for the detection and monitoring of high-intensity focused ultrasound ablation.

Numerous quantitative ultrasound imaging techniques have demonstrated superior monitoring performance for thermal ablation when compared to conventional ultrasonic B-mode imaging. However, the absence of comparative studies involving various quantitative ultrasound imaging techniques hinders further clinical exploration. In this study, we simultaneously reconstructed ultrasonic Nakagami imaging, ultrasonic horizontally normalized Shannon entropy (hNSE) imaging, and ultrasonic differential attenuation coefficient intercept (DACI) imaging from ultrasound backscattered envelope data collected during high-intensity focused ultrasound ablation treatment. We comprehensively investigated their performance differences through qualitative and quantitative analyses, including the calculation of contrast-to-noise ratios (CNR) for ultrasonic images, receiver operating characteristic (ROC) analysis with corresponding indicators, the analysis of lesion area fitting relationships, and computational time consumption comparison. The mean CNR of hNSE imaging was 10.98 ± 4.48 dB, significantly surpassing the 3.82 ± 1.40 dB (p < 0.001, statistically significant) of Nakagami imaging and the 2.45 ± 0.74 dB (p < 0.001, statistically significant) of DACI imaging. This substantial difference underscores that hNSE imaging offers the highest contrast resolution for lesion recognition. Furthermore, we evaluated the ability of multiple ultrasonic parametric imaging to detect thermal ablation lesions using ROC curves. The area under the curve (AUC) for hNSE was 0.874, exceeding the values of 0.848 for Nakagami imaging and 0.832 for DACI imaging. Additionally, hNSE imaging exhibited the strongest linear correlation coefficient (R = 0.92) in the comparison of lesion area fitting, outperforming Nakagami imaging (R = 0.87) and DACI imaging (R = 0.85). hNSE imaging also performs best in real-time monitoring with each frame taking 6.38 s among multiple ultrasonic parametric imaging. Our findings unequivocally demonstrate that hNSE imaging excels in monitoring HIFU ablation treatment and holds the greatest potential for further clinical exploration.

Deciphering the molecular mechanism of Bu Yang Huan Wu Decoction in interference with diabetic pulmonary fibrosis via regulating oxidative stress and lipid metabolism disorder.

BACKGROUND: Diabetes mellitus type 2 and pulmonary fibrosis have been found to be closely related in clinical practice. Diabetic pulmonary fibrosis (DPF) is a complication of diabetes mellitus, but its treatment has yet to be thoroughly investigated. Bu Yang Huan Wu Decoction (BYHWD) is a well-known traditional Chinese prescription that has shown great efficacy in treating pulmonary fibrosis with hypoglycemic and hypolipidemic effects. METHODS: The active ingredients of BYHWD and the corresponding targets were retrieved from the Traditional Chinese Medicine Systematic Pharmacology Database (TCMSP) and SymMap2. Disease-related targets were obtained from the GeneCard, OMIM and CTD databases. GO enrichment and KEGG pathway enrichment were carried out using the DAVID database. AutoDock Vina software was employed to perform molecular docking. Molecular dynamics simulations of proteinligand complexes were conducted by Gromacs. Animal experiments were further performed to validate the effects of BYHWD on the selected core targets, markers of oxidative stress, serum lipids, blood glucose and pulmonary fibrosis. RESULTS: A total of 84 active ingredients and 830 target genes were screened in BYHWD, among which 56 target genes intersected with DPF-related targets. Network pharmacological analysis revealed that the active ingredients can regulate target genes such as IL-6, TNF-α, VEGFA and CASP3, mainly through AGE-RAGE signaling pathway, HIF-1 signaling pathway and TNF signaling pathway. Molecular docking and molecular dynamics simulations suggested that IL6-astragaloside IV, IL6-baicalein, TNFα-astragaloside IV, and TNFα-baicalein docking complexes could bind stably. Animal experiments showed that BYHWD could reduce the expression of core targets such as VEGFA, CASP3, IL-6 and TNF-α. In addition, BYHWD could reduce blood glucose, lipid, and MDA levels in DPF while increasing the activities of SOD, CAT and GSH-Px. BYHWD attenuated the expression of HYP and collagen I, mitigating pathological damage and collagen deposition within lung tissue. CONCLUSIONS: BYHWD modulates lipid metabolism disorders and oxidative stress by targeting the core targets of IL6, TNF-α, VEGFA and CASP3 through the AGE-RAGE signaling pathway, making it a potential therapy for DPF.

Vessel and Airway Characteristics in One-Year CT-defined Rapid Emphysema Progression: SPIROMICS.

Rationale: Rates of emphysema progression vary in chronic obstructive pulmonary disease (COPD), and the relationship with vascular and airway pathophysiology remain unclear. Objective: We sought to determine if indices of peripheral (segmental and beyond) pulmonary arterial (PA) dilation measured via computed tomography (CT) are associated with a 1-year index of emphysema (EI: %voxels<-950HU) progression. Methods: 599 GOLD 0-3 former and never-smokers were evaluated from the SubPopulations and InterMediate Outcome Measures in COPD Study (SPIROMICS) cohort: rapid-emphysema-progressors (RP, n=188; 1-year ΔEI>1%), non-progressors (NP, n=301; 1-year ΔEI±0.5%) and never-smokers (NS: N=110). Segmental PA cross-sectional areas were standardized to associated airway luminal areas (Segmental : Pulmonary Artery-to-Airway Ratio: PAARseg). Full inspiratory CT scan-derived total (arteries + veins) pulmonary vascular volume (TPVV) was compared to vessel volume with radius smaller than 0.75mm (SVV.75/TPVV). Airway-to-lung ratios (an index of dysanapsis and COPD risk) were compared to TPVV-lung-volume-ratios. Results: Compared with NP, RP exhibited significantly larger PAARseg (0.73±0.29 vs. 0.67±0.23; p=0.001), lower TPVV-to-lung-volume ratio (3.21%±0.42% vs. 3.48%±0.38%; p=5.0 x 10-12), lower airway-to-lung-volume ratio (0.031±0.003 vs. 0.034±0.004; p=6.1 x 10-13) and larger SVV.75/TPVV (37.91%±4.26% vs. 35.53±4.89; p=1.9 x 10-7). In adjusted analyses, a 1-SD increment in PAARseg was associated with a 98.4% higher rate of severe exacerbations (95%CI: 29 to 206%; p = 0.002) and 79.3% higher in odds of being in the rapid emphysema progression group (95%CI: 24% to 157%; p = 0.001). At year-2 followup, the CT-defined RP group demonstrated a significant decline in post-bronchodilator-FEV1% predicted. Conclusion: Rapid one-year progression of emphysema was associated with indices indicative of higher peripheral pulmonary vascular resistance and a possible role played by pulmonary vascular-airway dysanapsis.

Integrated study reveals mechanism of Tripterygium Wilfordii against cholangiocarcinoma based on bioinformatics approaches and molecular dynamics simulation.

BACKGROUND: Tripterygium wilfordii Hook. f. (TW) shows anticancer activity, and no study has comprehensively investigated the effects of TW in treating cholangiocarcinoma (CHOL). This study was designed to identify the therapeutic role and the mechanism of TW against CHOL to obtain anti-CHOL candidate components and targets. METHODS: Ingredients of TW were collected from the Traditional Chinese Medicine System Pharmacology Database and literature. Limma package and weighted gene co-expression network analysis were used to identify the genes related to CHOL. Enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) was performed by R package Cluster-Profiler and Metascape, respectively. Protein-Protein Interaction (PPI) network was used to select core genes in the treatment of CHOL by TW, followed by GEPIA2, UALCAN database, and ROC curves to assess their diagnostic and prognostic capability. Molecular docking and molecular dynamics simulation were applied to explore the binding affinity and stability of the complex between the bioactive ingredients in TW and core targets. RESULTS: A total of 67 ingredients in TW were collected, and 495 genes were obtained as genes of CHOL. 55 common TW-CHOL targets were identified. 171 biological process terms and 100 KEGG pathways were enriched. 12 genes were regarded as core genes through PPI analysis, such as CYP3A4, CES1, GC, and PLG, whose good diagnostic and prognostic capability were identified. Ten ingredients were selected through the construction of Herb-Components-Targets-Disease network. Molecular docking and molecular dynamics simulation both confirmed the good binding affinity and stability of the ligand-protein complexes. CONCLUSION: This study identified the therapeutic role and predicted the mechanism of TW against CHOL, where TW may combat CHOL through the regulation of metabolic conditions of the body, bile acid secretion, xenobiotics metabolism, and the inflammatory response. Celastrol, triptonide, triptolide and wilforlide A emerged as promising anti-CHOL candidates. So, this study offered a reference for the treatment of CHOL and the development of anti-CHOL drugs.

Association between the systemic immune inflammation index and periodontitis: a cross-sectional study.

BACKGROUND: Periodontitis is a chronic oral inflammatory disease that seriously affects people's quality of life. The purpose of our study was to investigate the correlation between the systemic immune inflammation index (SII) and periodontitis by utilizing a large national survey. This will establish a reference for the early identification and management of periodontitis. METHODS: This study comprised the adult US population who participated in a national periodontitis surveillance project during the six years from 2009 to 2014. Through the utilization of univariate and multivariate weighted logistic regression, we investigated the correlation between the systemic immune inflammation index and periodontitis. Additionally, we employed sensitivity analyses to evaluate the robustness of our findings. RESULTS: The study involved 10,366 participants with an average age of 51.00 years, of whom 49.45% were male (N = 5126) and 50.55% were female (N = 5240). The prevalence of periodontitis is estimated to be about 38.43% in the US adults aged 30 or older population. Our logistic regression models indicated a positive association between a SII higher than 978 × 109/L and periodontitis. The elder group (aged 50 or older) with SII higher than 978 × 109/L demonstrated a significant correlation with periodontitis in the fully adjusted model (Odds Ratio [OR] = 1.409, 95% Confidence Interval [CI] 1.037, 1.915, P = 0.022). However, there is no statistical difference among adults aged 30 to 50. The robustness of our findings was confirmed through sensitivity analyses. CONCLUSIONS: Our study highlights that SII is associated with periodontitis in a nationally representative sample of US adults. And the SII is significantly associated with a high risk of periodontitis in individuals aged 50 or older.

Structural Predictors of Lung Function Decline in Young Smokers with Normal Spirometry.

RATIONALE: Chronic obstructive pulmonary disease (COPD) due to tobacco smoking commonly presents when extensive lung damage has occurred. OBJECTIVES: We hypothesised that structural change would be detected early in the natural history of COPD and would relate to loss of lung function with time. METHODS: We recruited 431 current smokers (median age 39 years, 16 pack-years smoked) and recorded symptoms by the COPD Assessment Test (CAT), spirometry and quantitative thoracic CT (QCT) scans at study entry. These scans results were compared to 67 never smoking controls. 368 participants were followed every six months with measurement of post-bronchodilator spirometry for a median of 32 months. The rate of FEV1 decline, adjusted for current smoking status, age and sex was related to the initial QCT appearances and symptoms, measured with the CAT. MEASUREMENTS AND MAIN RESULTS: There were no material differences in demography or subjective CT appearances between the young smokers and controls, but 55.7% of the former had a CAT score above 10 and 24.2% reported chronic bronchitis. QCT assessments of Disease Probability-defined functional small airways disease, ground glass opacification, bronchovascular prominence and small blood vessel to total pulmonary vessel volume ratio were increased compared to controls and were all associated with a faster FEV1 decline as was a higher CAT score. CONCLUSIONS: Radiologic abnormalities on CT are already established in young smokers with normal lung function and is associated with FEV1 loss independently of the impact of symptoms. Structural abnormalities are present early in the natural history of COPD and are markers of disease progression. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Exploring quality evaluation markers of Fructus Psoraleae based on chemometric analysis integrated with network pharmacology.

INTRODUCTION: Fructus Psoraleae (FP) is a well-known traditional Chinese medicine for the treatment of osteoporosis. However, major quality differences were witnessed owing to its various origins, thus influencing its safety and efficacy. OBJECTIVES: The study aimed to evaluate the quality of FP from different origins and predict its quality evaluation markers. METHODS: Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was employed for tentative characterisation of the constituents in 10 batches of FP, followed by the utilisation of multivariate statistical analysis methods including principal component analysis and orthogonal partial least squares discriminant analysis for quality evaluation. Network pharmacology approaches were utilised to explore the underlying mechanism of the screened chemotaxonomic markers in treating osteoporosis. RESULTS: Forty-one components in FP including, chalcones, coumarins, coumestans, flavonoids, iso-flavonoids, and phenolics, were characterised based on their fragmentation pathways. Ten batches of FP were basically divided into three categories, and eight chemotaxonomic markers including isopsoralen, calamenene, bakuchiol, psoralen, bavachinin, isoneobavaisoflavone, corylifol C, and neobavaisoflavone were screened. Network pharmacology revealed that the chemotaxonomic markers can act on targets such as AKT1, HSP90AA1, and EGFR and possess effects mainly through glycolysis and wnt/ß-catenin signalling to alleviate osteoporosis. Molecular docking and molecular dynamic simulation confirmed the good binding affinity and stability between proteins and selected markers. So, eight chemotaxonomic markers were all preferentially recommended as quality evaluation markers. CONCLUSION: The study not only provides a reference for the improvement of quality control of FP but also offers a theoretical basis for its further in-depth research in osteoporosis.

What is the impact of ferroptosis on diabetic cardiomyopathy: a systematic review.

Iron overload increases the production of harmful reactive oxygen species in the Fenton reaction, which causes oxidative stress in the body and lipid peroxidation in the cell membrane, and eventually leads to ferroptosis. Diabetes is associated with increased intracellular oxidative stress, inflammation, autophagy, microRNA alterations, and advanced glycation end products (AGEs), which cause cardiac remodeling and cardiac diastolic contractile dysfunction, leading to the development of diabetic cardiomyopathy (DCM). While these factors are also closely associated with ferroptosis, more and more studies have shown that iron-mediated ferroptosis is an important causative factor in DCM. In order to gain fresh insights into the functions of ferroptosis in DCM, this review methodically summarizes the traits and mechanisms connected with ferroptosis and DCM.

Association between antihypertensive drugs and oral cancer: a drug target Mendelian randomization study.

Background: Recent reports have suggested that antihypertensive drugs may play an oncogenic role in common cancers, but it is still uncertain whether this could influence the risk of oral cancer. Through two-sample Mendelian randomization (MR), we sought to assess the causal effect of antihypertensive drugs on oral cancer outcomes. Methods: To proxy the exposure of antihypertensive drugs, we utilized two genetic instruments, including expression quantitative trait loci of drug target genes and genetic variants within or around drug target genes related to blood pressure from genome-wide association studies. Inverse-variance-weighted MR (IVW-MR) and summary-data-based MR (SMR) were employed to compute the instrument effect estimates. Results: It was observed through IVW-MR analysis that there is a positive relationship between KCNH2 (target of beta-adrenoceptor blockers)-mediated blood pressure and oral cancer (odds ratio [OR] = 1.197, 95% confidence interval [CI] = 1.028-1.394). Similarly, SMR analysis demonstrated that a higher expression of KCNH2 (target of beta-adrenoceptor blockers) was linked to a greater risk of oral cancer (OR = 2.223, 95% CI = 1.094-4.516). Both analyses yielded no consistent evidence of other associations. Conclusion: This two-sample MR study proposed a latent causal association between KCNH2 (target of beta-adrenoceptor blockers) inhibition and diminished risk of oral cancer.

Exploring the role and mechanism of Astragalus membranaceus and radix paeoniae rubra in idiopathic pulmonary fibrosis through network pharmacology and experimental validation.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic disease with an unclear etiology and no effective treatment. This study aims to elucidate the pathogenic mechanism networks involving multiple targets and pathways in IPF. Extracts and metabolites of Astragalus membranaceus (AM) and Radix paeoniae rubra (RPR), two well-known traditional Chinese medicines, have demonstrated therapeutic effects on IPF. However, the underlying mechanisms of AM and RPR remain unclear. Utilizing network pharmacology analysis, differentially expressed genes (DEGs) associated with IPF were obtained from the GEO database. Targets of AM and RPR were identified using the TCM Systems Pharmacology Database and Analysis Platform and SwissTargetPrediction. A protein-protein interaction (PPI) network was subsequently constructed and analyzed using the STRING database and Cytoscape software. Gene ontology enrichment analysis and kyoto encyclopedia of genes and genomes analysis were conducted using Metascape. Additionally, a component-target-pathway network and a Sankey diagram were employed to identify the main active components, and molecular docking was performed between these components and proteins encoded by key targets. Finally, in vivo studies were conducted based on network pharmacology. A total of 117 common targets between DEGs of IPF and drug targets were identified and included in the PPI network, in which AKT1, MAPK3, HSP90AA1, VEGFA, CASP3, JUN, HIF1A, CCND1, PTGS2, and MDM2 were predicted as key targets. These 117 targets were enriched in the PI3K-AKT pathway, HIF-1 signaling pathway, apoptosis, and microRNAs in cancer. Astragaloside III, (R)-Isomucronulatol, Astragaloside I, Paeoniflorin, and ß-sitosterol were selected as the main active components. Docking scores ranged from - 4.7 to - 10.7 kcal/mol, indicating a strong binding affinity between the main active compounds and key targets. In vivo studies have indeed shown that AM and RPR can alleviate the pathological lung fibrotic damage caused by bleomycin treatment. The treatment with AM and RPR resulted in a reduction of mRNA levels for key targets AKT1, HSP90AA1, CASP3, MAPK3, and VEGFA. Additionally, the protein expression levels of AKT1, HSP90AA1, and VEGFA were also reduced. These results support the therapeutic potential of AM and RPR in ameliorating pulmonary fibrosis and provide insight into the molecular mechanisms involved in their therapeutic effects.

3D salient object detection based on light field integral imaging.

Potent usage of the multi-scale light field information for salient object detection (SOD) is the essential requirement of three-dimensional (3D) SOD. On this basis, a light field 3D-SOD scheme is proposed that employs the pixel mapping algorithm to achieve a more distinct representation of spatial and angular information in the four-dimensional (4D) light field, collaboratively mining the global saliency cues via the co-salient object detection (CoSOD) network. Compared with the previous method, our scheme filters out most of the noise by thoroughly leveraging the global dependence of the 4D light field, offering significant enhancements in saliency extraction performance and efficiency. Additionally, the 3D reconstruction results demonstrate the integral retention of the spatial and angular information of the original light field.

Association between Intestinal Microecological Changes and Atherothrombosis.

Atherosclerosis (AS) is a chronic inflammatory disease of large- and medium-sized arteries that causes ischemic heart disease, strokes, and peripheral vascular disease, collectively called cardiovascular disease (CVD), and is the leading cause of CVD resulting in a high rate of mortality in the population. AS is pathological by plaque development, which is caused by lipid infiltration in the vessel wall, endothelial dysfunction, and chronic low-grade inflammation. Recently, more and more scholars have paid attention to the importance of intestinal microecological disorders in the occurrence and development of AS. Intestinal G-bacterial cell wall lipopolysaccharide (LPS) and bacterial metabolites, such as oxidized trimethylamine (TMAO) and short-chain fatty acids (SCFAs), are involved in the development of AS by affecting the inflammatory response, lipid metabolism, and blood pressure regulation of the body. Additionally, intestinal microecology promotes the progression of AS by interfering with the normal bile acid metabolism of the body. In this review, we summarize the research on the correlation between maintaining a dynamic balance of intestinal microecology and AS, which may be potentially helpful for the treatment of AS.

Near-infrared light-controlled kartogenin delivery of multifunctional Prussian blue nanocomposites for cartilage defect repair.

Articular cartilage injury repair remains a challenge for clinicians and researchers. Mesenchymal stem cells (MSCs) have multiple differentiation potentials and can be induced to differentiate into the chondrogenic lineage for cartilage defect repair; however, the insufficient capacity of chondrogenic differentiation and excess reactive oxygen species (ROS)-mediated oxidative stress, which always lead to differentiation into hypertrophic chondrocytes, still need to be resolved. Accordingly, kartogenin (KGN), which can promote chondrogenic differentiation of MSCs, has shown promise in promoting infected cartilage repair. However, realizing controllable release to prolong its action time and avoid hypertrophic differentiation is critical. We herein developed a mesoporous Prussian blue nanoparticle (mPB)-based near-infrared (NIR) light-responsive controlled nanosystem. KGN was encapsulated in temperature-stimulated responsive phase change materials (PCMs), which were used as excellent gating materials (KGN-PCM@mPBs). In addition, the mPBs could efficiently scavenge ROS by their enzyme-like antioxidative activities. Our study demonstrates that the nanocomposites could efficiently promote chondrogenic differentiation and successfully inhibit the hypertrophic differentiation of MSCs. By intra-articular injection of KGN-PCM@mPBs and NIR-triggered precisely controlled release, satisfactory cartilage repair effects can be achieved in a rat chondral defect model. Thus, this constructed NIR-mediated KGN-PCM@mPB nanoplatform may represent an effective cartilage repair strategy with satisfactory biosafety in clinical applications.

Color 3D display and security via monochrome scenes.

Color three-dimensional (3D) displays have always been the ideal display method because of their strong sense of reality, whereas color 3D displays of monochrome scenes are still challenging and unexplored. A color stereo reconstruction algorithm (CSRA) is proposed to solve the issue. We design a deep learning-based color stereo estimation (CSE) network to obtain color 3D information of monochrome scenes. The vivid color 3D visual effect is verified by our self-made display system. Furthermore, an efficient CSRA-based 3D image encryption scheme is achieved by encrypting a monochrome image with two-dimensional double cellular automata (2D-DCA). The proposed encryption scheme fulfills the requirement for real-time and high-security 3D image encryption with a large key space and the parallel processing capability of 2D-DCA.

Integrative single-cell RNA and ATAC sequencing reveals that the FOXO1-PRDX2-TNF axis regulates tendinopathy.

Introduction: Tendinopathy, the most common form of chronic tendon disorder, leads to persistent tendon pain and loss of function. Profiling the heterogeneous cellular composition in the tendon microenvironment helps to elucidate rational molecular mechanisms of tendinopathy. Methods and results: In this study, through a multi-modal analysis, a single-cell RNA- and ATAC-seq integrated tendinopathy landscape was generated for the first time. We found that a specific cell subpopulation with low PRDX2 expression exhibited a higher level of inflammation, lower proliferation and migration ability, which not only promoted tendon injury but also led to microenvironment deterioration. Mechanistically, a motif enrichment analysis of chromatin accessibility showed that FOXO1 was an upstream regulator of PRDX2 transcription, and we confirmed that functional blockade of FOXO1 activity induced PRDX2 silencing. The TNF signaling pathway was significantly activated in the PRDX2-low group, and TNF inhibition effectively restored diseased cell degradation. Discussion: We revealed an essential role of diseased cells in tendinopathy and proposed the FOXO1-PRDX2-TNF axis is a potential regulatory mechanism for the treatment of tendinopathy.

Mechanism exploration and prognosis study of Astragali Radix-Spreading hedyotis herb for the treatment of lung adenocarcinoma based on bioinformatics approaches and molecular dynamics simulation.

Background: Herb pair of Astragali Radix (AR) and Spreading Hedyotis Herb (SH) has been frequently prescribed in clinical for the treatment of lung cancer owing to its favorable efficacy. Yet, the mechanism under the therapeutic effects remained unveiled, which has limited its clinical applications, and new drug development for lung cancer. Methods: The bioactive ingredients of AR and SH were retrieved from the Traditional Chinese Medicine System Pharmacology Database, with the targets of obtained components predicted by Swiss Target Prediction. Genes related to lung adenocarcinoma (LUAD) were acquired from GeneCards, OMIM and CTD databases, with the hub genes of LUAD screened by CTD database. The intersected targets of LUAD and AR-SH were obtained by Venn, with David Database employed to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Survival analysis of the hub genes of LUAD was carried out using TCGA-LUAD dataset. Molecular docking of core proteins and active ingredients was performed by Auto-Dock Vina software, followed by molecular dynamics simulations of protein-ligand complexes with well-docked conformations. Results: 29 active ingredients were screened out with 422 corresponding targets predicted. It is revealed that AR-SH can act on various targets such as EGFR, MAPK1, and KARS by ursolic acid (UA), Astragaloside IV(ASIV), and Isomucronulatol 7,2'-di-O-glucoside (IDOG) to alleviate the symptoms of LUAD. Biological processes involved are protein phosphorylation, negative regulation of apoptotic process, and pathways involved are endocrine resistance, EGFR tyrosine kinase inhibitor resistance, PI3K-Akt, and HIF-1 pathway. Molecular docking analysis indicated that the binding energy of most of the screened active ingredients to proteins encoded by core genes was less than -5.6 kcal/mol, with some active ingredients showing even lower binding energy to EGFR than Gefitinib. Three ligand-receptor complexes including EGFR-UA, MAPK1-ASIV, and KRAS-IDOG were found to bind relatively stable by molecular dynamics simulation, which was consistent with the results of molecule docking. Conclusion: We suggested that the herb pair of AR-SH can act on targets like EGFR, MAPK1 and KRAS by UA, ASIV and IDOG, to play a vital role in the treatment and the enhancement of prognosis of LUAD.

Imaging-based assessment of lung function in a population cooking indoors with biomass fuel: a pilot study.

Biomass fuels (wood) are commonly used indoors in underventilated environments for cooking in the developing world, but the impact on lung physiology is poorly understood. Quantitative computed tomography (qCT) can provide sensitive metrics to compare the lungs of women cooking with wood vs. liquified petroleum gas (LPG). We prospectively assessed (qCT and spirometry) 23 primary female cooks (18 biomass, 5 LPG) with no history of cardiopulmonary disease in Thanjavur, India. CT was obtained at coached total lung capacity (TLC) and residual volume (RV). qCT assessment included texture-derived ground glass opacity [GGO: Adaptive Multiple Feature Method (AMFM)], air-trapping (expiratory voxels ≤ -856HU) and image registration-based assessment [Disease Probability Measure (DPM)] of emphysema, functional small airways disease (%AirTrapDPM), and regional lung mechanics. In addition, within-kitchen exposure assessments included particulate matter <2.5 µm(PM2.5), black carbon, ß-(1, 3)-d-glucan (surrogate for fungi), and endotoxin. Air-trapping went undetected at RV via the threshold-based measure (voxels ≤ -856HU), possibly due to density shifts in the presence of inflammation. However, DPM, utilizing image-matching, demonstrated significant air-trapping in biomass vs. LPG cooks (P = 0.049). A subset of biomass cooks (6/18), identified using k-means clustering, had markedly altered DPM-metrics: greater air-trapping (P < 0.001), lower TLC-RV volume change (P < 0.001), a lower mean anisotropic deformation index (ADI; P < 0.001), and elevated % GGO (P < 0.02). Across all subjects, a texture measure of bronchovascular bundles was correlated to the log-transformed ß-(1, 3)-d-glucan concentration (P = 0.026, R = 0.46), and black carbon (P = 0.04, R = 0.44). This pilot study identified environmental links with qCT-based lung pathologies and a cluster of biomass cooks (33%) with significant small airways disease.NEW & NOTEWORTHY Quantitative computed tomography has identified a cluster of women (33%) cooking with biomass fuels (wood) with image-based markers of functional small airways disease and associated alterations in regional lung mechanics. Texture and image registration-based metrics of lung function may allow for early detection of potential inflammatory processes that may arise in response to inhaled biomass smoke, and help identify phenotypes of chronic lung disease prevalent in nonsmoking women in the developing world.