Low Levels of IgM Recognizing 4-Hydroxy-2-Nonenal-Modified Apolipoprotein A-I Peptide and Its Association with the Severity of Coronary Artery Disease in Taiwanese Patients.

Autoantibodies against apolipoprotein A-I (ApoA-I) are associated with cardiovascular disease risks. We aimed to examine the 4-hydroxy-2-nonenal (HNE) modification of ApoA-I in coronary artery disease (CAD) and evaluate the potential risk of autoantibodies against their unmodified and HNE-modified peptides. We assessed plasma levels of ApoA-I, HNE-protein adducts, and autoantibodies against unmodified and HNE-peptide adducts, and significant correlations and odds ratios (ORs) were examined. Two novel CAD-specific HNE-peptide adducts, ApoA-I251-262 and ApoA-I70-83, were identified. Notably, immunoglobulin G (IgG) anti-ApoA-I251-262 HNE, IgM anti-ApoA-I70-83 HNE, IgG anti-ApoA-I251-262, IgG anti-ApoA-I70-83, and HNE-protein adducts were significantly correlated with triglycerides, creatinine, or high-density lipoprotein in CAD with various degrees of stenosis (<30% or >70%). The HNE-protein adduct (OR = 2.208-fold, p = 0.020) and IgM anti-ApoA-I251-262 HNE (2.046-fold, p = 0.035) showed an increased risk of progression from >30% stenosis in CAD. HNE-protein adducts and IgM anti-ApoA-I251-262 HNE may increase the severity of CAD at high and low levels, respectively.

Sesamol Alleviates High-Fat Diet-Induced Hepatic Insulin Resistance in C57BL/6 J Mice Through AMPK Activation Mediated by Adipose Adiponectin.

Sesamol is the major bioactive constituent isolated from sesame seeds and has a variety of bioactivities. However, its role and mechanism in liver insulin resistance remain unknown. The current study was designed to investigate the underlying adipose-liver crosstalk mechanism of sesamol ameliorating hepatic insulin sensitivity. The therapeutic effect of sesamol was evaluated in high-fat diet (HFD)-fed C57BL/6 J mice (100 mg/kg for 8 weeks, XYGW-2021-75) and the mechanism was further explored in HepG2 cells with/without adiponectin and adenosine 5 '-monophosphate-activated protein kinase (AMPK) inhibitor administration. Our in vivo data showed that sesamol reduced hepatic insulin resistance in HFD-induced mice with obesity by modulating protein expression levels of glycogen synthase (GS), phosphoenolpyruvate carboxykinase (PEPCK) and protein kinase B (AKT). Moreover, sesamol not only increased the serum and adipose tissue adiponectin concentrations but also activated the phosphorylation of AMPK in the liver. Furthermore, in vitro studies using recombinant human adiponectin and an AMPK inhibitor revealed that adiponectin and sesamol have a synergic impact on increasing glycogenesis and reducing gluconeogenesis, of which the effects could be attenuated by the AMPK inhibitor. Taken together, our results suggested that sesamol stimulated adiponectin secretion from adipocytes, whereby exhibited a co-effect on activating the downstream signal of hepatic AMPK, resulting in the alleviation of hepatic insulin resistance. The novel findings of sesamol on hepatic effects provides prospective therapeutic approaches to treat insulin resistance.

A Novel Multi-Task Learning Model with PSAE Network for Simultaneous Estimation of Surface Quality and Tool Wear in Milling of Nickel-Based Superalloy Haynes 230.

For data-driven intelligent manufacturing, many important in-process parameters should be estimated simultaneously to control the machining precision of the parts. However, as two of the most important in-process parameters, there is a lack of multi-task learning (MTL) model for simultaneous estimation of surface roughness and tool wear. To address the problem, a new MTL model with shared layers and two task-specific layers was proposed. A novel parallel-stacked auto-encoder (PSAE) network based on stacked denoising auto-encoder (SDAE) and stacked contractive auto-encoder (SCAE) was designed as the shared layers to learn deep features from cutting force signals. To enhance the performance of the MTL model, the scaled exponential linear unit (SELU) was introduced as the activation function of SDAE. Moreover, a dynamic weight averaging (DWA) strategy was implemented to dynamically adjust the learning rate of different tasks. Then, the time-domain features were extracted from raw cutting signals and low-frequency reconstructed wavelet packet coefficients. Frequency-domain features were extracted from the power spectrum obtained by the Fourier transform. After that, all features were combined as the input vectors of the proposed MTL model. Finally, surface roughness and tool wear were simultaneously predicted by the trained MTL model. To verify the superiority and effectiveness of the proposed MTL model, nickel-based superalloy Haynes 230 was machined under different cutting parameter combinations and tool wear levels. Some other intelligent algorithms were also implemented to predict surface roughness and tool wear. The results showed that compared with the support vector regression (SVR), kernel extreme learning machine (KELM), MTL with SDAE (MTL_SDAE), MTL with SCAE (MTL_SCAE), and single-task learning with PSAE (STL_PSAE), the estimation accuracy of surface roughness was improved by 30.82%, 16.67%, 14.06%, 26.17%, and 16.67%, respectively. Meanwhile, the prediction accuracy of tool wear was improved by 46.74%, 39.57%, 41.51%, 38.68%, and 39.57%, respectively. For practical engineering application, the dimensional deviation and surface quality of the machined parts can be controlled through the established MTL model.

Design, synthesis, and biological evaluation of novel substituted thiourea derivatives as potential anticancer agents for NSCLC by blocking K-Ras protein-effectors interactions.

Mutation of the proto-oncogene K-Ras is one of the most common molecular mechanisms in non-small cell lung cancer. Many drugs for treating lung cancer have been developed, however, due to clinical observed K-Ras mutations, corresponding chemotherapy and targeted therapy for such mutation are not efficient enough. In this study, on the basis of the crystal structure of K-Ras, 21 analogues (TKR01-TKR21) containing urea or thiourea were rationally designed, which can effectively inhibit the lung cancer cell A549 growth. The designing of these compounds was based on the structure of K-Ras protein, and the related groups were replaced by bioisosteres to improve the affinity and selectivity. Biological testing revealed that compound TKR15 could significantly inhibit the proliferation of A549 cell with IC50 of 0.21 µM. Docking analysis showed that the TKR15 can effectively bind to the hydrophobic cavity and form a hydrogen bond with the Glu37. In addition, through flow apoptosis assay and immunofluorescence staining assay, it confirmed that this compound can inhibit A549 cell proliferation with the mechanism of blocking K-RasG12V protein and effector proteins interactions through the apoptotic pathway. In conclusion, our studies in finding novel potent compound (TKR15) with confirmed mechanism showed great potential for further optimisation and other medicinal chemistry relevant studies.

Exploring usage pattern variation of free-floating bike-sharing from a night travel perspective.

Free-floating bike sharing (FFBS) attracts increasing research focusing on usage patterns, determining factors, and integrated transportation. However, existing researchers tend to overlook the variation in usage characteristics over various time ranges, particularly the usage pattern at night. This paper is conducted to fill the gap through a series of analysis approaches on FFSB in Beijing. The characteristics of the usage pattern, including time-varying usage and traveling distance distributions, are initially illustrated. Subsequently, the spatial patterns of FFBS are visualized and thoroughly analyzed in different time ranges and origin-destination (O-D) flows. A statistical model evaluating the environmental effects of FFBS trips revealed the source of FFBS usage. In addition to focusing on the nighttime, the usage patterns varying day and night are compared through the analysis. The findings explain the usage pattern variation and the unique pattern at night, providing valuable insight for improving the management of the FFBS system.

Disparity of physician specialties in the management of chronic heart failure: trend analysis in Taiwan, 2000 - 2010.

OBJECTIVE: Chronic heart failure (CHF) is a condition that is daily confronted by clinicians in a variety of medical specialties, where physicians routinely seek optimum pharmacotherapy for their outpatients with CHF. We conducted a population- based study on pharmacotherapy for outpatients with CHF in Taiwan from 2000 to 2010, which focused on drug prescription patterns of different physician specialties. MATERIALS AND METHODS: We retrieved records from the National Health Insurance Research Database of patient ambulatory visits with diagnosed chronic heart failure, when cardiovascular drugs were prescribed. For purposes of this study, anti-chronic heart failure drugs were separated into categories: mortality reducing agents (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, ß-blockers, spironolactone, hydralazine plus nitrates) and symptom-relieving agents (digoxin, diuretics). Thereafter, the trends of prescription patterns related to different physician specialties were analyzed. RESULTS: From 2000 to 2010, the prescription rate of any mortality-reducing agent for CHF outpatients rose from 61.5% to 76.3% while the concomitant rate for digoxin decreased from 47.3% to 45.4%. Compared to internists and family physicians, cardiologists not only prescribed far more mortality-reducing agents from 2000 to 2010 (53.9 - 72.7%, 54.1 - 64.3%, 74.7 - 84.4%, respectively), but also prescribed two or three mortality-reducing drugs. CONCLUSION: There was a significant improvement of optimal pharmacotherapy for chronic heart failure in Taiwan. We observed that cardiologists were more aggressive than non-cardiologists when deciding whether to prescribe mortality-reducing drugs for heart failure management. However, those factors which influence the prescription patterns of internists and family physicians for their patients with CHF still require additional research.

Contamination and Health Risk Assessment of Polycyclic Aromatic Hydrocarbons in Seasoning Flour Products in Hunan, China.

Polycyclic aromatic hydrocarbons (PAHs) are persistent organic pollutants with carcinogenic, teratogenic, and mutagenic effects. Dietary intake is one of the significant exposure pathways of PAHs. In this study, gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) was used to detect 16 priority PAHs listed by the United States Environmental Protection Agency (USEPA) in seasoning flour products distributed in Hunan Province. The consumption of seasoning flour products by the Hunan population was investigated by questionnaire. The results showed that the detection rate of PAHs in seasoning flour products in Hunan Province was 92.41%. Among them, benzo[a]anthracene (BaA), phenanthrene (PHE), fluoranthene (FLA), and chrysene (CHR) were dominant. The total PAHs and benzo[a]pyrene (BaP) contents of soggy seasoning flour product samples were higher than those of crisp samples and chewy samples. The total amount of PAHs in rod-shaped and flaky samples were higher than that in filamentous and granular samples. The margin of exposure (MOE) values of various seasoning flour products and all age groups (children, adolescents, and adults) was much more significant than 10,000. Moreover, the incremental lifetime of cancer risk (ILCR) values of all age groups were below 1 × 10-5. The above results indicate that PAHs in seasoning flour products have a relatively low health risk for the Hunan population. Still, it is recommended that susceptible populations (children, adolescents, etc.) should control their intake of flour products.

Sesamol promotes browning of white adipocytes through liver-adipose crosstalk signal of hepatic fibroblast growth factor 21.

Sesamol (SEM), a lignan from sesame oil, exhibited potential benefits on obesity treatment by promoting browning of adipocytes, and the current study is aimed to explore the molecular mechanisms of SEM from the aspect of systemic liver-adipose crosstalk that mediated by hepatic fibroblast growth factor 21 (FGF21). Our in vivo data showed that SEM induced energy expenditure and white adipose tissue (WAT) browning by increasing the expression level of uncoupling protein-1 in high fat diet induced obese C57BL/6J mice. Elevated levels of circulating FGF21 associated with the increased expression of hepatic FGF21 were observed after SEM intervention. Simultaneously, the increased adipose fibroblast growth factor tyrosine kinase receptor 1/beta-klotho indicated that FGF21 sensitivity was enhanced by SEM in WAT. Furthermore, our in vitro results from HepG2 and 3T3-L1 cell lines confirmed the effects and revealed the mechanism of SEM on the white adipocytes browning. We found that with the specific inhibitors of PPARα, the SEM-mediated hepatic FGF21 expression was decreased, and with the specific inhibitors of PPARγ, the browning effect of adipocytes by SEM combining with FGF21 was significantly suppressed. Taken together, the mechanism of SEM for inducing the WAT browning might be the modulation of SEM on liver-adipose crosstalk mediated by FGF21, and the PPARs family might be the targets of SEM. The novel findings from the present study provided evidence that SEM could be a potent obesity-treating compound.

Permissible viewing times of educational projector and TV.

Projectors have become one major medium in modern teaching, with large area-size displays emerging as an alternative. What concerns the general public is whether such eLearning would impose threat on eyes, by noting blue enriched white light to be hazardous to retina and else. Especially, little was known about their permissible viewing time under a certain viewing clarity. We had hence carried out a quantitative study with the use of a blue-hazard quantification spectrometer to determine the permissible viewing time when using a projector and a large size TV screen for displaying. Surprisingly, the large TV screen could permit a much longer viewing time, meaning which is more eye-friendly. It is plausibly because its resolution is much higher than that of the projector. Two dilemmas were observed in such eLearning; those sitting in the front would suffer a much higher illuminance, leading to a much shorter viewing time, while those sitting in the back would need a far much larger font size to see clearly. To ensure both viewing clarity and a sufficiently long permissible viewing time, orange text on black background is suggested to replace the defaulted black text on white background. The permissible viewing time could hence drastically increase from 1.3 to 83 h at 2 m by viewing a 30 pt font for the TV and from 0.4 to 54 h for the projection. At 6 m, the permissible viewing time was increased from 12 to 236 h for the TV and from 3 to 160 h for the projection, based on a viewable 94 pt font. These results may help educators and other e-display users to wisely apply the display tools with safety.

Factors influencing the social participation ability of rural older adults in China: A cross-sectional study.

Objective: To investigate the epidemiology and influencing factors of social participation ability of rural older adults in China. Methods: From March to April 2021, 3450 older adults in poverty aged 60 and above registered in Jishishan County (J County) were selected by cluster sampling for a cross-sectional questionnaire survey and their social participation ability was assessed using the Ability Assessment of older adults (MZ/T039-2013). The results were statistically analyzed and an ordered multi-category logistic regression analysis was used to analyze the effect of influencing factors on the social participation ability of rural older adults. Results: 3,346 questionnaires were collected, with an effective recovery rate of 96.99%. Out of all the participants, 1,355 (40.5%) of the 3,346 cases had intact social participation ability, while 1,991 (59.5%) had different degrees of loss of social participation ability, of which 1,393 (41.14%) were mildly impaired, 419 (12.5%) were moderately impaired and 179 (5.3%) were severely impaired. Age, educational level, religious belief, living status, whether suffering from dementia and the occurrence of accidents in recent 30 days were influencing factors on the social participation ability (p < 0.05). Conclusion: The rate of impaired social participation ability among older adults was >50% and age, educational level, religious beliefs, living status, whether suffering from dementia, and the occurrence of accidents in recent 30 days (such as falls, choking, loss) were significant factors influencing the ability of social participation of rural older adults.

An easy-to-apply method for determining permissible exposure limit of retina to light.

Long exposure to intensive artificial light imposes threats to the retina. It is crucial to know the permissible exposure time to prevent photoretinitis. One complicated quantification method is available, which, however, also requires instrumentally measured spectrum and illuminance. We present herein an easy-to-apply formula and a ready-to-use table derived therefrom to determine the permissible exposure limit for any given desk lamp at any viewing distance. One only needs to acquire its color temperature and luminous flux labeled on the product. The method can be used to assist the general public in quickly assessing the potential hazardous status of their desk lamps, if any, and guide the field experts in designing human-eye-friendly lighting.

Sesamol Reverses Myofiber-Type Conversion in Obese States via Activating the SIRT1/AMPK Signal Pathway.

Obesity can evoke changes of skeletal muscle structure and function, which are characterized by the conversion of myofiber from type I to type II, leading to a vicious cycle of metabolic disorders. Reversing the muscle fiber-type conversion in obese states is a novel strategy for treating those with obesity. Sesamol, a food ingredient compound isolated from sesame seeds, exerted potential antiobesity effects. The present research aimed to explore the therapeutic effects of sesamol on obesity-related skeletal muscle-fiber-type conversion and elucidate the underlying molecular mechanisms through utilizing a high-fat-diet-induced obese C57BL/6J mice model and palmitic acid-exposed C2C12 myotubes. The results showed that sesamol attenuated obesity-related metabolic disturbances, elevated exercise endurance of obese mice, and decreased lipid accumulation and insulin resistance in skeletal muscle. After the treatment with sesamol, the muscular mitochondrial content and biogenesis were increased, accompanied by the enzyme activities and myosin heavy-chain isoform changed from type II fiber to type I fiber. Mechanistic studies revealed that the effects of sesamol on reversing skeletal muscle-fiber-type conversion in obese states were associated with the stimulation of the muscular sirtuin 1 (SIRT1)/AMP-activated protein kinase (AMPK) signal pathway, and these effects could be inhibited by a specific inhibitor of SIRT1, EX-527. In conclusion, our research provided novel evidence that sesamol could regulate myofiber-type conversion to treat obesity and obesity-related metabolic disorders by stimulating the muscular SIRT1/AMPK signal pathway.

Corrigendum: Utility of S100A12 as an Early Biomarker in Patients With ST-Segment Elevation Myocardial Infarction.

[This corrects the article DOI: 10.3389/fcvm.2021.747511.].

ceRNA regulatory network of FIH inhibitor as a radioprotector for gastrointestinal toxicity by activating the HIF-1 pathway.

Given the relentless renewal ability of intestinal crypt-base stem cells, small intestine in the gastrointestinal (GI) tract is more vulnerable to radiation-induced disruption. Through promoting epithelial integrity and reducing intracellular reactive oxygen species (ROS) levels, hypoxia-inducible factors (HIFs) have been proved to exhibit radioprotective effects in the GI tract. Therefore, enhancing stability or transcriptional activity of HIFs might be a therapeutic strategy for developing radioprotectors. Factor inhibiting HIF (FIH or HIF-1AN) can hamper transcriptional capacity of HIF-1α via interacting with Asn803 in its C-terminal domain. Previously, we discovered promoting HIF-1α transcriptional activity in vitro by FIH inhibitor-N-oxalyl-D-phenylalanine (NOFD) exerts radioprotection on cells. However, the radioprotective effect of FIH inhibitor on the GI tract and its competing endogenous RNA (ceRNA) regulatory network from the FIH/HIF axis has never been addressed. Here we verified radioprotection of NOFD for the GI tract by an animal model and performed whole-transcriptome analysis to fully elucidate the radioprotective mechanism from the FIH/HIF axis against GI syndrome. We identified two novel circular RNAs (circRNAs) (circRNA_2909 and circRNA_0323) and two long non-coding RNAs (lncRNAs) (NONMMUT140549.1 and NONMMUT148249.1) that promote expression of HIF1A and NOS2 in the HIF-1 pathway by sponging microRNAs (miRNAs), especially mmu-miR-92a-1-5p. The de-repression of HIF-1α transcriptional capacity by inhibiting FIH proteomic activity suggests a new therapeutic strategy in alleviating radiation-induced GI syndrome.

Using Anti-Malondialdehyde Modified Peptide Autoantibodies to Import Machine Learning for Predicting Coronary Artery Stenosis in Taiwanese Patients with Coronary Artery Disease.

Machine learning (ML) algorithms have been applied to predicting coronary artery disease (CAD). Our purpose was to utilize autoantibody isotypes against four different unmodified and malondialdehyde (MDA)-modified peptides among Taiwanese with CAD and healthy controls (HCs) for CAD prediction. In this study, levels of MDA, MDA-modified protein (MDA-protein) adducts, and autoantibody isotypes against unmodified peptides and MDA-modified peptides were measured with enzyme-linked immunosorbent assay (ELISA). To improve the performance of ML, we used decision tree (DT), random forest (RF), and support vector machine (SVM) coupled with five-fold cross validation and parameters optimization. Levels of plasma MDA and MDA-protein adducts were higher in CAD patients than in HCs. IgM anti-IGKC76-99 MDA and IgM anti-A1AT284-298 MDA decreased the most in patients with CAD compared to HCs. In the experimental results of CAD prediction, the decision tree classifier achieved an area under the curve (AUC) of 0.81; the random forest classifier achieved an AUC of 0.94; the support vector machine achieved an AUC of 0.65 for differentiating between CAD patients with stenosis rates of 70% and HCs. In this study, we demonstrated that autoantibody isotypes imported into machine learning algorithms can lead to accurate models for clinical use.

Generation of avian-derived anti-B7-H4 antibodies exerts a blockade effect on the immunosuppressive response.

For highly conserved mammalian protein, chicken is a suitable immune host to generate antibodies. Monoclonal antibodies have been successfully targeted with immunity checkpoint proteins as a means of cancer treatment; this treatment enhances tumor-specific immunity responses through immunoregulation. Studies have identified the importance of B7-H4 in immunoregulation and its use as a potential target for cancer treatment. High levels of B7-H4 expression are found in tumor tissues and are associated with adverse clinical and pathological characteristics. Using the phage display technique, this study isolated specific single-chain antibody fragments (scFvs) against B7-H4 from chickens. Our experiment proved that B7-H4 clearly induced the inhibition of T-cell activation. Therefore, use of anti-B7-H4 scFvs can effectively block the exhaustion of immunity cells and also stimulate and activate T-cells in peripheral blood mononuclear cells. Sequence analysis revealed that two isolated scFv S2 and S4 have the same VH complementarity-determining regions (CDRs) sequence. Molecule docking was employed to simulate the complex structures of scFv with B7-H4 to analyze the interaction. Our findings revealed that both scFvs employed CDR-H1 and CDR-H3 as main driving forces and had strong binding effects with the B7-H4. The affinity of scFv S2 was better because the CDR-L2 loop of the scFv S2 had three more hydrogen bond interactions with B7-H4. The results of this experiment suggest the usefulness of B7-H4 as a target for immunity checkpoints; the isolated B7-H4-specific chicken antibodies have the potential for use in future cancer immunotherapy applications.

Utility of S100A12 as an Early Biomarker in Patients With ST-Segment Elevation Myocardial Infarction.

Importance: S100A12 is a calcium binding protein which is involved in inflammation and progression of atherosclerosis. Objective: We sought to investigate the utility of S100A12 as a biomarker for the early diagnosis and prognostication of patients presenting with ST-segment elevation myocardial infarction (STEMI). Design, Setting, and Participants: S100A12 was measured in 1023 patients presenting to the emergency department with acute chest pain between June 2012 and November 2015. An independent cohort of 398 patients enrolled at 3 different hospitals served as a validation cohort. Main Outcomes and Measures: The primary clinical endpoint of interest was major adverse cardiac and cerebral events (MACCE) defined as a composite of all-cause death, MI, stroke, or hospitalization for heart failure. Results: A total of 438/1023 patients (42.8%) in the diagnosis cohort were adjudicated as STEMI, among whom plasma S100A12 levels increased within 30 min and peaked 1-2 h after symptom onset. Compared with high-sensitivity cardiac troponin T and creatine kinase-MB isoenzyme, S100A12 more accurately identified STEMI, especially within the first 2 h after symptom onset (area under the curve 0.963 compared with 0.860 for hscTnT and 0.711 for CK-MB, both P < 0.05). These results were consistent in the 243-patient validation cohort. The 1-year rate of MACCE was greatest in patients in the highest peak S100A12 tertile, intermediate in the middle tertile and least in the lowest tertile (9.3 vs. 5.7 vs. 3.0% respectively, Ptrend = 0.0006). By multivariable analysis the peak plasma concentration of S100A12 was an independent predictor of MACCE within 1 year after STEMI (HR, 1.001, 95%CI, 1.000-1.002; P = 0.0104). Conclusions and Relevance: S100A12 rapidly identified patients with STEMI, more accurately than other cardiac biomarkers, especially within the first 2 h after symptom onset. The peak plasma S100A12 level was a strong predictor of 1-year prognosis after STEMI.

Overexpression of activin A in oral squamous cell carcinoma: association with poor prognosis and tumor progression.

BACKGROUND: Both activin A, a member of transforming growth factor beta superfamily, and its inhibitor follistatin have been shown to be overexpressed in various cancers. We examined the potential role of activin A and follistatin in tissue and blood samples from patients with oral squamous cell carcinoma. METHODS: For activin A and follistatin, the expression of tissue samples from 92 patients was examined by immunohistochemical study, and the serum levels of blood samples from 111 patients and 91 healthy controls were measured by enzyme-linked immunosorbent assay. RESULTS: We found that overexpression of immunohistochemically detected activin A was correlated with positive N stage, poor histological differentiation, and perineural invasion (P = 0.029, 0.002, and 0.014, respectively). In survival analyses, patients with oral squamous cell carcinoma, whose tumors overexpressed activin A, had a worse prognosis for overall survival and disease-free survival (P = 0.009 and 0.007). However, expression of follistatin in tumor was not correlated with overall survival or disease-free survival. Serum activin A and follistatin levels in 111 untreated patients were neither significantly different from those of 91 control samples nor associated with any clinicopathological manifestations. In vitro suppression of activin A expression in OC3 cells using specific interfering RNA-attenuated cell proliferation, migration, and invasiveness. CONCLUSIONS: These findings suggest that activin A overexpression in oral squamous cell carcinomas is associated with patients' survival and may contribute to tumor progression and metastasis.

Molecular Targets and Pathways Contributing to the Effects of Wenxin Keli on Atrial Fibrillation Based on a Network Pharmacology Approach.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with high rates of mortality and morbidity. The traditional Chinese medicine Wenxin Keli (WXKL) can effectively improve clinical symptoms and is safe for the treatment of AF. However, the active substances in WXKL and the molecular mechanisms underlying its effects on AF remain unclear. In this study, the bioactive compounds in WXKL, as well as their molecular targets and associated pathways, were evaluated by systems pharmacology. MATERIALS AND METHODS: Chemical constituents and potential targets of WXKL were obtained via the Traditional Chinese Medicine Systems Pharmacology (TCMSP). The TTD, DrugBank, DisGeNET, and GeneCards databases were used to collect AF-related target genes. Based on common targets related to both AF and WXKL, a protein interaction network was generated using the STRING database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway enrichment analyses were performed. Network diagrams of the active component-target and protein-protein interactions (PPIs) were constructed using Cytoscape. RESULTS: A total of 30 active ingredients in WXKL and 219 putative target genes were screened, including 83 genes identified as therapeutic targets in AF; these overlapping genes were considered candidate targets for subsequent analyses. The effect of treating AF was mainly correlated with the regulation of target proteins, such as IL-6, TNF, AKT1, VEGFA, CXCL8, TP53, CCL2, MMP9, CASP3, and NOS3. GO and KEGG analyses revealed that these targets are associated with the inflammatory response, oxidative stress reaction, immune regulation, cardiac energy metabolism, serotonergic synapse, and other pathways. CONCLUSIONS: This study demonstrated the multicomponent, multitarget, and multichannel characteristics of WXKL, providing a basis for further studies of the mechanism underlying the beneficial effects of WXKL in AF.

Role of Neutrophil-Derived S100B in Acute Myocardial Infarction Patients From the Han Chinese Population.

Objective: This study aimed to clarify the novel role of homeostatic calmodulin S100B and determined whether S100B genetic variants affected atherosclerosis progression in acute myocardial infarction (AMI) patients. Methods: Plasma levels of S100B were measured systemically in AMI patients, stable angina pectoris patients, and control subjects. S100B was obtained from the human coronary artery thrombi using a thrombectomy catheter and quantified via immunohistochemical analysis, qRT-PCR and Western blot analyse. We also screened for S100B variations (rs9722, rs9984765, rs2839356, rs1051169, and rs2186358) via direct sequencing, and investigated the relationship between these variants and AMI patients in the Chinese Han population. Results: Plasma S100B levels increased significantly in AMI patients compared to the levels in stable angina pectoris patients and control subjects (119.45 ± 62.46, 161.96 ± 73.30, and 312.91 ± 127.59 pg/ml, respectively). Immunohistochemical staining results showed that S100B expression was increased in the neutrophils of coronary artery thrombi obtained from AMI patients, as compared to that in normal blood clot, and S100B expression was significantly increased in fresh thrombi tissues, as compared to that in organized thrombi tissues. Western blot and qRT-PCR analysis showed that S100B expression increased in coronary artery thrombi, as compared to that in normal blood clots. After pre-treating the neutrophils with siRAGE, the neutrophils migration induced by S100B were abolished through the NFκB-IL1ß/IL6 signaling pathway. Compared to their corresponding wild-type genotypes, the S100B rs9722 variant was associated with increased susceptibility to AMI (OR = 1.35, 95%CI: 1.12-1.65, P = 0.02). Individuals with the S100B 9722 A allele had higher plasma S100B levels than those with the G allele in control subjects and AMI patients (141.70 ± 76.69 vs. 107.31 ± 56.05 and 347.13 ± 148.94 vs. 273.05 ± 133.62, respectively). Conclusions: Levels of neutrophil-derived S100B, a novel homeostatic calmodulin, were elevated in the early stages of myocardial infarction. The S100B rs9722 allele was independently associated with AMI patients in the Han Chinese population.