Jaceosidin induces apoptosis and inhibits migration in AGS gastric cancer cells by regulating ROS-mediated signaling pathways.

Jaceosidin (JAC) is a natural flavonoid with anti-oxidant and other pharmacological activities; however, its anti-cancer mechanism remains unclear. We investigated the mechanism of action of JAC in gastric cancer cells. Cytotoxicity and apoptosis assays showed that JAC effectively killed multiple gastric cancer cells and induced apoptosis in human gastric adenocarcinoma AGS cells via the mitochondrial pathway. Network pharmacological analysis suggested that its activity was linked to reactive oxygen species (ROS), AKT, and MAPK signaling pathways. Furthermore, JAC accumulated ROS to up-regulate p-JNK, p-p38, and IκB-α protein expressions and down-regulate the p-ERK, p-STAT3, and NF-κB protein expressions. Cell cycle assay results showed that JAC accumulated ROS to up-regulate p21 and p27 protein expressions and down-regulate p-AKT, CDK2, CDK4, CDK6, Cyclin D1, and Cyclin E protein expressions to induce G0/G1 phase arrest. Cell migration assay results showed JAC accumulated ROS to down-regulate Wnt-3a, p-GSK-3ß, N-cadherin, and ß-catenin protein expressions and up-regulate E-cadherin protein expression to inhibit migration. Furthermore, N-acetyl cysteine pre-treatment prevented the change of these protein expressions. In summary, JAC induced apoptosis and G0/G1 phase arrest and inhibited migration through ROS-mediated signaling pathways in AGS cells.

Network pharmacology analysis and experimental verification of the antitumor effect and molecular mechanism of isocryptomerin on HepG2 cells.

Isocryptomerin (ISO) is a flavonoid isolated from the natural medicine Selaginellae Herba, which has various pharmacological activities. This study investigated the antitumor effect and underlying molecular mechanism of ISO on hepatocellular carcinoma (HCC) HepG2 cells. The cell viability assay revealed that ISO has a considerable killing effect on HCC cell lines. The apoptosis assay showed that ISO induced mitochondria-dependent apoptosis through the Bad/cyto-c/cleaved (cle)-caspase-3/cleaved (cle)-PARP pathway. The network pharmacological analysis found 13 key target genes, and epidermal growth factor receptor (EGFR), AKT, mitogen-activated protein kinase (MAPK), and reactive oxygen species (ROS) signaling pathways were strongly associated with ISO against HCC. Further verification of the results showed that ISO induced apoptosis by increasing p-p38 and p-JNK expression and decreasing p-EGFR, p-SRC, p-ERK, and p-STAT3 expression. Furthermore, ISO induced G0/G1 phase arrest by downregulating p-AKT, Cyclin D, and CDK 4 expression and upregulating p21 and p27 expression in HepG2 cells. Moreover, ISO inhibited HepG2 cell migration by decreasing p-GSK-3ß, ß-catenin, and N-cadherin expression and increasing E-cadherin expression. Additionally, ISO promoted ROS accumulation in HepG2 cells, and ISO-induced apoptosis, arrest cell cycle, and inhibition of migration were reversed by an ROS scavenger, N-acetyl- l-cysteine. Overall, ISO induced cell apoptosis and cell cycle arrest and inhibited cell migration by ROS-mediated EGFR, AKT, and MAPK signaling pathways in HepG2 cells.

Hypermethylated CDO1 and CELF4 in cytological specimens as triage strategy biomarkers in endometrial malignant lesions.

Objective: Developing a non-invasive and reliable triage test for endometrial malignant lesions is an important goal, as it could help to reduce the number of invasive diagnostic procedures required and improve patient survival. We aimed to estimate the diagnostic value of DNA methylation levels in cervical cytological samples of endometrial cancer (EC) and endometrial atypical hyperplasia (AH). Methods: A total of 607 women who had indications for endometrial biopsy in the Department of Obstetrics and Gynecology of Cangzhou Central Hospital from October 2022 to April 2023 were enrolled in this study. The cervical exfoliated cells were collected for gene methylation before endometrial biopsy. Clinical information, tumor biomarkers, and endometrial thickness (ET) of transvaginal ultrasonography (TVS) were also collected. With endometrial histopathology as the gold standard, multivariate unconditional logistic regression was applied to analyze the risk factors of endometrial malignant lesions. The role of cysteine dioxygenase type 1 (CDO1) and CUGBP Elav-like family member 4 (CELF4) gene methylation as a triage strategy biomarker in endometrial malignant lesions was specifically explored. Results: Multivariate logistic regression analysis showed that premenopausal ET ≥ 11 mm or postmenopausal ET ≥ 5 mm, CDO1 ΔCt ≤ 8.4, or CELF4 ΔCt ≤ 8.8 were the risk factors for AH and EC, with odds ratios (ORs) (95%CI) of 5.03 (1.83-13.82) and 6.92 (1.10-43.44), respectively (p-values < 0.05). The sensitivity and specificity of CDO1/CELF4 dual-gene methylation assay for AH and EC reached 84.9% (95%CI: 75.3%-94.5%) and 86.6% (95%CI: 83.8%-89.5%), respectively. ET combined with DNA methylation detection further improved the specificity to (94.9%, 95%CI: 93.1%-96.8%). Conclusion: The accuracy of cervical cytology DNA methylation is superior to that of other clinical indicators in the non-invasive examination of endometrial malignant lesions. DNA methylation combined with TVS can further improve the specificity and is a promising biomarker triage strategy in women with suspected endometrial lesions.

Cortical Amyloid Burden Relates to Basal Forebrain Volume in Subjective Cognitive Decline.

BACKGROUND: Atrophy of cholinergic basal forebrain (BF) nuclei is a frequent finding in magnetic resonance imaging (MRI) volumetry studies that examined patients with prodromal or clinical Alzheimer's disease (AD), but less clear for individuals in earlier stages of the clinical AD continuum. OBJECTIVE: To examine BF volume reductions in subjective cognitive decline (SCD) participants with AD pathologic changes. METHODS: The present study compared MRI-based BF volume measurements in age- and sex-matched samples of N = 24 amyloid-positive and N = 24 amyloid-negative SCD individuals, based on binary visual ratings of Florbetaben positron emission tomography (PET) measurements. Additionally, we assessed associations of BF volume with cortical amyloid burden, based on semiquantitative Centiloid (CL) analyses. RESULTS: Group differences approached significance for BF total volume (p = 0.061) and the Ch4 subregion (p = 0.059) only, showing the expected relative volume reductions for the amyloid-positive subgroup. There were also significant inverse correlations between BF volumes and CL values, which again were most robust for BF total volume and the Ch4 subregion. CONCLUSIONS: The results are consistent with the hypothesis that amyloid-positive SCD individuals, which are considered to represent a transitional stage on the clinical AD continuum, already show incipient alterations of BF integrity. The negative association with a continuous measure of cortical amyloid burden also suggests that this may reflect an incremental process. Yet, further research is needed to evaluate whether BF changes already emerge at "grey zone" levels of amyloid accumulation, before amyloidosis is reliably detected by PET visual readings.

MicroRNA-142-3P suppresses the progression of papillary thyroid carcinoma by targeting FN1 and inactivating FAK/ERK/PI3K signaling.

OBJECTIVES: miR-142-3P is a tumor suppressor in various malignant cancers. However, the function of miR-142-3P in papillary thyroid carcinoma (PTC) remains to be elucidated. The aim of this study was to explore the function and mechanism of miR-142-3P in PTC. METHODS: Real Time Quantitative PCR (RT-qPCR) was used to assess the expression of miR-142-3P and Fibronectin 1 (FN1) in PTC. The correlation between FN1 and miR-142-3P expression was analyzed by Spearman's correlation analysis. Cell Counting Kit 8 (CCK8), 5-ethynyl-2'-deoxyuridine (EDU) assay, cell migration and invasion assay and wound healing measures evaluated the effect of miR-142-3P and FN1 on cell proliferation, migration and invasion. Dural Luciferase reported gene assay evaluated the interaction between miR-142-3P and 3' untranslated region (UTR) of FN1. The Epithelial-Mesenchymal-Transition (EMT) and apoptosis related marker genes were measured using western blot analysis (WB). RESULTS: miR-142-3P was significantly decreased in both PTC specimens and relevant cell lines. Functionally, miR-142-3P inhibited cell proliferation, migration, invasion and EMT, and induced the cell apoptosis in PTC. In addition, miR-142-3P bound directly with 3' UTR of FN1 and negatively regulated the expression of FN1 in PTC. FN1 expression is elevated in PTC, and its aberrant high correlated with declines in recurrence-free survival (RFS). Moreover, FN1 promoted cell proliferation, migration, invasion and EMT, induced cell apoptosis in PTC cells. Depletion of FN1 rescues the effect of miR-142-3P inhibitor on cell proliferation, invasion, apoptosis and EMT via inactivating Focal Adhesion Kinase (FAK)/Extracellular Signal-Regulated Kinase (ERK) / Phosphoinostide 3-kinase (P13K) signaling. CONCLUSION: miR-142-3P suppressed cell proliferation, migration, invasion and EMT through modulating FN1/FAK/ERK/PI3K signaling in PTC, suggesting it as a potential therapeutic target for PTC.

Lusianthridin Exerts Streptozotocin-Induced Gestational Diabetes Mellitus in Female Rats via Alteration of TLR4/MyD88/NF-κB Signaling Pathway.

Gestational diabetes mellitus (GDM) is characterized via enhanced the glucose intolerance in the pregnant women, which further lead the expansion of gestational hypertension, hepatic damage, pre eclampsia and renal damage. Lusianthridin is the active phytoconstituent of Dendrabium venustu and exhibited the antioxidant and anti-inflammatory effects. In this protocol, we examined the GDM protective effect of lusianthridin (LSD) against streptozotocin (STZ) induced GDM in the female rats. Single intraperitoneal injection of STZ (40 mg/kg) was used for the induction of diabetes in the pregnant female rats. The rats were orally treated with the LSD (10, 20 and 40 mg/kg, body weight) for 18 days and blood glucose level, body weight and plasma insulin were estimated at regular time intervals. at end of the study, fetal weight, placental weight, number of live and dead fetuses were estimated. The antioxidant, lipid and cytokines level were also estimated. GDM rats treated with LSD remarkably improved the body weight of female rats along with fetal weight and suppressed the placental weight. LSD enhanced the live fetuses and suppressed the dead fetuses with reduction of reduced the dead ratio. LSD considerably suppressed the glucose level and improved the insulin level and suppressed the HOMA-IR. LSD significantly (p < 0.001) increased the level of hemoglobin, glycogen and suppressed the level of glycalated hemoglobin. LSD significantly (p < 0.001) altered the level of lipid parameters and inflammatory cytokines. LSD altered the level of antioxidant parameters in the liver and pancreas tissue. LSD significantly (p < 0.001) decreased the mRNA expression of troll like receptor (TLR)4, myeloid differentiation primary response 88 (MyD88), Nuclear factor kappa B (NF-κB)p65 and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3), respectively. The results suggest that LSD has a protective effect on GDM in female rats induced by STZ, possibly through reducing the activity of the TLR4/MyD88/NF-κB signaling pathway.

Development and validation of dynamic nomogram of frailty risk for older patients hospitalized with heart failure.

Objective: This study aimed to establish and validate a dynamic online nomograph for predicting the risk of frailty in older patients hospitalized with heart failure in China. Methods: A total of 451 older adults with heart failure hospitalized were selected between December 2021 and November 2022 at the Department of Cardiovascular Medicine in a Class A tertiary hospital in Shandong, China. The data of patients were obtained by using Barthel Index, instrumental activity of daily living scale, mini nutrition assessment-short form, Pittsburgh sleep quality index scale, Morse fall risk assessment scale and general information scale. The brain natriuretic peptide and echocardiographic indexes of patients were collected by electronic medical records. All participants were randomly divided into the training set (n = 319) and the validation set (n = 132) at the ratio of 7:3. The training set is used for model construction, and the validation set is used for internal validation. Using the Least Absolute Shrinkage and Selection Operator (LASSO) regression method to filter modeling variables, while the multivariable logistic regression was used to establish the nomogram based on the screened optimal variables. The performance of the model was evaluated by the area under the curve (AUC) of the receiver operator characteristic (ROC) curve, Hosmer-Lemeshow test, calibration plot, and decision curve analysis (DCA). Results: The prevalence of frailty in 451 patients was 50.6%, 51.4%, and 48.5% in the training and validation sets, respectively. Drinking, grip strength, New York Heart Association (NYHA) class, multimorbidity, hospitalization history of heart failure, Barthel Index, the instrumental activities of daily living, nutritional status, sleep, fall, and left atrial end-diastolic diameter were used for LASSO regression analysis as the significant predictors of frailty. According to internal validation, the AUC of the ROC curve for the nomogram was 0.920, with a sensitivity of 86.8% and specificity of 84.4%. Moreover, in the validation set, the P-values of the H-L test were 0.742, and the calibration curve had good concordance between the estimated frailty risk and actual observation, indicating the model was well-calibrated. The DCA results confirmed that the nomogram had a well-performance in clinical suitability. Conclusions: An online dynamic nomogram predicting frailty for older patients hospitalized for heart failure in China was well-established and identified in this study. This model benefits medical professionals in identifying high-risk frailty in older hospitalized patients with heart failure, which could reduce the medical and disease burden of heart failure to a certain extent. However, further verification is needed in the future.

Value of red blood cell distribution width in prediction of diastolic dysfunction in cirrhotic cardiomyopathy.

BACKGROUND: Clinical diagnosis of cirrhotic cardiomyopathy (CCM) often encounters challenges of lack of timeliness and disease severity, with the commonly positive indicator usually associated with advanced heart failure. AIM: To explore suitable biomarkers for early CCM prediction. METHODS: A total of 505 eligible patients were enrolled in this study and divided into four groups according to Child-Pugh classification: Group I, Class A without CCM (105 cases); Group II, Class A with CCM (175 cases); Group III, Class B with CCM (139 cases); and Group IV, Class C with CCM (86 cases). Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to determine whether red blood cell distribution width (RDW) was an independent risk factor for CCM risk. The relationships between RDW and Child-Pugh scores, Model for End-Stage Liver Disease (MELD) scores, and N-terminal pro-brain natriuretic peptide (NT-proBNP) were analyzed by Pearson correlation analysis. RESULTS: A constant RDW increase was evident from Group I to Group IV (12.54 ± 0.85, 13.29 ± 1.19, 14.30 ± 1.96, and 16.25 ± 2.13, respectively). Pearson correlation analysis showed that RDW was positively correlated with Child-Pugh scores (r = 0.642, P < 0.001), MELD scores (r = 0.592, P < 0.001), and NT-proBNP (r = 0.715, P < 0.001). Furthermore, between Group I and Group II, RDW was the only significant index (odds ratio: 2.175, 95% confidence interval [CI]: 1.549-3.054, P < 0.001), and it reached statistical significance when examined by ROC curve analysis (area under the curve: 0.686, 95%CI: 0.624-0.748, P < 0.001). CONCLUSION: RDW can serve as an effective and accessible clinical indicator for the prediction of diastolic dysfunction in CCM, in which a numerical value of more than 13.05% may indicate an increasing CCM risk.

Serum metabolomic analyses reveal the potential metabolic biomarkers for prediction of amatoxin poisoning.

Amatoxin poisoning leads to over 90% of deaths in mushroom poisoning. The objective of present study was to identify the potential metabolic biomarkers for early diagnosis of amatoxin poisoning. Serum samples were collected from 61 patients with amatoxin poisoning and 61 healthy controls. An untargeted metabolomics analysis was performed using the ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS). Multivariate statistical analysis revealed that the patients with amatoxin poisoning could be clearly separated from healthy controls on the basis of their metabolic fingerprints. There were 33 differential metabolites including 15 metabolites up-regulated metabolites and 18 down-regulated metabolites in patients with amatoxin poisoning compared to healthy controls. These metabolites mainly enriched in the lipid metabolism and amino acid metabolism pathways, such as Glycerophospholipid metabolism, Sphingolipid metabolism, Phenylalanine tyrosine and typtophan biosynthesis, Tyrosine metabolism, Arginine and proline metabolism, which may serve important roles in the amatoxin poisoning. Among the differential metabolites, a total of 8 significant metabolic markers were identified for discriminating patients with amatoxin poisoning from healthy controls, including Glycochenodeoxycholate-3-sulfate (GCDCA-S), 11-Oxo-androsterone glucuronide, Neomenthol-glucuronide, Dehydroisoandrosterone 3-glucuronide, Glucose 6-phosphate (G6P), Lanthionine ketimine, Glycerophosphocholine (GPC) and Nicotinamide ribotide, which achieved satisfactory diagnostic accuracy (AUC>0.8) in both discovery and validation cohorts. Strikingly, the Pearson's correlation analysis indicated that 11-Oxo-androsterone glucuronide, G6P and GCDCA-S were positively correlated with the liver injury induced by amatoxin poisoning. The findings of the current study may provide insight into the pathological mechanism of amatoxin poisoning and screened out the reliable metabolic biomarkers to contribute the clinical early diagnosis of amatoxin poisoning.

Altered functional connectivity of anterior cingulate cortex in chronic insomnia: A resting-state fMRI study.

The aim of our present study was to explore the connectivity pattern change between the anterior cingulate cortex (ACC) and the voxels from the whole brain in chronic insomnia (CI). With region of interest (ROI)-based functional connectivity, a two-sample t-test was performed on individual FC correlation maps from two groups based on the resting-state fMRI data acquired from 57 CI patients and 46 healthy controls (GRF correction, voxel-level P < 0.001 and cluster-level P < 0.001). A correlation analysis was performed to evaluate the relationship between the clinical features and the abnormal FC. Compared to the healthy controls, the CI patients show increased connectivity between the ACC and the right middle frontal gyrus, with decreased connectivity between the ACC and the bilateral precuneus gyrus. Correlation analysis indicated that the decreased connectivity showed positive correlations with Self-Rating Anxiety Scale (SAS) scores. Our study shows the alterations of CI patients in the level of functional integration and may indicate the dysfunction of communication within brain regions of the default mode network (DMN). These changes and their correlation with negative emotions may provide additional evidence to understand the possible neural mechanisms of CI.

Acteoside Derived from Cistanche Improves Glucocorticoid-Induced Osteoporosis by Activating PI3K/AKT/mTOR Pathway.

OBJECTIVE: Glucocorticoids are widely used in clinical practice; however, they can cause side effects, such as osteoporosis. Acteoside (ACT) from Cistanche has been used to combat a variety of diseases. The study was conducted to evaluate the efficacy of ACT in glucocorticoid-induced osteoporosis (GIOP) and its potential mechanism. METHODS: Dexamethasone (Dex) was injected intramuscularly to induce osteoporosis in a rat model, and ACT was given orally. ACT was supplemented in vivo in Dex-stimulated osteoblastic MC3T3-E1 cells. RT-qPCR was performed to assess the mRNA levels of bone formation (Runx2, CoL1A1), and bone resorption (OPG and RANKL). A commercial ELISA kit was applied to assess serum OC and CTX levels. Western blot was performed to assess protein levels in the PI3K/AKT/mTOR signaling pathway. CCK-8 assay and flow cytometry were performed to assess osteoblast viability and apoptosis. RESULTS: ACT reduced Dex-induced bone microstructure deterioration, increased serum levels of OC, and decreased the levels of CTX (P < 0.05). In the MC3T3-E1 cells, Dex inhibited cell viability and promoted apoptosis; however, this effect was greatly attenuated by ACT (P < 0.05). Concurrently, ACT reversed the reduction in Runx2, osterix, CoL1A1, and OPG mRNA levels, ALP activity, and the promotion of RANKL by Dex. Additionally, ACT attenuated Dex-induced inhibition of p-AKT/AKT, p-mTOR/mTOR, and p-PI3K/PI3K protein levels by Dex (P < 0.05), while the PI3K/AKT/mTOR pathway inhibitor LY294002 diminished the potential effect of ACT (P < 0.05). CONCLUSION: ACT from Cistanche may exert osteoprotective effects by activating the PI3K/AKT/mTOR signaling pathway to alleviate Dex-induced osteoporosis.

Altered functional connectivity strength in chronic insomnia associated with gut microbiota composition and sleep efficiency.

Background: There is limited evidence on the link between gut microbiota (GM) and resting-state brain activity in patients with chronic insomnia (CI). This study aimed to explore the alterations in brain functional connectivity strength (FCS) in CI and the potential associations among altered FCS, GM composition, and neuropsychological performance indicators. Materials and methods: Thirty CI patients and 34 age- and gender-matched healthy controls (HCs) were recruited. Each participant underwent resting-state functional magnetic resonance imaging (rs-fMRI) for the evaluation of brain FCS and was administered sleep-, mood-, and cognitive-related questionnaires for the evaluation of neuropsychological performance. Stool samples of CI patients were collected and subjected to 16S rDNA amplicon sequencing to assess the relative abundance (RA) of GM. Redundancy analysis or canonical correspondence analysis (RDA or CCA, respectively) was used to investigate the relationships between GM composition and neuropsychological performance indicators. Spearman correlation was further performed to analyze the associations among alterations in FCS, GM composition, and neuropsychological performance indicators. Results: The CI group showed a reduction in FCS in the left superior parietal gyrus (SPG) compared to the HC group. The correlation analysis showed that the FCS in the left SPG was correlated with sleep efficiency and some specific bacterial genera. The results of CCA and RDA showed that 38.21% (RDA) and 24.62% (CCA) of the GM composition variation could be interpreted by neuropsychological performance indicators. Furthermore, we found complex relationships between Alloprevotella, specific members of the family Lachnospiraceae, Faecalicoccus, and the FCS alteration, and neuropsychological performance indicators. Conclusion: The brain FCS alteration of patients with CI was related to their GM composition and neuropsychological performance indicators, and there was also an association to some extent between the latter two, suggesting a specific interaction pattern among the three aspects: brain FCS alteration, GM composition, and neuropsychological performance indicators.

Distinct alterations of functional connectivity of the basal forebrain subregions in insomnia disorder.

Background: Cholinergic basal forebrain (BF) plays an important role in sleep-wake regulation and is implicated in cortical arousal and activation. However, less is known currently regarding the abnormal BF-related neuronal circuit in human patients with insomnia disorder (ID). In this study, we aimed to explore alterations of functional connectivity (FC) in subregions of the BF and the relationships between FC alterations and sleep and mood measures in ID. Materials and methods: One hundred and two ID patients and ninety-six healthy controls (HC) were included in this study. Each subject underwent both resting-state fMRI and high-resolution anatomical scanning. All participants completed the sleep and mood questionnaires in ID patients. Voxel-based resting-state FC in each BF subregion (Ch_123 and Ch_4) were computed. For the voxel-wise FC differences between groups, a two-sample t-test was performed on the individual maps in a voxel-by-voxel manner. To examine linear relationships with sleep and mood measures, Pearson correlations were calculated between FC alterations and sleep and mood measures, respectively. Results: The ID group showed significantly decreased FC between the medial superior frontal gyrus and Ch_123 compared to HC. However, increased FC between the midbrain and Ch_4 was found in ID based on the voxel-wise analysis. The correlation analysis only revealed that the altered FC between the midbrain with Ch_4 was significantly negatively correlated with the self-rating anxiety scale. Conclusion: Our findings of decreased FC between Ch_123 and medial superior frontal gyrus and increased FC between midbrain and Ch4 suggest distinct roles of subregions of BF underlying the neurobiology of ID.

Arms Race between the Host and Pathogen Associated with Fusarium Head Blight of Wheat.

Fusarium head blight (FHB), or scab, caused by Fusarium species, is an extremely destructive fungal disease in wheat worldwide. In recent decades, researchers have made unremitting efforts in genetic breeding and control technology related to FHB and have made great progress, especially in the exploration of germplasm resources resistant to FHB; identification and pathogenesis of pathogenic strains; discovery and identification of disease-resistant genes; biochemical control, and so on. However, FHB burst have not been effectively controlled and thereby pose increasingly severe threats to wheat productivity. This review focuses on recent advances in pathogenesis, resistance quantitative trait loci (QTLs)/genes, resistance mechanism, and signaling pathways. We identify two primary pathogenetic patterns of Fusarium species and three significant signaling pathways mediated by UGT, WRKY, and SnRK1, respectively; many publicly approved superstar QTLs and genes are fully summarized to illustrate the pathogenetic patterns of Fusarium species, signaling behavior of the major genes, and their sophisticated and dexterous crosstalk. Besides the research status of FHB resistance, breeding bottlenecks in resistant germplasm resources are also analyzed deeply. Finally, this review proposes that the maintenance of intracellular ROS (reactive oxygen species) homeostasis, regulated by several TaCERK-mediated theoretical patterns, may play an important role in plant response to FHB and puts forward some suggestions on resistant QTL/gene mining and molecular breeding in order to provide a valuable reference to contain FHB outbreaks in agricultural production and promote the sustainable development of green agriculture.

Neurotoxicity of Chronic Co-Exposure of Lead and Ionic Liquid in Common Carp: Synergistic or Antagonistic?

Previous studies have indicated that the harmful heavy metal lead (Pb) contamination in aquatic systems has caused intelligence development disorders and nervous system function abnormalities in juveniles due to the increased permeability of the blood-brain barrier. Ionic liquids (ILs) are considered "green" organic solvents that can replace traditional organic solvents. Studies have found the presence of ILs in soil and water due to chemical applications or unintentional leakage. Therefore, what would happen if Pb interacted with ILs in a body of water? Could ILs enable Pb to more easily cross the blood-brain barrier? Therefore, we examined the combined exposure of Pb and ILs in common carp at low concentration (18.3 mg L-1 of Pb(CH3COO)2•3 H2O and 11 mg L-1 of the IL 1-methyl-3-octylimidazolium chloride, 5% of their LC50) for 28 days in the present study. The result of a neurobehavioral assay showed that chronic exposure of lead at lower concentrations significantly altered fish movement and neurobehaviors, indicating that lead exposure caused neurotoxicity in the carp. Increases in the neurotransmitter dopamine levels and injuries in the fish brain accounted for neurobehavioral abnormalities induced by lead exposure. Moreover, we also found that lead could easily cross the blood-brain barrier and caused significant bioaccumulation in the brain. Particularly, our study indicated that the ionic liquid could not synergistically promote blood-brain barrier permeability and hence failed to increase the absorption of lead in the fish brain, suggesting that the combined exposure of lead and ILs was not a synergistic effect but antagonism to the neurotoxicity. The results of this study suggested that ILs could recede the Pb induced neurotoxicity in fish.

Atractylodin Induces Apoptosis and Inhibits the Migration of A549 Lung Cancer Cells by Regulating ROS-Mediated Signaling Pathways.

Atractylodin (ATR) has anticancer effects on some tumor cells by inducing apoptosis, but its mechanism in lung cancer remains unclear. This study investigates the inhibitory effect of ATR on A549 lung cancer cells. Cell viability was detected by the Cell Counting Kit-8 assay, and results showed that ATR could significantly inhibit the proliferation of A549 cells. Apoptosis was detected by Annexin V-FITC/PI staining, and apoptosis rate and mitochondrial membrane potential were detected by flow cytometry. Results showed that the effect of ATR on the apoptosis of A549 cells was negatively correlated with the change in mitochondrial membrane potential. Western blot analysis showed that ATR regulated apoptosis induced by mitogen-activated protein kinase, signal transducer and activator of transcription 3, and nuclear factor kappa B signaling pathways. Analyses of reactive oxygen species (ROS), cell cycle, and cell migration showed that ATR induced intracellular ROS accumulation as an initiation signal to induce cell cycle arrest regulated by the AKT signaling pathway and cell migration inhibition regulated by the Wnt signaling pathway. Results showed that ATR can inhibit cell proliferation, induce cell apoptosis, induce cell cycle arrest, and inhibit the migration of A549 cells (p < 0.05 was considered statistically significant, * p < 0.05, ** p < 0.01 and *** p < 0.001).

The Early Predictive Value of Circulating Monocytes and Eosinophils in Coronary DES Restenosis.

Background: Monocytes and eosinophils are involved in intracoronary inflammatory responses, aggravating coronary artery plaque instability and in-stent restenosis (ISR). Aims: To investigate an early prediction of ISR in patients undergoing stenting by circulating monocytes and eosinophils. Methods: The single-center data of patients undergoing successful drug-eluting stents (DES) implantation from January 1, 2017 to April 30, 2020 were retrospectively analyzed. Of the 4,392 patients assessed, 140 patients with restenosis and 141 patients without restenosis were enrolled. A scheduled postoperative follow-up was proceeded in four sessions: 0-3 months, 3-6 months, 6-12 months, and >12 months. The hematological and biochemical measurement was collected. The angiographic review was completed within two postoperative years. Results: Significant associations of monocyte count and percentage with ISR were evident [odds ratio (OR): 1.44, 95% CI: 1.23-1.68, P < 0.001; OR: 1.47, 95%CI: 1.24-1.74, P < 0.001, respectively], which began at 3 months postoperatively and persisted throughout the follow-up period. Eosinophil count and percentage were associated with ISR (OR: 1.22, 95%CI: 1.09-1.36, P = 0.001; OR: 1.23, 95%CI: 1.07-1.40, P = 0.003, respectively), with ISR most significantly associated with the baseline eosinophils. The receiver operating characteristic (ROC) curve analysis showed that the cutoff points of monocyte count and percentage in the ISR prediction were 0.46× 109/L and 7.4%, respectively, and those of eosinophil count and percentage were 0.20 × 109/L and 2.5%, respectively. Conclusion: This study, with a long-term follow-up, first provides evidence that the elevated monocytes at three postoperative months and baseline eosinophils may be strong early predictors of ISR after drug-eluting stent implantation. Persistent elevation of monocytes may also be a signal of ISR after percutaneous coronary intervention (PCI).

[Analysis on the Incidence and Economic Burden of Patients with Lung Cancer].

BACKGROUND: The previous study has indicated that lung cancer has a high incidence and mortality in China, and has caused a large economic burden. The purpose of this study was to analyze the incidence and economic burden of lung cancer by analyzing the information on the home page of discharge history of lung cancer patients in Hebei Tumor Hospital, and to provide scientific basis for the prevention and treatment of lung cancer. METHODS: The information of all of the discharges, new cases, surgical patients, age, gender, length of stay and hospitalization cost of lung cancer patients in Hebei Tumor Hospital from January 2012 to December 2019 were retrieved based on the medical record management system, and the incidence trend, gender and age distribution as well as the economic burden of the disease were statistically described. RESULTS: The number of new cases of lung cancer increased year by year, from 2,235 cases in 2012 to 5,012 cases in 2019. The number of males always outnumbered females, but the gender ratio decreased year by year, from 2.25 in 2012 to 1.56 in 2019. Among new cases of lung cancer, the proportion of surgical treatment increased year by year, from 28.14% in 2012 to 44.83% in 2019. Except for 2012, the proportion of surgical operations in female patients was higher than that in male patients from 2013 to 2019. The proportion of surgical operations in male and female patients was 23.52% and 28.07% in 2013, and 36.14% and 58.37% in 2019, respectively. The median age at the onset of lung cancer has increased year by year, from 61 years old in 2012 to 63 years old in 2019. The median age of onset in all lung cancer patients was higher in males than in females. The number of new lung cancer patients and surgical patients both showed an increasing trend with the increase of age, and both reached the maximum value in the age group of 60-69 years old. With the increase of age, the number of patients gradually decreased. The median length of hospital stay for all discharged lung cancer patients or surgical patients decreased year by year, from 10 d and 19 d in 2012 to 8 d and 17 d in 2019, respectively, while the median hospitalization cost increased year by year. It increased from 10,611.46 yuan and 38,750.13 yuan in 2012 to 17,187.15 yuan and 84,030.16 yuan in 2019, respectively. CONCLUSIONS: Lung cancer is still one of the main cancers endangering the health of Chinese residents. The incidence of lung cancer is increasing year by year, and the distribution of gender and age has certain characteristics. In order to reduce the number of cases and the economic burden, effective prevention and control measures should be formulated and medical reform should be strengthened.

2-(Naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone induces apoptosis via ROS-mediated MAPK, AKT, and STAT3 signaling pathways in HepG2 human hepatocellular carcinoma cells.

1,4-naphthoquinone and its derivatives have attracted widespread attention due to their multiple biological activities, such as induction of cancer cell apoptosis; however, most of these compounds have high cytotoxicity. In this study, in order to reduce their toxicity and increase their potential anti-tumor effects, we synthesized a novel 1,4-naphthoquinone derivative named 2-(naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone (NTDMNQ), and investigated its apoptotic effects and underlying mechanism. Our results showed that NTDMNQ inhibited the viability of HepG2, Hep3B, and Huh7 human hepatocellular carcinoma (HCC) cells. It also increased the accumulation of cells in the G0/G1 phase of the cell cycle by increasing the expression levels of p-p53, p21 and p27, while decreasing the levels of Cyclin D1, Cyclin E, Cyclin-dependent kinase 2 (CDK2), CDK4, and CDK6. Inhibition of reactive oxygen species (ROS) by the ROS scavenger N-acetyl-L-cysteine (NAC) decreased apoptosis in NTDMNQ-treated cells. Western blot analysis showed that NTDMNQ increased the phosphorylation of p38 and c-Jun N-terminal kinase (JNK), and decreased the phosphorylation of extracellular signal-regulated kinase (ERK), AKT, and signal transducer and activator of transcription-3 (STAT3); these effects were blocked by NAC. Both the JNK inhibitor (SP600125) and p38 inhibitor (SB203580) reversed the phosphorylation of STAT3, and the ERK inhibitor (FR180204) and AKT inhibitor (LY294002) reduced the expression of STAT3. Taken together, these findings suggest that NTDMNQ induces apoptosis via ROS-mediated MAPK, AKT and STAT3 signaling pathways in HepG2 cells, and may be a potent anticancer agent.

Factors associated with progression of different prediabetic status to Diabetes: A Community-based cohort study.

AIMS: To examine the predictive factors associated with the progression of different prediabetic status to diabetes. METHODS: A two-year retrospective cohort study was conducted on 5741 participants aged 40 years or older. Finally, 1685 participants with prediabetes defined by IFG (impaired fasting glucose), IGT (impaired glucose tolerance) and CGI (combined IFG and IGT) were included. Logistic regression model was used to evaluate the risk of prediabetes progression to diabetes. RESULTS: Of the 1685 subjects with prediabetes at baseline, 212 (12.6%) subjects progressed to diabetes and 1473 (87.4%) subjects did not. Logistic regression analysis demonstrated that people with CGI were associated with an increased risk of progressing to diabetes compared to those with IFG (OR, 95% CI: 3.127, 2.047-4.776). Moreover, males, obese people, people with increased BMI and WHR (Waist/ Hip ratio), and hypertension were positively associated with the progression to diabetes, while HOMA-ß was negatively associated with the progression to diabetes. CONCLUSIONS: Subjects with CGI are prone to progressed to diabetes compared to those with IFG or IGT in middle-aged and older person in China. More attention should be paid to male and obese prediabetic subjects, and measures should be taken to control the increase in their BMI and WHR.