Pseudognaphalium affine Extract Alleviates COPD by Inhibiting the Inflammatory Response via Downregulation of NF-κB.

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with limited therapeutic options. Pseudognaphalium affine (D. Don) Anderb. is a medicinal and edible plant used to treat cough, asthma, and COPD for a long time in folk medicine. The objective of this study is to evaluate the effect of Pseudognaphalium affine (D. Don) Anderb. extract (GAE) and investigate the possible underlying mechanism in vivo and in vitro. In vivo, the administration of GAE in a rat COPD model could significantly ameliorate lung damage and pulmonary function by inhibiting the production of pro-inflammatory cytokines. Western blot and real-time PCR results showed that GAE could suppress nuclear translocation of nuclear factor-kappa B (NF-κB), which indicated that GAE down-regulated the NF-κB pathway. Moreover, GAE protected against tumor necrosis factor (TNF)-α induced inflammatory response in BEAS-2B and inhibited the NF-κB pathway. All data suggested that GAE exhibited its anti-COPD effect by inhibiting pro-inflammatory cytokines, which may be associated with the inhibition of the NF-κB pathway.

Pygo1 regulates pathological cardiac hypertrophy via a ß-catenin-dependent mechanism.

Wnt/ß-catenin signaling plays a key role in pathological cardiac remodeling in adults. The identification of a tissue-specific Wnt/ß-catenin interaction factor may provide a tissue-specific clinical targeting strategy. Drosophila Pygo encodes the core interaction factor of Wnt/ß-catenin. Two Pygo homologs (Pygo1 and Pygo2) have been identified in mammals. Different from the ubiquitous expression profile of Pygo2, Pygo1 is enriched in cardiac tissue. However, the role of Pygo1 in mammalian cardiac disease is yet to be elucidated. In this study, we found that Pygo1 was upregulated in human cardiac tissues with pathological hypertrophy. Cardiac-specific overexpression of Pygo1 in mice spontaneously led to cardiac hypertrophy accompanied by declined cardiac function, increased heart weight/body weight and heart weight/tibial length ratios, and increased cell size. The canonical ß-catenin/T-cell transcription factor 4 (TCF4) complex was abundant in Pygo1-overexpressing transgenic (Pygo1-TG) cardiac tissue, and the downstream genes of Wnt signaling, that is, Axin2, Ephb3, and c-Myc, were upregulated. A tail vein injection of ß-catenin inhibitor effectively rescued the phenotype of cardiac failure and pathological myocardial remodeling in Pygo1-TG mice. Furthermore, in vivo downregulated pygo1 during cardiac hypertrophic condition antagonized agonist-induced cardiac hypertrophy. Therefore, our study is the first to present in vivo evidence demonstrating that Pygo1 regulates pathological cardiac hypertrophy in a canonical Wnt/ß-catenin-dependent manner, which may provide new clues for tissue-specific clinical treatment via targeting this pathway.NEW & NOTEWORTHY In this study, we found that Pygo1 is associated with human pathological hypertrophy. Cardiac-specific overexpression of Pygo1 in mice spontaneously led to cardiac hypertrophy. Meanwhile, cardiac function was improved when expression of Pygo1 was interfered in hypertrophy-model mice. Our study is the first to present in vivo evidence demonstrating that Pygo1 regulates pathological cardiac hypertrophy in a canonical Wnt/ß-catenin-dependent manner, which may provide new clues for a tissue-specific clinical treatment targeting this pathway.

Molecular biology of the SARs-CoV-2 spike protein: A review of current knowledge.

The global coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an unprecedented worldwide public health emergency. Despite the concerted efforts of the scientific field, by April 25, 2021, SARS-CoV-2 had spread to over 192 countries/regions, causing more than 146 million confirmed cases including 31 million deaths. For now, an established treatment for patients with COVID-19 remains unavailable. The key to tackling this pandemic is to understand the mechanisms underlying its infectivity and pathogenicity. As a predominant focus, the coronavirus spike (S) protein is the key determinant of host range, infectivity, and pathogenesis. Thereby comprehensive understanding of the sophisticated structure of SARS-CoV-2 S protein may provide insights into possible intervention strategies to fight this ongoing global pandemic. Herein, we summarize the current knowledge of the molecular structural and functional features of SARS-CoV-2 S protein as well as recent updates on the cell entry mechanism of the SARS-CoV-2, paving the way for exploring more structure-guided strategies against SARS-CoV-2.

Mutation analysis of 21 autosomal short tandem repeats in Han population from Hunan, China.

Background: Short tandem repeats (STRs) are powerful genetic markers widely used in human genetics. Population data and locus-specific mutation rates of STRs are crucial for the evaluation and interpretation of genetic evidence in forensic and population genetics.Aim: To investigate the mutation rates of 21 autosomal STRs in a population from central south China.Subjects and methods: This study analysed 3420 paternity cases with a Combined Paternity Index >10,000 from Han population in Hunan. A total of 68,743 meiotic transfers were analysed and 62 mutations were identified.Results: The overall mutation rate of STR loci was 0.9 × 10-3 (95% CI, 0.0007-0.0011) and the locus-specific mutation rates were estimated ranging from 0.0000-0.0023. Locus D1S1656 exhibited the highest mutation rate of 2.3 × 10-3 (95% CI, 0.0005-0.0006), followed by D12S391 with a mutation rate of 2.0 × 10-3 (95% CI, 0.0007-0.0044). No mutation was observed at TPOX, D2S1338 or Penta D. One-step mutation cases accounted for 96.77% of total mutations and the ratio of paternal vs maternal mutations was ∼4.85:1. Inter-population comparisons of locus-specific mutation rates of several STRs revealed significant differences between Han in Hunan and Han in other regions of China. Conclusion: The data justified the use of geographical data in further genetic applications.

CXXC5 regulates differentiation of C2C12 myoblasts into myocytes.

CXXC5 is a member of the CXXC-type zinc-finger domain containing protein family, which is suggested to function in gene transcription, cell adhesion and cytoskeleton organization. Previous studies have revealed that CXXC5 is expressed in skeletal muscle, but whether it regulates skeletal myogenesis is yet unknown. Here, we screened for the possible signaling pathways in which CXXC5 might participate using luciferase gene reporters. The results indicated that CXXC5 significantly increased the activities of the promoters of genes involved in skeletal muscle differentiation. We therefore studied the role of CXXC5 during skeletal myogenesis in C2C12 myoblasts. Our findings suggest that overexpression of CXXC5 in C2C12 myoblasts facilitated myocyte differentiation, while RNAi interference of CXXC5 significantly inhibited the differentiation of C2C12 myoblasts. This study suggests that CXXC5 plays a significant role in regulating skeletal myogenesis.

LncRNA-LINC00472 suppresses the malignant progression of non-small cell lung cancer via modulation of the miRNA-1275/Homeobox A2 axis.

BACKGROUND: Long non-coding RNAs (lncRNAs) are increasingly observed as regulatory factors for the initiation and progression of varying kinds of cancers. However, studies on lncRNAs in non-small cell lung cancer (NSCLC) progression are currently lacking. OBJECTIVES: We intended to determine the role of lncRNA LINC00472 and its downstream regulatory mechanism in NSCLC, thus providing novel ideas for targeted therapies for NSCLC. MATERIAL AND METHODS: The target signaling axis comprising the lncRNA/microRNA/mRNA was identified through bioinformatics analysis. Subcellular localization of LINC00472 was assessed with fluorescence in situ hybridization (FISH). Cellular function experiments were conducted to examine the proliferation, migration, invasion, and apoptosis of NSCLC cells, and dual-luciferase and RNA binding protein immunoprecipitation assays were performed to validate the binding relationship. Quantitative real-time polymerase chain reaction (qPCR) and western blot were utilized to assess the expression levels of the investigated gene and protein, respectively. RESULTS: The LINC00472 expression was markedly decreased in NSCLC tissues and cells. The FISH, combined with nuclear-cytoplasm separation assay, demonstrated that LINC00472 was mainly located in the cytoplasm. The overexpression of LINC00472 restrained proliferation and metastasis of NSCLC in vitro. The LINC00472 could target and repress miR-1275 level, and overexpression of LINC00472 reduced the miR-1275-dependent malignant cell phenotype in NSCLC. Further study revealed that HOXA2 was a downstream target of miR-1275 and was negatively modulated by miR-1275. Rescue assays exhibited that the overexpression of miR-1275 or inhibition of HOXA2 reversed the impact of LINC00472 overexpression on the malignant progression of NSCLC cells. The LINC00472 repressed the epithelial-mesenchymal transition (EMT) of NSCLC cells through miR-1275/HOXA2. CONCLUSIONS: The LINC00472 functioned as a competing endogenous RNA to modulate HOXA2 level by sponging miR-1275 in NSCLC. Simultaneously, the LINC00472/miR-1275/HOXA2 axis may be a possible therapeutic target and biomarker for NSCLC.

A retrospective study of combination therapy with glucocorticoids and pirfenidone for PD-1 inhibitor-related immune pneumonitis.

Immune checkpoint inhibitor pneumonitis (ICIP) is thought to be a self-limiting disease; however, an effective treatment option does not currently exist. This study aimed to determine the clinical efficacy of combination therapy with glucocorticoids and pirfenidone for ICIP related to programmed cell death protein-1 (PD-1) inhibitors. We conducted a retrospective analysis of 45 patients with advanced non-small cell lung cancer who developed ICIP following PD-1 inhibitor and albumin-bound paclitaxel or carboplatin treatment at our hospital. The PD-1 inhibitor was discontinued, and glucocorticoids were used alone or in combination with pirfenidone to treat ICIP. The relevant clinical data of these patients were collected and analyzed. Compared with the glucocorticoid alone group, the glucocorticoid-pirfenidone group showed significant improvement in forced vital capacity (FVC), carbon monoxide diffusing capacity [%], peripheral capillary oxygen saturation, and 6-minute walk distance (P < .05). There were benefits with respect to the St. George's Respiratory Questionnaire score and the recurrence rate of ICIP, but there was no significant difference between the 2 groups (P > .05). Adding pirfenidone to glucocorticoid treatment was shown to be safe and may be more beneficial than glucocorticoids alone for improving pulmonary interstitial lesions, reversing ICIP, and preventing its recurrence.

Construction of a prognostic model based on memory CD4+ T cell-associated genes for lung adenocarcinoma and its applications in immunotherapy.

The association between memory CD4+ T cells and cancer prognosis is increasingly recognized, but their impact on lung adenocarcinoma (LUAD) prognosis remains unclear. In this study, using the cell-type identification by estimating relative subsets of RNA transcripts algorithm, we analyzed immune cell composition and patient survival in LUAD. Weighted gene coexpression network analysis helped identify memory CD4+ T cell-associated gene modules. Combined with module genes, a five-gene LUAD prognostic risk model (HOXB7, MELTF, ABCC2, GNPNAT1, and LDHA) was constructed by regression analysis. The model was validated using the GSE31210 data set. The validation results demonstrated excellent predictive performance of the risk scoring model. Correlation analysis was conducted between the clinical information and risk scores of LUAD samples, revealing that LUAD patients with disease progression exhibited higher risk scores. Furthermore, univariate and multivariate regression analyses demonstrated the model independent prognostic capability. The constructed nomogram results demonstrated that the predictive performance of the nomogram was superior to the prognostic model and outperformed individual clinical factors. Immune landscape assessment was performed to compare different risk score groups. The results revealed a better prognosis in the low-risk group with higher immune infiltration. The low-risk group also showed potential benefits from immunotherapy. Our study proposes a memory CD4+ T cell-associated gene risk model as a reliable prognostic biomarker for personalized treatment in LUAD patients.

Construction of lung cancer serum markers based on ReliefF feature selection.

Serum miRNAs are available clinical samples for cancer screening. Identifying early serum markers in lung cancer (LC) is essential for patients' early diagnosis and clinical treatment. Expression data of serum miRNAs of lung adenocarcinoma (LUAD) patients and healthy individuals were downloaded from the Gene Expression Omnibus (GEO). These data were normalized and subjected to differential expression analysis to obtain differentially expressed miRNAs (DEmiRNAs). The DEmiRNAs were subsequently subjected to ReliefF feature selection, and subsets closely related to cancer were screened as candidate feature miRNAs. Thereafter, a Gaussian Naive Bayes (NB), Support Vector Machine (SVM), and Random Forest (RF) classifier were constructed based on these candidate feature miRNAs. Then the best diagnostic signature was constructed through NB combined with incremental feature selection (IFS). Thereafter, these samples were subjected to principal component analysis (PCA) based on miRNAs with optimal predictive performance. Finally, the peripheral serum miRNAs of 64 LUAD patients and 59 normal individuals were extracted for qRT-PCR analysis to validate the performance of the diagnostic model in respect of clinical detection. Finally, according to area under the curve (AUC) and accuracy values, the NB classifier composed of miR-5100 and miR-663a manifested the most outstanding diagnostic performance. The PCA results also revealed that the 2-miRNA diagnostic signature could effectively distinguish cancer patients from healthy individuals. Finally, qRT-PCR results of clinical serum samples revealed that miR-5100 and miR-663a expression in tumor samples was remarkably higher than that in normal samples. The AUC of the 2-miRNA diagnostic signature was 0.968. In summary, we identified markers (miR-5100 and miR-663a) in serum for early LUAD screening, providing ideas for developing early LUAD diagnostic models.

SNHG15 enhances cisplatin resistance in lung adenocarcinoma by affecting the DNA repair capacity of cancer cells.

BACKGROUND: Lung adenocarcinoma (LUAD) is a prevalent malignancy. SNHG15 has been demonstrated to be oncogenic in many kinds of cancers, however the mechanism of SNHG15 in LUAD cisplatin (DDP) resistance remains unclear. In this study, we demonstrated the effect of SNHG15 on DDP resistance in LUAD and its related mechanism. METHODS: Bioinformatics analysis was adopted to assess SNHG15 expression in LUAD tissues and predict the downstream genes of SNHG15. The binding relationship between SNHG15 and downstream regulatory genes was proved through RNA immunoprecipitation, chromatin immunoprecipitation and dual-luciferase reporter assays. Cell counting kit-8 assay was adopted to evaluate LUAD cell viability, and gene expression was determined by Western blot and quantitative real-time polymerase chain reaction. We then performed comet assay to assess DNA damage. Cell apoptosis was detected by Tunnel assay. Xenograft animal models were created to test the function of SNHG15 in vivo. RESULTS: SNHG15 was up-regulated in LUAD cells. Moreover, SNHG15 was also highly expressed in drug-resistant LUAD cells. Down-regulated SNHG15 strengthened the sensitivity of LUAD cells to DDP and induced DNA damage. SNHG15 could elevate ECE2 expression through binding with E2F1, and it could induce DDP resistance by modulating the E2F1/ECE2 axis. In vivo experiments verified that the SNHG15 could enhance DDP resistance in LUAD tissue. CONCLUSION: The results suggested that SNHG15 could up-regulate ECE2 expression by recruiting E2F1, thereby enhancing the DDP resistance of LUAD.

Identification and validation of a hypoxia-immune signature for overall survival prediction in lung adenocarcinoma.

Objective: The interaction between immunity and hypoxia in tumor microenvironment (TME) has clinical significance, and this study aims to explore immune-hypoxia related biomarkers in LUAD to guide accurate prognosis of patients. Methods: The LUAD gene expression dataset was downloaded from GEO and TCGA databases. The immune-related genes and hypoxia-related genes were acquired from ImmPort and MSigDB databases, respectively. Genes related to immune and hypoxia in LUAD were obtained by intersection. The significantly prognostic genes in LUAD were obtained by LASSO and Cox regression analyses and a prognostic model was constructed. Kaplan-Meier and receiver operating characteristic curves were generated to evaluate and validate model reliability. Single-sample gene set enrichment analysis (ssGSEA) and gene set variation analysis (GSVA) were employed to analyze immune cell infiltration and pathway differences between high- and low-risk groups. Nomogram and calibration curves for survival curve and clinical features were drawn to measure prognostic value of the model. Results: The prognosis model of LUAD was constructed based on seven immune-hypoxia related genes: S100P, S100A16, PGK1, TNFSF11, ARRB1, NCR3, and TSLP. Survival analysis revealed a poor prognosis in high-risk group. ssGSEA result suggested that activities of immune cells in high-risk group was remarkably lower than in low-risk group, and GSVA result showed that immune-related pathway was notably activated in low-risk group. Conclusion: Immune-hypoxia related genes were found to be prognostic biomarkers for LUAD patients, based on which a 7-immune-hypoxia related gene-signature was constructed. This model can assess immune status of LUAD patients, and provide clinical reference for individualized prognosis, treatment and follow-up of LUAD patients.

PAR2 promotes tumor-associated angiogenesis in lung adenocarcinoma through activating EGFR pathway.

BACKGROUND: Metastasis of advanced lung adenocarcinoma (LUAD) is a key cause of cancer-related death, and angiogenesis is the main feature of tumor growth and metastasis. METHODS: The expression level of F2R like trypsin receptor 1(F2RL1) which encodes protease-activated receptor 2 (PAR2) protein in LUAD tissues was analyzed by bioinformatics. The effects of F2RL1 overexpression/silencing on cell proliferation and sphere-forming were analyzed by Cell Counting Kit-8 and colony formation assays, stem cell sphere-forming assay, and angiogenesis assay, respectively. The F2RL1 mRNA expression level and the PAR2 protein expression level, vascular endothelial growth factor A (VEGFA), and epidermal growth factor receptor (EGFR) in lung cancer cell lines were evaluated by real-time quantitative polymerase chain reaction and western blot. The level of VEGFA secreted by lung cancer cells was analyzed by Enzyme-linked immunosorbent assay (ELISA). The effect of F2RL1-mediated EGFR signaling on angiogenesis was further explored by EGFR inhibitor AG1478. RESULTS: F2RL1 was substantially up-regulated in LUAD tissues and cells, and overexpression of F2RL1 could promote proliferation and stem cell sphere-forming of lung cancer cell lines, as well as formation of blood vessels and branch points of human umbilical vein endothelial cells (HUVECs). Meanwhile, overexpression of F2RL1 significantly upregulated VEGFA expression and promoted EGFR phosphorylation. EGFR inhibitor AG1478 treatment significantly down-regulated pEGFR, and AG1478 treatment reversed the promoting effect of cancer cell cultured medium (oe-F2RL1) on HUVEC angiogenesis. SIGNIFICANCE: In summary, this study revealed the molecular mechanism of PAR2 promoting LUAD angiogenesis by activating EGFR signaling pathway, which further improves our understanding of LUAD angiogenesis, and provides a potential therapeutic strategy for LUAD treatment.

Engagement of gcFKBP5/TRAF2 by spring viremia of carp virus to promote host cell apoptosis for supporting viral replication in grass carp.

Spring viremia of carp virus (SVCV) causes severe morbidity and mortality in grass carp (Ctenopharyngodon idellus) in Europe, America and several Asian countries. We found that FKBP5 (FK506-binding protein 5) is an SVCV infection response factor; however, its role in the innate immune mechanism caused by SVCV infection remains unknown. This study cloned gcFKBP5 (grass carp FKBP5) and made its mimic protein structure for function discussion. We found that gcFKBP5 expression in the primary innate immune organs of grass carp, including intestine, liver and spleen, was highly upregulated by SVCV in 24 h, with a similar result in fish cells by poly(I:C) treatment. gcFKBP overexpression aggravates viral damage to cells and increases viral replication. Furthermore, SVCV engages gcFKBP5 interacting with TRAF2 (tumour necrosis factor receptor-associated factor 2) to promote host cell apoptosis for supporting viral replication. The enhanced viral replication seems not to be due to the repression of IFN and other antiviral factors as expected. For the first time, these data show the pivotal role of gcFKBP5 in the innate immune response of grass carp to SVCV infection.

Transmembrane protein 121 as a novel inhibitor of cervical cancer metastasis.

Transmembrane protein 121 (TMEM121) is isolated from the chicken heart using subtraction hybridisation. A previous study by the authors indicated that TMEM121 is highly expressed in adult mouse hearts and acts as an inhibitor of pathological cardiac hypertrophy. In the present study, the association between TMEM121 and cancer was investigated using bioinformatics tools, including Tumour Immune Estimation Resource (TIMER) 2.0, cBioPortal, LinkedOmics analysis, Kaplan-Meier plotter and UALCAN analysis. The expression, genetic variation, gene interaction network and co-expression pattern of TMEM121 in tumours were analysed. The results revealed that TMEM121 was expressed in various tumours and significantly downregulated in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) when compared with its expression in paracancerous tissues, whereas the methylation level of its promoter was increased in tumour tissues. Additionally, associations between TMEM121 and the PI3K/AKT signalling pathway, as well as the expression of cancer-related molecules, were detected. The aforementioned bioinformatics analysis suggests that TMEM121 may be involved in the development of cervical cancer. Therefore, gain-of-function and loss-of-function experiments in HeLa cells were conducted to verify the role of TMEM121 in cervical cancer. The assay using Cell Counting Kit-8 (CCK-8) revealed that the cell viability of HeLa cells with TMEM121 overexpression was significantly reduced. High TMEM121 expression inhibited HeLa cell migration, as indicated by the decrease in the cell scratch healing rate. The western blot assay revealed that TMEM121 overexpression downregulated the expression of B-cell lymphoma 2 (BCL-2), cyclin D1, cyclin E2 and phosphorylated (p)-AKT, while upregulating that of p27, E-cadherin and p-p38. When TMEM121 was knocked down, retinoblastoma protein (RB), p53, p27, E-cadherin, p-JNK and p-p38 were inhibited, but cyclin E1 was promoted. By combining bioinformatics and experimental biology in the present study, the results demonstrated for the first time, to the best of our knowledge, that TMEM121 may be a novel inhibitor of cervical cancer that is linked to multiple signalling pathways, paving the way for the development of novel diagnostic and therapeutic strategies.

miR-202-3p negatively regulates MMP-1 to inhibit the proliferation, migration and invasion of lung adenocarcinoma cells.

Lung adenocarcinoma (LUAD) is one of the common cancers. Studies show that MMP-1 is involved in tumor progression, yet relevant regulatory mechanism in LUAD remains to be further elucidated. Here, we demonstrated from bioinformatics analysis for GEO data that MMP-1 was differentially up-regulated in LUAD. miR-202-3p, identified as the upstream regulator of MMP-1 by both bioinformatics and dual-luciferase assays, was differentially down-regulated in LUAD and presented a negative correlation with MMP-1. Following cell biological experiments proved that knocking down the expression of MMP-1 inhibited the proliferation, migration and invasion of LUAD cells, while overexpressed miR-202-3p posed a similar suppressive effect on cancer progression. Additionally, rescue assay further identified that overexpression of MMP-1 attenuated the suppressive effect of up-regulated miR-202-3p on malignant progression of LUAD cells. In all, this research suggests a mechanism by which MMP-1 under the regulation of miR-202-3p modulates the proliferation, migration and invasion of LUAD cells, which may contribute to the development of new therapeutic strategies.

Prevalence and risk factors for hyperhomocysteinemia: a population-based cross-sectional study from Hunan, China.

OBJECTIVES: Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases. We aimed to investigate the prevalence and risk factors for hyperhomocysteinemia, especially modifiable lifestyle factors, such as smoking behaviour and dietary factors. DESIGN: Population-based cross-sectional study. SETTING: Hunan Province, China PARTICIPANTS: A total of 4012 participants completed the study, between July 2013 and March 2014. The median age is 55 (interquartile range: 45-63) years, with 1644 males (41%) and 2368 females (59%). MAIN OUTCOME MEASURES: Homocysteine level were measured by the microplate enzyme immunoassay method. Hyperthomocysteinemia was defined as ≥15 µmol/L. Questionnaire was used to investigate potential risk factors of hyperhomocysteinemia. Crude odd ratio (OR) or adjusted OR with 95% CI were determined by using univariable or multivariable logistic regression models. RESULTS: The prevalence of hyperhomocysteinemia is 35.4% (45.4% vs 28.5% for men, women, respectively). One-year increase in age is significantly associated with 2% higher risk of hyperhomocysteinemia (OR=1.02, 95% CI: 1.01 to 1.03). One unit increase of BMI is associated with 5% higher risk of hyperhomocysteinemia (OR=1.05, 95% CI: 1.03 to 1.07). Compared with the non-smoker, smoking participants have a 24% higher risk of hyperhomocysteinemia (OR=1.24, 95% CI: 1.006 to 1.53), while the risk for those quitting smoking are not significantly different (OR=1.14, 95% CI: 0.85 to 1.54). compared with those consuming fruit and vegetable at least once every day, those consuming less than once every day had a significantly higher risk of hyperhomocysteinemia (OR=1.29, 95% CI:1.11 to 1.50). In addition, we found there were significant sex interaction with education level or alcohol drinking on the risk of hyperhomocysteinemia (pinteraction <0.05). CONCLUSIONS: Higher BMI and older age are potential risk factors for hyperhomocysteinemia. Current smoking but not quitting smoking is associated with higher risk of hyperhomocysteinemia. Fruit and vegetable consumption may have protective effect against hyperhomocysteinemia. Alcohol consumption or education level might interact to influence the risk of hyperhomocysteinemia.

Bullying Victimization and Life Satisfaction Among Rural Left-Behind Children in China: A Cross-Sectional Study.

Objectives: This study aimed to evaluate the associations between bullying victimization and life satisfaction in primary school children and also investigate the interactive effects of left-behind status and bullying victimization on life satisfaction. Materials and Methods: Bullying victimization was measured using the Chinese version of the revised Olweus Bully/Victim Questionnaire. Life satisfaction was assessed using the Multidimensional Students' Life Satisfaction Scale (MSLSS). Life satisfaction is composed of five domains, namely, family, school, friends, environment, and self-satisfaction. Left-behind status of rural children was defined as one or both their parents migrating to working in cities. The data were analyzed using Mann-Whitney U tests, Chi-square tests, and multivariate linear and logistic regression analyses. Results: A total of 810 primary school children were involved, of which 8.5% reported bullying victimization, and 44.3% were left-behind children (LBC). We found that bullying victimization was negatively associated with all domains of life satisfaction (all p < 0.05). With further left-behind status-stratified analysis, we found that negative association between bullying victimization and friend satisfaction was more profound in the LBC group than in the non-LBC group [b(SE)= -0.133 (0.03) vs. -0.061 (0.026) for LBC and non-LBC, respectively, p < 0.05]. When further interaction analysis was conducted, we identified interaction effects between left-behind status and bullying victimization on friend satisfaction (p interaction = 0.048). Similar interaction effect between bullying victimization and left-behind status on school satisfaction was also found (p interaction = 0.004). Conclusions: Bullying victimization was associated with low life satisfaction (including lower family, friends, school, self, and environment satisfaction). There were significant interactions between left-behind status and bullying victimization on friend satisfaction, as well as school satisfaction. Left-behind status of children may exaggerate the impact of bullying victimization on friends/school satisfaction rating.

Impact of short-term change of adiposity on risk of high blood pressure in children: Results from a follow-up study in China.

This study aimed to examine the impact of short-term adiposity change on risk of high blood pressure (HBP), and to assess the low limit range of body mass index (BMI) and waist-to-height ratio (WHtR) reduction proposed to decrease the HBP risk in children. Children were longitudinally surveyed at baseline and after a short-term follow-up. General obesity (GOB) is categorized by age and gender-specific BMI cut-off points, abdominal obesity (AOB) by WHtR. Logistic regression model was used to estimate relations between adiposity change and HBP risk with adjustment of covariates. A total of 28,288 children (median of baseline age:10 years) were involved with follow-up of 6.88±1.20 months. After the follow-up, 9.4% of the children had persistent general obesity (GOB), 2.8% converted from GOB to non-GOB, 0.9% had newly developed GOB. When compared with children remained non-GOB, children with continuous GOB status, newly developed GOB, converting from GOB to non-GOB had 5.03-fold (95%CI: 4.32~5.86), 3.35-fold (95%CI: 1.99~5.65), 2.72-fold (2.03~3.63) HBP risk, respectively. Similar findings were observed for abdominal obesity (AOB). Reduction of 0.21-0.88 kg/m2 of baseline BMI (0.86-3.59%) or 0.009-0.024 of baseline WHtR (1.66-4.42%) in GOB or AOB children, respectively, was associated with significant decrease in HBP risk. Children with persistent obesity, newly developed obesity, or converting from obese to non-obese had significantly higher HBP risk. For children with GOB or AOB, reduction of <3.6% in BMI or <4.5% in WHtR could decrease the HBP risk.

BVES downregulation in non-syndromic tetralogy of fallot is associated with ventricular outflow tract stenosis.

BVES is a transmembrane protein, our previous work demonstrated that single nucleotide mutations of BVES in tetralogy of fallot (TOF) patients cause a downregulation of BVES transcription. However, the relationship between BVES and the pathogenesis of TOF has not been determined. Here we reported our research results about the relationship between BVES and the right ventricular outflow tract (RVOT) stenosis. BVES expression was significantly downregulated in most TOF samples compared with controls. The expression of the second heart field (SHF) regulatory network genes, including NKX2.5, GATA4 and HAND2, was also decreased in the TOF samples. In zebrafish, bves knockdown resulted in looping defects and ventricular outflow tract (VOT) stenosis, which was mostly rescued by injecting bves mRNA. bves knockdown in zebrafish also decreased the expression of SHF genes, such as nkx2.5, gata4 and hand2, consistent with the TOF samples` results. The dual-fluorescence reporter system analysis showed that BVES positively regulated the transcriptional activity of GATA4, NKX2.5 and HAND2 promoters. In zebrafish, nkx2.5 mRNA partially rescued VOT stenosis caused by bves knockdown. These results indicate that BVES downregulation may be associated with RVOT stenosis of non-syndromic TOF, and bves is probably involved in the development of VOT in zebrafish.

FKBP51 induces p53-dependent apoptosis and enhances drug sensitivity of human non-small-cell lung cancer cells.

Lung cancer is one of the most prevalent cancer types worldwide, and non-small-cell lung cancer (NSCLC) accounts for ~85% of all lung cancer cases. Despite the notable prevalence of NSCLC, the mechanisms underlying its progression remain unclear. The present study investigated the involvement of FK506-binding protein 51 (FKBP51) in NSCLC development and determined the factors associated with FKBP51 modification for NSCLC treatment. Immunohistochemical analysis was performed to analyze FKBP51 expression in human NSCLC tissue samples. Additionally, flow cytometry was performed to observe the apoptosis of FKBP51-overexpressing A549 cells. A dual-luciferase reporter assay was performed to confirm the association between FKBP51 and p53 expression, and western blotting was performed to analyze the effects of FKBP51 on the p53 signaling pathway. Finally, cell viability was measured using a Cell Counting Kit-8 assay. The results suggested FKBP51 downregulation in human lung cancer. Furthermore, apoptosis rates may be increased in FKBP51-overexpressing A549 cells. Moreover, FKBP51 promoted p53 expression and subsequent p53 signaling pathway activation. These results indicated that FKBP51 promoted A549 cell apoptosis via the p53 signaling pathway. Additionally, FKBP51 enhanced the sensitivity of A549 cells to cisplatin. Collectively, these data suggested that FKBP51 could serve as a biomarker for human lung cancer and can thus be tailored for incorporation into NSCLC therapy in the future.