Predictive value of intravascular ultrasound for the function of intermediate coronary lesions.

BACKGROUND: Intravascular ultrasound (IVUS) can provide detailed coronary anatomic parameters. The purpose of our study was to evaluate the parameters measured by IVUS for the prediction of intermediate coronary lesions function by referencing quantitative fraction ratio (QFR) ≤ 0.80 (vs. > 0.80). METHODS: Eighty four cases with 92 intermediate coronary lesions in vessels with a diameter ≥ 2.50 mm were enrolled. Paired assessment of IVUS and cQFR was available, and vessels with cQFR ≤ 0.8 were considered the positive reference standard. Logistic regression was used to select model variables by a maximum partial likelihood estimation test and receiver operating characteristic curve (ROC) analysis to evaluate the diagnostic value of different indices. RESULTS: Plaque burden (PB) and lesion length (LL) of IVUS were independent risk factors for the function of coronary lesions. The predictive probability P was derived from the combined PB and LL model. The area under the curve (AUC) of PB, (minimum lumen area) MLA, and LL and the predicted probability P are 0.789,0.732,0731, and 0.863, respectively (P < 0.01). The AUC of the predicted probability P was the biggest among them; the prediction accuracy of cQFR ≤ 0.8 was 84.8%, and the sensitivity of the diagnostic model was 0.826, specificity was 0. 725, and P < 0.01. CONCLUSION: PB and LL of IVUS were independent risk factors influencing the function of intermediate coronary lesions. The model combining the PB and LL may predict coronary artery function better than any other single parameter.

Multiscale feature pyramid network based on activity level weight selection for infrared and visible image fusion.

At present, deep-learning-based infrared and visible image fusion methods have the problem of extracting insufficient source image features, causing imbalanced infrared and visible information in fused images. To solve the problem, a multiscale feature pyramid network based on activity level weight selection (MFPN-AWS) with a complete downsampling-upsampling structure is proposed. The network consists of three parts: a downsampling convolutional network, an AWS fusion layer, and an upsampling convolutional network. First, multiscale deep features are extracted by downsampling convolutional networks, obtaining rich information of intermediate layers. Second, AWS highlights the advantages of the l1-norm and global pooling dual fusion strategy to describe the characteristics of target saliency and texture detail, and effectively balances the multiscale infrared and visible features. Finally, multiscale fused features are reconstructed by the upsampling convolutional network to obtain fused images. Compared with nine state-of-the-art methods via the publicly available experimental datasets TNO and VIFB, MFPN-AWS reaches more natural and balanced fusion results, such as better overall clarity and salient targets, and achieves optimal values on two metrics: mutual information and visual fidelity.

Nonlinear response of nitrate to NOx reduction in China during the COVID-19 pandemic.

In recent years, nitrate plays an increasingly important role in haze pollution and strict emission control seems ineffective in reducing nitrate pollution in China. In this study, observations of gaseous and particulate pollutants during the COVID-19 lockdown, as well as numerical modelling were integrated to explore the underlying causes of the nonlinear response of nitrate mitigation to nitric oxides (NOx) reduction. We found that, due to less NOx titration effect and the transition of ozone (O3) formation regime caused by NOx emissions reduction, a significant increase of O3 (by ∼ 69%) was observed during the lockdown period, leading to higher atmospheric oxidizing capacity and facilitating the conversion from NOx to oxidation products like nitric acid (HNO3). It is proven by the fact that 26-61% reduction of NOx emissions only lowered surface HNO3 by 2-3% in Hebi and Nanjing, eastern China. In addition, ammonia concentration in Hebi and Nanjing increased by 10% and 40% during the lockdown, respectively. Model results suggested that the increasing ammonia can promote the gas-particle partition and thus enhance the nitrate formation by up to 20%. The enhanced atmospheric oxidizing capacity together with increasing ammonia availability jointly promotes the nitrate formation, thereby partly offsetting the drop of NOx. This work sheds more lights on the side effects of a sharp NOx reduction and highlights the importance of a coordinated control strategy.

TNFSF15 promoter polymorphisms increase the susceptibility to small cell lung cancer: a case-control study.

BACKGROUND: Tumor necrosis factor superfamily member 15 (TNFSF15) is closely related to tumorigenesis and development. This study aimed to investigate the correlations between TNFSF15 polymorphisms and genetic susceptibility to lung cancer. METHODS: This case-control study included 209 small cell lung cancer patients (SCLC), 340 non- small cell lung cancer patients (NSCLC) and 460 health controls. TNFSF15-638 A > G and - 358 T > C polymorphisms were genotyped by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) analysis. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by unconditional logistic regression. RESULTS: Our results showed that subjects carrying the TNFSF15-638GG genotype or -358CC genotype were more likely to develop SCLC (-638GG, OR = 1.84, 95%CI = 1.13-2.99; -358CC, OR = 2.44, 95%CI = 1.46-4.06), but not NSCLC (P > 0.05). In stratified analysis, -638GG genotype was related to SCLC among males (OR = 1.95, 95%CI = 1.09-3.45, P = 0.023) and older patients (OR = 2.93, 95%CI = 1.44-8.68, P = 0.006). However, -358CC genotype was associated with SCLC among females (OR = 8.42, 95%CI = 2.22-31.89, P = 0.002) and older subjects with OR (95%CI) of 11.04 (3.57-34.15) (P < 0.001). Moreover, TNFSF15 -358CC was linked with a higher risk of SCLC among non-smokers (OR = 2.54, 95%CI = 1.20-5.35, P = 0.015) but not among smokers (OR = 1.88, 95%CI = 0.92-3.84, P = 0.086). CONCLUSION: These findings highlight the importance of TNFSF15 polymorphisms in the development of SCLC.

CSB affected on the sensitivity of lung cancer cells to platinum-based drugs through the global decrease of let-7 and miR-29.

BACKGROUND: Transcription-coupled nucleotide excision repair (TC-NER) plays a prominent role in the removal of DNA adducts induced by platinum-based chemotherapy reagents. Cockayne syndrome protein B (CSB), the master sensor of TCR, is also involved in the platinum resistant. Let-7 and miR-29 binding sites are highly conserved in the proximal 3'UTR of CSB. METHODS: We conducted immunohistochemisty to examine the expression of CSB in NSCLC. To determine whether let-7 family and miR-29 family directly interact with the putative target sites in the 3'UTR of CSB, we used luciferase reporter gene analysis. To detect the sensitivity of non-small cell lung cancer (NSCLC) cells to platinum-based drugs, CCK analysis and apoptosis analysis were performed. RESULTS: We found that let-7 and miR-29 negatively regulate the expression of CSB by directly targeting to the 3'UTR of CSB. The endogenous CSB expression could be suppressed by let-7 and miR-29 in lung cancer cells. The suppression of CSB activity by endogenous let-7 and miR-29 can be robustly reversed by their sponges. Down-regulation of CSB induced apoptosis and increased the sensitivity of NSCLC cells to cisplatin and carboplatin drugs. Let-7 and miR-29 directly effect on cisplatin and carboplatin sensitivity in NSCLC. CONCLUSIONS: In conclusion, the platinum-based drug resistant of lung cancer cells may involve in the regulation of let-7 and miR-29 to CSB.

Abundant NH3 in China Enhances Atmospheric HONO Production by Promoting the Heterogeneous Reaction of SO2 with NO2.

High levels of HONO have frequently been observed in Chinese haze periods and underestimated by current models due to some unknown sources and formation mechanisms. Combining lab-chamber simulations and field measurements in Xi'an and Beijing, China, we found that NH3 can significantly promote HONO formation via the reduction-oxidation of SO2 with NO2 in the aqueous phase of hygroscopic particles (e.g., NaCl). Concentrations of HONO formed in the aerosol phase showed an exponential increase (R2 = 0.91) with NH3 levels under the chamber conditions and a linear growth with NH3 levels in the two Chinese cities. The uptake coefficient of NO2 on NaCl particles ranged from 2.0 × 10-5 to 1.7 × 10-4, 3-4 orders of magnitude larger than that on water droplets. Our results further showed that HONO formed from the aerosol phase accounted for 4-33% of the total in the chamber, indicating that aerosol-phase formation is an important source of HONO in China, especially in haze periods. Since NH3, SO2, and NO2 abundantly coexist in China, the positive effect of NH3 on HONO formation could enhance the atmospheric oxidizing capacity in the country, causing severe secondary aerosol pollution. Our work suggests that NH3 emission control is imperative for mitigating air pollution in China.

Review of Current Strategies for Delivering Alzheimer's Disease Drugs across the Blood-Brain Barrier.

Effective therapy for Alzheimer's disease is a major challenge in the pharmaceutical sciences. There are six FDA approved drugs (e.g., donepezil, memantine) that show some effectiveness; however, they only relieve symptoms. Two factors hamper research. First, the cause of Alzheimer's disease is not fully understood. Second, the blood-brain barrier restricts drug efficacy. This review summarized current knowledge relevant to both of these factors. First, we reviewed the pathophysiology of Alzheimer's disease. Next, we reviewed the structural and biological properties of the blood-brain barrier. We then described the most promising drug delivery systems that have been developed in recent years; these include polymeric nanoparticles, liposomes, metallic nanoparticles and cyclodextrins. Overall, we aim to provide ideas and clues to design effective drug delivery systems for penetrating the blood-brain barrier to treat Alzheimer's disease.

Chemical characteristics of haze particles in Xi'an during Chinese Spring Festival: Impact of fireworks burning.

Fireworks burning releases massive fine particles and gaseous pollutants, significantly deteriorating air quality during Chinese Lunar New Year (LNY) period. To investigate the impact of the fireworks burning on the atmospheric aerosol chemistry, 1-hr time resolution of PM2.5 samples in Xi'an during the winter of 2016 including the LNY were collected and detected for inorganic ions, acidity and liquid water content (LWC) of the fine aerosols. PM2.5 during the LNY was 167±87µg/m3, two times higher than the China National Ambient Air Quality Standard (75µg/m3). K+ (28wt.% of the total ion mass) was the most abundant ion in the LNY period, followed by SO42- (25wt.%) and Cl- (18wt.%). In contrast, NO3- (34wt.%) was the most abundant species in the haze periods (hourly PM2.5>75µg/m3), followed by SO42- (29.2wt.%) and NH4+ (16.3wt.%), while SO42 - (35wt.%) was the most abundant species in the clean periods (hourly PM2.5<75µg/m3), followed by NO3- (23.1wt.%) and NH4+ (11wt.%). Being different from the acidic nature in the non-LNY periods, aerosol in the LNY period presented an alkaline nature with a pH value of 7.8±1.3. LWC during the LNY period showed a robust linear correlation with K2SO4 and KCl, suggesting that aerosol hygroscopicity was dominated by inorganic salts derived from fireworks burning. Analysis of correlations between the ratios of NO3-/SO42- and NH4+/SO42- indicated that heterogeneous reaction of HNO3 with NH3 was an important formation pathway of particulate nitrate and ammonium during the LNY period.

Mitochondrial genome complexity in Stemona sessilifolia: nanopore sequencing reveals chloroplast gene transfer and DNA rearrangements.

Mitochondria are semi-autonomous organelles in eukaryotic cells with their own genome. Plant mitogenomes differ from animal mitogenomes in size, structure, and repetitive DNA sequences. Despite larger sizes, plant mitogenomes do not have significantly more genes. They exhibit diverse structures due to variations in size, repetitive DNA, recombination frequencies, low gene densities, and reduced nucleotide substitution rates. In this study, we analyzed the mitochondrial genome of Stemona sessilifolia using Nanopore and Illumina sequencing. De-novo assembly and annotation were conducted using Unicycler, Geseq, tRNAscan-SE and BLASTN, followed by codon usage, repeat sequence, RNA-editing, synteny, and phylogenetic analyses. S. sessilifolia's mitogenome consisted of one linear contig and six circular contigs totaling 724,751 bp. It had 39 protein-coding genes, 27 tRNA genes, and 3 rRNA genes. Transfer of chloroplast sequences accounted for 13.14% of the mitogenome. Various analyses provided insights into genetic characteristics, evolutionary dynamics, and phylogenetic placement. Further investigations can explore transferred genes' functions and RNA-editing's role in mitochondrial gene expression in S. sessilifolia.

Serum Vitamin D3 Concentration, Sleep, and Cognitive Impairment among Older Adults in China.

BACKGROUND: Cognitive decline in older adults has become one of the critical challenges to global health. This study aims to examine both cross-sectional and longitudinal associations of levels of serum 25-hydroxyvitamin D3 (25(OH)D3) (briefed as VD3) concentration and sleep quality/duration, especially their interactions, with risk of cognitive impairment among older adults in China. METHODS: We utilized a special subsample of adults aged 65-105 years (individuals = 3412, observations = 4816) from eight provinces in China derived from the 2011/2012 and 2014 waves of the Chinese Longitudinal Healthy Longevity Survey. Cognitive impairment was measured by the Mini-Mental State Examination scale. Sleep quality was classified as good versus fair/poor, and sleep duration was classified into short (<7 h), normal (≥7 but <9 h), and long (≥9 h). The VD3 concentration was divided into three levels: deficiency (VD3 < 25 nmol/L), insufficiency (25 nmol/L ≤ VD3 < 50 nmol/L), and sufficiency (VD3 ≥ 50 nmol/L). A wide set of covariates that include demographics, socioeconomic status, family support, health practice, and health conditions was adjusted for robust findings. Multilevel random intercept logit regression models were used to examine the cross-sectional associations between VD3, sleep, and cognitive impairment, whereas logit regression models were applied to investigate the longitudinal associations. RESULTS: In the cross-sectional analyses, when all covariates were adjusted, VD3 sufficiency was significantly associated with a 33% lower risk of cognitive impairment compared with VD3 deficiency; good sleep quality was associated with 34% lower odds of cognitive impairment compared with fair/poor sleep quality; sleep hours were not associated with cognitive impairment, although a long sleep duration (≥9 h) was associated with 30% higher odds of being cognitively impaired when baseline health was not controlled. Interaction analyses reveal that VD3 sufficiency could help to additionally reduce the risk of cognitive impairment for good sleep quality and normal sleep hours. In the longitudinal analyses, the association of VD3 sufficiency remains significant, whereas sleep quality and sleep duration were not significant associates. CONCLUSIONS: Good sleep quality, normal sleep hours, and VD3 sufficiency are positively associated with good cognitive function. VD3 sufficiency could enhance the associations between sleep and cognitive impairment.

LINC01936 inhibits the proliferation and metastasis of lung squamous cell carcinoma probably by EMT signaling and immune infiltration.

Purpose: To discover the biological function and potential mechanism of LINC01936 in the development of lung squamous cell carcinoma (LUSC). Methods: Transcriptome data of LUSC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to analyze the differentially expressed lncRNAs in LUSC and normal tissues by R "DEseq2", "edgeR" and "limma" packages. The subcellular localization of LINC01936 was predicted by lncLocator. Cell proliferation and apoptosis were measured by CCK-8, MTT assay and Hoechst fluorescence staining. The migration and invasion were detected by Transwell assay. The function and pathway enrichment analysis were performed by Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and gene set variation analysis (GSVA). The downstream targets of LINC01936 were predicted using RNA-Protein Interaction Prediction (RPISeq) program. The effect of LINC01936 on tumor immune infiltration was analyzed using Pearson Correlation Analysis using R "ggpubr" package. Results: Based on the gene expression data of LUSC from TCGA database, 1,603, 1,702 and 529 upregulated and 536, 436 and 630 downregulated lncRNAs were obtained by DEseq2, edgeR and limma programs, respectively. For GSE88862 dataset, we acquired 341 differentially expressed lncRNAs (206 upregulated and 135 downregulated). Venn plot for the intersection of above differential expressed lncRNAs showed that there were 29 upregulated and 23 downregulated genes. LINC01936 was one of downregulated lncRNAs in LUSC tissues. The biological analysis showed that the overexpression of LINC01936 significantly reduced proliferation, migration and invasion of LUSC cells, and promoted cell apoptosis. The knockdown of LINC01936 promoted cell proliferation and metastasis. Pathway and GSVA analysis indicated that LINC01936 might participated in DNA repair, complement, cell adhesion and EMT, etc. LINC01936 was predicted to interact with TCF21, AOC3, RASL12, MEOX2 or HSPB7, which are involved in EMT and PI3K-AKT-MTOR pathway, etc. The expression of LINC01936 was also positively correlated with the infiltrating immune cells in LUSC. Conclusions: LINC01936 is downregulated in LUSC. LINC01936 affected proliferation, migration and invasion of LUSC cells probably by EMT and immune infiltration, which might serve as a new target for the treatment of LUSC.

TLR4 regulatory region variants reduce the susceptibility of small-cell lung cancer in Chinese population.

OBJECTIVES: Toll-like receptors (TLRs) participate in the induction and regulation of immune responses and are closely related to the occurrence and development of small-cell lung cancer (SCLC). This study aimed to investigate the impact of polymorphisms in the regulatory regions of TLRs on the susceptibility of SCLC. METHODS: The case-control study included 304 SCLC patients and 304 healthy controls. TLRs gene polymorphisms were genotyped by PCR-restrictive fragment length polymorphism analysis and TaqMan assay. Unconditional logistic regression was used to estimate odds ratio (OR) and its 95% confidence interval (95% CI). RESULTS: Our results showed that TLR4 rs1927914 GG genotype and TLR4 rs7869402 TT genotype reduced the risk of SCLC with OR (95% CI) of 0.54 (0.32-0.90) and 0.47 (0.28-0.80), respectively. Stratified analysis suggested that TLR4 rs1927914 GG genotypes significantly reduced the risk of SCLC among male (OR = 0.35; 95% CI, 0.18-0.69; P < 0.01), the younger patients (OR = 0.49; 95% CI, 0.26-0.94; P = 0.03) and non-drinkers (OR = 0.47; 95% CI, 0.24-0.89; P = 0.02). TLR4 rs7869402 CT or TT genotype significantly reduced the susceptibility to SCLC among male patients (OR = 0.37; 95% CI, 0.19-0.71, P < 0.01), the younger patients (OR = 0.41; 95% CI, 0.22-0.79; P < 0.01), smokers (OR = 0.25; 95% CI, 0.10-0.60; P < 0.01) and drinkers (OR = 0.31; 95% CI, 0.11-0.88; P = 0.03). TLR3 rs5743303, TLR4 rs11536891, TLR5 rs1640816 and TLR7 rs3853839 had no significant correlation with the risk of SCLC. CONCLUSIONS: These findings emphasized the important role of TLR4 in the development of SCLC.

Functional genetic variants in complement component 7 confer susceptibility to gastric cancer.

BACKGROUND: Complement system plays an important role in innate immunity which involved in the changes tumor immune microenvironment by mediating the inflammatory response. This study aims to explore the relationship between complement component 7 (C7) polymorphisms and the risk of gastric cancer (GC). MATERIALS AND METHODS: All selected SNPs of C7 were genotyped in 471 patients and 471 controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional Logistic regression to analyze the relationship between each genotype and the genetic susceptibility to gastric cancer. The level of C7 expression in GC was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) and detected by Enzyme Linked Immunosorbent Assay. Kaplan-Meier plotter were used to reveal C7 of prognostic value in GC. We examined SNPs associated with the expression of C7 using the GTEx database. The effect of C7 polymorphisms on the regulatory activity of C7 was detected by luciferase reporter assay. RESULTS: Unconditional logistic regression showed that individuals with C7 rs1376178 AA or CA genotype had a higher risk of GC with OR (95% CI) of 2.09 (1.43-3.03) and 1.88 (1.35-2.63), respectively. For C7 rs1061429 C > A polymorphism, AA genotype was associated with the elevated risk for developing gastric cancer (OR = 2.16, 95% CI [1.37-3.38]). In stratified analysis, C7 rs1376178 AA genotype increased the risk of GC among males (OR = 2.88, 95% CI [1.81-4.58]), but not among females (OR = 1.06, 95% CI [0.55-2.06]). Individuals carrying rs1061429 AA significantly increased the risk of gastric cancer among youngers (OR = 2.84, 95% CI [1.39-5.80]) and non-smokers (OR = 2.79, 95% CI [1.63-4.77]). C7 was overexpressed in gastric cancer tissues and serum of cancer patients and was significantly associated with the prognosis. C7 rs1061429 C > A variant contributed to reduced protein level of C7 (P = 0.029), but rs1376178 didn't. Luciferase reporter assay showed that rs1376178C-containing plasmid exhibited 2.86-fold higher luciferase activity than rs1376178 A-containing plasmid (P < 0.001). We also found that rs1061429A allele contributed 1.34-fold increased luciferase activity than rs1061429C allele when co-transfected with miR-591 (P = 0.0012). CONCLUSIONS: These findings highlight the role of C7 in the development of gastric cancer.

Identification of Hub Genes of Lung Adenocarcinoma Based on Weighted Gene Co-Expression Network in Chinese Population.

Purpose: Lung adenocarcinoma is one of the most common malignancies. Though some historic breakthroughs have been made in lung adenocarcinoma, its molecular mechanisms of development remain elusive. The aim of this study was to identify the potential genes associated with the lung adenocarcinoma progression and to provide new ideas for the prognosis evaluation of lung adenocarcinoma. Methods: The transcriptional profiles of ten pairs of snap-frozen tumor and adjacent normal lung tissues were obtained by performing RNA-seq. Weighted gene co-expression network analysis (WGCNA) was used to construct free-scale gene co-expression networks in order to explore the associations of gene sets with the clinical features and to investigate the functional enrichment analysis of co-expression genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Gene Set Enrichment Analysis (GSEA) analyses were performed using clusterProfiler. The protein-protein network (PPI) was established using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and hub genes were identified using Cytohubba in Cytoscape. Transcription factor enrichment analysis was performed by the RcisTarget program in R language. Results: Based on RNA-seq data, 1,545 differentially expressed genes (DEGs) were found. Eight co-expression modules were identified among these DEGs. The blue module exhibited a strong correlation with LUAD, in which ADCY4, RXFP1, AVPR2, CALCRL, ADRB1, RAMP3, RAMP2 and VIPR1 were hub genes. A low expression level of RXFP1, AVPR2, ADRB1 and VIPR1 was detrimental to the survival of LUAD patients. Genes in the blue module enriched in 86 Gene Ontology terms and five KEGG pathways. We also found that transcription factors EGR3 and EXOSC3 were related to the biological function of the blue module. Overall, this study brings a new perspective to the understanding of LUAD and provides possible molecular biomarkers for prognosis evaluation of LUAD.

Review of Current Strategies for Delivering Alzheimer's Disease Drugs Across the Blood-Brain Barrier.

(Appeared originally in the International Journal of Molecular Sciences 2019; 20:381) Reprinted under Creative Commons CC-BY license.

Geographical patterns of Fejervarya limnocharis gut microbiota by latitude along mainland China's coastline.

The gut microbiota affects many aspects of host biology and plays key roles in the coevolutionary association with its host. Geographical gradients may play a certain role on gut microbiota variation in the natural environment. However, the distribution pattern of amphibian gut microbiota in the latitudinal gradient remains largely unexplored. Here, we sampled six natural populations of Fejervarya limnocharis along the eastern coastline of mainland China (spanning 20°-30° N = 1,300 km) using 16S rRNA amplicon sequencing to characterize the gut microbiota. First of all, a significant correlation between gut microbial diversity and latitude was observed in our research system. Second, we discovered that latitude influenced the composition of the gut microbiota of F. limnocharis. Finally, we detected that geographical distance could not determine gut microbiota composition in F. limnocharis. These results indicate that latitude can play an important role in shaping the gut microbial diversity of amphibian. Our study offers the first evidence that gut microbial diversity of amphibian presents a latitudinal pattern and highlights the need for increased numbers of individuals to be sampled during microbiome studies in wild populations along environmental gradients.

Protective effect of Glechoma hederacea extract against gallstone formation in rodent models.

BACKGROUND: Our current study aimed to evaluate the effect of an Glechoma hederacea extract (Hitrechol®) in normal rats and gallstone diseased mice to explore its underlying mechanisms. Normal rats and C57BL/6 mice with/without cholesterol gallstone were used in this study. METHODS: To monitor the effect of Hitrechol® on bile secretion, bile flow rates at 15 min interval until 2 h post-dosing in normal rats treated with vehicle and Hitrechol® were compared using multiple t-test with a p < 0.05 considered as statistically significant different. To further evaluate the effect of Hitrechol® against the development of gallstone in lithogenic diet treated mice, mice were treated with vehicle or Hitrechol® (QD-once daily or TID-three times daily) for 3 weeks followed by comparing the levels of bile composition among the treatment groups. In addition, the anti-oxidative biomarkers in liver and anti-inflammatory biomarkers in serum were detected and compared among all the treatment groups to evaluate the hepato-protective effect of Hitrechol®. The obtained levels of biomarkers and bile composition were compared among different treatment groups using one-way ANOVA tests followed by Tukey's multiple comparisons with p < 0.05 considered as statistically significant. RESULTS: Despite no significant impact on the bile flow rate, Hitrechol® TID treatment dramatically decreased size and amount of gallstone crystals and total cholesterol level (p < 0.05), as well as total bile acid (p < 0.05) and several types of bile acid (p < 0.05) levels in gallstone disease model mice. Hitrechol® TID treatment could significantly decrease the frequencies of hepatocyte necrosis and lipid aggregation notably as well as increase the antioxidant enzyme level (p < 0.05) in the liver. CONCLUSIONS: Our findings for the first time demonstrated the beneficial effect of Hitrechol® against gallstone via its litholytic, liver-protective and antioxidant activities.

TLR4 promoter rs1927914 variant contributes to the susceptibility of esophageal squamous cell carcinoma in the Chinese population.

BACKGROUND: Toll-like receptor 4 (TLR4), as a key regulator of both innate and acquired immunity, has been linked with the development of various cancers, including esophageal cancer. This study aims to analyze the association of potential functional genetic polymorphisms in TLR4 with the risk of esophageal cancer. METHODS: This case-control study involved in 480 ESCC patients and 480 health controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to genotype TLR4 rs1927914 polymorphism. Taqman probe method was used to determine the genotypes of TLR4 rs11536891 and rs7873784 variants. The relationship between TLR4 genetic variation and ESCC risk was analyzed by Logistic regression model by calculating the odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: Compared with TLR4 rs1927914 AA genotype carriers, GG carriers had a lower ESCC risk (OR = 0.59, 95% CI [0.38-0.93], P = 0.023). Stratification analysis by age showed that TLR4 rs1927914 GG could affect the risk of ESCC in elderly people (OR = 0.59, 95% CI [0.36-0.97]). Smoking stratification analysis indicated that rs1927914 GG carriers were related to ESCC susceptibility among non-smokers (OR = 0.36, 95% CI [0.18-0.73]). Dual luciferase reporter assay suggested that rs1927914 G-containing TLR4 promoter displayed a 1.76-fold higher luciferase activity than rs1927914 A-containing counterpart in KYSE30 cells. Electrophoretic mobility shift assay (EMSA) showed the KYSE30 cell nuclear extract was able to bind the probe with rs1927914 G allele and this DNA-protein interaction could be eliminated by competition assays with unlabeled rs1927914 G probe, which indicating that the binding is sequence-specific. Our results also showed that TLR4 rs7873784 (G>C) and rs11536891 (T>C) conformed to complete genetic linkage. The genotype distributions of TLR4 rs11536891 variant among ESCC patients and normal controls have no statistical significance. CONCLUSION: The TLR4 rs1927914 variant contributes to the ESCC risk by effecting the promoter activity.

XAB2 TagSNP Is Associated with the Risk of Gastric Cancer in Chinese Population: A Case-Control Study.

XAB2 protein (xeroderma pigmentosum group A-binding protein 2) plays a significant role in the nucleotide excision repair pathway. Polymorphisms in the XAB2 gene may have an effect on the capability of DNA repair and further contribute to the risk of developing various cancers. In order to investigate the relationship between XAB2 genetic variants and the risk of gastric cancer, we performed a hospital-based case-control study. XAB2 tagSNPs were selected and then genotyped by iPlex Gold Genotyping Assay and Sequenom MassArray. By performing logistic regression analysis, odds ratio (OR) and 95% confidence interval (CI) were used to estimate the association of XAB2 tagSNPs with the risk of gastric cancer. Our results showed that XAB2 rs794078AA genotype was associated with a significantly lower risk of gastric cancer compared with GG genotype with OR (95% CI) of 0.33 (0.12-0.91). Stratified analysis indicated a significantly decreased risk for gastric cancer among smokers with rs794078AA genotype compared with nonsmokers with GG genotype (OR = 0.11, 95% CI = 0.01-0.91, p = 0.040). The gene-gene interactions by multifactor dimensionality reduction (MDR) showed that tagSNP rs794078 was the best predictive element for gastric cancers (Testing Bal. Acc = 51.68%, p = 0.055, cross-validation consistency = 9). Therefore, the XAB2 tagSNP rs794078 may play an important role in the development of gastric cancer.