Lower HBV DNA level is associated with more severe liver fibrosis in HBeAg-positive chronic hepatitis B with normal alanine transaminase.

BACKGROUND: The association of hepatitis B virus (HBV) DNA levels and liver fibrosis in chronic hepatitis B (CHB) patients with immune-tolerant phase remains unclear. We explored the association between liver fibrosis and HBV DNA levels in HBeAg-positive CHB patients with normal alanine transaminase (ALT) with relatively high HBV DNA. METHODS: Six hundred and twenty-two HBeAg-positive CHB patients with normal ALT were included. Patients were divided into three categories: low (6 log10 IU/mL ≤ HBV DNA < 7 log10 IU/mL), moderate (7 log10 IU/mL ≤ HBV DNA < 8 log10 IU/mL), and high (HBV DNA ≥ 8 log10 IU/mL). APRI, FIB-4, transient elastography, or liver biopsy were used to assess liver fibrosis. RESULTS: The median age of patients was 33.0 years and 57.9% patients were male. 18.8%, 52.1%, and 29.1% of patients had low, moderate, and high HBV DNA levels, respectively. The APRI (0.33 vs. 0.26 vs. 0.26, P < 0.001), FIB-4 (1.03 vs. 0.71 vs. 0.68, P < 0.001), and LSM values (7.6 kPa vs. 5.6 kPa vs. 5.5 kPa, P = 0.086) were higher in low HBV DNA group than other two groups. Low HBV DNA group had higher proportions of significant fibrosis (24.8% vs. 9.9% vs. 3.3%, P < 0.001) and cirrhosis (7.7% vs. 2.5% vs. 1.1%, P = 0.004) than moderate and high HBV DNA groups. Moderate (OR 3.095, P = 0.023) and low (OR 4.968, P = 0.003) HBV DNA were independent risk factors of significant fibrosis. CONCLUSION: Lower HBV DNA level was associated with more severe liver fibrosis in HBeAg-positive CHB patients with ALT.

A review of spatial distribution of typical antibiotic resistance genes in marine environment surrounding China.

Antibiotic resistance genes (ARGs) have been steadily increasing due to the extensive overuse of antibiotics in the marine environment. Currently, the research considering ARGs distribution in marine ecosystems gains more interest. As the coastal sea has been regarded as one of the most polluted areas by antibiotic contaminants in China. However, no comprehensive review of the spatial distribution of ARGs in marine environment surrounding China. The main objective of this review is to investigate the level, characteristic, and spatial distribution of ARGs in the marine environment (seawater and sediments) surrounding China. Key sea areas, such as Bohai Sea, Yellow Sea, East China Sea, and South China Sea were selected in this review. The marine environment was the reservoir of ARGs, and ARGs in seawater were generally 1 to 2 orders of magnitude higher than that in sediments. Total ARGs were more abundant in the Yellow Sea, followed by the Bohai Sea, the East China Sea, and the South China Sea. This study raises questions regarding the spread and distribution for antibiotic resistance in marine environments.

Clinical outcomes of treatment-naïve HBeAg-negative patients with chronic hepatitis B virus infection with low serum HBsAg and undetectable HBV DNA.

Serum hepatitis B surface antigen (HBsAg) level < 100 IU/ml and undetectable hepatitis B virus (HBV) DNA have been recently proposed as an alternate endpoint of "partial cure" in chronic hepatitis B (CHB). We investigated clinical outcomes of hepatitis B e antigen (HBeAg)-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA. Treatment-naïve HBeAg-negative CHB patients with undetectable HBV DNA and normal alanine aminotransferase were retrospectively included from three institutions. Patients were classified into the low HBsAg group (<100 IU/ml) and the high HBsAg group (≥100 IU/ml). Liver fibrosis was evaluated by noninvasive tests (NITs). A total of 1218 patients were included and the median age was 41.5 years. Patients with low HBsAg were older (45.0 vs. 40.0 years, P < 0.001) than those in the high HBsAg group, while the NIT parameters were comparable between groups. During a median follow-up of 25.7 months, patients with low HBsAg achieved a higher HBsAg clearance rate (13.0% vs. 0%, P < 0.001) and a lower rate of significant fibrosis development (2.2% vs. 7.0%, P = 0.049) compared to patients with high HBsAg. No patient developed HCC in either group. HBsAg level was negatively associated with HBsAg clearance (HR 0.213, P < 0.001) and patients with HBsAg < 100 IU/ml had a low risk of significant fibrosis development (HR 0.010, P = 0.002). The optimal cutoff value of HBsAg for predicting HBsAg clearance was 1.1 Log10 IU/ml. Treatment-naïve HBeAg-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA had favourable outcomes with a high rate of HBsAg clearance and a low risk of fibrosis progression.

A novel nomogram for predicting HBeAg seroclearance in HBeAg-positive chronic hepatitis B patients treated with nucleos(t)ide analogues.

INTRODUCTION AND OBJECTIVES: Seroclearance of hepatitis B e antigen (HBeAg) is an important treatment goal for patients with chronic hepatitis B (CHB). This study developed a nomogram for predicting HBeAg seroclearance in CHB patients treated with nucleos(t)ide analogues (NAs). PATIENTS AND METHODS: Five hundred and sixty-nine CHB patients treated with NAs from two institutions between July 2016 to November 2021 were retrospectively included. One institution served as the training set (n = 374) and the other as the external validation set (n = 195). A predictive nomogram was established based on cox regression analysis. RESULTS: The overall HBeAg seroclearance rates were 27.3 and 21.5 % after the median follow-up of 100.2 weeks and 65.1 weeks in the training set and validation set, respectively. In the training set, baseline aspartate aminotransferase, gamma-glutamyl transpeptidase, HBeAg, and hepatitis B core antibody levels were independently associated with HBeAg seroclearance and were used to establish the HBEAg SeroClearance (ESC)-nomogram. The calibration curve revealed that the ESC-nomogram had a good agreement with actual observation. The ESC-nomogram showed relatively high accuracy for predicting 48 weeks, 96 weeks, and 144 weeks of HBeAg seroclearance in the training set (AUCs: 0.782, 0.734 and 0.671) and validation set (AUCs: 0.699, 0.718 and 0.689). The patients with high ESC-nomogram scores (≥ 79.51) had significantly higher cumulative incidence of HBeAg seroclearance and seroconversion than patients with low scores (< 79.51) in both sets (P < 0.01). CONCLUSIONS: The novel ESC-nomogram showed good performance for predicting antiviral efficacy in HBeAg-positive CHB patients with NAs treatment.

Development and Validation of a Nomogram to Predict Significant Liver Inflammation in Patients with Chronic Hepatitis B.

Background: Noninvasive diagnosis of liver inflammation is important for patients with chronic hepatitis B (CHB). This study aimed to develop a nomogram to predict significant liver inflammation for CHB patients. Methods: CHB patients who underwent liver biopsy were retrospectively collected and randomly divided into a development set and a validation set. The least absolute shrinkage and selection operator regression and logistic regression analysis were used to select independent predictors of significant liver inflammation, and a nomogram was developed. The performance of nomogram was assessed by receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA). Results: A total of 1019 CHB patients with a median age of 39.0 years were included. Alanine aminotransaminase (ALT, P = 0.018), gamma-glutamyl transpeptidase (P = 0.013), prothrombin time (P < 0.001), and HBV DNA level (P = 0.030) were identified as independent predictors of significant liver inflammation in the development set. A model namely AGPD-nomogram was developed based on the above parameters. The area under the ROC curve in predicting significant inflammation was 0.765 (95% CI: 0.727-0.803) and 0.766 (95% CI: 0.711-0.821) in the development and validation sets, which were significantly higher than other indexes. The AGPD-nomogram had a high predictive value in patients with normal ALT. Moreover, the nomogram was proven to be clinically useful by DCA. Conclusion: A visualized AGPD-nomogram which incorporated routine clinical parameters was proposed to facilitate the prediction of significant liver inflammation in CHB patients. This nomogram had high accuracy in the identification of significant liver inflammation and would be a useful tool for the better management of CHB patients, especially for those with normal ALT.

Effect of antibiotics, antibiotic-resistant bacteria, and extracellular antibiotic resistance genes on the fate of ARGs in marine sediments.

Surface runoff is a prevalent source via which emerging pollutants (i.e., antibiotics, antibiotic-resistant bacteria (ARB), and antibiotic resistance genes (ARGs)) enter marine sediments. However, few studies have investigated the effect of emerging pollutants on the fate of ARGs in marine sediments. Therefore, three systems were established to measure the relative abundances of four common ARGs (i.e., blaTEM, tetA, tetC, and aphA) and the integron-integrase gene (intI1) after exposure to emerging pollutants in marine sediments from the Bohai Sea, the Yellow Sea, the East China Sea, and the South China Sea in China. The results revealed that antibiotic exposure could decrease the relative abundance of most ARGs (including blaTEM, tetA, and tetC) in these marine sediment samples. The exceptions were the relative abundance of blaTEM in the Bohai Sea marine sediments under ampicillin exposure and tetC in the Yellow Sea marine sediments under tetracycline exposure, which increased significantly. Among marine sediments challenged with ARB, the relative abundance of aphA in all four marine sediments displayed a decreasing trend, whereas the abundances of blaTEM and tetA in the marine sediments from the Bohai Sea and the South China Sea showed an increasing trend. The relative abundance of tetA in the marine sediments from the Yellow Sea and the East China Sea dropped markedly when exposed to extracellular ARG (eARG). Significant changes in blaTEM abundance were observed in the four marine sediments under eARG exposure. Gene aphA abundance showed the same trend as the intI1 abundance. IntI1 showed a decreasing trend under the exposure of antibiotic, ARB, or eARG, apart from the East and the South China Sea marine sediments under ampicillin conditions and the South China Sea marine sediments under RP4 plasmid condition. These findings suggest that dosing with emerging pollutants does not increase ARG abundance in marine sediments.

Tea polyphenols and catechins postpone evolution of antibiotic resistance genes and alter microbial community under stress of tetracycline.

Relying on the high mobility of water flow, the dissemination of antibiotic resistance genes (ARGs) in the water tends to be exacerbated and enlarged. It caused negative impacts on a wider scope of the environment. The ARGs dissemination monitoring and the methods efficiently reducing their concentration in water became the focus of interest. Green chemicals with antibacterial effects such as tea polyphenols (TPs) and catechins (CA) have been considered as auxiliary disinfectants for ARGs removal in the water environment. However, the antibacterial performance of TPs and CA under the stress of external antibiotics still lacks sufficient research. The results show that more operational taxonomic units can be observed in water samples with TPs and CA than in those without the ingredients under pressure of tetracycline. An unexpected increase along with the increase of ARGs concentrations and the diversity of microbial communities under the low-concentration TPs or CA (1 mg/L). Besides, under the stress of tetracycline, the inhibition of TPs was detected to be strengthened for increase of inti1 and tetC but weakened towards for the increase of tetA. Whilst CA substantially diminished abundances of tetC and tetA under tetracycline pressure. This research demonstrated that TPs and CA are able to assuage development of ARGs under the pressure of antibiotic in water system.

Diagnostic accuracy of apparent diffusion coefficient values combined with γ-glutamyl transpeptidase-to-platelet ratio parameters for predicting hepatitis B-related fibrosis.

OBJECTIVES: The accuracy of non-invasive liver fibrosis diagnosis based on the apparent diffusion coefficient (ADC) value combined with the γ-glutamyl transpeptidase-to-platelet ratio (GPR) model to predict the stage of hepatitis B-related fibrosis has not been reported. This study aimed to evaluate the diagnostic efficacy of ADC value combined with GPR for liver fibrosis grading. METHODS: The data of 180 patients with chronic hepatitis B (CHB) diagnosed by liver biopsy were analyzed. The ADC value, GPR, and their combination were assessed in different cirrhosis stages using receiver operating characteristic curve analysis to evaluate their value in diagnosing liver fibrosis. RESULTS: We observed that liver fibrosis stages were inversely associated with ADC values (r=-0.691, P<0.001), and positively associated with GPR (r=0.502, P<0.001). The area under the curve for diagnostic efficacy of ADC values, GPR, and their combination for F≥2 liver fibrosis was 0.831, 0.749, and 0.858, respectively, and for F≥3 was 0.872, 0.771, and 0.903, respectively. The diagnostic cutoffs of the combination for each stage were -7.07, -12.21 and -37.75, respectively. CONCLUSIONS: The combined diagnostic tool of ADC and GPR may improve the accuracy of hepatitis B-related liver fibrosis diagnosis, especially for F≥3.

The association of clinical features and laboratory findings of COVID-19 infection with computed pneumonia volume.

ABSTRACT: Coronavirus disease 2019 (COVID-19) was first detected in China in December 2019, and declared as a pandemic by the World Health Organization (WHO) on March 11, 2020.To study the clinical features of patients with COVID-19, we analyzed the correlation between some inflammation-related indicators in patients' serum and the severity of the disease, especially PV (pneumonia volume under CT scan) and pneumonia volume ratio (PVR).Sixty-six COVID-19 patients in Huai'an, China were selected as the research subjects. We collected the clinical data, including general characteristics, clinical symptoms, serum test results and CT performance, explored the relationship between inflammation-related indexes, oxygenation index, PV, PVR, while indicators of mild to moderate patients and severe patients were compared.The most prominent manifestations of COVID-19 patients were fever (47, 71.2%); cough (41, 62.1%), with or without respiratory and other systemic symptoms; There was no difference in gender (P = .567) and age (P = .865) between mild to moderate and severe groups. High sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), and interleukin-6 (IL-6) of overall patients were higher than the normal range (P < .001, respectively). hs-CRP was negatively correlated with oxygenation index (OI) (r = -0.55), whereas positively correlated with PV, PVR and ESR (r = 0.89; r = 0.87; r = 0.47, respectively); ESR was negatively correlated with OI (r = -0.45), meanwhile it was positively correlated with PV and PVR (r = 0.44; r = 0.46, respectively). OI was negatively correlated with PV and PVR (r = -0.6, respectively). PV had a clear correlation with PVR (r = 1). Severe patients' hs-CRP, PV, PVR were higher than mild to moderate group (P = .006; P = .001; P < .001, respectively), but OI was lower (P < .001).The clinical features of COVID-19 were similar to general viral pneumonia. hs-CRP, ESR showed a certain correlation with the PV and PVR, which might play a certain role in assessing the severity of COVID-19.

Microplastics can selectively enrich intracellular and extracellular antibiotic resistant genes and shape different microbial communities in aquatic systems.

Microplastics (MPs), as emerging contaminants, are posing potential risks to environment, and animal and human health. The ubiquitous presence of MPs in natural ecosystems provides favorable platform to selectively adsorb antibiotic resistant genes (ARGs) and bacteria (ARB) and bacterial assemblages, especially in wastewater which is hotspot for MPs, ARGs and ARB. In this study, the selective capture of intracellular ARGs (iARGs), extracellular ARGs (eARGs), and bacterial assemblages by MPs with different materials (i.e. polyethylene, polyvinylchloride, and polyethylene terephthalate) and sizes (200 µm and 100 µm) was investigated. The results showed that iARGs (i.e. i-TetA, i-TetC, i-TetO, i-sul1), integron-integrase gene (intI1), and eARGs (i.e. e-TetA and e-blaTEM) were selectively enriched on MPs. Relative abundances of i-sul1, i-TetA, and intI1 were generally higher than that of i-TetC and i-TetO on all MPs. Moreover, MPs also have strong effects on the formation of microflora in wastewater, which resulted in different bacterial communities and functions in the wastewater and on the MPs. These findings suggested that MPs could affect the selective enrichment of ARB and ARGs in water environment.

Expression of plasma IFN signaling-related miRNAs during acute SARS-CoV-2 infection and its association with RBD-IgG antibody response.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a huge challenge worldwide. Although previous studies have suggested that type I interferon (IFN-I) could inhibit the virus replication, the expression characteristics of IFN-I signaling-related miRNAs (ISR-miRNAs) during acute severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and its relationship with receptor-binding domain (RBD) IgG antibody response at the recovery phase remain unclear. METHODS: Expression profiles of 12 plasma ISR-miRNAs in COVID-19 patients and healthy controls were analyzed using RT-qPCR. The level of RBD-IgG antibody was determined using the competitive ELISA. Spearman correlation was done to measure the associations of plasma ISR-miRNAs with clinical characteristics during acute SARS-CoV-2 infection and RBD-IgG antibody response at the recovery phase. RESULTS: Compared with the healthy controls, COVID-19 patients exhibited higher levels of miR-29b-3p (Z = 3.15, P = 0.002) and miR-1246 (Z = 4.98, P < 0.001). However, the expression of miR-186-5p and miR-15a-5p were significantly decreased. As the results shown, miR-30b-5p was negatively correlated with CD4 + T cell counts (r = - 0.41, P = 0.027) and marginally positively correlated with fasting plasma glucose in COVID-19 patients (r = 0.37, P = 0.052). The competitive ELISA analysis showed the plasma level of miR-497-5p at the acute phase was positively correlated with RBD-IgG antibody response (r = 0.48, P = 0.038). CONCLUSIONS: Our present results suggested that the expression level of ISR-miRNAs was not only associated with acute SARS-CoV-2 infection but also with RBD-IgG antibody response at the recovery phase of COVID-19. Future studies should be performed to explore the biological significance of ISR-miRNAs in SARS-CoV-2 infection.

Influence of diabetes mellitus on the severity and fatality of SARS-CoV-2 (COVID-19) infection.

AIM: To evaluate the influence of diabetes on the severity and fatality of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. MATERIALS AND METHODS: The medical records of 66 hospitalized coronavirus disease 2019 (COVID-19) patients were collected and classified into non-severe (mild/moderate cases) and severe (severe/critical cases) groups. Logistic regression analysis was used to estimate the risk of severe COVID-19 (severe/critical infection). In addition, a meta-analysis including published studies reported the impact of diabetes on the severity and fatality of COVID-19. The current study was conducted using fixed effects models. RESULTS: There were 22 diabetes and 44 non-diabetes cases among the 66 hospitalized COVID-19 patients. Seven patients with diabetes (31.82%) were diagnosed as severe COVID-19 cases, which was significantly higher than that in the non-diabetes group (4/44, 9.09%, P = .033). After adjustment for age and gender, diabetes was significantly associated with COVID-19 severity (OR: 5.29, 95% CI: 1.07-26.02). A meta-analysis further confirmed the positive association between diabetes and COVID-19 severity (pooled OR = 2.58, 95% CI: 1.93-3.45). Moreover, the patients with diabetes infected with SARS-CoV-2 had a 2.95-fold higher risk of fatality compared with those patients without diabetes (95% CI: 1.93-4.53). CONCLUSIONS: Our findings provide new evidence that diabetes is associated with a higher risk of severity and fatality of COVID-19. Therefore, intensive monitoring and antidiabetic therapy should be considered in patients with diabetes with SARS-CoV-2 infection.

Integrated analysis identifies low microRNA-215 expression as associated with a poor prognosis of patients with colorectal cancer through the IKß-α signaling pathway.

BACKGROUND: miRNA expression data on colorectal cancer (CRC) are constantly updated. Therefore, integrated analysis of these datasets prior to experiments is necessary in translational medicine and oncology research. Abnormal low expression of hsa-miRNA-215-5p (miR-215) is detected in several cancer types, but the role of miR-215 in CRC remains unclear. Therefore, the aim of this work was to identify the expression and role of miR-215 involved in CRC. METHODS: An integrated analysis of 4 sets of miRNA microarray data of CRC in GEO was implemented. The low expression of miR-215 in CRC was confirmed by TCGA datasets. In addition, frozen tissue and paired formalin-fixed paraffin-embedded samples were collected from 214 CRC patients who underwent CRC surgery at the Affiliated Hospital of Jiangnan University, China, and used as an independent clinical validation study. Furthermore, colon cancer cells HCT116 and SW480 transfected with miR-215 mimic/inhibitor were used to evaluate its mechanism of action and to perform experiments to confirm our results obtained from human samples. RESULTS: CRC patients with a decreased miR-215 expression in adenocarcinoma tissues had a significantly poor prognosis with lower cumulative survival as revealed by the TCGA-COAD dataset. In our 214 CRC patients cohort study this result was confirmed and it was also found that low miR-215 expression was inversely correlated with the expression of IKß-α. Downregulation of miR-215 in HCT116 and SW480 cells resulted in an upregulation of TRAF5 and TAK1 protein expression, and interfered with IKß-α protein expression. Furthermore, with the inhibition of miR-215, important Epithelial-Mesenchymal Transition (EMT) biomarker proteins were significantly upregulated in HCT116 and SW480 cells. Moreover, an inhibition was obtained using miR-215-mimic. CONCLUSIONS: Our integrated microRNA dataset approach identified miR-215 as an independent factor associated with the prognosis of CRC patients. In addition, our results demonstrated that miR-215 might be considered as a potential biomarker for poor prognosis in CRC patients and its role as a potent suppressor of IKß-α and TRAF5.

Risk of reduced platelet counts in patients with nonalcoholic fatty liver disease (NAFLD): a prospective cohort study.

BACKGROUND: The production of peripheral platelet is mainly regulated by thrombopoietin, which is a glycoprotein hormone predominantly synthesized in the liver. Previously, many studies have reported that there was an inverse correlation between the degree of chronic viral hepatitis and the peripheral platelet count. However, the effect of nonalcoholic fatty liver disease (NAFLD) on the peripheral platelet counts remains unclear. METHODS: With 1303 participants from "The prevention of MS and multi-metabolic disorders in Jiangsu province of China (PMMJS)" cohort study, we investigated the associations between NAFLD and the risk of platelet counts reduction in Chinese adults. The paired-samples T test was used to explore the platelet counts changes between baseline and follow-up. Multivariate logistic regression was used to examine the association between presence of NAFLD and the risk of platelet reduction by calculating the odds ratios (ORs) and 95% confidence interval (CI). RESULTS: After five years of follow-up, platelet counts were markedly reduced from 220.6 ± 42.22 (109/L) at baseline to 208.41 ± 40.70 (109/L) at follow-up in NAFLD group (P < 0.0001). However, platelet counts were slightly lowered from 213.2 ± 43.26(109/L) at baseline to 211.8 ± 41.65 (109/L) at follow-up in non-NAFLD people (P = 0.2349). Meanwhile, there was a significant association between NAFLD and the risks of platelet count reduction, even after adjustment for confounding variables (OR: 1.68, 95% CI: 1.06-2.67). Additionally, among the participants with BMI ≤ 23 kg/m2 and SUA ≤ 344.3 µmol/L, the NAFLD participants have an increased risk of platelet count reduction compared to the persons in non-NAFLD group. CONCLUSIONS: Our present results suggested that NAFLD individuals have an increased risk of platelet counts reduction.

Correlation of IDH1 and B7H3 expression with prognosis of CRC patients.

BACKGROUND: B7H3 is an immuno-stimulatory glycoprotein that is overexpressed in cancer. However, its functional contributions to cancer development and progression are not well understood. In several reports, it was demonstrated that B7H3 reprograms lipid metabolism and regulates glucose metabolism. Isocitrate dehydrogenase 1 (IDH1), a metabolic enzyme in the TCA cycle, its reaction product is involved in lipid synthesis. Thus, we aimed to identify a novel marker to predict the prognosis of CRC patients and to investigate the relationship between IDH1 and B7H3. METHODS: We analyzed IDH1 and B7H3 expression levels in 225 CRC specimens by immunochemistry. Moreover, in vitro studies were performed to demonstrate the correlation between IDH1 and B7H3. RESULTS: Among 225 tissues, the positive rates of IDH1 and B7H3 were 37.8% (85/225) and 87.6% (197/225), respectively. In CRC samples, IDH1 significantly correlated with B7H3 expression (P = 0.044). Moreover, multivariate analyses revealed that high expression of both B7H3 and IDH1 and a high tumor grade were related to the prognosis of CRC patients. Kaplan-Meier survival analysis revealed that patients with co-expression of IDH1 and B7H3 had a poor overall survival. In SW480B7H3-EGFP cells, which highly express B7H3, IDH1 was up-regulated. Similarly, knockdown of B7H3 expression in Caco-2-shB7-H3 contributed to reduced IDH1 levels. CONCLUSIONS: Although IDH1 and B7H3 cannot be used as independent prognostic factors, co-expression of IDH1 and B7H3 significantly correlated with the prognosis of CRC patients and may serve as a combined predictive marker. Thus, the correlation between IDH1 and B7H3 has been proven in vivo and in vitro.

Evaluation of candidate genes associated with hepatitis A and E virus infection in Chinese Han population.

BACKGROUND: Recent GWAS-associated studies reported that single nucleotide polymorphisms (SNPs) in ABCB1, TGFß1, XRCC1 genes were associated with hepatitis A virus (HAV) infection, and variants of APOA4 and APOE genes were associated with and hepatitis E virus (HEV) infection in US population. However, the associations of these loci with HAV or HEV infection in Chinese Han population remain unclear. METHODS: A total of 3082 Chinese Han persons were included in this study. Anti-HAV IgG and anti-HEV IgG were detected by enzyme-linked immunosorbent assay (ELISA). Genotypes in ABCB1, TGFß1, XRCC1, APOA4 and APOE SNPs were determined by TaqMan MGB technology. RESULTS: In Chinese Han population, rs1045642 C to T variation in ABCB1 was significantly associated with the decreased risk of HAV infection (P < 0.05). However, the effect direction was different with the previous US study. Rs1001581 A to G variation in XRCC1, which was not identified in US population, was significantly associated with the protection against HAV infection in our samples (P < 0.05). In addition, our results suggested that rs7412 C to T variation in APOE was significantly associated with lower risk of HEV infection in males (adjusted OR < 1.0, P < 0.05) but not in females. CONCLUSIONS: ABCB1 and XRCC1 genes variants are significantly associated with the protection against HAV infection. Additionally, Chinese Han males with rs7412 C to T variation in APOE gene are less prone to be infected by HEV.

ACOT1 expression is associated with poor prognosis in gastric adenocarcinoma.

Acyl-CoA thioesterase 1 (ACOT1) is an important isoform of the ACOT family that catalyzes the reaction of fatty acyl-CoAs to CoA-SH and free fatty acids. Recent studies of gastrointestinal tumor metabolism suggest that there is abnormal metabolism of lipids and fatty acids during tumor progression. However, the function and contribution of ACOT1 in gastric cancer development are still poorly understood. In addition, GLI3 is a major transcription factor in the regulation of hedgehog signaling. GLI3 mutations induce glandular expansion and intestinal metaplasia in gastric cancer, which indicates a role for GLI3 in the preneoplastic process. Thus, we investigated the relationship between ACOT1 expression and GLI3 in gastric adenocarcinoma. A tissue microarray was constructed from 280 cases of gastric adenocarcinoma. The immunohistochemistry method was performed on tissue sections of 4 µm from each tissue microarray block. We found a significant correlation between ACOT1 expression and poor histologic grade, a lower T category, TNM stage, and increased GLI3 expression. In addition, the survival analysis revealed that the ACOT1-positive group had significantly decreased overall survival rates compared with the ACOT1-negative group. Furthermore, GLI3 expression had a significant positive correlation with ACOT1 expression in gastric adenocarcinoma cells. In summary, these findings demonstrate that increased expression of ACOT1 is correlated with pivotal clinicopathological parameters and poor prognosis in gastric adenocarcinoma through increased expression of the potential tumor-promoting protein GLI3.

Long Noncoding RNA XIST Regulates miR-137-EZH2 Axis to Promote Tumor Metastasis in Colorectal Cancer.

We aimed to investigate the significant role of long noncoding RNA X inactive specific transcript (XIST) in regulating tumor metastasis in colorectal cancer (CRC), as well as its possible mechanism. Expression of lncRNA XIST in CRC tissues and CRC cells was detected. CRC cells were transfected with pc-XIST, blank control si-XIST, or si-control, and then the effects of lncRNA XIST on CRC cell migration and invasion were investigated, along with the interaction between lncRNA XIST and miR-137. lncRNA XIST was upregulated in CRC tissues. Compared with HT29 cells that had low metastatic potential, XIST was markedly more highly expressed in LoVo cells that had a higher metastatic potential. Overexpression of XIST promoted the migratory and invasive potential of HT29 cells, while knockdown of XIST inhibited the migratory and invasive potential of LoVo cells. Moreover, epithelial-mesenchymal transition (EMT) markers, including E-cadherin, N-cadherin, and vimentin, exhibited corresponding expression changes. In addition, miR-137 was inhibited by XIST, and inhibition of miR-137 could reverse the effects of knockdown of XIST on the migratory and invasive potential of LoVo cells. Furthermore, enhancer of zeste homolog 2 (EZH2) was confirmed as a target of miR-137. Our data reveal that lncRNA XIST may promote tumor metastasis in CRC possibly through regulating the miR-137-EZH2 axis. lncRNA XIST may serve as a prognostic indicator for CRC progression.

Expression of CYP1B1 and B7-H3 significantly correlates with poor prognosis in colorectal cancer patients.

Cytochrome P450 1B1 (CYP1B1) is a phase I xenobiotic-metabolizing enzyme (XME) that is overexpressed in colorectal cancer (CRC) tissue, but the prognosis value of CYP1B1 in CRC remains elusive. Additionally, B7-H3 has a key role in tumor cell immune evasion by inhibiting functions of T cells. Thus, in this study, we aimed to identify a new marker for predicting the prognosis of CRC and to study the relationship between tumor metabolism and tumor immunity. We analyzed CYP1B1 and B7-H3 expression in 231 patients with CRC using immunohistochemistry, and we investigated the relationship between CYP1B1 and B7-H3 expression using real-time PCR and Western blot analysis in two human CRC cell lines. Kaplan-Meier survival analysis was used to calculate overall survival (OS) rates, and Cox proportional regression model was performed for multivariate analysis. We found that both CYP1B1 and B7-H3 expression were aberrantly increased in CRC tissues compared to normal colorectal tissues. Moreover, high expression of CYP1B1 was significantly correlated with poor OS, and multivariate analysis indicated that CYP1B1 was a valuable independent prognostic biomarker. Furthermore, CYP1B1 expression was significantly correlated with B7-H3 expression in CRC tissues samples and two human CRC cell lines. In conclusion, these results indicate that CYP1B1 may be a novel predictive biomarker for prognosis of CRC patients, and there is a strong correlation between CYP1B1 and B7-H3 in vivo and in vitro.