Attenuation of Experimental Autoimmune Hepatitis in Mice with Bone Mesenchymal Stem Cell-Derived Exosomes Carrying MicroRNA-223-3p

Yong-Ping Chen,Feng-Bin Lu,Da-Zhi Chen,Lu Chen,En-De Hu,Jin-Lu Wu,Hui Li,Yue-Wen Gong,Zhuo Lin,Xiao-Dong Wang,Ji Li,Xiao-Ya Jin,Lan-Man Xu 한국분자세포생물학회 2019 Molecules and cells Vol.42 No.12

MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.

CCDC26 Gene Polymorphism and Glioblastoma Risk in the Han Chinese Population

Wei, Xiao-Bing,Jin, Tian-Bo,Li, Gang,Geng, Ting-Ting,Zhang, Jia-Yi,Chen, Cui-Ping,Gao, Guo-Dong,Chen, Chao,Gong, Yong-Kuan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.8

Background: Glioblastoma (GBM) is an immunosuppressive tumor whose median survival time is only 12-15 months, and patients with GBM have a uniformly poor prognosis. It is known that heredity contributes to formation of glioma, but there are few genetic studies concerning GBM. Materials and Methods: We genotyped six tagging SNPs (tSNP) in Han Chinese GBM and control patients. We used Microsoft Excel and SPSS 16.0 statistical package for statistical analysis and SNP Stats to test for associations between certain tSNPs and risk of GBM in five different models. ORs and 95%CIs were calculated for unconditional logistic-regression analysis with adjustment for age and gender. The SHEsis software platform was applied for analysis of linkage disequilibrium, haplotype construction, and genetic associations at polymorphism loci. Results: We found rs891835 in CCDC26 to be associated with GBM susceptibility at a level of p=0.009. The following genotypes of rs891835 were found to be associated with GBM risk in four different models of gene action: i) genotype GT (OR=2.26; 95%CI, 1.29-3.97; p=0.019) or GG (OR=1.33; 95%CI, 0.23-7.81; p=0.019) in the codominant model; ii) genotypes GT and GG (OR=2.18; 95%CI, 1.26-3.78; p=0.0061) in the dominant model; iii) GT (OR=2.24; 95%CI, 1.28-3.92; p=0.0053) in the overdominant model; iv) the allele G of rs891835 (OR=1.85; 95%CI, 1.14-3.00; p=0.015) in the additive model. In addition, "CG" and "CGGAG" were found by haplotype analysis to be associated with increased GBM risk. In contrast, genotype GG of CCDC26 rs6470745 was associated with decreased GBM risk (OR=0.34; 95%CI, 0.12-1.01; p=0.029) in the recessive model. Conclusions: Our results, combined with those from previous studies, suggest a potential genetic contribution of CCDC26 to GBM progression among Han Chinese.

Construction of a Ginsenoside Content-predicting Model based on Hyperspectral Imaging

Ning, Xiao Feng,Gong, Yuan Juan,Chen, Yong Liang,Li, Hongbo Korean Society for Agricultural Machinery 2018 바이오시스템공학 Vol.43 No.4

Purpose: The aim of this study was to construct a saponin content-predicting model using shortwave infrared imaging spectroscopy. Methods: The experiment used a shortwave imaging spectrometer and ENVI spectral acquisition software sampling a spectrum of 910 nm-2500 nm. The corresponding preprocessing and mathematical modeling analysis was performed by Unscrambler 9.7 software to establish a ginsenoside nondestructive spectral testing prediction model. Results: The optimal preprocessing method was determined to be a standard normal variable transformation combined with the second-order differential method. The coefficient of determination, $R^2$, of the mathematical model established by the partial least squares method was found to be 0.9999, while the root mean squared error of prediction, RMSEP, was found to be 0.0043, and root mean squared error of calibration, RMSEC, was 0.0041. The residuals of the majority of the samples used for the prediction were between ${\pm}1$. Conclusion: The experiment showed that the predicted model featured a high correlation with real values and a good prediction result, such that this technique can be appropriately applied for the nondestructive testing of ginseng quality.

Prevalence and Age, Gender and Geographical Area Distribution of Esophageal Squamous Cell Carcinomas in North China from 1985 to 2006

Feng, Xiao-Shan,Yang, Yan-Tong,Gao, She-Gan,Ru, Yi,Wang, Gong-Ping,Zhou, Bo,Wang, Yu-Feng,Zhang, Peng-Fei,Li, Pu-Yu,Liu, Yong-Xuan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.5

Objective: To establish the prevalence and distribution profile of esophageal squamous cell carcinomas (ESCCs) over a 22-yr period in North China. Methods: Using endoscopy for primary diagnosis and histological analysis for the further confirmation, a total of 74,854 ESCC patients aged 20-89 between January 1985 and December 2006 were investigated to analyze the epidemiological profile including prevalence rates, distribution of age-of-onset, gender and geographical area of ESCC in Luoyang, the highest incidence area of North China. Results: A total of 4092 cases of ESCC were finally diagnosed among 74,854 patients who had their first endoscopies. The prevalence among males was higher than that among females (p<0.01), resulting in an overall male:female OR of 1.2 (95%CI, 1.2-1.3). The prevalence in rural areas was higher than in urban areas (p<0.01), resulting in an overall rural:urban OR of 2.6 (95%CI, 2.4-2.9). The rural:urban ORs and the 95% CI increased continuously from 2.6, 2.3-3.0 to 2.7, 2.2-3.3, respectively, for 4 consecutive periods during the 22-yr study period. Moreover, the median age of onset among females was higher than that among males (p<0.01). For both sexes and in both areas, the prevalence rates declined and the median age of onset rose for 4 consecutive periods in the 22-yrs time frame (p<0.01). Conculsions: These data reveal the epidemiological profile of ESCC in the area of North China, and suggest that urban areas and rural people account for a growing proportion of the ESCC patients although the prevalence of ESCC significantly declined and the median age-of-onset postponed over the 22-yrs period. Moreover, the prevalence status of ESCC in rural areas also underlines the need for public health initiatives aimed at reducing risk factors of this fatal disease.

Composition and abundance of microbiota in the pharynx in patients with laryngeal carcinoma and vocal cord polyps

Hongli Gong,Boyan Wang,Yi Shi,Yong Shi,Xiyan Xiao,Pengyu Cao,Lei Tao,Yuezhu Wang,Liang Zhou 한국미생물학회 2017 The journal of microbiology Vol.55 No.8

The pharynx is an important site of microbiota colonization, but the bacterial populations at this site have been relatively unexplored by culture-independent approaches. The aim of this study was to characterize the microbiota structure of the pharynx. Pyrosequencing of 16S rRNA gene libraries was used to characterize the pharyngeal microbiota using swab samples from 68 subjects with laryngeal cancer and 28 subjects with vocal cord polyps. Overall, the major phylum was Firmicutes, with Streptococcus as the predominant genus in the pharyngeal communities. Nine core operational taxonomic units detected from Streptococcus, Fusobacterium, Prevotella, Granulicatella, and Veillonella accounted for 21.3% of the total sequences detected. However, there was no difference in bacterial communities in the pharynx from patients with laryngeal cancer and vocal cord polyps. The relative abundance of Firmicutes was inversely correlated with Fusobacteria, Proteobacteria, Actinobacteria, and Bacteroidetes. The correlation was evident at the genus level, and the relative abundance of Streptococcus was inversely associated with Fusobacterium, Leptotrichia, Neisseria, Actinomyces, and Prevotella. This study presented a profile for the overall structure of the microbiota in pharyngeal swab samples. Inverse correlations were found between Streptococcus and other bacterial communities, suggesting that potential antagonism may exist among pharyngeal microbiota.

Association of TERT rs2736098 Polymorphism with Cancer Risk: a Meta-analysis

Zhang, Xiao-Jing,Xu, Zhi,Gong, Yong-Ling,Tang, Cui-Ju,Chen, Jin-Fei Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.10

Studies have reported an association between the TERT rs2736098 single nucleotide polymorphism (SNP) and cancer susceptibility, but the results remain inconclusive. Toprovide a more precise estimation of the relationship, a meta-analysis of 8 published studies including 8,070 cases and 10,239 controls was performed. Stratification by sample size, genotyping method, source of controls and ethnicity were used to explore the source of heterogeneity. In the overall analysis, no significant association was found between the TERT rs2736098 polymorphism and cancer risk. However, the result showed the rs2736098 was significantly associated with an increased cancer risk and the heterogeneity was effectively decreased for homozygote comparison by removal of two studies: OR = 1.337 (95% CI = 1.183-1.511; Pheterogeneity = 0.087). In the subgroup analysis by ethnicity, a significantly increased risk of cancers was found among Asians (OR = 1.413, 95% CI = 1.187-1.683 for AA versus GG). Our meta-analysis did not show that the TERT rs2736098 plays an important role in cancer risk. More studies with larger sample size and well-matched controls are needed to confirm the findings.

BMB Reports : Heat shock protein 90β inhibits apoptosis of intestinal epithelial cells induced by hypoxia through stabilizing phosphorylated Akt

( Shuai Zhang ),( Yong Sun ),( Zhi Qiang Yuan ),( Ying Li ),( Xiao Lu Li ),( Zhen Yu Gong ),( Yi Zhi Peng ) 생화학분자생물학회(구 한국생화학분자생물학회) 2013 BMB Reports Vol.46 No.1

Intestinal epithelial cell (IEC) apoptosis induced by hypoxia compromise intestinal epithelium barrier function. Both Akt and Hsp90 have cytoprotective function. However, the specific role of Akt and Hsp90β in IEC apoptosis induced by hypoxia has not been explored. We confirmed that hypoxia-induced apoptosis was reduced by Hsp90β overexpression but enhanced by decreasing Hsp90β expression. Hsp90β overexpression enhanced BAD phosphorylation and thus reduced mitochondrial release of cytochrome C. Reducing Hsp90β expression had opposite effects. The protective effect of Hsp90β against apoptosis was negated by LY294002, an Akt inhibitor. Further study showed that Akt phosphorylation was enhanced by Hsp90β, which was not due to the activation of upstream PI3K and PDK1 but because of stabilization of pAkt via direct interaction between Hsp90β and pAkt. These results demonstrate that Hsp90β may play a significant role in protecting IECs from hypoxia-induced apoptosis via stabilizing pAkt to phosphorylate BAD and reduce cytochrome C release. [BMB Reports 2013; 46(1): 47-52]

Development and validation of risk score for predicting spontaneous rupture of hepatocellular carcinoma

Feng Ye,Di Ma,Xiao-Yong Gong,Yu-Chen Yang,Yong-Jun Chen 대한외과학회 2020 Annals of Surgical Treatment and Research(ASRT) Vol.99 No.5

Purpose: Spontaneous rupture is a potentially serious complication of liver cancer. A risk score was developed and validated for predicting spontaneous rupture based on a retrospective study. Methods: Multiple logistic regression analysis was used to study the relationship between clinical variables and spontaneous rupture. The independent rupture predictors were converted into a score based on the odds ratio. Predicted attributes of the developed scores were then verified using a dataset in 2019. Results: The incidence of spontaneous rupture was 5.5% from 2002 to 2019. A 10-point score (α-FP of ≥400 μg/L, 1; protrusion from liver surface, 2; ascites, 3; tumor size of >5 cm, 4) was derived for prediction of rupture and area under the receiver-operating characteristic curve was 0.9 (95% confidence interval, 0.87–0.92). When applying a cutoff value of 5 points or more, the specificity was 0.87 and the sensitivity was 0.84. A validation cohort consisting of 202 hepatocellular carcinoma patients reproduces the predictive, identification, and calibration characteristics. The observed rate of spontaneous rupture according to risk stratification of the score was 0.6% for those with a score of 0–4, 21.6% for a score of 5–7, and 36.4% for a score of 8–10 in the validation cohort. Conclusion: Here, based on routine clinical data, we determine the factors that affect prognosis and propose an effective tool for predicting spontaneous rupture, which may be useful in guiding priority treatment of high-risk patients or clinical routine preventive treatment.

Diabetes Medication Use in Association with Survival among Patients of Breast, Colorectal, Lung, or Gastric Cancer

Michelle L. Baglia,Yong Cui,Tao Zheng,Gong Yang,Honglan Li,Mingrong You,Liling Xu,Harvey Murff,Yu-Tang Gao,Wei Zheng,Yong-Bing Xiang,Xiao-Ou Shu 대한암학회 2019 Cancer Research and Treatment Vol.51 No.2

Purpose Studies suggest that regular use of metformin may decrease cancer mortality. We investigated the association between diabetes medication use and cancer survival. Materials and Methods The current study includes 633 breast, 890 colorectal, 824 lung, and 543 gastric cancer cases identified from participants of two population-based cohort studies in Shanghai. Information on diabetes medication use was obtained by linking to electronic medical records. The associations between diabetes medication use (metformin, sulfonylureas, and insulin) and overall and cancer-specific survival were evaluated using time-dependent Cox proportional hazards models. Results After adjustment for clinical characteristics and treatment factors, use of metformin was associated with better overall survival among colorectal cancer patients (hazards ratio [HR], 0.55; 95% confidence interval [CI], 0.34 to 0.88) and for all four types of cancer combined (HR, 0.75; 95% CI, 0.57 to 0.98). Ever use of insulin was associated with worse survival for all cancer types combined (HR, 1.89; 95% CI, 1.57 to 2.29) and for the four cancer types individually. Similar associations were seen for diabetic patients. Sulfonylureas use was associated with worse overall survival for breast or gastric cancer (HR, 2.87; 95% CI, 1.22 to 6.80 and HR, 2.05; 95% CI, 1.09 to 3.84, respectively) among diabetic patients. Similar association patterns were observed between diabetes medication use and cancer-specific survival. Conclusion Metformin was associated with improved survival among colorectal cancer cases, while insulin use was associated with worse survival among patients of four major cancers. Further investigation on the topic is needed given the potential translational impact of these findings.

0346 Occupational Exposure to Lead and Cancer in Two Cohort Studies of Men and Women in Shanghai, China

Liao, Linda M,Friesen, Melissa C,Xiang, Yong-Bing,Cai, Hui,Koh, Dong-Hee,Ji, Bu-Tian,Yang, Gong,Li, Hong-Lan,Locke, Sarah J,Rothman, Nathaniel,Zheng, Wei,Gao, Yu-Tang,Shu, Xiao-Ou,Purdue, Mark P BMJ Publishing Group Ltd 2014 Occupational and environmental medicine Vol.71 No.suppl1

<P><B>Objectives</B></P><P>Epidemiologic studies of occupational lead exposure have suggested increased risks of cancers of the brain, kidney, lung, meninges, and stomach; however, the totality of the evidence is inconsistent. To clarify whether lead is a carcinogen, we investigated the relationship between occupational lead exposure and risks of these five cancer sites in two prospective cohort studies in Shanghai, China.</P><P><B>Method</B></P><P>Annual job/industry-specific estimates of lead fume and lead dust exposure were derived from a statistical model that combined expert ratings of lead intensity with inspection measurements collected by the Shanghai Centre for Disease Control and Prevention. The job/industry estimates were applied to the lifetime work histories of subjects from the Shanghai Women’s Health Study (73 363 participants) and the Shanghai Men’s Health Study (61 379 participants) to estimate cumulative exposure to lead dust and lead fume. Cohort-specific relative hazard rate ratios (RRs) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression models and then pooled using a random effects meta-analysis model.</P><P><B>Results</B></P><P>We observed a statistically significant increased risk of meningioma among individuals with estimated occupational exposure to lead dust or fumes (RR=2.4, 95% CI:1.1–5.0), and in particular among those with an above-median cumulative exposure to dust or fumes (RR=3.1, 95% CI:1.3–7.4). We observed suggestive associations with lead exposure for cancers of the kidney (RR=1.4, 95% CI:0.9–2.3) and brain (RR=1.8, 95% CI:0.7–4.8), and null findings for cancers of the lung and stomach.</P><P><B>Conclusions</B></P><P>Our findings provide additional evidence that occupational lead exposure increases risk of meningioma.</P>