Whole Cell-mediated Biocatalytic Synthesis of Helicid Cinnamylate and Its Biological Evaluation as a Novel Tyrosinase Inhibitor

Rong-ling Yang,Xi Chen,Yu-ye Song,Qian-lin Zhu,Muhammad Bilal,Yu Wang,Zheng Tong,Ting-ting Wu,Zhao-Yu Wang,Hong-zhen Luo,Xiang-jie Zhao,Ting-ting He 한국생물공학회 2022 Biotechnology and Bioprocess Engineering Vol.27 No.3

Tyrosinase inhibitors are clinically effective for treating some dermatological disorders related to melanin hyperpigmentation. Accordingly, the discovery and development of tyrosinase inhibitors have great value in the pharmaceutical and cosmetic industry. Here, a novel tyrosinase inhibitor, 6′-O-cinnamoyl-helicid (helicid cinnamylate) was successfully synthesized by a simple and effective biocatalytic approach with Aspergillus oryzae cells. Investigation of the effects of several key variables on helicid cinnamylate synthesis found that the reaction conversion, reaction rate and regioselectivity reached 99%, 9.40 mM/h and > 99%, respectively, at the optimal conditions with anhydrous acetone as the solvent, whole-cell concentration of 40 mg/mL, and the molar ratio of vinyl cinnamate to helicid of 10 at 45°C. The whole-cells retained 68.87% of its initial activity after reusing for seven batches, indicating a potent application potential in non-aqueous biocatalytic systems. It was worth noting that helicid cinnamylate demonstrated a more potent tyrosinase inhibitory activity with an IC50 value of 3.55 mM than helicid (IC50 = 4.48 mM) and arbutin (IC50 = 5.48 mM), which suggest that helicid cinnamylate could be developed as a more potential tyrosinase inhibitor. In conclusion, this study provides a novel whole-cell catalytic approach for the synthesis of helicid cinnamylate and insight into its application as a tyrosinase inhibitor.

Genetic diversity and population structure of the amylolytic yeast Saccharomycopsis fibuligera associated with Baijiu fermentation in China

Wang Ju-Wei,Han Pei-Jie,Han Da-Yong,Zhou Sen,Li Kuan,He Peng-Yu,Zhen Pan,Yu Hui-Xin,Liang Zhen-Rong,Wang Xue-Wei,Bai Feng-Yan 한국미생물학회 2021 The journal of microbiology Vol.59 No.8

The amylolytic yeast Saccharomycopsis fibuligera is a predominant species in starters and the early fermentation stage of Chinese liquor (Baijiu). However, the genetic diversity of the species remains largely unknown. Here we sequenced the genomes of 97 S. fibuligera strains from different Chinese Baijiu companies. The genetic diversity and population structure of the strains were analyzed based on 1,133 orthologous genes and the whole genome single nucleotide polymorphisms (SNPs). Four main lineages were recognized. One lineage contains 60 Chinese strains which are exclusively homozygous with relatively small genome sizes (18.55–18.72 Mb) and low sequence diversity. The strains clustered in the other three lineages are heterozygous with larger genomes (21.85–23.72 Mb) and higher sequence diversity. The genomes of the homozygous strains showed nearly 100% coverage with the genome of the reference strain KPH12 and the sub-genome A of the hybrid strain KJJ81 at the above 98% sequence identity level. The genomes of the heterozygous strains showed nearly 80% coverage with both the sub-genome A and the whole genome of KJJ81, suggesting that the Chinese heterozygous strains are also hybrids with nearly 20% genomes from an unidentified source. Eighty-three genes were found to show significant copy number variation between different lineages. However, remarkable lineage specific variations in glucoamylase and α-amylase activities and growth profiles in different carbon sources and under different environmental conditions were not observed, though strains exhibiting relatively high glucoamylase activity were mainly found from the homozygous lineage.

Epidemiology of Esophageal Cancer in Yanting - Regional Report of a National Screening Programme in China

Wang, Xiao,Fan, Jin-Chuan,Wang, An-Rong,Leng, Yue,Li, Jun,Bao, Yu,Wang, Ying,Yang, Qing-Feng,Ren, Yu Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.4

Background and Objectives: Yanting in Sichuan Province is one of the highest risk areas of esophageal cancer (EC) in the world. We here summarize the epidemiology of EC in Yanting using data from the national screening programme during 2006-2011. Methods: Random cluster sampling was used to select a proportion of natural villages from six towns in Yanting, and residents aged 40-69 years old were invited for screening. Participants were screened using endoscopy with iodine staining and then confirmed by histological examinations. Results: The overall detection rates of low-grade hyperplasia (LH), moderate hyperplasia (MH), high-grade hyperplasia (HH), carcinoma in situ (CIS), intramucosal carcinoma (IC) and invasive carcinoma (INC) were 5.33%, 1.28%, 0.68%, 0.15%, 0.06% and 0.29%, respectively. The detection rates of LH, MH, HH and INC increased with age, reaching the peak among those aged 60-65 years, and the prevalences of LH and MH were higher among men than among women. In addition, the detection rates of hyperplasia were much higher in mountainous than in hilly areas. Conclusions: Among the high risk population, there are a great number of people with early-stage EC or precancerous conditions who do not have presenting symptoms. In particular, the elderly, men, or those living in mountainous areas are the most vulnerable population. It is therefore important to reinforce health education and screening services among such high risk populations.

Association of Six Susceptibility Loci with Prostate Cancer in Northern Chinese Men

Zhang, Yu-Rong,Xu, Yong,Yang, Kuo,Liu, Ming,Wei, Dong,Zhang, Yao-Guang,Shi, Xiao-Hong,Wang, Jian-Ye,Yang, Fan,Wang, Xin,Liang, Si-Ying,Zhao, Cheng-Xiao,Wang, Fei,Chen, Xin,Sun, Liang,Zhu, Xiao-Quan,Zh Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12

Background/Aim: Six prostate cancer (PCa) susceptibility loci were identified in a genome-wide association study (GWAS) in populations of European decent. However, the associations of these 6 single-nucleotide polymorphisms (SNPs) with PCa has remained tobe clarified in men in Northern China. This study aimed to explore the loci associated with PCa risk in a Northern Chinese population. Methods: Blood samples and clinical information of 289 PCa patients and 288 controls from Beijing and Tianjin were collected. All risk SNPs were genotyped using polymerase chain reaction (PCR)-high resolution melting curve technology and gene sequencing. Associations between PCa and clinical covariates (age at diagnosis, prostate-specific antigen [PSA], Gleason score, tumor stage, and level of aggressiveness) and frequencies of alleles and genotypes of these SNPs were analyzed using genetic statistics. Results: Among the candidate SNPs, 11p15 (rs7127900, A) was associated with PCa risk (P = 0.02, odds ratio [OR] = 1.64, 95% confidence interval [CI] = 1.09-2.46). Genotypes showed differences between cases and controls on 11p15 (rs7127900, A), 11q13 (rs7931342, T), and HNF1B (rs4430796, A) (P = 0.03, P = 0.01, and P = 0.04, respectively). The genotype TG on 11q13 (rs7931342, T) was positively associated with an increased Gleason score (P = 0.04, OR = 2.15, 95% CI = 1.02-4.55). Patients carrying TG on 17q24 (rs1859962, G) were negatively associated with an increased body mass index (BMI) (P = 0.03, OR = 0.44, 95% CI = 0.21-0.92) while those with AG on HNF1B (rs4430796, A) were more likely to have PSA increase (P = 0.002). Conclusion: Our study suggests that 11p15 (rs7127900, A) could be a susceptibility locus associated with PCa in Northern Chinese. Genotype TG on 11q13 (rs7931342, T) could be related to an increased Gleason score, AG on HNF1B (rs4430796, A) could be associated with PSA increase, and TG on 17q24 (rs1859962, G) could be negatively associated with an increased BMI in Chinese men with PCa.

Effect of Gel-spun Solution Concentration on the Structure and Properties of UHMWPE Monofilaments with Coarse Denier

Hongqiu Wang,Rong Liu,Jun Rong Yu,Jing Zhu,Yan Wang,Zu Ming Hu 한국섬유공학회 2022 Fibers and polymers Vol.23 No.7

Even though many efforts about the preparation of ultra-high molecular weight polyethylene (UHMWPE) fibershave been reported since last century, the spinning technology of high solution concentration UHMWPE fibers was stillpursued by many researchers and industry members. Not only because solution concentration is a key factor that significantlyinfluences the structure and properties of gel-spun UHMWPE fibers, but also because the high concentration UHMWPEspinning technology could greatly improve the production efficiency and reduce the spinning cost. In this study, highabrasion resistance UHMWPE fibers were prepared via gel-spinning with UHMWPE solution concentration of 8-16 wt%,subsequently extracting, drying and ultra-drawing. The effects of solution concentration on the fiber solvent phase separation,crystallization properties, abrasion resistance properties and mechanical capacities were investigated in detail. The resultsindicated that increasing solution concentration can reduce the time to reach phase separation equilibrium state that couldefficiently shorten the productive time; meanwhile, the abrasion resistance of the fibers was also significantly improved.

Value of PAX1 Methylation Analysis by MS-HRM in the Triage of Atypical Squamous Cells of Undetermined Significance

Li, Shi-Rong,Wang, Zhen-Ming,Wang, Yu-Hui,Wang, Xi-Bo,Zhao, Jian-Qiang,Xue, Hai-Bin,Jiang, Fu-Guo Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.14

Background: Detection of cervical high grade lesions in patients with atypical squamous cells of undetermined significance (ASCUS) is still a challenge. Our study tested the efficacy of the paired boxed gene 1 (PAX1) methylation analysis by methylation-sensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in ASCUS and compared performance with the hybrid capture 2 (HC2) human papillomavirus (HPV) test. Materials and Methods: A total of 463 consecutive ASCUS women from primary screening were selected. Their cervical scrapings were collected and assessed by PAX1 methylation analysis (MS-HRM) and high-risk HPV-DNA test (HC2). All patients with ASCUS were admitted to colposcopy and cervical biopsies. The Chisquare test was used to test the differences of PAX1 methylation or HPV infection between groups. Results: The specificity, sensitivity, and accuracy for detecting CIN2 + lesions were: 95.6%, 82.4%, and 94.6%, respectively, for the PAX1 MS-HRM test; and 59.7%, 64.7%, and 60.0% for the HC2 HPV test. Conclusions: The PAX1 methylation analysis by MS-HRM demonstrated a better performance than the high-risk HPV-DNA test for the detection of high grade lesions (CIN2 +) in ASCUS cases. This approach could screen out the majority of low grade cases of ASCUS, and thus reduce the referral rate to colposcopy.

Metastasis associated genomic aberrations in stage II rectal cancer

Hong Zhao,Zhi-Zhou Shi,Rui Jiang,Dong-Bing Zhao,Hai-Tao Zhou,Jian-Wei Liang,Xin-Yu Bi,Jian-Jun Zhao,Zhi-Yu Li,Jian-Guo Zhou,Zhen Huang,Ye-Fan Zhang,Jian Wang,Xin Xu,Yan Cai,Ming-Rong Wang,Yu Zhang 한국유전학회 2016 Genes & Genomics Vol.38 No.11

Genomic aberrations of rectal carcinoma, especially DNA copy number changes associated with metastasis were largely unclear. We aim to identify the metastasis associated biomarkers in stage II rectal cancer. Formalin-fixed, paraffin-embedded primary tumor tissues of stage II rectal carcinoma were analyzed by array-based comparative genomic hybridization, and genomic aberrations were identified by Genomic Workbench and SAM software. Copy number changes and mRNA expressions were validated by Real-time PCR in an independent rectal cancer samples. The results showed that the most frequent gains in stage II rectal cancer were at 1q21.2-q23.1, 3p21.31, 11q12.2-q23.3, 12q24.11-q24.31, 12q13.11-q14.1 and losses in 18q11.2-q23, 17q21.33-q22, 13q31.1-q31.3, 21q21.1-q21.3, 8p23.3-p23.1 and 4q22.1-q23. Twenty-two amplifications and five homozygous deletions were also identified. We further found that S100A1 (1q21.3-q23.1), MCM7 (7q22.1) and JUND (19p13.11) were amplified and overexpressed in stage II rectal cancer. Interestingly, the genomic aberrations affected 14 signaling pathways including VEGF signaling pathway and fatty acid metabolism. Most importantly, loss of 13q31.1-q34 and gain of 1q44 were associated with distant metastasis. Our results indicated that these metastasis associated genomic changes may be useful to reveal the pathogenesis of rectal cancer metastasis and identify candidate biomarkers.

Clinical Utility of Haptoglobin in Combination with CEA, NSE and CYFRA21-1 for Diagnosis of Lung Cancer

Wang, Bing,He, Yu-Jie,Tian, Ying-Xing,Yang, Rui-Ning,Zhu, Yue-Rong,Qiu, Hong Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

Purpose: To investigate the clinical value in lung cancer of a combination of four serum tumor markers, haptoglobin (Hp), carcinoembryonic antigen (CEA), neuron specific enolase (NSE) as well as the cytokeratin 19 fragment (CYFRA21-1). Materials and Methods: Serum Hp (with immune-turbidimetric method), CEA, NSE, CYFRA21-1 (with chemiluminescence method) level were assessed in 193 patients with lung cancer, 87 patients with benign lung disease and 150 healthy controls. Differences of expression were compared among groups, and joint effects of these tumor markers for the diagnosis of lung cancer were analyzed. Results: Serum tumor marker levels in patients with lung cancer were obviously higher than those with benign lung disease and normal controls (p<0.01). The sensitivities of Hp, CEA, NSE and CYFRA21-1 were 43.5%, 40.9%, 23.3% and 41.5%, with specificities of 90.7%, 99.2%, 97.9% and 97.9%. Four tumor markers combined together could produce a positive detection rate of 85.0%, significantly higher than that of any single test. With squamous carcinomas, the positive detection rates with Hp and CYFRA21-1 were higher than that of other markers. In the adenocarcinoma case, the positive detection rate of CEA was higher than that of other markers. For small cell carcinomas, the positive detection rate of NSE was highest. The area under receiver operating characteristic curve ($AUC^{ROC}$) of Hp in squamous carcinoma (0.805) was higher than in adenocarcinoma (0.664) and small cell carcinoma (0.665). Conclusions: Hp can be used as a new serum tumor marker for lung cancer. Combination detection of Hp, CEA, NSE and CYFRA21-1 could significantly improve the sensitivity and specificity in diagnosis of lung cancer, and could be useful for pathological typing.

Notch Inhibitor: a Promising Carcinoma Radiosensitizer

Yu, Shu-Dong,Liu, Fen-Ye,Wang, Qi-Rong Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.11

Radiotherapy is an important part of modern cancer management for many malignancies, and enhancing the radiosensitivity of tumor cells is critical for effective cancer therapies. The Notch signaling pathway plays a key role in regulation of numerous fundamental cellular processes. Further, there is accumulating evidence that dysregulated Notch activity is involved in the genesis of many human cancers. As such, Notch inhibitors are attractive therapeutic agents, although as for other anticancer agents, they exhibit significant and potential side effects. Thus, Notch inhibitors may be best used in combination with other agents or therapy. Herein, we describe evidence supporting the use of Notch inhibitors as novel and potent radiosensitizers in cancer therapy.

Anti-VEGF Therapy with Bevacizumab - Limited Cardiovascular Toxicity

Yu, Jing,Cao, Xu-Fen,Zheng, Ye,Zhao, Rong-Cheng,Yan, Li-Qiu,Zhao, Lei,Wang, Jia-Wang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24

Purpose: This analysis was conducted to evaluate cardiovascular toxicity of commonly used anti-VEGF therapeutic agent, bevacizumab, in treating patients with cancer. Methods: Clinical studies evaluating the efficacy and safety of bevacizumab-based regimens on response and safety for patients with cancer were identified using a predefined search strategy, allowing cardiovascular toxicity and other side effects of treatment to be estimated. Results: In bevacizumab based regimens, 4 clinical studies including 282 patients with advanced cancer (including gliomas, cervical, breast and ovarian cancer) were considered eligible for inclusion. These bevacizumab-based regimens included docetaxel, irinitecan and carboplatin. Systematic analysis suggested that, of 282 patients treated by bevacizumab based regimens, hypertension and thrombo-embolism occurred in 2.5% (7/282), while only 3 patients reported cardiovascular events (1.1%). No treatment related death occurred in bevacizumab based treatment. Conclusion: This systemic analysis suggests that bevacizumab based regimens are associated with reasonable and accepted cardiovascular toxicity when treating patients with gliomas, cervical, breast and ovarian cancer.