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.

EA-D p45-IgG as a Potential Biomarker for Nasopharyngeal Carcinoma Diagnosis

Chen, Hao,Luo, Yao-Ling,Zhang, Lin,Tian, Li-Zhen,Feng, Zhi-Ting,Liu, Wan-Li Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

Aim: To identify new biomarkers for NPC diagnosis with an anti-EBV Western blot test kit. Methods: Serum samples from 64 NPC patients and healthy subjects with four specific VCA-IgA/EA-IgA profiles were tested with an anti-EBV Western blot test kit from EUROIMMUN AG. Proteins were quantified with scores of intensity visually assigned to the protein bands. The markers which showed statistical differences between the NPC and non-NPC subjects were further evaluated in another 32 NPC patients and 32 controls in comparison with established biomarkers including VCA-IgA, EA-IgA, EBV-related protein IgG, and EBV DNA. Results: Among the markers screened, EA-D p45-IgG showed a statistically significant difference (p < 0.05) between NPC and non-NPC subjects with VCA-IgA positivy. In 32 VCA-IgA positive NPC patients and 32 control subjects, the diagnostic accuracy of EA-D p45-IgG was 78.1% with a positive predictive value of 77.8% and a negative predictive value of 78.6%. In the verification experiment, the specificity and sensitivity of EA-D p45-IgG were 75.0% and 90.6 %, respectively. Conclusions: EA-D p45-IgG might be a potential biomarker for NPC diagnosis, especially among VCA-IgA positive subjects.

Synthesis, Characterization, and Micellization of pH-Responsive Poly(4-vinylpyridine)-block-Poly(methacrylic acid) Four-Armed Star-Shaped Block Copolymers

Feng Xu,Shu-Zhen Zheng,Yan-Ling Luo,Ting-Ting Chen 한국고분자학회 2013 Macromolecular Research Vol.21 No.9

pH-sensitive poly(4-vinylpyridine)-block-poly(methacrylic acid) (P4VP-b-PMAA) four-armed starshaped block copolymers were synthesized by two-step atom transfer radical polymerization (ATRP), followed by hydrolysis of P4VP-b-poly(tert-butyl methacrylate) (P4VP-b-PtBMA). The chemical structure and molecular weight of the as-synthesized block copolymers were characterized by Fourier transform infrared spectrometry (FTIR), nuclear magnetic resonance (1H and 13C NMR), and gel permeation chromatography (GPC) determinations. The solution behavior was investigated by surface tension technique, ultraviolet visible (UV-vis) transmittance,transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potentials measurements. The experimental results indicated that the copolymers can spontaneously assemble into spherical-shaped core-shell micelle aggregates, with a critical micelle concentration (CMC) about 200 mg L-1, hydrodynamic diameters from 90to 210 nm, depending on the environmental pH values and compositional ratios. The transmittance measurements revealed that the block copolymers produce evident phase transition in aqueous solution at pH from 6.5 to 7.0. Zeta potential data revealed high micelle stability. The as-synthesized block copolymers are anticipated to find their applications in the realms of specific drug release, metal loading and heterogeneous catalysis.

Wnt/β-Catenin Promotes the Osteoblastic Potential of BMP9 Through Down-Regulating Cyp26b1 in Mesenchymal Stem Cells

Yao Xin-Tong,Li Pei-pei,Liu Jiang,Yang Yuan-Yuan,Luo Zhen-Ling,Jiang Hai-Tao,He Wen-Ge,Luo Hong-Hong,Deng Yi-Xuan,He Bai-Cheng 한국조직공학과 재생의학회 2023 조직공학과 재생의학 Vol.20 No.5

BACKGROUND: All-trans retinoic acid (ATRA) promotes the osteogenic differentiation induced by bone morphogenetic protein 9 (BMP9), but the intrinsic relationship between BMP9 and ATRA keeps unknown. Herein, we investigated the effect of Cyp26b1, a critical enzyme of ATRA degradation, on the BMP9-induced osteogenic differentiation in mesenchymal stem cells (MSCs), and unveiled possible mechanism through which BMP9 regulates the expression of Cyp26b1. METHODS: ATRA content was detected with ELISA and HPLC–MS/MS. PCR, Western blot, and histochemical staining were used to assay the osteogenic markers. Fetal limbs culture, cranial defect repair model, and micro–computed tomographic were used to evaluate the quality of bone formation. IP and ChIP assay were used to explore possible mechanism. RESULTS: We found that the protein level of Cyp26b1 was increased with age, whereas the ATRA content decreased. The osteogenic markers induced by BMP9 were increased by inhibiting or silencing Cyp26b1 but reduced by exogenous Cyp26b1. The BMP9-induced bone formation was enhanced by inhibiting Cyp26b1. The cranial defect repair was promoted by BMP9, which was strengthened by silencing Cyp26b1 and reduced by exogenous Cyp26b1. Mechanically, Cyp26b1 was reduced by BMP9, which was enhanced by activating Wnt/b-catenin, and reduced by inhibiting this pathway. b-catenin interacts with Smad1/5/9, and both were recruited at the promoter of Cyp26b1. CONCLUSIONS: Our findings suggested the BMP9-induced osteoblastic differentiation was mediated by activating retinoic acid signalling, viadown-regulating Cyp26b1. Meanwhile, Cyp26b1 may be a novel potential therapeutic target for the treatment of bone-related diseases or accelerating bone-tissue engineering.

Liver Cancer Mortality Characteristics and Trends in China from 1991 to 2012

Fang, Jia-Ying,Wu, Ku-Sheng,Zeng, Yang,Tang, Wen-Rui,Du, Pei-Ling,Xu, Zhen-Xi,Xu, Xiao-Ling,Luo, Jia-Yi,Lin, Kun Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.5

Purpose: To investigate the distribution of liver cancer mortality as well as its developing trend from 1991 to 2012, forecast the future five-year trend, and provide a basis for the comprehensive prevention and management. Materials and Methods: Mortality data for liver cancer in China from 1991 to 2012 were used to describe characteristics and distribution of liver cancer mortality. Trend surface analysis was used to study the geographical distribution of liver cancer mortality. Curve estimation, time series modeling, gray modeling (GM) and joinpoint regression were used to predict and forecast future trends. Results: The mortality rate of liver cancer has constantly increased in China since 1991. Rates in rural areas are higher than in urban areas, and in males are higher than in females. In addition, our data predicted that the trend will continue to increase in the next 5 years. The age-specific mortality of liver cancer increases with age and peaks in the group of 80-84 years old. Geographical analysis showed the liver mortality rate was higher in the southeast provinces, such as Jiangsu, Zhejiang and Guangdong, and southwest regions like Guangxi Province. Conclusions: The standardized mortality rate of liver cancer in China has consistently increased from 1991 to 2012, and the upward trend is predicted to continue in the future. Much better prevention and management of liver cancer is needed in high mortality areas (the southwestern and southeastern parts of China) and high mortality age groups (80- to 84-year-olds), especially in rural areas.