Methods on improvements of the poor oral bioavailability of ginsenosides: Pre-processing, structural modifi cation, drug combination, and micro- or nano- delivery system

Qi-rui Hu,Huan Hong,Zhi-hong Zhang,Hua Feng,Ting Luo,Jing Li,Ze-yuan Deng,Fang Chen 고려인삼학회 2023 Journal of Ginseng Research Vol.47 No.6

Panax ginseng Meyer is a traditional Chinese medicine that is widely used as tonic in Asia. The mainpharmacologically active components of ginseng are the dammarane-type ginsenosides, which havebeen shown to have anti-cancer, anti-inflammatory, immunoregulatory, neuroprotective, and metabolicregulatory activities. Moreover, some of ginsenosides (eg, Rh2 and Rg3) have been developed intonutraceuticals. However, the utilization of ginsenosides in clinic is restrictive due to poor permeability incells and low bioavailability in human body. Obviously, the dammarane skeleton and glycosyls of ginsenosidesare responsible for these limitations. Therefore, improving the oral bioavailability of ginsenosideshas become a pressing issue. Here, based on the structures of ginsenosides, we summarized theunderstanding of the factors affecting the oral bioavailability of ginsenosides, introduced the methods toenhance the oral bioavailability and proposed the future perspectives on improving the oral bioavailabilityof ginsenosides.

The ways for ginsenoside Rh2 to fight against cancer: the molecular evidences in vitro and in vivo.

Qi-rui Hu,Yao Pan,Han-cheng Wu,Zhen-zhen Dai,Qing-xin Huang,Ting Luo,Jing Li,Ze-yuan Deng,Fang Chen The Korean Society of Ginseng 2023 Journal of Ginseng Research Vol.47 No.2

Cancer is a global public health issue that becomes the second primary cause of death globally. Considering the side effects of radio- or chemo-therapy, natural phytochemicals are promising alternatives for therapeutic interventions to alleviate the side effects and complications. Ginsenoside Rh2 (GRh2) is the main phytochemical extracted from Panax ginseng C.A. Meyer with anticancer activity. GRh2 could induce apoptosis and autophagy of cancer cells and inhibit proliferation, metastasis, invasion, and angiogenesis in vitro and in vivo. In addition, GRh2 could be used as an adjuvant to chemotherapeutics to enhance the anticancer effect and reverse the adverse effects. Here we summarized the understanding of the molecular mechanisms underlying the anticancer effects of GRh2 and proposed future directions to promote the development and application of GRh2.

Fabrication Process of Triple-Layer Small-Diameter Vascular Scaffold with Microchannel Structure in the Inner Layer for Accelerated Endothelialization

Qingxi Hu,Qi Wang,Suihong Liu,Ye Lu,Zhaoxiang Zeng,Jiaxuan Feng,Rui Feng,Haiguang Zhang 한국섬유공학회 2023 Fibers and polymers Vol.24 No.2

Nowadays, many studies focus on the preparation of small-diameter vascular scaffolds, but some issues still existed that needto be urgently solved, but there are still problems such as slow endothelialization and failure to keep the vessels open for a longtime that need to be solved. In this paper, a composite process of preparing triple-layer vascular scaffolds with microchannelstructure in the inner layer is proposed to guide cell growth and accelerate the endothelialization process. The PCL patternwas printed as the intermediate layer of the vascular scaffold by 3D printing method, and the width of the microchannel inthe inner layer of the scaffold was controlled by the printing spacing. The inner and outer layers were prepared by electrospinning. Heparin is often used as an anticoagulant in vascular tissue engineering to improve the problem of thrombosisand blockage of vascular scaffold after transplantation into the body. Here, the inner layer carries heparin immobilized withsilk fibroin by coaxial electrospinning, so that heparin can be released slowly. The addition of silk fibroin also improvedthe hydrophilicity of PCL electrospinning film by water contact angle test. The mechanical properties of vascular scaffoldswith double intermediate layers (DIL) are better than those with single intermediate layers (SIL) and also better than pureelectrospinning scaffolds. In vitro cell experiments showed that cells grow directionally on microchannel structures of innerlayer and randomly on electrospinning film without microchannel structure. The results showed that the microchannels weremore conducive to cell growth and proliferation at a diameter of 0.25 mm. The composite electrospinning films with silkfibroin and heparin facilitated cell adhesion and proliferation compared to the pure PCL films. All these results indicate thatthe vascular scaffolds have potential applications in clinic for vascular tissue regeneration.

miR-1246 inhibits NFATc1 phosphorylation and regulates Th17 cell activation in the pathogenesis of severe alopecia areata

Si-si Qi,Ying Miao,You-yu Sheng,Rui-ming Hu,Jun Zhao,Qin-ping Yang 대한피부과학회 2023 Annals of Dermatology Vol.35 No.1

Background: We found microRNA (miR)-1246 to be significantly differentially expressedbetween severe active alopecia areata (AA) patients and healthy individuals. Objective: To explore the role and mechanism of miR-1246 in severe AA. Methods: Expression of miR-1246, dual-specific tyrosine phosphorylation-regulated kinase1A (DYRK1A), and nuclear factor of activated T cells 1c (NFATc1) in peripheral CD4+ Tcells and in scalp tissues of patients were detected using RT-qPCR, Western blot, and immunohistochemistryassays. Peripheral CD4+ T cells from the AA patients were transfectedwith lentiviral vectors overexpressing miR-1246. RT-qPCR and Western blot analysis wereused to measure mRNA or protein expression of retinoic-acid-receptor-related orphan nuclearreceptor gamma (ROR-γt), interleukin (IL)-17, DYRK1A, NFATc1, and phosphorylatedNFATc1. Flow cytometry was used to assay the CD4+IL-17+ cells proportion. ELISA wasused to measure cytokine levels. Results: miR-1246 levels decreased and DYRK1A and NFATc1 mRNA levels significantlyincreased in the peripheral CD4+ T cells and scalp tissues of severe active AA samples. NFATc1 protein expression was also significantly increased in the peripheral CD4+ T cellsbut not in the scalp tissues. NFATc1 positive cells were mainly distributed among infiltratinginflammatory cells around hair follicles. In peripheral CD4+ T cells of severe active AA,overexpression of miR-1246 resulted in significant downregulation of DYRK1A, NFATc1,ROR-γt, and IL-17 mRNA and phosphorylated NFATc1 protein, as well as a decrease in theCD4+IL-17+ cells proportion and the IL-17F level. Conclusion: miR-1246 can inhibit NFAT signaling and Th17 cell activation, which may bebeneficial in the severe AA treatment.

Super-resolution fluorescent materials: an insight into design and bioimaging applications

Yang, Zhigang,Sharma, Amit,Qi, Jing,Peng, Xiao,Lee, Dong Yeop,Hu, Rui,Lin, Danying,Qu, Junle,Kim, Jong Seung The Royal Society of Chemistry 2016 Chemical Society reviews Vol.45 No.17

<P>Living organisms are generally composed of complex cellular processes which persist only within their native environments. To enhance our understanding of the biological processes lying within complex milieus, various techniques have been developed. Specifically, the emergence of super-resolution microscopy has generated a renaissance in cell biology by redefining the existing dogma towards nanoscale cell dynamics, single synaptic vesicles, and other complex bioprocesses by overcoming the diffraction-imposed resolution barrier that is associated with conventional microscopy techniques. Besides the typical technical reliance on the optical framework and computational algorithm, super-resolution imaging microscopy resorts largely to fluorescent materials with special photophysical properties, including fluorescent proteins, organic fluorophores and nanomaterials. In this tutorial review article, with the emphasis on cell biology, we summarize the recent developments in fluorescent materials being utilized in various super-resolution techniques with successful integration into bio-imaging applications. Fluorescent proteins (FP) applied in super-resolution microscopy will not be covered herein as it has already been well summarized; additionally, we demonstrate the breadth of opportunities offered from a future perspective.</P>

ANXA2 Regulates the Behavior of SGC-7901 Cells

Sun, Meng-Yao,Xing, Rui-Huan,Gao, Xiao-Jie,Yu, Xiang,He, Hui-Min,Gao, Ning,Shi, Hong-Yan,Hu, Yan-Yan,Wang, Qi-Xuan,Xu, Jin-Hui,Hou, Ying-Chun Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.10

ANXA2, a member of the annexin family, is overexpressed and plays important roles in tumor development. However, the significance of ANXA2 expression in gastric carcinoma has not been clarified.To elucidate its roles in growth of gastric cancer, ANXA2 expression in SGC-7901 cells was inhibited with a designated siRNA, then cell proliferation, cell cycling, apoptosis and motility were determined by MTT assay, flow cytometry, Hoechst 33342 staining and wound healing assay, respectively. To further assess the behavior of ANXA2 deleted SGC-7901 cells, changes of microstructures were observed under fluorescence microscopy, laser scanning confocal microscopy and electron microscopy. We found that inhibition of ANXA2 expression caused cell proliferation to decrease significantly with G1 arrest, motility to be reduced with changes in pseudopodia/filopodia structure and F-actin and ${\beta}$-tubulin expression, and apoptosis to be enhanced albeit without significance. At the same time, ANXA2 deletion resulted in fewer pseudopodia/filopodia, non-stained areas were increased, contact inhibition among cells reappeared, and expression of F-actin and ${\beta}$-tubulin was decreased, with induction of polymerized disassembled forms. Taken together, these data suggest that ANXA2 overexpression is important to maintain the malignancy of cancer cells, and this member of the annexin family has potential to be considered as a target for the gene therapy of gastric carcinoma.

The USP21/YY1/SNHG16 axis contributes to tumor proliferation, migration, and invasion of non-small-cell lung cancer

Pei Xu,Haibo Xiao,Qi Yang,Rui Hu,Lianyong Jiang,Rui Bi,Xueyan Jiang,Lei Wang,Ju Mei,Fangbao Ding,Jianbing Huang 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-

Deubiquitinases (DUBs) and noncoding RNAs have been the subjects of recent extensive studies regarding their roles in lung cancer, but the mechanisms involved are largely unknown. In our study, we used The Cancer Genome Atlas data set and bioinformatics analyses and identified USP21, a DUB, as a potential contributor to oncogenesis in nonsmall-cell lung cancer (NSCLC). We further demonstrated that USP21 was highly expressed in NSCLCs. We then conducted a series of in vitro and in vivo assays to explore the effect of USP21 on NSCLC progression and the underlying mechanism involved. USP21 promoted NSCLC cell proliferation, migration, and invasion and in vivo tumor growth by stabilizing a well-known oncogene, Yin Yang-1 (YY1), via mediating its deubiquitination. Furthermore, YY1 transcriptionally regulates the expression of SNHG16. Moreover, StarBase bioinformatics analyses predicted that miR4500 targets SNHG16 and USP21. A series of in vitro experiments indicated that SNHG16 increased the expression of USP21 through miR-4500. In summary, the USP21/YY1/SNHG16 axis plays a role in promoting the progression of NSCLC. Therefore, the USP21/YY1/SNHG16/miR-4500 axis may be a potential therapeutic target in NSCLC treatment.

A High-Throughput Method Based on Microculture Technology for Screening of High-Yield Strains of Tylosin-Producing Streptomyces fradiae

Yao Zhiming,Fan Jingyan,Dai Jun,Yu Chen,Zeng Han,Li Qingzhi,Hu Wei,Yan Chaoyue,Hao Meilin,Li Haotian,Li Shuo,Liu Jie,Huang Qi,Li Lu,Zhou Rui 한국미생물·생명공학회 2023 Journal of microbiology and biotechnology Vol.33 No.6

Tylosin is a potent veterinary macrolide antibiotic produced by the fermentation of Streptomyces fradiae; however, it is necessary to modify S. fradiae strains to improve tylosin production. In this study, we established a high-throughput, 24-well plate screening method for identifying S. fradiae strains that produce increased yields of tylosin. Additionally, we constructed mutant libraries of S. fradiae via ultraviolet (UV) irradiation and/or sodium nitrite mutagenesis. A primary screening of the libraries in 24-well plates and UV spectrophotometry identified S. fradiae mutants producing increased yields of tylosin. Mutants with tylosin yield 10% higher than the wild-type strain were inoculated into shake flasks, and the tylosin concentrations produced were determined by highperformance liquid chromatography (HPLC). Joint (UV irradiation and sodium nitrite) mutagenesis resulted in higher yields of mutants with enhanced tylosin production. Finally, 10 mutants showing higher tylosin yield were re-screened in shake flasks. The yield of tylosin A by strains UN-C183 (6767.64 ± 82.43 μg/ml) and UN-C137 (6889.72 ± 70.25 μg/ml) was significantly higher than that of the wild-type strain (6617.99 ± 22.67 μg/ml). These mutant strains will form the basis for further strain breeding in tylosin production.

Knocking Down Nucleolin Expression Enhances the Radiosensitivity of Non-Small Cell Lung Cancer by Influencing DNA-PKcs Activity

Xu, Jian-Yu,Lu, Shan,Xu, Xiang-Ying,Hu, Song-Liu,Li, Bin,Qi, Rui-Xue,Chen, Lin,Chang, Joe Y. Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.8

Nucleolin (C23) is an important anti-apoptotic protein that is ubiquitously expressed in exponentially growing eukaryotic cells. In order to understand the impact of C23 in radiation therapy, we attempted to investigate the relationship of C23 expression with the radiosensitivity of human non-small cell lung cancer (NSCLC) cells. We investigated the role of C23 in activating the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), which is a critical protein for DNA double-strand breaks (DSBs) repair. As a result, we found that the expression of C23 was negatively correlated with the radiosensitivity of NSCLC cell lines. In vitro clonogenic survival assays revealed that C23 knockdown increased the radiosensitivity of a human lung adenocarcinoma cell line, potentially through the promotion of radiation-induced apoptosis and adjusting the cell cycle to a more radiosensitive stage. Immunofluorescence data revealed an increasing quantity of ${gamma}$-H2AX foci and decreasing radiation-induced DNA damage repair following knockdown of C23. To further clarify the mechanism of C23 in DNA DSBs repair, we detected the expression of DNA-PKcs and C23 proteins in NSCLC cell lines. C23 might participate in DNA DSBs repair for the reason that the expression of DNA-PKcs decreased at 30, 60, 120 and 360 minutes after irradiation in C23 knockdown cells. Especially, the activity of DNA-PKcs phosphorylation sites at the S2056 and T2609 was significantly suppressed. Therefore we concluded that C23 knockdown can inhibit DNA-PKcs phosphorylation activity at the S2056 and T2609 sites, thus reducing the radiation damage repair and increasing the radiosensitivity of NSCLC cells. Taken together, the inhibition of C23 expression was shown to increase the radiosensitivity of NSCLC cells, as implied by the relevance to the notably decreased DNA-PKcs phosphorylation activity at the S2056 and T2609 clusters. Further research on targeted C23 treatment may promote effectiveness of radiotherapy and provide new targets for NSCLC patients.

Structural and Functional Neural Alterations in Internet Addiction: A Study Protocol for Systematic Review and Meta-Analysis

Jun-Li Liu,Jing-Ting Sun,Hui-Lin Hu,Hao-Yuan Wang,Yun-Xi Kang,Tian-Qi Chen,Zhu-Hong Chen,Yu-Xuan Shang,Yu-Ting Li,Bo Hu,Rui Liu 대한신경정신의학회 2023 PSYCHIATRY INVESTIGATION Vol.20 No.1

A growing number of neuroimaging studies have revealed abnormal brain structural and functional alterations in subjects with internet addiction (IA), however, with conflicting conclusions. We plan to conduct a systematic review and meta-analysis on the studies of voxelbased morphometry (VBM) and resting-state functional connectivity (rsFC), to reach a consolidated conclusion and point out the future direction in this field. A comprehensive search of rsFC and VBM studies of IA will be conducted in the PubMed, Cochrane Library, and Web of Science databases to retrieve studies published from the inception dates to August 2021. If the extracted data are feasible, activation likelihood estimation and seed-based d mapping methods will be used to meta-analyze the brain structural and functional changes in IA patients. This study will hopefully reach a consolidated conclusion on the impact of IA on human brain or point out the future direction in this field.