Screening and Anti-virulent Study of N-Acyl Homoserine Lactones DNA Aptamers against Pseudomonas aeruginosa Quorum Sensing

Zu-Guo Zhao,Yun Mei Yu,Bi Yu Xu,Shuang-Shuang Yan,Jun-Fa Xu,Fang Liu,Guo-Ming Li,Yuan Lin Ding,Shu Qing Wu 한국생물공학회 2013 Biotechnology and Bioprocess Engineering Vol.18 No.2

In Pseudomonas aeruginosa, a quorum sensing (QS) system regulates the expression of many virulence factors. N-acyl homoserine lactone (HSL) is the signal molecule of QS system. In order to find a novel HSL binder to interfere with QS signaling and to attenuate P. aeruginosa virulence, an amino lactam surrogate (ALS) of HSL was used as a target to screen HSL aptamers with the technique of systematic evolution of ligands by exponential enrichment (SELEX). Eight HSL aptamers with high affinities for 3O-C12-HSL (20 nM ≤ Kd < 35 nM) or C4-HSL (25 nM < Kd < 50 nM) were finally obtained. In vitro QS-inhibiting study of P. aeruginosa showed that HSL aptamers could inhibit virulence in a dose-dependent manner. ALSap-8 which bound C4-HSL primarily acted on the rhl system and inhibited the secretion of pyocyanin. ALSap-5 which bound 3O-C12-HSL not only showed strong inhibitory activity on biofilm formation as well as secretions of LasA protease and LasB elastase, but also reduced pyocyanin secretion. Since the las system is capable of activating the rhl system mildly, we speculated that ALSap-5 can simultaneously interfere with the las and rhl systems. High-affinity aptamers against HSL in this study are novel QS and virulence-inhibitors, and may have potential as drug candidates for the treatment of P. aeruginosa infection.

An Aqueous Extract of Yunnan Baiyao Inhibits the Quorum-Sensing-Related Virulence of Pseudomonas aeruginosa

Zu-Guo Zhao,Shuang-Shuang Yan,Yun-Mei Yu,Na Mi,La-Xi Zhang,Jun Liu,Xiao-Ling Li,Fang Liu,Jun-Fa Xu,Wei-Qing Yang,Guo-Ming Li 한국미생물학회 2013 The journal of microbiology Vol.51 No.2

Yunnan Baiyao is a famous Chinese medicine that has long been directly applied to wounds to reduce bleeding, pain, and swelling without causing infection. However, little is known about its ability to prevent infection. The present study aimed to assess in vitro the anti-virulence activity of an aqueous extract of Yunnan Baiyao (YBX) using Pseudomonas aeruginosa as a pathogenic model. We found that a sub-MIC (2.5 mg/ml) of YBX can efficiently interfere with the quorum-sensing (QS) signaling circuit. Real-time polymerase chain reaction analysis showed that a sub-MIC of YBX downregulated the transcriptions of lasR, lasI, rhlR, and rhlI,which resulted in global attenuation of QS-regulated virulence activities, such as biofilm formation, and secretion of LasA protease, LasB elastase and pyocyanin. Further, YBX reduced the motility of P. aeruginosa related to QS, and impaired the formation of biofilms. These results suggest that YBX may possess global inhibitory activity against the virulence of P. aeruginosa and that YBX may also exhibit antimicrobial activity in vivo. The present study suggests that Yunnan Baiyao represents a potential source for isolating novel, safe, and efficacious antimicrobial agents.

Construction of antibacterial nano-silver embedded bioactive hydrogel to repair infectious skin defects

Qi Dong,Dan Zu,Lingqiang Kong,Sunfang Chen,Jun Yao,Jiawei Lin,Lei Lu,Bing Wu,Bin Fang 한국생체재료학회 2022 생체재료학회지 Vol.26 No.3

Background: Hydrogels loaded with antimicrobial agents have been widely used for treating infected wound defects. However, hydrogels derived from a porcine dermal extracellular matrix (PADM), containing silver nanoparticles (AgNPs), have not yet been studied. Therefore, we investigated the therapeutic effect of an AgNP-impregnated PADM (AgNP–PADM) hydrogel on the treatment of infected wounds. Methods: An AgNP–PADM hydrogel was synthesized by embedding AgNPs into a PADM hydrogel. We examined the porosity, moisture retention, degradation, antibacterial properties, cytotoxicity, antioxidant properties, and ability of the PADM and AgNP–PADM hydrogels to treat infected wounds in animals. Results: The PADM and AgNP–PADM hydrogels were pH sensitive, which made them flow dynamically and solidify under acidic and neutral conditions, respectively. The hydrogels also exhibited porous network structures, satisfactory moisture retention, and slow degradation. Additionally, the AgNP–PADM hydrogel showed a slow and sustained release of AgNPs for at least 7 days without the particle size changing. Thus, the AgNPs exhibited adequate antibacterial ability, negligible toxicity, and antioxidant properties in vitro. Moreover, the AgNP–PADM hydrogel promoted angiogenesis and healed infected skin defects in vivo. Conclusions: The AgNP–PADM hydrogel is a promising bioderived antibacterial material for clinical application to infected wound dressings

Case Reports : Surgical Treatment for 11 Cases of Penile Verrucous Carcinoma

( Chuan Yu Sun ),( Xu Ke ),( Zheng Jie ),( Guo Wei Xia ),( Zu Jun Fang ),( Qiang Ding ) 대한피부과학회 2011 Annals of Dermatology Vol.23 No.3s

Penile verrucous carcinoma is a rare, well-differentiated and low-grade tumor. The surgeons are deficiently aware about the biological behavior and the clinicopathological characteristic of this disease, which raises difficulties during the treatment. In our present study, the clinical and pathological data of 11 patients with penile verrucous carcinoma, aged between 49 to 85 years was retrospectively analyzed. The tumors exhibited exophytic, papillary, caulifower-like or verrucose lesions of great dimensions measuring between 2 to 10 cm on the penises. The tumors were located at glans in 6 cases, invaded the coronoid sulcus in 4 cases and invaded the shaft of the penis in 1 case. Eight cases underwent partial penectomy, while the other 3 were treated with local excision. The diagnosis of penile verrucous carcinoma was confirmed by histopathologic examination of the specimens with the negative surgical margins in all the cases. Within the period of 12 to 60 months of follow-up, all the patients were disease-free with no case of recurrence and metastasis. The novel knowledge and experience of the treatment of penile verrucous carcinoma will be a useful clinical guide for surgeons in the future. (Ann Dermatol 23(S3) S346~S349, 2011)

Distinctive Slow β Relaxation and Its Impact on Mechanical Property of LaCe Based Bulk Metallic Glasses

Xiao Cui,Jing Guo,Qi‑dong Zhang,Xiao‑jun Meng,Bing‑chuan Bian,Ren‑gao Zhao,Yu‑bai Ma,Fang‑qiu Zu 대한금속·재료학회 2020 METALS AND MATERIALS International Vol.26 No.10

The slow β relaxation which occurring at temperatures far below glass transition temperature, typically playing importantroles in the plastic deformation behavior of metallic glasses. Compared with polymer glasses, most of the metallic glasses donot exhibit obvious β relaxation based on dynamic mechanical analysis. In the current work, prominent β relaxation behaviorsof a series (LaxCe100−x) Al10Co25(x = 50, 60, 70, 80) bulk metallic glasses (BMGs) at low temperature are observed usingdynamic mechanical analysis. Compared with other BMGs, the LaCe based BMGs show a pronounced β relaxation peak andrelative low peak temperature, the activation energy of the β relaxation based on Arrhenius equation are calculated around79.3 kJ/mol to 86.4 kJ/mol, which obey an empirical rule that Eβ ≈ (26 ± 4) RTg, with the coefficient of 23. Experimentalresults from room temperature compression tests for the LaCe based BMGs indicate that low temperature activated β relaxationbehaviors facilitate the good plasticity of the LaCe based BMGs.

Pokemon Inhibits Transforming Growth Factor β-Smad4-Related Cell Proliferation Arrest in Breast Cancer through Specificity Protein 1

Ling Chen,Jing Zhong,Jiang-Hua Liu,Duan-Fang Liao,Ying-Ying Shen,Xiao-Lin Zhong,Xiao Xiao,Wen-Jun Ding,Xiu-Da Peng,Wei Xiong,Xu-Yu Zu 한국유방암학회 2019 Journal of breast cancer Vol.22 No.1

Purpose: Pokemon, also known as ZBTB7A, belongs to the POZ and Krüppel (POK) family of transcription repressors and is implicated in tumor progression as a key proto-oncogene. This present study aimed at determining the mechanism by which Pokemon inhibits transforming growth factor β (TGFβ)-Smad4 pathway-dependent proliferation arrest of breast cancer cells via specificity protein 1 (SP1). Methods: Over-expressing plasmid or small interfering RNA (siRNA) transfection was used to regulate Pokemon levels. The EdU incorporation assay, MTS assay, and clone formation were used to identify the inhibitory effect of Pokemon siRNA on cell proliferation. Quantitative real-time polymerase chain reaction assay confirmed that Pokemon deletion inhibited the expression of proliferation-associated genes. The dual-luciferase reporter assay, electrophoretic mobility shift assay, and co-immunoprecipitation assay were used to analyze binding between Pokemon, Smad4, and SP1. Results: Pokemon deletion induced proliferation arrest of breast cancer cells and inhibited the expression of proliferation-associated genes, especially Smad4. Pokemon bound with SP1 to interdict Smad4 promoter activity. Information on clinical samples was obtained from The Cancer Genome Atlas data, in which the Pokemon mRNA levels showed a negative correlation with Smad4 levels in different subtypes of breast cancer in two independent datasets. Conclusion: We demonstrated that Pokemon binds to SP1 to down-regulate Smad4 expression, thereby promoting proliferation of breast cancer cells. This suggests that Pokemon is a potential TGFβ-signaling participant in breast cancer progression.

Fangchinoline Inhibits Cell Proliferation Via Akt/GSK-3beta/cyclin D1 Signaling and Induces Apoptosis in MDA-MB-231 Breast Cancer Cells

Wang, Chang-Dong,Yuan, Cheng-Fu,Bu, You-Quan,Wu, Xiang-Mei,Wan, Jin-Yuan,Zhang, Li,Hu, Ning,Liu, Xian-Jun,Zu, Yong,Liu, Ge-Li,Song, Fang-Zhou Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.2

Fangchinoline (Fan) inhibits cell proliferation and induces apoptosis in several cancer cell lines. The effects of Fan on cell growth and proliferation in breast cancer cells remain to be elucidated. Here, we show that Fan inhibited cell proliferation in the MDA-MB-231 breast cancer cell line through suppression of the AKT/Gsk-3beta/cyclin D1 signaling pathway. Furthermore, Fan induced apoptosis by increasing the expression of Bax (relative to Bcl-2), active caspase 3 and cytochrome-c. Fan significantly inhibited cell proliferation of MDA-MB-231 cells in a concentration and time dependent manner as determined by MTT assay. Flow cytometry analysis demonstrated that Fan treatment of MDA-MB-231 cells resulted in cell cycle arrest at the G1 phase, which correlated with apparent downregulation of both mRNA and protein levels of both PCNA and cyclin D1. Further analysis demonstrated that Fan decreased the phosphorylation of AKT and GSK-3beta. In addition, Fan up-regulated active caspase3, cytochrome-c protein levels and the ratio of Bax/Bcl-2, accompanied by apoptosis. Taken together, these results suggest that Fan is a potential natural product for the treatment of breast cancer.