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Janus hydrogel with dual antibacterial and angiogenesis functions for enhanced diabetic wound healing

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Chinese Chemical Letters 2023年第4期34卷 122-126页

作者： guiting Liu Yuan Zhou Zejun Xu Ziting Bao Li Zheng Jun Wu The State Key Laboratory of Polymer Materials Engineering Polymer Research Institute of Sichuan UniversityChengdu 610065China Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat-sen Memorial Hospital Sun Yat-sen UniversityGuangzhou 510120China School of Biomedical Engineering Sun Yat-sen UniversityGuangzhou 510006China Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration Life Science InstitutesGuangxi Medical UniversityNanning 530021China Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry Guangxi Medical UniversityNanning 530021China

Anti-infection and neovascularization at the wound site are two vital factors that accelerate diabetic wound healing. However, for a wound healing dressing, the two functions need to work at different sites(inner and outer), giving big challenges for dressing design. In this study, we fabricated a novel sodium alginate/chitosan(SA/CS) Janus hydrogel dressing by the assembly of SA hydrogel loaded with silver nanoparticles(Ag NPs) and CS hydrogel impregnated with L-arginine loaded sodium alginate microspheres(Arg MSs) based on electrostatic interactions to combine the two functions. The outer SA-Ag NP hydrogel could prevent infection while avoiding the deposition of Ag NPs in the wound site, and the inner CS-Arg MS hydrogel on the wound surface could realize the sustained release of L-arginine and promote vascular regeneration. The composition, morphology and swelling/degradation of the SA-Ag NP/CS-Arg MS hydrogel were characterized systematically. L-Arginine release behavior has been tested and SA-Ag NP/CSArg MS hydrogel has been confirmed for excellent biocompatibility. Antibacterial and angiogenesis assays demonstrated the antibacterial and angiogenesis characteristics of the SA-Ag NP/CS-Arg MS hydrogel. Finally, in vivo diabetic wound healing assay demonstrated that the SA-Ag NP/CS-Arg MS hydrogel could significantly accelerate re-epithelialization, granulation tissue formation, collagen deposition and angiogenesis, thereby resulting in enhanced diabetic wound healing。

关键词： Janus hydrogel Antibacterial Angiogenesis Diabetic wound Wound healing

Emerging neuromodulatory molecules for the treatment of neurogenic erectile dysfunction caused by cavernous nerve injury

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Asian Journal of Andrology 2008年第1期10卷 54-59页

作者： Anthony J. Bella guiting Lin Ilias Cagiannos Tom F. Lue Department of Surgery Division of UrologyUniversity of Ottawa Ottawa KIY4E9 Canada Department of Neuroscience Ottawa Health Research Institute University of Ottawa Ottawa KIY4E9 Canada Knuppe Molecular Urology Laboratory San Francisco CA 94143 USA Department of Urology University of California San Francisco CA 94143 USA

Advances in the neurobiology of growth factors, neural development, and prevention of cell death have resulted in a heightened clinical interest for the development of protective and regenerative neuromodulatory strategies for the cavernous nerves （CNs）, as therapies for prostate cancer and other pelvic malignancies often result in neuronal damage and debilitating loss of sexual function. Nitric oxide released from the axonal end plates of these nerves within the corpora cavernosa causes relaxation of smooth muscle, initiating the haemodynamic changes of penile erection as well as contributing to maintained tumescence; the loss of CN function is primarily responsible for the development of erectile dysfunction （ED） after pelvic surgery and serves as the primary target for potential neuroprotective or regenerative strategies. Evidence from pre-clinical studies for select neuromodulatory approaches is reviewed, including neurotrophins, glial cell line-derived neurotrophic factors （GDNF）, bone morphogenic proteins, immunophilin ligands, erythropoetin （EPO）, and stem cells.

关键词： erectile dysfunction prostate cancer radical prostatectomy postoperative complications neuroprotection nerve regeneration neurotrophins brain-derived nerve growth factor immunophilin ligands stem cells

Hyaluronic acid-methacrylic anhydride/polyhexamethylene biguanide hybrid hydrogel with antibacterial and proangiogenic functions for diabetic wound repair

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Chinese Chemical Letters 2022年第12期33卷 5030-5034页

作者： Yike Li Huiyu Zheng Yaxian Liang Ming Xuan guiting Liu Huixu Xie State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologyState Key Laboratory of Polymer Materials EngineeringSichuan UniversityChengdu 610041China

Diabetic wounds lead to a decrease in quality of life and an increase in *** treatment strategies include preventing bacterial adhesion while improving *** a new type of wound dressing that imitates natural skin,hydrogel has gradually emerged with its excellent ***,existing hydrogels rarely achieve satisfactory results in promoting wound repair and antibacterial *** this case,we prepared methacrylic anhydride chemically modified hyaluronic acid as a hydrogel matrix,added polyhexamethylene biguanide as an antibacterial component,and loaded sodium alginate/salidroside composite microspheres which could sustainably release salidroside and thus promote *** hydrogel(HAMA/PHMB-Ms)was synthesized via photocrosslinking,and its chemical structure,particle size distribution and microstructure were *** satisfactory antibacterial properties of the HAMA/PHMB(15%)-Ms hydrogel were studied in vitro,and its antibacterial rates against *** and *** were 97.85%and 98.56%,*** addition,after demonstrating its good biocompatibility,we verified that the HAMA/PHMB-Ms hydrogel has increased granulation tissue formation,more collagen deposition,more subcutaneous capillary formation,and better wound healing than blank control,HAMA and HAMA/PHMB hydrogel on the back wound model of diabetic *** results confirmed that HAMA/PHMB-Ms hydrogel was a promising material for the treatment of the diabetic wounds.

关键词： Hydrogel Diabetic wounds Antibacterial Angiogenesis

Discriminated sgRNAs-Based SurroGate System Greatly Enhances the Screening Efficiency of Plant Base-Edited Cells

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Molecular Plant 2020年第1期13卷 169-180页

作者： Wen Xu Yongxing yang Ya Liu guiting Kang Feipeng Wang Lu Li Xinxin Lv Si Zhao Shuang Yuan Jinling Song Ying Wu Feng Feng Xiaoqing He Chengwei Zhang Wei Song Jiuran Zhao Jinxiao yang Beijing Key Laboratory of Maize DNA Fingerprinting and Molecular Breeding Beijing Academy of Agriculture&Forestry SciencesBeijing 100080China

The development of CRISPR/Cas9-mediated base editing has made genomic modification more efficient. However, selection of genetically modified cells from millions of treated cells, especially plant cells, is still challenging. In this study, an efficient surrogate reporter system based on a defective hygromycin resistance gene was established in rice to enrich base-edited cells. After step-by-step optimization, the Discriminated sgRNAs-based SurroGate system (DisSUGs) was established by artificially differentiating the editing abilities of a wild-type single guide RNA (sgRNA) targeting the surrogate reporter gene and an enhanced sgRNA targeting endogenous sites. The DisSUGs enhanced the efficiency of screening base-edited cells by 3- to 5-fold for a PmCDA1-based cytosine-to-tyrosine base editor (PCBE), and 2.5- to 6.5-fold for an adenine base editor (ABE) at endogenous targets. These targets showed editing efficiencies of <25% in the conventional systems. The DisSUGs greatly enhanced the frequency of homozygous substitutions and expanded the activity window slightly for both a PCBE and an ABE. Analyses of the total number of single-nucleotide variants from whole-genome sequencing revealed that, compared with the no-enrichment PCBE strategy, the DisSUGs did not alter the frequency of genome-wide sgRNA-independent off-target mutations, but slightly increased the frequency of target-dependent off-target mutations. Collectively, the DisSUGs developed in this study greatly enhances the efficiency of screening plant base-edited cells and will be a useful system in future applications.

关键词： cell enrichment surrogate reporter cytosine base editors adenine base editors

Icariin on relaxation effect of corpus cavernosum smooth muscle

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Chinese Science Bulletin 2001年第14期46卷 1186-1191页

作者： XIN Zhongcheng Kim Euikyung TIAN Zhenji LIN guiting QUO Yinglu Department of Urology The First HospitalPeking UniversityBeijing100034China Department of Life Science Pohang University of Science and TechnologyPohangKorea

NO-cGMP pathway in penile corpus cavernosal smooth muscle plays an important role in penile erection. The level of cGMP is regulated by a balance between the rate of synthesis by guanylate cyclase and the rate of hydrolytic breakdown to guanosine 5’ monophosphate (GMP) by phos-phodiesterase 5(PDE5). Icariin is isolated from natural drug Epimedii herba, it is shown to have the relaxation effect on corpus cavernosal smooth muscle of rabbit (IC50: 4×10-4 mol/L), and the mechanism of the relaxation effect of Icariin on corpus cavernosum believed to have the inhibiting effect on PDE5 and activation of NO-cGMP pathway to enhancing penile erection.

关键词： Icariin corpus cavernosm cGMP erection.

Molecular Yin and yang of erectile function and dysfunction

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Asian Journal of Andrology 2008年第3期10卷 433-440页

作者： Ching-Shwun Lin Zhong-Cheng Xin Zhong Wang guiting Lin Tom E Lue Knuppe Molecular Urology Laboratory Department of Urology School of Medicine University of California San Francisco CA 94143 USA Andrology Center Peking University First Hospital Beijing 100009 China Department of Urology Ninth Hospital Shanghai Second Medical University Shanghai 200011 China

In regard to erectile function, Yin is flaccidity and yang erection. In the past decade, research has mostly focused on the yang aspect of erectile function. However, in recent years, the Yin side is attracting increasingly greater attention. This is due to the realization that penile flaccidity is no less important than penile erection and is actively maintained by mechanisms that play critical roles in certain types of erectile dysfunction （ED）; for example, in diabetic patients. In addition, there is evidence that the Yin and yang signaling pathways interact with each other during the transition from flaccidity to erection, and vice versa. As such, it is important that we view erectile function from not only the yang but also the Yin side. The purpose of this article is to review recent advances in the understanding of the molecular mechanisms that regulate the Yin and yang of the penis. Emphasis is given to the Rho kinase signaling pathway that regulates the Yin, and to the cyclic nucleotide signaling pathway that regulates the yang. Discussion is organized in such a way so as to follow the signaling cascade, that is, beginning with the extracellular signaling molecules （e.g., norepinephrin and nitric oxide） and their receptors, converging onto the intracellular effectors （e.g., Rho kinase and protein kinase G）, branching into secondary effectors, and finishing with contractile molecules and phosphodiesterases. Interactions between the Yin and yang signaling pathways are discussed as well.

关键词： erectile function erectile dysfunction molecular mechanisms Rho kinase signaling cyclic nucleotide signaling Yin-yang

Recruiting endogenous stem cells： a novel therapeutic approach for erectile dysfunction

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Asian Journal of Andrology 2016年第1期18卷 10-15页

作者： Zhong-Cheng Xin Yong-De Xu guiting Lin Tom FLue Ying-Lu Guo Andrology Center Peking University First Hospital Peking University Beijing 100034 China Knuppe Molecular Urology Laboratory Department of Urology School of Medicine University of California San Francisco CA USA.

Transplanted stem cells （SCs）, owing to their regenerative capacity, represent one of the most promising methods to restore erectile dysfunction （ED）. However, insufficient source, invasive procedures, ethical and regulatory issues hamper their use in clinical applications. The endogenous SCs/progenitor cells resident in organ and tissues play critical roles for organogenesis during development and for tissue homeostasis in adulthood. Even without any therapeutic intervention, human body has a robust self-healing capability to repair the damaged tissues or organs. Therefore, SCs-for-ED therapy should not be limited to a supply-side approach. The resident endogenous SCs existing in patients could also be a potential target for ED therapy. The aim of this review was to summarize contemporary evidence regarding：（1） SC niche and SC biological features in vitro; （2） localization and mobilization of endogenous SCs; （3） existing evidence of penile endogenous SCs and their possible mode of mobilization. We performed a search on PubMed for articles related to these aspects in a wide range of basic studies. Together, numerous evidences hold the promise that endogenous SCs would be a novel therapeutic approach for the therapy of ED.

关键词： endogenous stem cell erectile dysfunction homing niche

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江西某钨矿深部开采微震监测研究

中国钨业 2024年第2期39卷 33-37页

作者：刘家胜钟晓阳曾贵庭方鑫邓金荣江西铁山垅钨业有限公司江西于都342307

江西某钨矿矿区深部区域大采采场周边围岩中巷道变形、冒顶片帮等地压问题显现明显,严重影响了矿山生产安全。本文简要介绍了矿区的开采历史,主要采矿方法及地压的显现方式,指出了矿山深部地压的危害性,论述了采用多通道微震监测技术的... 详细信息

江西某钨矿矿区深部区域大采采场周边围岩中巷道变形、冒顶片帮等地压问题显现明显,严重影响了矿山生产安全。本文简要介绍了矿区的开采历史,主要采矿方法及地压的显现方式,指出了矿山深部地压的危害性,论述了采用多通道微震监测技术的必要性及其系统的组成与特点。建立微震监测系统后,通过统计矿区每日产生的微震信号的幅值及次数,分析其变化规律,成功对巷道冒顶事件进行了预警;同时系统收集到老采空区的微震定位事件,表明老采空区的岩体结构并不稳定。实际情况表明,微震监测系统能够对矿山岩体的状态进行评估,对一定的岩体灾害进行预警,为矿山生产安全提供保障。

关键词：地压深部开采微震监测灾害预警

Interaction of hTCF4 by yeast two-hybrid system

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Chinese Science Bulletin 2000年第21期45卷 1973-1977页

作者： LIN guiting ZHANG Zhiwen ZANG long XIN Dianqi CHANG Zhijie GUO Yinglu Urology Institute Beijing Medical UniversityBeijing 100034China Physiology Department Beijing Medical UniversityBeijing 100034China Biology Department Qinghua UniversityBeijing 100084China

To investigate the interaction of hTCF4, the yeast two-hybrid system has been used for testing the interaction of mutants of hTCF4 with themselves. Mutants of hTCF4 (hTCF4 Ⅰ ) and hTCF4 Ⅱ) have been obtained by polymerase chain reaction (PCR). Bait (hTCF4 Ⅰ -pDBLeu and hTCF4Ⅱ-pDBLeu) and prey (hTCF4 Ⅰ -pPC86 and hTCF4Ⅱ-pPC86) have been constructed by DNA recombination for yeast two-hybrid. Interaction of hTCF4Ⅱ with itself is found in the reverse yeast two-hybrid system (GIBCOBRL Co.). However, no interactions are found in hTCF4Ⅱ with hTCF4 Ⅰ and in hTCF4 Ⅰ with hTCF4 Ⅰ . These results suggest that hTCF4 could interact with itself to form homodimer or homocopolymer and perform the transcriptional activating function through LZ or HLH motifs in nucleus of renal cell carcinoma.

关键词： Wnt/Frizzled hTCF4 yeast two-hybrid.