Publications by authors named "Lingling Xiao"

7 Publications

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Ultra-strong bio-glue from genetically engineered polypeptides.

Nat Commun 2021 06 14;12(1):3613. Epub 2021 Jun 14.

Zernike Institute for Advanced Materials, University of Groningen, Groningen, The Netherlands.

The development of biomedical glues is an important, yet challenging task as seemingly mutually exclusive properties need to be combined in one material, i.e. strong adhesion and adaption to remodeling processes in healing tissue. Here, we report a biocompatible and biodegradable protein-based adhesive with high adhesion strengths. The maximum strength reaches 16.5 ± 2.2 MPa on hard substrates, which is comparable to that of commercial cyanoacrylate superglue and higher than other protein-based adhesives by at least one order of magnitude. Moreover, the strong adhesion on soft tissues qualifies the adhesive as biomedical glue outperforming some commercial products. Robust mechanical properties are realized without covalent bond formation during the adhesion process. A complex consisting of cationic supercharged polypeptides and anionic aromatic surfactants with lysine to surfactant molar ratio of 1:0.9 is driven by multiple supramolecular interactions enabling such strong adhesion. We demonstrate the glue's robust performance in vitro and in vivo for cosmetic and hemostasis applications and accelerated wound healing by comparison to surgical wound closures.
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http://dx.doi.org/10.1038/s41467-021-23117-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203747PMC
June 2021

Novel Thiochromanone Derivatives Containing a Sulfonyl Hydrazone Moiety: Design, Synthesis, and Bioactivity Evaluation.

Molecules 2021 May 14;26(10). Epub 2021 May 14.

School of Liquor and Food Engineering, Guizhou University, Guiyang 550025, China.

A series of novel thiochromanone derivatives containing a sulfonyl hydrazone moiety were designed and synthesized. Their structures were determined by H-NMR, C-NMR, and HRMS. Bioassay results showed that most of the target compounds revealed moderate to good antibacterial activities against pv. , pv. , and pv. . Compound had the best inhibitory activity against pv. , pv. , and pv. , with the EC values of 8.67, 12.65, and 10.62 μg/mL, which were superior to those of Bismerthiazol and Thiodiazole-copper. Meanwhile, bioassay results showed that all of the target compounds proved to have lower antifungal activities against , , , , , and than those of Carbendazim.
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http://dx.doi.org/10.3390/molecules26102925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156870PMC
May 2021

Genetically Engineered Polypeptide Adhesive Coacervates for Surgical Applications.

Angew Chem Int Ed Engl 2021 Apr 22. Epub 2021 Apr 22.

Tsinghua University, Department of Chemistry, qinghua yuan, 100084, Beijing, CHINA.

Adhesive hydrogels have been developed for wound healing applications. However, their adhesive performance is impaired dramatically due to their high swelling on wet tissues. To tackle this challenge, we fabricated a new type of non-swelling protein adhesive for underwater and in vivo applications. In this soft material, the electrostatic complexation between supercharged polypeptides with oppositely charged surfactants containing 3,4-dihydroxylphenylalanine or azobenzene moieties plays an important role for the formation of ultra-strong adhesive coacervates. Remarkably, the adhesion capability is superior to commercial cyanoacrylate when tested in ambient conditions. Moreover, the adhesion is stronger than other reported protein-based adhesives in underwater environment. The ex vivo and in vivo experiments demonstrate the persistent adhesive performance and outstanding behaviors for wound sealing and healing. Thus, this new type of genetically engineered adhesive coacervates is a very promising alternative for surgical applications.
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http://dx.doi.org/10.1002/anie.202100064DOI Listing
April 2021

An Artificial Phase-Transitional Underwater Bioglue with Robust and Switchable Adhesion Performance.

Angew Chem Int Ed Engl 2021 05 16;60(21):12082-12089. Epub 2021 Apr 16.

State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.

Complex coacervation enables important wet adhesion processes in natural and artificial systems. However, existed synthetic coacervate adhesives show limited wet adhesion properties, non-thermoresponsiveness, and inferior biodegradability, greatly hampering their translations. Herein, by harnessing supramolecular assembly and rational protein design, we present a temperature-sensitive wet bioadhesive fabricated through recombinant protein and surfactant. Mechanical performance of the bioglue system is actively tunable with thermal triggers. In cold condition, adhesion strength of the bioadhesive was only about 50 kPa. By increasing temperature, the strength presented up to 600 kPa, which is remarkably stronger than other biological counterparts. This is probably due to the thermally triggered phase transition of the engineered protein and the formation of coacervate, thus leading to the enhanced wet adhesion bonding.
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http://dx.doi.org/10.1002/anie.202102158DOI Listing
May 2021

Berberine promotes osteogenic differentiation of mesenchymal stem cells with therapeutic potential in periodontal regeneration.

Eur J Pharmacol 2019 May 15;851:144-150. Epub 2019 Feb 15.

Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University, 30 Zhongyang Road, Nanjing, Jiangsu 210008, China. Electronic address:

Periodontal disease is a bacterial infection-associated disease of the periodontal tissues characterized by the destruction of tooth-supporting structures, including alveolar bone. The ideal goal of periodontal therapy is the complete regeneration of alveolar bone in a healthy microenvironment free of infection. In this study, we found that berberine, a benzylisoquinoline plant alkaloid from Coptidis Rhizoma, strongly inhibited the growth of Porphyromonas gingivalis. Gingipain is the most important virulence factor of Porphyromonas gingivalis in the process of periodontal tissue destruction. Berberine also had an inhibitory effect on gingipain activity in a concentration dependent manner. Remarkably, berberine restored the downregulation of osteogenesis-related genes expression in bone mesenchymal stem cells (BMSCs) induced by Porphyromonas gingivalis infection, and significantly increased the expression of osteogenesis-related genes such as OSX, COLI, ALP, OCN and OPN compared to the control group. This results suggested that berberine may directly promote osteogenesis. Further in-vitro studies demonstrated that berberine statistically significantly promoted the osteogenic differentiation of BMSCs at concentrations of 1-10 μM. In the research on the mechanisms, we found that both total β-catenin and nuclear β-catenin accumulation were statistically significantly increased by berberine. And the transcriptional activity of β-catenin/TCF was about 2 folds higher than the control group. Furthermore, Wnt signalling specific inhibitor DKK-1 blocked the above effects of berberine. These demonstrated that Wnt/β-catenin signalling pathway was involved in the osteogenic differentiation induced by berberine. The antibacterial actions in combination with the promotion role in osteogenic differentiation position berberine as a prospective drug for periodontal tissue regeneration.
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http://dx.doi.org/10.1016/j.ejphar.2019.02.026DOI Listing
May 2019

AMP-activated protein kinase activation in mediating phenylalanine-induced neurotoxicity in experimental models of phenylketonuria.

J Inherit Metab Dis 2018 07 11;41(4):679-687. Epub 2017 Dec 11.

Department of Neonatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, People's Republic of China.

Phenylketonuria (PKU), one of the most prevalent autosomal recessive disorders of amino acid metabolism, is characterized by abnormal accumulation of phenylalanine, which can lead to intellectual disability. The main pathologic changes in the central nervous system of untreated phenylketonuric patients are reductions in the number of axons, dendrites, and synapses in the brain. Such alterations are thought to be mainly associated with the toxic effects caused by phenylalanine. However, the underlying molecular mechanisms have not been fully elucidated. The present study shows that a high concentration of phenylalanine remarkably inhibited neuronal neurite formation in vitro. Interestingly, AMP-activated protein kinase (AMPK), the energy status sensor, was activated in cultured cerebral cortical neurons upon phenylalanine treatment. Pretreatment with an AMPK inhibitor ameliorated the reduction of neurite formation caused by phenylalanine. In addition, the levels of the phosphorylated AMPK, the active form of AMPK, were significantly higher in the cerebral cortices of PKU mice with elevated phenylalanine levels in this brain region compared to those in wild-type control mice, whereas the density of dendritic spines on basal secondary dendrites of pyramidal neurons in prefrontal cortices of PKU mice was significantly decreased. Collectively, these findings indicate that AMPK activation is a key event in impaired neuronal dendritic development in PKU and consequently, a potential therapeutic target for developing neuroprotective strategies against phenylalanine-evoked brain injury in PKU.
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http://dx.doi.org/10.1007/s10545-017-0115-6DOI Listing
July 2018

Enzymatic synthesis of N-succinyl chitosan-collagen peptide copolymer and its characterization.

Carbohydr Polym 2017 Jun 7;166:45-54. Epub 2017 Jan 7.

Department of Anatomy, College of Medicine, Huazhong University of Science and Technology, Wuhan 430074, China.

Collagen peptide (COP) grafted N-succinyl chitosan (NSC) was prepared by using microbial transglutaminase (MTGase) as biocatalyst. The catalyzed reaction displayed high efficiency, high selectivity, mild reaction condition and environmental friendliness. The degree of substitution (DS) of N-succinyl chitosan-collagen peptide (NSC-COP)depended on the reaction time, the reaction temperature, the mass ratio of COP to NSC and the mass ratio of MTGase to NSC. NSC-COP showed excellent moisture absorption and retention properties. Antioxidant activities of varying DS and concentration of NSC-COP were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl. Methylthiazol tetrazolium (MTT) assay exhibited that at a suitable concentration NSC-COP with different DS value could promote L929 mouse fibroblasts effectively. The animal experiment indicated that the wound covered with NSC-COP were completely filled with new epithelium within 2 weeks without any significant adverse side reactions. Therefore, the results may contribute to finding the application of NSC-COP in pharmaceutical and biomedical fields.
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http://dx.doi.org/10.1016/j.carbpol.2017.01.012DOI Listing
June 2017