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Article ; Online: Hematoxylin modulates tau-RD protein fibrillization and ameliorates Alzheimer's disease-like symptoms in a yeast model.

Yin, Huan-Huan / Han, Yin-Lei / Yan, Xiao / Guan, Yi-Xin

International journal of biological macromolecules

2023 Volume 250, Page(s) 126140

Abstract: Alzheimer's disease (AD) is one of the most serious neurodegenerative diseases with no effective treatment options available. The formation of insoluble amyloid fibrils of the hyperphosphorylated tau protein is intimately associated with AD, hence the ... ...

Abstract	Alzheimer's disease (AD) is one of the most serious neurodegenerative diseases with no effective treatment options available. The formation of insoluble amyloid fibrils of the hyperphosphorylated tau protein is intimately associated with AD, hence the tau protein has been a key target for AD drug development. In this work, hematoxylin was discovered as a dual functional compound, that is, acting in the inhibition of repeat domain of tau (tau-RD) protein fibrillogenesis and remodeling of pre-formed tau-RD fibrils in vitro. Meanwhile, hematoxylin was able to reduce the accumulation of tau-RD aggregates in Saccharomyces cerevisiae. Experimental and computational studies indicated that hematoxylin directly interacts with tau-RD protein through hydrophobic forces, hydrogen bonds, π-cation interactions, and π-π stackings. In addition, cellular viability assays showed that hematoxylin greatly reduced cytotoxicity induced by tau-RD aggregates. In summary, hematoxylin might be a promising candidate for further development as a potential therapeutic drug for AD patients.
Language	English
Publishing date	2023-08-04
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2023.126140
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Article ; Online: Hematoxylin modulates tau-RD protein fibrillization and ameliorates Alzheimer's disease-like symptoms in a yeast model

Yin, Huan-Huan / Han, Yin-Lei / Yan, Xiao / Guan, Yi-Xin

International Journal of Biological Macromolecules. 2023 Oct., v. 250 p.126140-

2023

Abstract	Alzheimer's disease (AD) is one of the most serious neurodegenerative diseases with no effective treatment options available. The formation of insoluble amyloid fibrils of the hyperphosphorylated tau protein is intimately associated with AD, hence the tau protein has been a key target for AD drug development. In this work, hematoxylin was discovered as a dual functional compound, that is, acting in the inhibition of repeat domain of tau (tau-RD) protein fibrillogenesis and remodeling of pre-formed tau-RD fibrils in vitro. Meanwhile, hematoxylin was able to reduce the accumulation of tau-RD aggregates in Saccharomyces cerevisiae. Experimental and computational studies indicated that hematoxylin directly interacts with tau-RD protein through hydrophobic forces, hydrogen bonds, π-cation interactions, and π-π stackings. In addition, cellular viability assays showed that hematoxylin greatly reduced cytotoxicity induced by tau-RD aggregates. In summary, hematoxylin might be a promising candidate for further development as a potential therapeutic drug for AD patients.
Keywords	Alzheimer disease ; Saccharomyces cerevisiae ; active ingredients ; amyloid ; cell viability ; cytotoxicity ; drug development ; drugs ; hydrogen ; hydrophobicity ; models ; therapeutics ; yeasts ; Alzheimer's disease ; Tau protein ; Hematoxylin ; Aggregation ; Disaggregation ; Molecular dynamics simulation
Language	English
Dates of publication	2023-10
Publishing place	Elsevier B.V.
Document type	Article ; Online
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2023.126140
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Article ; Online: Understanding the Molecular Mechanisms of Polyphenol Inhibition of Amyloid β Aggregation.

Han, Yin-Lei / Yin, Huan-Huan / Xiao, Chao / Bernards, Matthew T / He, Yi / Guan, Yi-Xin

ACS chemical neuroscience

2023 Volume 14, Issue 22, Page(s) 4051–4061

Abstract: Alzheimer's disease (AD) is highly associated with self-aggregation of amyloid β (Aβ) proteins into fibrils. Inhibition of Aβ aggregation by polyphenols is one of the major therapeutic strategies for AD. Among them, four polyphenols (brazilin, ... ...

Abstract	Alzheimer's disease (AD) is highly associated with self-aggregation of amyloid β (Aβ) proteins into fibrils. Inhibition of Aβ aggregation by polyphenols is one of the major therapeutic strategies for AD. Among them, four polyphenols (brazilin, resveratrol, hematoxylin, and rosmarinic acid) have been reported to be effective at inhibiting Aβ aggregation, but the inhibition mechanisms are still unclear. In this work, these four polyphenols were selected to explore their interactions with the Aβ17-42 pentamer by molecular dynamics simulation. All four polyphenols can bind to the pentamer tightly but prefer different binding sites. Conversion of the β-sheet to the random coil, fewer interchain hydrogen bonds, and weaker salt bridges were observed after binding. Interestingly, different Aβ17-42 pentamer destabilizing mechanisms for resveratrol and hematoxylin were found. Resveratrol inserts into the hydrophobic core of the pentamer by forming hydrogen bonds with Asp23 and Lys28, while hematoxylin prefers to bind beside chain A of the pentamer, which leads to β-sheet offset and dissociation of the β1 sheet of chain E. This work reveals the interactions between the Aβ17-42 pentamer and four polyphenols and discusses the relationship between inhibitor structures and their inhibition mechanisms, which also provides useful guidance for screening effective Aβ aggregation inhibitors and drug design against AD.
MeSH term(s)	Humans ; Amyloid beta-Peptides ; Polyphenols/pharmacology ; Resveratrol/pharmacology ; Hematoxylin ; Alzheimer Disease/drug therapy ; Molecular Dynamics Simulation ; Amyloid ; Peptide Fragments
Chemical Substances	Amyloid beta-Peptides ; Polyphenols ; Resveratrol (Q369O8926L) ; Hematoxylin (YKM8PY2Z55) ; Amyloid ; Peptide Fragments
Language	English
Publishing date	2023-10-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1948-7193
ISSN (online)	1948-7193
DOI	10.1021/acschemneuro.3c00586
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Article ; Online: Surface-anchored microbial enzyme-responsive solid lipid nanoparticles enabling colonic budesonide release for ulcerative colitis treatment.

Zhang, Yipeng / Wang, Liying / Wang, Zi-Dan / Zhou, Quan / Zhou, Xuefei / Zhou, Tianhua / Guan, Yi-Xin / Liu, Xiangrui

Journal of nanobiotechnology

2023 Volume 21, Issue 1, Page(s) 145

Abstract: Colon-targeted oral drug delivery systems (CDDSs) are desirable for the treatment of ulcerative colitis (UC), which is a disease with high relapse and remission rates associated with immune system inflammation and dysregulation localized within the ... ...

Abstract	Colon-targeted oral drug delivery systems (CDDSs) are desirable for the treatment of ulcerative colitis (UC), which is a disease with high relapse and remission rates associated with immune system inflammation and dysregulation localized within the lining of the large bowel. However, the success of current available approaches used for colon-targeted therapy is limited. Budesonide (BUD) is a corticosteroid drug, and its rectal and oral formulations are used to treat UC, but the inconvenience of rectal administration and the systemic toxicity of oral administration restrict its long-term use. In this study, we designed and prepared colon-targeted solid lipid nanoparticles (SLNs) encapsulating BUD to treat UC by oral administration. A negatively charged surfactant (NaCS-C12) was synthesized to anchor cellulase-responsive layers consisting of polyelectrolyte complexes (PECs) formed by negatively charged NaCS and cationic chitosan onto the SLNs. The release rate and colon-specific release behavior of BUD could be easily modified by regulating the number of coated layers. We found that the two-layer BUD-loaded SLNs (SLN-BUD-2L) with a nanoscale particle size and negative zeta potential showed the designed colon-specific drug release profile in response to localized high cellulase activity. In addition, SLN-BUD-2L exhibited excellent anti-inflammatory activity in a dextran sulfate sodium (DSS)-induced colitis mouse model, suggesting its potential anti-UC applications.
MeSH term(s)	Animals ; Mice ; Colitis, Ulcerative/drug therapy ; Budesonide ; Colon ; Nanoparticles ; Colitis/chemically induced ; Cellulases/therapeutic use ; Disease Models, Animal
Chemical Substances	Budesonide (51333-22-3) ; Lipid Nanoparticles ; Cellulases (EC 3.2.1.-)
Language	English
Publishing date	2023-05-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2100022-0
ISSN	1477-3155 ; 1477-3155
ISSN (online)	1477-3155
ISSN	1477-3155
DOI	10.1186/s12951-023-01889-0
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Article ; Online: Preparation of pH-responsive DOX-loaded chitosan nanoparticles using supercritical assisted atomization with an enhanced mixer.

Peng, Hu-Hong / Hong, Dong-Xiao / Guan, Yi-Xin / Yao, Shan-Jing

International journal of pharmaceutics

2019 Volume 558, Page(s) 82–90

Abstract: Chemotherapeutics are used extensively in cancer and encapsulating the drug in nanoparticles is an effective method to enhance therapeutic efficacy and reduce side effect. In this work, DOX-loaded chitosan nanoparticles were prepared using supercritical ... ...

Abstract	Chemotherapeutics are used extensively in cancer and encapsulating the drug in nanoparticles is an effective method to enhance therapeutic efficacy and reduce side effect. In this work, DOX-loaded chitosan nanoparticles were prepared using supercritical fluid assisted atomization introduced by a hydrodynamic cavitation mixer (SAA-HCM) from aqueous solution. The influences of solution concentration, CO
MeSH term(s)	Antibiotics, Antineoplastic/administration & dosage ; Antibiotics, Antineoplastic/chemistry ; Cell Survival/drug effects ; Chitosan/administration & dosage ; Chitosan/chemistry ; Doxorubicin/administration & dosage ; Doxorubicin/chemistry ; Drug Compounding/methods ; Drug Liberation ; HeLa Cells ; Humans ; Hydrogen-Ion Concentration ; Nanoparticles/administration & dosage ; Nanoparticles/chemistry
Chemical Substances	Antibiotics, Antineoplastic ; Doxorubicin (80168379AG) ; Chitosan (9012-76-4)
Language	English
Publishing date	2019-01-09
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	428962-6
ISSN	1873-3476 ; 0378-5173
ISSN (online)	1873-3476
ISSN	0378-5173
DOI	10.1016/j.ijpharm.2018.12.077
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Article ; Online: Preparation of micrometric powders of parathyroid hormone (PTH1-34)-loaded chitosan oligosaccharide by supercritical fluid assisted atomization.

Hong, Dong-Xiao / Yun, Yu-Long / Guan, Yi-Xin / Yao, Shan-Jing

International journal of pharmaceutics

2018 Volume 545, Issue 1-2, Page(s) 389–394

Abstract: Parathyroid hormone (PTH1-34)-loaded dry powders were fabricated from aqueous solution for pulmonary administration using supercritical fluid assisted atomization introduced by a hydrodynamic cavitation mixer (SAA-HCM). Herein, chitosan oligosaccharide ( ... ...

Abstract	Parathyroid hormone (PTH1-34)-loaded dry powders were fabricated from aqueous solution for pulmonary administration using supercritical fluid assisted atomization introduced by a hydrodynamic cavitation mixer (SAA-HCM). Herein, chitosan oligosaccharide (CSO) was selected as a carrier in an effort to enhance transmucosal absorption of the drug. Well-defined, separated and spherical PTH(1-34)/CSO composite microparticles were obtained, and the particles size could be well controlled with narrow distribution. Aerodynamic performance was determined using next generation impactor (NGI), and the mass median aerodynamic diameter (MMAD) ranged strictly 1-5 μm range with fine particle fraction (FPF) up to 63.51%. The structural integrity of coprecipitated PTH(1-34) was validated by HPLC, FT-IR and circular dichroism, and a high loading efficiency up to 92.8% was obtained. TGA analyses revealed its thermal stability was preserved and XRD patterns showed amorphous structure of particles. The SAA-HCM process is proposed as a green technique for preparation of inhalable protein/polymer composite dry powders without use of any organic solvents.
MeSH term(s)	Administration, Inhalation ; Aerosols ; Chitosan/chemistry ; Chromatography, High Pressure Liquid ; Circular Dichroism ; Crystallography, X-Ray ; Drug Carriers ; Drug Compounding ; Drug Stability ; Dry Powder Inhalers ; Oligosaccharides/chemistry ; Parathyroid Hormone/administration & dosage ; Parathyroid Hormone/chemistry ; Particle Size ; Powders ; Spectroscopy, Fourier Transform Infrared ; Technology, Pharmaceutical/methods ; Thermogravimetry
Chemical Substances	Aerosols ; Drug Carriers ; Oligosaccharides ; Parathyroid Hormone ; Powders ; Chitosan (9012-76-4)
Language	English
Publishing date	2018-05-08
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	428962-6
ISSN	1873-3476 ; 0378-5173
ISSN (online)	1873-3476
ISSN	0378-5173
DOI	10.1016/j.ijpharm.2018.05.022
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Article ; Online: Chromatographic separation of phenyllactic acid from crude broth using cryogels with dual functional groups.

Guan, Jintao / Guan, Yi-Xin / Yun, Junxian / Yao, Shan-Jing

Journal of chromatography. A

2018 Volume 1554, Page(s) 92–100

Abstract: Phenyllactic acid (PLA) is an important organic acid with wide antimicrobial activities against gram-positive and gram-negative bacteria and some fungi. This interesting compound can be synthesized by the microbial fermentation or the bioconversion using ...

Abstract	Phenyllactic acid (PLA) is an important organic acid with wide antimicrobial activities against gram-positive and gram-negative bacteria and some fungi. This interesting compound can be synthesized by the microbial fermentation or the bioconversion using phenylpyruvic acid (PPA) as the key substrate and microorganisms as the whole-cell biocatalysts. However, the isolation of high-purity PLA with a high recovery from the crude fermentation or conversion broth is a challenging task. In this work, the separation of PLA from the crude conversion broth prepared by employing Lactobacillus buchneri cells as the whole-cell catalysts was achieved by the chromatography using the poly(hydroxyethyl methacrylate) (pHEMA)-based cryogel with a combination of anion-exchange and hydrophobic benzyl groups. The static adsorption behaviors of PLA under different salt concentrations and the adsorption capacities of PLA on the cryogel were measured experimentally. The chromatographic performance of PLA from the crude conversion broth was compared with that from the clarified broth. The results showed that the pHEMA-based cryogel has a high capacity of PLA, i.e., 14.64 mg mL
MeSH term(s)	Adsorption ; Chromatography, High Pressure Liquid ; Cryogels/chemistry ; Culture Media/chemistry ; Hydrophobic and Hydrophilic Interactions ; Ion Exchange ; Lactic Acid/analogs & derivatives ; Lactic Acid/analysis ; Lactic Acid/isolation & purification ; Polyhydroxyethyl Methacrylate/chemistry
Chemical Substances	Cryogels ; Culture Media ; Polyhydroxyethyl Methacrylate (25249-16-5) ; Lactic Acid (33X04XA5AT)
Language	English
Publishing date	2018-06-15
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1171488-8
ISSN	1873-3778 ; 0021-9673
ISSN (online)	1873-3778
ISSN	0021-9673
DOI	10.1016/j.chroma.2018.04.043
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Article ; Online: Supercritical fluid assisted production of micrometric powders of the labile trypsin and chitosan/trypsin composite microparticles.

Shen, Yu-Bin / Guan, Yi-Xin / Yao, Shan-Jing

International journal of pharmaceutics

2015 Volume 489, Issue 1-2, Page(s) 226–236

Abstract: Supercritical fluid assisted atomization introduced by a hydrodynamic cavitation mixer (SAA-HCM) was used to prepare micrometric particles of a labile protein, i.e., trypsin from aqueous solution without use of any organic solvents. The trypsin particles ...

Abstract	Supercritical fluid assisted atomization introduced by a hydrodynamic cavitation mixer (SAA-HCM) was used to prepare micrometric particles of a labile protein, i.e., trypsin from aqueous solution without use of any organic solvents. The trypsin particles precipitated had various morphologies under different process conditions, with particle diameters ranging from 0.2 to 4 μm. FTIR, SDS-PAGE, CD and fluorescence spectra were performed to analyze the structural stability of the protein, and trypsin retained above 70% of the biological activity. Besides, chitosan was selected as the polymer carrier in an effort to prepare trypsin composite microparticles via SAA-HCM process. The influences of chitosan molecular weight, polymer/protein ratio and solution concentration on the particle morphology and size distribution were investigated in detail. Non-coalescing spherical composite microparticles with a narrow particle distribution (0.2-3 μm) could be obtained. The SAA-HCM prepared particles were amorphous as demonstrated by XRD and had a loading efficiency about 90%. The protein release profiles of the composite microparticles were evaluated using both the immersion condition and a Franz diffusion cell. Finally, the distribution of the protein within the particles was characterized through CLSM analysis of FITC-labeled trypsin-loaded chitosan microparticles. The SAA-HCM process is demonstrated to be a protein-friendly and promising technique for production of protein and polymer/protein composite particles formulations from aqueous solutions for drug delivery systems.
MeSH term(s)	Carbon Dioxide/chemistry ; Chitosan/chemistry ; Circular Dichroism ; Delayed-Action Preparations/chemistry ; Drug Liberation ; Electrophoresis, Polyacrylamide Gel ; Particle Size ; Powders ; Spectroscopy, Fourier Transform Infrared ; Thermogravimetry ; Trypsin/chemistry ; X-Ray Diffraction
Chemical Substances	Delayed-Action Preparations ; Powders ; Carbon Dioxide (142M471B3J) ; Chitosan (9012-76-4) ; Trypsin (EC 3.4.21.4)
Language	English
Publishing date	2015-07-15
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	428962-6
ISSN	1873-3476 ; 0378-5173
ISSN (online)	1873-3476
ISSN	0378-5173
DOI	10.1016/j.ijpharm.2015.05.004
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Article ; Online: Development of metformin hydrochloride loaded dissolving tablets with novel carboxymethylcellulose/poly-l-lysine/TPP complex.

Wu, Qing-Xi / Wang, Zi-Dan / Zheng, Meng-Fei / Su, Ting / Wang, Xiao-Hui / Guan, Yi-Xin / Chen, Yan

International journal of biological macromolecules

2020 Volume 155, Page(s) 411–420

Abstract: Natural polymers like polysaccharides, polypeptides and their derivatives are broadly applied in drug delivery due to excellent biocompatibility and biodegradability. In this study, the dissolving tablets, formed with carboxymethylcellulose/poly-l-lysine/ ...

Abstract	Natural polymers like polysaccharides, polypeptides and their derivatives are broadly applied in drug delivery due to excellent biocompatibility and biodegradability. In this study, the dissolving tablets, formed with carboxymethylcellulose/poly-l-lysine/tripolyphosphate (CMC/PLL/TPP) complex, were prepared using metformin hydrochloride (MetHCl) as model drug. Confocal laser scanning microscopy observation manifested that FITC-labeled PLL interacted with CMC and formed a uniform interior microstructure. Scanning electron microscope images showed the drug-loaded tablets had well-formed shapes with smooth surfaces. MetHCl embedded interior the microstructures of the tablets and represented in a crystal form. Thermo-gravimetric analysis and differential scanning calorimetry indicated that the drug-loaded tablets had stable thermal properties with less moisture content (3.52%). Fourier transform infrared spectrometer confirmed that the CMC/PLL/TPP complex was fabricated via the electrostatic interactions between -NH
MeSH term(s)	Carboxymethylcellulose Sodium/chemistry ; Delayed-Action Preparations ; Drug Liberation ; Humans ; Hypoglycemic Agents/chemistry ; Hypoglycemic Agents/metabolism ; Metformin/chemistry ; Metformin/metabolism ; Polylysine/chemistry ; Polymers/chemistry ; Polyphosphates/chemistry ; Solubility ; Tablets/chemistry
Chemical Substances	Delayed-Action Preparations ; Hypoglycemic Agents ; Polymers ; Polyphosphates ; Tablets ; Polylysine (25104-18-1) ; Metformin (9100L32L2N) ; Carboxymethylcellulose Sodium (K679OBS311) ; triphosphoric acid (NU43IAG5BC)
Language	English
Publishing date	2020-03-26
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2020.03.191
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Article: Development of metformin hydrochloride loaded dissolving tablets with novel carboxymethylcellulose/poly-l-lysine/TPP complex

Wu, Qing-Xi / Wang, Zi-Dan / Zheng, Meng-Fei / Su, Ting / Wang, Xiao-Hui / Guan, Yi-Xin / Chen, Yan

International journal of biological macromolecules. 2020 July 15, v. 155

2020

Abstract	Natural polymers like polysaccharides, polypeptides and their derivatives are broadly applied in drug delivery due to excellent biocompatibility and biodegradability. In this study, the dissolving tablets, formed with carboxymethylcellulose/poly-l-lysine/tripolyphosphate (CMC/PLL/TPP) complex, were prepared using metformin hydrochloride (MetHCl) as model drug. Confocal laser scanning microscopy observation manifested that FITC-labeled PLL interacted with CMC and formed a uniform interior microstructure. Scanning electron microscope images showed the drug-loaded tablets had well-formed shapes with smooth surfaces. MetHCl embedded interior the microstructures of the tablets and represented in a crystal form. Thermo-gravimetric analysis and differential scanning calorimetry indicated that the drug-loaded tablets had stable thermal properties with less moisture content (3.52%). Fourier transform infrared spectrometer confirmed that the CMC/PLL/TPP complex was fabricated via the electrostatic interactions between -NH3+, -COO− and -[P2O54-]− groups. The drug-loaded tablets had a high drug loading efficiency of 85.76% and drug encapsulation efficiency of 81.47%, and a shorter wetting time of 2.16 min in SSF (pH 6.8) and lower swelling ratio of 233.34%. The drug loaded in the samples could be released completely within 10 min in simulated saliva fluid (SSF pH 6.8), indicating a rapid drug release and dissolving profile in the environment, which could be developed for dissolving tablets.
Keywords	Fourier transform infrared spectroscopy ; biocompatibility ; biodegradability ; biopolymers ; carboxymethylcellulose ; confocal laser scanning microscopy ; differential scanning calorimetry ; electrostatic interactions ; encapsulation ; metformin ; microstructure ; models ; pH ; polypeptides ; saliva ; scanning electron microscopes ; thermal properties ; thermogravimetry ; tripolyphosphates ; water content
Language	English
Dates of publication	2020-0715
Size	p. 411-420.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2020.03.191
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