Review
Biochemistry & Molecular Biology
Shinji Takai, Denan Jin
Summary: Chymase-activated MMP-9 is closely related to the pathogenesis of various diseases, especially inflammation-related diseases. Upregulated chymase and MMP-9 have been observed in tissues from patients and animal models of these diseases. Chymase inhibitors attenuate MMP-9 formation and reduce inflammatory cell numbers, thereby ameliorating the development and progression of these disorders.
Article
Biochemistry & Molecular Biology
Ya-Tang Chiang, Yu-Bai Xiao, Shan-hui Hsu, Shu-Wei Chang, Chia-Ching Chou
Summary: Tannic acid (TA) has antibacterial, antioxidant, and anti-inflammatory properties and acts as an adhesive, hemostatic, and crosslinking agent in hydrogels. TA has been reported to inhibit MMP-2/- 9 activities, thereby improving tissue remodeling and wound healing. In this study, atomistic modeling was used to explore the mechanisms and structures of TA binding with MMP-2 and MMP-9, revealing the specific binding regions and molecular interactions involved. Understanding the binding mechanism and dynamics of TA with these MMPs provides crucial knowledge on the effects of TA on MMPs.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Review
Biochemistry & Molecular Biology
Zainab Ahmed Rashid, Sanaa K. Bardaweel
Summary: Matrix metalloproteinases (MMPs), especially MMP-9, play a significant role in cancer pathogenesis and progression. However, no effective MMP-9 inhibitor has been approved by the FDA. This review focuses on exploring the strategies for designing MMP-9 inhibitors and their anticancer effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Physical
Shuo Chen, Shuai Yuan, Qing Bian, Bo Wu
Summary: This study presents a novel spiropyran-based organic-inorganic composite nanogel (NG) prepared through emulsion polymerization using upconverting nanoparticles, spiropyran, acrylic acid, and N,N′-bis(acryloyl)cystamine (BAC) compounds. The crosslinked multi-stimulus responsive nanogels can adjust the release rate by altering various parameters, making it suitable for controlling drug release in complex biological environments. The composite NGs demonstrated highly-efficient and controllable release performance for loaded drugs, providing a wide range of options for novel stimulus-responsive nanocarriers.
Article
Chemistry, Physical
Adrian Ges Naranjo, Herlys Viltres Cobas, Nishesh Kumar Gupta, Katy Rodriguez Lopez, Aldo Martinez Pena, Daniel Sacasas, Ruben Alvarez Brito
Summary: Nanogels offer a promising approach for enhancing cancer therapy by increasing the concentration of anti-tumor agents at tumor sites and prolonging their effects on cancer cells without significantly impacting normal tissues.
JOURNAL OF MOLECULAR LIQUIDS
(2022)
Article
Medicine, General & Internal
Ionut Luchian, Mihaela Moscalu, Ancuta Goriuc, Ludovica Nucci, Monica Tatarciuc, Ioana Martu, Mihai Covasa
Summary: Periodontitis results in destructive effects on periodontium, with increased levels of MMP-9. Periodontal treatment alone or combined with orthodontic treatment can improve clinical parameters and lower MMP-9 levels. The degree of malocclusion affects the treatment's impact on MMP-9 levels.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Chemistry, Medicinal
Sanjib Das, Sk Abdul Amin, Tarun Jha
Summary: Matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) play significant roles in solid tumor invasion, metastasis, and angiogenesis, while their role in hematological malignancies is less understood. Recent studies have shown correlations between gelatinases and hematological malignancies, leading to the development of potential inhibitors for these conditions.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Jiaqi Guo, Weiyi Tan, Hongjian He, Bing Xu
Summary: This study demonstrates that diglycine-activated succinic esters can significantly enhance the cellular uptake of supramolecular assemblies or prodrugs by converting nanofibers into nanoparticles through autohydrolysis. The autohydrolysis of diglycine-activated succinic esters and drug conjugates also restores the efficacy of the drugs. The U-turn conformation of diglycine promotes intramolecular hydrolysis of diglycine-activated succinic esters, providing a nonenzymatic bond cleavage approach for effective intracellular targeting.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Yihe Wang, Christine Y. Chuang, Clare L. Hawkins, Michael J. Davies
Summary: Matrix metalloproteinase-9 (MMP9) plays a crucial role in the degradation of extracellular matrix (ECM) proteins. This study demonstrates that MMP9 can be activated by both chloramines and oxidation. The activation of MMP9 and ECM degradation are interdependent processes that may contribute to the progression of diseases.
Article
Physics, Fluids & Plasmas
Ke Xiao, Rui Ma, Chen-Xu Wu
Summary: The study investigates the theoretical model and phenomenon of active entry of self-propelled pathogens into host cells, revealing a wrapping transition triggered by active force. The results may offer guidance for research on the cellular entry of active particles driven by activity.
Review
Biochemistry & Molecular Biology
Zhenshengnan Li, Jia Wei, Bowen Chen, Yaoqi Wang, Shuai Yang, Kehui Wu, Xianying Meng
Summary: Matrix metalloproteinase-9 (MMP-9) is a zinc-dependent proteolytic metalloenzyme that degrades the extracellular matrix (ECM) and has been proven to be elevated in various pathological conditions, including thyroid carcinoma. Its expression level in malignant or metastatic thyroid tumor tissues is higher than in normal or benign tissues, and it correlates closely with clinical features such as lymph node metastasis, TNM stage, and tumor size.
Article
Surgery
Jing Shen, Jian-bo Song, Jun Fan, Zhe Zhang, Zheng-jia Yi, Shuo Bai, Xiao-lin Mu, Yao-bo Yang, Liang Xiao
Summary: This study simulated the process of neointima generation and regression after stent implantation, demonstrating the spatial distribution and dynamic changes of MMP-2, MMP-9, and collagen in ISR. The expression of MMP-2 and MMP-9 decreased and collagen content reached its maximum when ISR occurred, suggesting their potential contribution to ISR.
EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY
(2021)
Article
Chemistry, Multidisciplinary
Junjie Deng, Weide Xu, Siyun Lei, Wanyu Li, Qinghua Li, Kaiqiang Li, Jianxin Lyu, Jilong Wang, Zhen Wang
Summary: This study addresses the challenges in immunotherapy for low immunogenic tumors by using responsive nanogels to promote NK cell activation and induce DC recruitment. By modifying the tumor microenvironment, this strategy effectively inhibits tumor growth and recurrence.
Article
Nanoscience & Nanotechnology
Liuwei Zhang, Jingyun Wang, Hongyan Cui, Haonan Zheng, Xiaolan Yin, Jiaqi Lin, Yue Wang, Yan Zhao, Haidong Li, Qixian Chen
Summary: Tumors that can escape immune clearance can be effectively treated by a chemotherapeutic nanomedicine that targets the tumors and delivers siRNA payloads to knock down immune suppressive molecules, resulting in the reactivation of anti-tumor immunities. This study demonstrated significant anti-tumor effects in triple-negative breast tumors by using a chemotherapeutic nanomedicine that combines targeted delivery and RNA interference.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Engineering, Biomedical
Shumin Hu, Qiuli Cheng, Yulu Shang, Zhihao Wang, Rui Zhu, Leitao Zhang, Wenlan Wu, Shouren Zhang, Junbo Li
Summary: A zwitterionic polymer containing quaternary ammonium cation and sulfonamide anion was synthesized and coated onto gold nanoparticles for pH-responsive behavior in tumors. The modified nanoparticles exhibited high sensitivity and reversible positive charge conversion at tumor acidic microenvironment, leading to enhanced cellular uptake and tumor accumulation. This pH-responsive polymer holds great potential for cancer nanomedicine applications.
BIOMEDICAL MATERIALS
(2023)
Article
Biochemical Research Methods
Catherine Y. Tremblay, Patanachai Limpikirati, Richard W. Vachet
Summary: Identifying changes in the higher-order structure (HOS) of therapeutic monoclonal antibodies is crucial for ensuring efficacy and preventing adverse effects. This study demonstrates that DEPC-CL/MS and HDX/MS can be used together to provide valuable structural information about subtle conformational changes that traditional techniques may not detect. The combination of the two techniques proves to be effective in identifying likely aggregation sites and complementary in reporting changes in side chain orientation and backbone dynamics.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2021)
Article
Chemistry, Analytical
Sarah E. Biehn, Patanachai Limpikirati, Richard W. Vachet, Steffen Lindert
Summary: DEPC labeling analyzed with mass spectrometry can provide important insights into higher order protein structures. Developing a Rosetta algorithm that utilizes labeled and unlabeled residues to assess their hydrophobic environment improves protein structure prediction. Application of DEPC covalent labeling data has the potential to be used for accurate higher order structure determination.
ANALYTICAL CHEMISTRY
(2021)
Article
Biochemical Research Methods
Jutiporn Yukird, Cameron J. Kaminsky, Orawon Chailapakul, Nadnudda Rodthongkum, Richard W. Vachet
Summary: Nanomaterials have been demonstrated to enhance peptide ionization and detection in MALDI-MS analyses through the coffeering effect, with the possibility of selectively detecting specific peptides in complex mixtures by careful design of nanomaterial surface properties.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2021)
Article
Chemistry, Analytical
Xiao Pan, Zachary J. Kirsch, Richard W. Vachet
Summary: By using DEPC-based covalent labeling with LC-MS/MS analysis, researchers can distinguish histidine tautomers in peptides and proteins and determine their ratios. This method is simpler, faster, and more precise than 2D NMR, providing a valuable tool for understanding the structure and function of histidine residues in proteins. The ability of DEPC labeling/MS to differentiate histidine tautomers equips researchers with a deeper insight into the structure and function of histidine residues in proteins.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Analytical
Catherine Y. Tremblay, Zachary J. Kirsch, Richard W. Vachet
Summary: In this study, DEPC covalent labeling-mass spectrometry was used to analyze antigen-antibody interactions, revealing that residues buried in the epitope show decreased labeling while residues at the edges of the epitope show increased labeling. The increased labeling of certain residues is caused by the formation of hydrophobic pockets upon antibody binding. Overall, changes in solvent exposure and residue microenvironment play a significant role in DEPC labeling of antigen-antibody complexes.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Analytical
Dheeraj K. Agrohia, Peidong Wu, Uyen Huynh, S. Thayumanavan, Richard W. Vachet
Summary: This article introduces a metal-coded mass tagging approach that enables the multiplexed quantification of the PNC uptake in cells using mass spectrometry. The conjugation of different metals to the PNCs allows the simultaneous multiplexed analysis of multiple distinct PNCs, which should improve the design and optimization of PNCs.
ANALYTICAL CHEMISTRY
(2022)
Article
Materials Science, Biomaterials
Hazel C. Davis, Xiao Pan, Zachary J. Kirsch, Richard W. Vachet, Gregory N. Tew
Summary: Explored the physical interactions between noncovalent polymer-protein binding and used the method of covalent labeling-mass spectrometry to investigate the differences at the intermolecular surface.
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2022)
Article
Biochemical Research Methods
Catherine Y. Tremblay, Zachary J. Kirsch, Richard W. Vachet
Summary: Characterizing antibody-antigen interactions is crucial for the development of therapeutic antibodies, understanding their mechanisms, and patenting new drug molecules. By combining HDX mass spectrometry measurements with DEPC-CL, more comprehensive information about the structural changes and dynamics of antibody-antigen interactions can be obtained. These two techniques synergistically provide insights into binding sites, protein stabilization, and solvent exposure.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2022)
Article
Chemistry, Multidisciplinary
Stacey Nash, Richard W. Vachet
Summary: Proteins can adopt different conformational states that are crucial for their function and dysfunction. This study demonstrates the use of collision-induced unfolding and ion mobility-mass spectrometry to distinguish subtly different conformational states for protein complexes. Molecular modeling is used to understand the unfolding process and the impact of solution structure. This research provides insights into gas-phase unfolding pathways and has implications for understanding protein complex dissociation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemical Research Methods
Xiao Pan, Thomas Tran, Zachary J. Kirsch, Lynmarie K. Thompson, Richard W. Vachet
Summary: Membrane-associated proteins are important for cellular function and therapeutics. Mass spectrometry and labeling techniques can be used to study their structures and binding interactions, but measurement challenges arise from the use of artificial membrane systems. This study demonstrates the use of DEPC as a labeling reagent to characterize the binding interactions between a membrane-associated protein and its binding partners, providing structural and binding information consistent with the model of this complex system.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Article
Chemistry, Analytical
Zachary J. Kirsch, Jeanna M. Blake, Uyen Huynh, Dheeraj K. Agrohia, Catherine Y. Tremblay, Eric M. Graban, Robert C. Vaughan, Richard W. Vachet
Summary: Membrane proteins are essential components of the human proteome and major drug targets. This study demonstrates the use of DEPC covalent labeling mass spectrometry to characterize the binding sites of membrane proteins in living cells. The results show changes in labeling extent and location upon antibody binding, indicating alterations in the structure and interactions of the membrane protein. Overall, DEPC-based covalent labeling mass spectrometry offers an effective method for studying membrane protein properties in a cellular context.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Myrat Kurbanov, Zachary J. Kirsch, Jithu Krishna, Ranit Dutta, Richard W. Vachet, S. Thayumanavan
Summary: Targeted modification of endogenous proteins without genetic manipulation has wide applications. This study presents ligand-directed triggerable Michael acceptors (LD-TMAcs) for rapid protein labeling. LD-TMAcs possess unique reactivity allowing multiple modifications on a single target protein, enabling the mapping of ligand binding site. The selectivity and utility of LD-TMAcs are demonstrated in cell lysates and live cells, suggesting their potential in target identification and studying membrane proteins.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Chemistry, Analytical
Teerapong Jantarat, Joshua D. D. Lauterbach, Jeerapat Doungchawee, Dheeraj K. K. Agrohia, Richard W. W. Vachet
Summary: A new platform using spiked gelatin standards has been developed for quantitative imaging, allowing for the determination of sub-organ distributions of metal-based nanomaterials in tissues. This approach provides insights into the fate of nanomaterials in vivo and enables quantitative co-localization of nanomaterials and their cargo, making it a valuable tool in the development of nanomaterial drug delivery systems.
Article
Chemistry, Analytical
Laura J. Castellanos-Garcia, Kristen N. Sikora, Jeerapat Doungchawee, Richard W. Vachet
Summary: Laser ablation inductively-coupled plasma mass spectrometry (LA-ICP-MS) imaging and matrix assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) are complementary methods used to measure distributions of elements and biomolecules in tissue sections. A computational workflow written in Python is described to achieve accurate registration between datasets from these two imaging modalities, allowing for pixel-by-pixel comparisons. The registration process provides deeper insights into how nanomaterial delivery systems influence lipid biochemistry in tissues and allows for improved segmentation in MALDI-MS images for identification of lipids associated with different sub-organ regions in tissues.
Article
Chemistry, Multidisciplinary
Kristen N. Sikora, Laura J. Castellanos-Garcia, Joseph M. Hardie, Yuanchang Liu, Michelle E. Farkas, Vincent M. Rotello, Richard W. Vachet
Summary: A dual-mode mass spectrometry imaging method was used to evaluate the distributions and biochemical effects of anti-TNF-alpha nanoparticle stabilized capsules in mice, revealing that most anticipated biochemical changes occur in sub-organ regions separate from where the nanomaterials accumulate. The study demonstrates the power of matrix-assisted laser desorption/ionization mass spectrometry imaging in evaluating both expected and unexpected outcomes associated with complex therapeutic delivery systems.
