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4. Predictive Factors for the Efficacy of Radioactive Iodine Treatment of Graves' Disease: An Experience From 613 Chinese Patients.

Author

Feng, Wenwen, Shi, He, Yang, Yanli, Liu, Jing, Chen, Shiying, Ren, Minghui, Li, Yajie, Liu, Wei, Cui, Dai, and Falhammar, Henrik

Abstract

Objective: The utilization of radioactive iodine‐131I (RAI) has long been established as a cost‐effective and conventional treatment for managing Graves' disease (GD). However, the accurate prediction of the clinical response to RAI treatment remains difficult. The successful resolution of GD through RAI therapy is typically characterized by the induction of hypothyroidism or euthyroidism. Thus, the principal aim of this study was to identify plausible predictors of RAI efficacy in the treatment of GD. Methods: The clinical data of 613 GD patients, who underwent RAI treatment for the first time, were retrospectively analyzed, including age, gender, duration of hyperthyroidism, presence or absence of ocular signs, thyroid volume, thyroid weight, thyroid function (FT3, FT4, and TSH), radioactive iodine uptake (RAIU) at 2 h/6 h/24 h (2‐h/6‐h/24‐h RAIU) prior to RAI treatment, the highest RAIU (RAIUmax), and administered activity of 131I and 131I activity per gram of thyroid tissue. Success of RAI treatment was defined as achieving hypothyroidism or euthyroidism for more than 1 year after the initial treatment. Univariate and multivariate logistics regression analyses were conducted to identify factors that influence the efficacy of RAI treatment for GD. And at last, based on the results of the multivariate logistic regression analysis, a nomogram model was established. Results: In this study, the success rate of RAI treatment for GD was 91.2% (559/613). Univariate analysis demonstrated that several factors, including age (p = 0.005), thyroid volume (p = 0.001), thyroid‐stimulating hormone (TSH, p = 0.042), ratio of RAIU at 6 h to 24 h (6‐h/24‐h RAIU, p = 0.048), total 131I activity (p = 0.026), and 131I activity per gram of thyroid tissue (p = 0.001), were significantly associated with treatment outcome. Multivariate logistic regression analysis indicated thyroid volume and 131I activity per gram of thyroid tissue as significant independent predictors of radioactive iodine therapy (RIT) efficacy. The area under the ROC curve of the established nomogram model was 0.769 (95% confidence interval [CI]: 0.692–0.846), indicating that the model has good discriminatory ability. Conclusion: Calculated‐dose RAI is effective in the treatment of GD. The smaller thyroid volume and the higher 131I activity per gram of thyroid tissue are predictors of RAI efficacy in the treatment of GD. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Self‐healing, adhesive, photothermal responsive, stretchable, and strain‐sensitive supramolecular nanocomposite hydrogels based on host–guest interactions.

Author

Chen, Shiying, Nie, Yixuan, Huang, Yingying, Yang, Yuxuan, Chen, Hongyi, and Zhang, Xiongzhi

Abstract

The development of multifunctional supramolecular nanocomposite hydrogels remains challenging. Here, the dynamic host–guest interactions involving the host molecule CB[8] and guest units were utilized to prepare Fe3O4 hybrid supramolecular nanocomposite hydrogels. The results showed that the hydrogels obtained possessed a porous structure. The CB[8]‐modified Fe3O4 (Fe3O4@CB[8]) nanoparticles served as cross‐linkers in forming the network of hydrogels. By adjusting the Fe3O4@CB[8] content, the mechanical properties of the hydrogels could be controlled. The tensile stress was measured at 160 kPa with a fracture strain of 1380%, while the compression stress was 230 kPa at 70% compression strain. The self‐healing efficiency of the hydrogels at room temperature reached 95% after 24 h. The as‐obtained hydrogels show strain sensitivity and have the potential for applications in detecting elbow and finger movements. Our supramolecular nanocomposite hydrogels exhibit multiple functions, including self‐healing, injectability, photothermal responsiveness, and conductivity, making them suitable for integration into flexible electronics. Highlights: Fe3O4@CB[8] nanoparticles serve as cross‐linkers for the nanocomposite hydrogels.CB[8] based host–guest interactions enable hydrogels to self‐heal.Fe3O4@CB[8] endow hydrogels with stretchability and photothermal responsiveness.Hydrogels exhibit injectability, NIR responsiveness, and conductive ability. [ABSTRACT FROM AUTHOR]

Published
2024
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11. An Integrated Analysis Reveals Ciliary Abnormalities in Antrochoanal Polyps

Author

Zi,Xiaoxue, Peng,Yang, Zang,Yiran, Chen,Shiying, Li,Mengshi, Yu,Kena, Liang,Xu, Jin,Peng, Wang,Deyun, Shi,Li, Zi,Xiaoxue, Peng,Yang, Zang,Yiran, Chen,Shiying, Li,Mengshi, Yu,Kena, Liang,Xu, Jin,Peng, Wang,Deyun, and Shi,Li

Abstract

Xiaoxue Zi,1,* Yang Peng,2,* Yiran Zang,1 Shiying Chen,2 Mengshi Li,3 Kena Yu,1 Xu Liang,1 Peng Jin,1 Deyun Wang,4 Li Shi1 1Department of Otolaryngology, The Second Hospital of Shandong University, Jinan, People’s Republic of China; 2State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, People’s Republic of China; 3State Key Laboratory of Respiratory Disease, Department of Respiratory Pathology, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 4Department of Otolaryngology, National University of Singapore, National University Health System, Singapore*These authors contributed equally to this workCorrespondence: Peng Jin, Department of Otolaryngology, The Second Hospital of Shandong University, 247 Beiyuan Avenue, Jinan, Shandong, 250033, People’s Republic of China, Tel +86 531 85875317, Fax +86 531 88962544, Email jinpeng0215@126.comObjective: The mechanisms underlying the antrochoanal polyps (ACPs) remained unclear. We aimed to identify the differentially expressed genes (DEGs) profile, the cilia-related genes expression levels and the morphological characteristics of ciliated cells in patients with ACPs.Methods: We obtained ACPs biopsy samples from 28 patients and uncinate process from 27 healthy controls. Whole-transcriptome RNA sequencing, immunofluorescence staining, quantitative polymerase chain reaction, and scanning electron microscopy were performed.Results: 3739 DEGs were detected between ACPs and controls, and Gene Ontology analysis on these DEGs implicated cilium assembly, cilium motility, cilia component, cilia function, inflammatory response and immune system process were includ

Published
2023

19. Macrocyclization of an all-d linear α-helical peptide imparts cellular permeability† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c9sc06383h

Author

Kannan, Srinivasaraghavan, Aronica, Pietro G. A., Ng, Simon, Gek Lian, Dawn Thean, Frosi, Yuri, Chee, Sharon, Shimin, Jiang, Yuen, Tsz Ying, Sadruddin, Ahmad, Kaan, Hung Yi Kristal, Chandramohan, Arun, Wong, Jin Huei, Tan, Yaw Sing, Chang, Zi Wei, Ferrer-Gago, Fernando J., Arumugam, Prakash, Han, Yi, Chen, Shiying, Rénia, Laurent, Brown, Christopher J., Johannes, Charles W., Henry, Brian, Lane, David P., Sawyer, Tomi K., Verma, Chandra S., and Partridge, Anthony W.

Subjects
Chemistry
Abstract

Peptide-based molecules hold great potential as targeted inhibitors of intracellular protein–protein interactions (PPIs)., Peptide-based molecules hold great potential as targeted inhibitors of intracellular protein–protein interactions (PPIs). Indeed, the vast diversity of chemical space conferred through their primary, secondary and tertiary structures allows these molecules to be applied to targets that are typically deemed intractable via small molecules. However, the development of peptide therapeutics has been hindered by their limited conformational stability, proteolytic sensitivity and cell permeability. Several contemporary peptide design strategies are aimed at addressing these issues. Strategic macrocyclization through optimally placed chemical braces such as olefinic hydrocarbon crosslinks, commonly referred to as staples, may improve peptide properties by (i) restricting conformational freedom to improve target affinities, (ii) improving proteolytic resistance, and (iii) enhancing cell permeability. As a second strategy, molecules constructed entirely from d-amino acids are hyper-resistant to proteolytic cleavage, but generally lack conformational stability and membrane permeability. Since neither approach is a complete solution, we have combined these strategies to identify the first examples of all-d α-helical stapled and stitched peptides. As a template, we used a recently reported all d-linear peptide that is a potent inhibitor of the p53–Mdm2 interaction, but is devoid of cellular activity. To design both stapled and stitched all-d-peptide analogues, we used computational modelling to predict optimal staple placement. The resultant novel macrocyclic all d-peptide was determined to exhibit increased α-helicity, improved target binding, complete proteolytic stability and, most notably, cellular activity.

Published
2020

22. Macrocyclization of an all-D linear peptide improves target affinity and imparts cellular activity: A novel stapled α-helical peptide modality

Author

Kannan, Srinivasaraghavan, Aronica, Pietro G. A., Ng, Simon, Thean, Dawn, Frosi, Yuri, Chee, Sharon, Shimin, Jiang, Yuen, Tsz Ying, Sadruddin, Ahmad, Kaan, Hung Yi Kristal, Chandramohan, Arun, Wong, Jin Huei, Tan, Yaw Sing, Ferrer, Fernando J., Arumugam, Prakash, Han, Yi, Chen, Shiying, Brown, Christopher J., Johannes, Charles W., Henry, Brian, Lane, David P., Sawyer, Tomi K., Verma, Chandra S., and Partridge, Anthony W.

Abstract

Peptide-based inhibitors hold great potential for targeted modulation of intracellular protein-protein interactions (PPIs) by leveraging vast chemical space relative to primary structure via sequence diversity as well as conformationally through varying secondary and tertiary structures. However, the development of peptide therapeutics has been hindered because of their limited conformational stability, proteolytic sensitivity and cell permeability. Several contemporary peptide design strategies address these issues to varying degrees. Strategic macrocyclization through optimally placed chemical braces such as olefinic hydrocarbon crosslinks, commonly referred to as staples, may address these issues by i) restricting conformational freedom to improve target affinities, ii) improving proteolytic resistance, and iii) enhancing cell permeability. Conversely, molecules constructed entirely from D-amino acids are hyper-resistant to proteolytic cleavage, but generally lack conformational stability and membrane permeability. Since neither approach is a complete solution, we have combined these strategies to identify the first examples of all-D α-helical stapled and stitched peptides. As a template, we used a recently reported all D-linear peptide that is a potent inhibitor of the p53-Mdm2 interaction, but is devoid of cellular activity. To design both stapled and stitched all-D-peptide analogues, we used computational modelling to predict optimal staple placement. The resultant novel macrocyclic all D-peptide was determined to exhibit increased α-helicity, improved target binding, complete proteolytic stability and, most notably, cellular activity.

Published
2019

23. Omomyc Reveals New Mechanisms To Inhibit the MYC Oncogene

Author

Demma, Mark J., primary, Mapelli, Claudio, additional, Sun, Angie, additional, Bodea, Smaranda, additional, Ruprecht, Benjamin, additional, Javaid, Sarah, additional, Wiswell, Derek, additional, Muise, Eric, additional, Chen, Shiying, additional, Zelina, John, additional, Orvieto, Federica, additional, Santoprete, Alessia, additional, Altezza, Simona, additional, Tucci, Federica, additional, Escandon, Enrique, additional, Hall, Brian, additional, Ray, Kallol, additional, Walji, Abbas, additional, and O’Neil, Jennifer, additional

Published
2019
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25. Incorporation of Putative Helix-Breaking Amino Acids in the Design of Novel Stapled Peptides: Exploring Biophysical and Cellular Permeability Properties

Author

Partridge, Anthony W., primary, Kaan, Hung Yi Kristal, additional, Juang, Yu-Chi, additional, Sadruddin, Ahmad, additional, Lim, Shuhui, additional, Brown, Christopher J., additional, Ng, Simon, additional, Thean, Dawn, additional, Ferrer, Fernando, additional, Johannes, Charles, additional, Yuen, Tsz Ying, additional, Kannan, Srinivasaraghavan, additional, Aronica, Pietro, additional, Tan, Yaw Sing, additional, Pradhan, Mohan R., additional, Verma, Chandra S., additional, Hochman, Jerome, additional, Chen, Shiying, additional, Wan, Hui, additional, Ha, Sookhee, additional, Sherborne, Brad, additional, Lane, David P., additional, and Sawyer, Tomi K., additional

Published
2019
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29. Discovery of Novel Tricyclic Heterocycles as Potent and Selective DPP-4 Inhibitors for the Treatment of Type 2 Diabetes

Author

Wu, Wen-Lian, primary, Hao, Jinsong, additional, Domalski, Martin, additional, Burnett, Duane A., additional, Pissarnitski, Dmitri, additional, Zhao, Zhiqiang, additional, Stamford, Andrew, additional, Scapin, Giovanna, additional, Gao, Ying-Duo, additional, Soriano, Aileen, additional, Kelly, Terri M., additional, Yao, Zuliang, additional, Powles, Mary Ann, additional, Chen, Shiying, additional, Mei, Hong, additional, and Hwa, Joyce, additional

Published
2016
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36. Molecular Cloning of Human FKBP51 and Comparisons of Immunophilin Interactions with Hsp90 and Progesterone Receptor

Author

Nair, Satish C., Rimerman, Ronald A., Toran, Eric J., Chen, Shiying, Prapapanich, Viravan, Butts, Rinalda N., and Smith, David F.

Abstract

A cDNA for human FKBP51 has been cloned and sequenced, and protein products have been expressed in both in vitro and bacterial systems. The deduced amino acid sequence for human FKBP51 is 90% identical to sequences of recently described murine proteins and is 55% identical to the sequence of human FKBP52. Human FKBP51 mRNA is expressed in a wide range of tissues, and the protein has peptidylprolyl isomerase activity that is inhibited by FK506 but not cyclosporine. FKBP51 is the same as a previously described progesterone receptor-associated immunophilin that, similar to FKBP52 and cyclophilin 40, is an Hsp90-binding protein and appears in functionally mature steroid receptor complexes along with Hsp90 and p23. Each of the three receptor-associated immunophilins displays interactions with progesterone receptor that are more dynamic than Hsp90-receptor interactions. Whereas FKBP52 and FKBP51 compete about equally well for binding to Hsp90 in a purified system, FKBP51 accumulates preferentially in progesterone receptor complexes assembled in a cell-free system. This observation provides a precedent for differential interactions between Hsp90-associated immunophilins and target proteins such as steroid receptors.

Published
1997
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37. Advances in understanding the molecular mechanisms of borderline ovarian tumors.

Author

Chen S, Huang L, Liang M, Xie Y, Zhou Z, Ke Y, and Wu Z

Abstract

Borderline ovarian tumors (BOTs), which are a special type of epithelial tumor of the ovary, lie between benign and malignant tumors and have low malignant potential. Due to the fact that the early symptoms of these tumors are relatively subtle, they are not easy to diagnose clinically. This study explores advancements in clinical detection methods and provides a comprehensive overview of molecules such as cell migration factors, cell transcription factors, cell damage repair factors, cell cycle regulators, and tumor suppressor genes that are related to the development of BOTs and their related mechanisms in recent years, thus aiming to provide more sensitive, specific, and efficient differential diagnosis and treatment plans for patients to improve their prognosis and survival outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer HL declared a shared affiliation with the author ZW to the handling editor at the time of review., (Copyright © 2024 Chen, Huang, Liang, Xie, Zhou, Ke and Wu.)

Published
2024
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