Article
Biochemistry & Molecular Biology
Giuseppina Chianese, Annalisa Lopatriello, Carmina Sirignano, Alessandro Andreani, Andrea Gambini, Eric De Combarieu, Mariano Stornaiuolo, Orazio Taglialatela-Scafati
Summary: Two unprecedented cyclopamine analogues, 18-hydroxycyclopamine and 24R-hydroxycyclopamine, with modifications on rings D-F, were isolated from the mother liquors obtained from crystallization of cyclopamine extracted from corn lily. The stereostructures of these new natural compounds were determined through detailed MS and 1D/2D NMR investigation. Their inhibition of the hedgehog pathway was evaluated using the dual-luciferase bioassay, providing new insights into the structure-activity relationships for this class of compounds.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Yibin Pan, Jiena Zhou, Weidan Zhang, Lili Yan, Meifei Lu, Yongdong Dai, Hanjing Zhou, Songying Zhang, Jianhua Yang
Summary: The study found up-regulation of SHH and accumulation of SQSTM1/P62 in epithelial ovarian cancer. Cyp induced autophagy through the PI3K/AKT signaling pathway, and low-dose Cyp and chloroquine (CQ) significantly promoted the migratory ability of SKOV3 cells. The findings suggest that inhibition of the SHH pathway and autophagy may be a potential and effective therapy for the treatment of ovarian cancer.
Article
Cell Biology
Natalia Garcia, Ayman Al-Hendy, Edmund C. Baracat, Katia Candido Carvalho, Qiwei Yang
Summary: This study investigated the expression profile of Hedgehog pathway markers in uterine leiomyosarcoma (LMS) cells and the inhibitory effects of targeted drugs on LMS cell behavior. Inhibiting SMO, GLI, and DNMTs showed promising results in reducing LMS proliferation, migration, and invasion, suggesting potential therapeutic targets for this aggressive tumor. Blocking multiple components in the Hedgehog pathway exhibited potentiated effects on inhibiting LMS malignant features, warranting further investigation for clinical applications.
Article
Surgery
Ronan J. Kelly, Amir M. Ansari, Tomoharu Miyashita, Marianna Zahurak, Frank Lay, A. Karim Ahmed, Louis J. Born, Maryam K. Pezhouh, Kevan J. Salimian, Christopher Ng, Aerielle E. Matsangos, Anne-Heloise Stricker-Krongrad, Ken-ichi Mukaisho, Guy P. Marti, Christine H. Chung, Marcia I. Canto, Michelle A. Rudek, Stephen J. Meltzer, John W. Harmon
Summary: Itraconazole significantly reduces the development of esophageal adenocarcinoma and SHH expression in a preclinical animal model of Barrett's Metaplasia. In humans, BE tissue expresses higher levels of SHH, Indian Hedgehog, and bone morphogenic protein compared to normal squamous esophageal epithelium.
Review
Infectious Diseases
Janarthanan Venkatesan, Dhanashree Murugan, Loganathan Rangasamy
Summary: Targeted protein degradation, through the use of proteolysis-targeting chimeras (PROTACs), is a promising new approach in drug discovery for selectively eliminating disease-associated proteins. It has significant potential in the field of cancer research and shows promise as a new weapon against pathogenic viruses and bacteria.
Article
Veterinary Sciences
Aryung Nam, Woo-Jin Song, Ju-Hyun An, Robert B. Rebhun, Hwa-Young Youn, Kyoung-Won Seo
Summary: This study reveals that the Hh/SMO signaling pathway is activated in canine OSA cell lines and that cyclopamine suppresses the survival of OSA cells by inhibiting SMO. This suggests that the Hh/SMO signaling pathway could be a potential therapeutic target for canine OSA.
VETERINARY AND COMPARATIVE ONCOLOGY
(2022)
Article
Cell Biology
Jangham Jung, Jaehun Kim, Tae-Lin Huh, Myungchull Rhee
Summary: TRIM46 is a RING finger E3 ligase that plays a role in neuronal polarity and axon specification. The zebrafish homologue trim46a is regulated by transcription factor Foxa2 and affects the development of the midbrain and MHB. Inhibition of SHH signaling pathway by cyclopamine leads to developmental defects in midbrain and MHB through trim46a regulation.
ANIMAL CELLS AND SYSTEMS
(2021)
Article
Developmental Biology
Celio J. da Costa Fernandes, Marcel Rodrigues Ferreira, Willian Fernando Zambuzzi
Summary: The cellular events of bone maintenance, remodeling, and repair have their origins in embryonic bone production. Shh signaling plays a crucial role in bone development by modifying osteoblast activity. It is important to investigate its association with nuclear control for future applications.
CELLS & DEVELOPMENT
(2023)
Article
Biochemistry & Molecular Biology
Xiangyang Li, Rui Sun, Hao Wu, Chaonan Zheng, Ya-Qiu Long
Summary: English Summary: The Hedgehog/Glioma-associated oncogene (Hh/Gli) signaling pathway is crucial for embryonic development and tissue homeostasis, and its dysregulation is associated with various human malignancies. Gli1, a downstream transcription factor of the Hh pathway, is a common regulator of tumorigenic pathways in Hh-independent cancers, making it a promising drug target. However, the development of small molecules that target Gli1 protein has been slow due to lack of efficacy and selectivity. In this study, researchers developed novel Gli1 degraders based on the hydrophobic tagging (HyT) strategy, which effectively inhibited the proliferation of colorectal cancer cells and induced Gli1 degradation. These small molecules showed stronger potency in suppressing Hh target genes compared to the canonical Hh antagonist Vismodegib, and they overcame resistance to current Smoothened (SMO) antagonists. This study provides a new avenue for developing therapeutic approaches targeting the Hh/Gli1 signaling pathway.
BIOORGANIC CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Xiaohua Liu, Yu Zhang, Yalei Li, Juan Wang, Huaqian Ding, Wenjing Huang, Chunyong Ding, Hongchun Liu, Wenfu Tan, Ao Zhang
Summary: Medulloblastoma is a childhood malignant brain tumor with heterogeneous characteristics and lacks effective molecular targeted therapy. Compounds 25 and 35 show high potency in inhibiting hedgehog signaling and interacting with the transcriptional factor GLI, with potential to combat resistant and wild type smoothened receptor.
ACTA PHARMACEUTICA SINICA B
(2021)
Review
Biochemistry & Molecular Biology
Atif Khurshid Wani, Nahid Akhtar, Tahir ul Gani Mir, Rattandeep Singh, Prakash Kumar Jha, Shyam Kumar Mallik, Shruti Sinha, Surya Kant Tripathi, Abha Jain, Aprajita Jha, Hari Prasad Devkota, Ajit Prakash
Summary: Apoptosis is the process of eliminating non-essential, neoplastic, and infected cells through regulated pathways. Loss of apoptosis control can lead to cancer cell survival, accumulation of mutations, and tumor progression. The apoptotic pathway has been studied as a potential drug target in cancer treatment, but concerns regarding off-target activities have emerged. Phytochemicals and plant-based nanoparticles show promise in cancer treatment by targeting programmed cell death network.
Article
Orthopedics
Timur B. Kamalitdinov, Keitaro Fujino, Sinaia Keith Lang, Xi Jiang, Rashad Madi, Mary Kate Evans, Miltiadis H. Zgonis, Andrew F. Kuntz, Nathaniel A. Dyment
Summary: This study reveals a biphasic role for Hh signaling during the tendon-to-bone integration process after ACLR. In addition, the Hh pathway is a promising therapeutic target to improve tendon-to-bone repair outcomes.
OSTEOARTHRITIS AND CARTILAGE
(2023)
Article
Cell Biology
Weiyi Gong, Wenxuan Zhao, Gang Liu, Lei Shi, Xia Zhao
Summary: BDDD-721, a curcumin analogue, exhibits stronger anti-tumor activity than curcumin on medulloblastoma. It effectively inhibits the proliferation, migration, invasion, and promotes apoptosis of medulloblastoma cells. The study also discovered that BDDD-721 targets the Shh/Gli1 signaling pathway to exert its anticancer effects.
Article
Chemistry, Medicinal
Shady Burayk, Kentaro Oh-hashi, Mahmoud Kandeel
Summary: This study discovered two novel benzimidazole piperidine and phenoxy pyridine derivatives that achieve anti-inflammatory effects through selective inhibition of COX-2, and they have favorable safety profiles.
Review
Pharmacology & Pharmacy
Hongdan He, Xiaoni Shao, Yanan Li, Ribu Gihu, Haochen Xie, Junfu Zhou, Hengxiu Yan
Summary: This review summarizes the common signaling pathways in malignant tumors and the research progress related to them, including the Wnt/β-catenin, PI3K/AKT/mTOR, Notch, and NF-kB pathways, as well as the important role of miRNAs. It also briefly introduces the anti-tumor molecular drugs targeting these signaling pathways.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Marisa E. Hom, Alison E. Ondrus, Tomoyo Sakata-Kato, Paul G. Rack, James K. Chen
Article
Developmental Biology
Karen Mruk, Paulina Ciepla, Patrick A. Piza, Mohammad A. Alnaqib, James K. Chen
Article
Biology
J. Aaron Crapster, Paul G. Rack, Zane J. Hellmann, Austen D. Le, Christopher M. Adams, Ryan D. Leib, Joshua E. Elias, John Perrino, Barry Behr, Yanfeng Li, Jennifer Lin, Hong Zeng, James K. Chen
Article
Green & Sustainable Science & Technology
James K. C. Chen
Article
Multidisciplinary Sciences
Patricia R. Nano, Taylor K. Johnson, Takamasa Kudo, Nancie A. Mooney, Jun Ni, Janos Demeter, Peter K. Jackson, James K. Chen
Summary: ARHGAP36 is an atypical member of the Rho GTPase-activating protein (GAP) family, with multiple functional domains and regulatory modes. It influences spinal cord development and tumorigenesis by regulating Gli transcription factor activation and interaction with other proteins.
Article
Green & Sustainable Science & Technology
James K. C. Chen, Thitima Sriphon
Summary: Employees are crucial assets for an organization and their engagement in teamwork is vital for long-term organizational development. Good managers with excellent leadership skills are needed, but the strategies implemented during the COVID-19 pandemic have impacted relationships among organizational employees. Trust, communal relationships, and social exchange relationships are key for organizational leadership, and the pandemic has affected leadership, emphasizing the importance of communication and adaptability for leaders.
Article
Chemistry, Multidisciplinary
Kristie Darrah, Joshua Wesalo, Bradley Lukasak, Michael Tsang, James K. Chen, Alexander Deiters
Summary: Conditionally activated caged morpholino antisense agents (cMOs) are tools that allow for investigation of gene expression, regulation, and function during embryonic development. The synthesis of small molecule-responsive cMOs with a flexible linker design enables rapid decaging via Staudinger reduction, leading to gene knockdown in zebrafish embryos. This represents a novel bioorthogonal approach to gene knockdown.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Green & Sustainable Science & Technology
James K. C. Chen, Thitima Sriphon
Summary: This study explores the associations among authentic leadership, trust, and social exchange relationships under the influence of leader behavior. The findings indicate that authentic leadership positively impacts trust and social exchange relationships, while trust directly affects social exchange relationships. During the COVID-19 pandemic, leader behaviors with ability, ethics, and positive relationships have a positive impact on the relationship between authentic leadership, trust, and social exchange relationships. Trust serves as a positive mediator between authentic leadership and social exchange relationships.
Article
Biochemistry & Molecular Biology
Zhiping Feng, Marisa E. Hom, Thomas E. Bearrood, Zachary C. Rosenthal, Daniel Fernandez, Alison E. Ondrus, Yuchao Gu, Aaron K. McCormick, Madeline G. Tomaske, Cody R. Marshall, Toni Kline, Che-Hong Chen, Daria Mochly-Rosen, Calvin J. Kuo, James K. Chen
Summary: Aldehyde dehydrogenases (ALDHs) are potential cancer drug targets, specifically certain isoforms essential for the survival of stem-like tumor cells. Selective inhibitors of ALDH1B1 have been identified, an enzyme essential for promoting colorectal and pancreatic cancer. Bicyclic imidazoliums and guanidines that target the ALDH1B1 active site have been described, with comparable molecular interactions and potencies. These inhibitors effectively suppress ALDH1B1 function in cells, with guanidines avoiding off-target mitochondrial toxicity observed with imidazoliums. A lead isoform-selective guanidinyl antagonist of ALDHs demonstrates proteome-wide target specificity and selectively hinders the growth of colon cancer spheroids and organoids. The ALDH1B1-dependent transcriptome, involving genes regulating mitochondrial metabolism and ribosomal function, has been elucidated through genetic and chemical perturbations. The importance of ALDH1B1 in colorectal cancer is supported, offering molecular probes for ALDH1B1 studies and potential leads for targeted therapies.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sankha Pattanayak, Bhagyesh R. Sarode, Alexander Deiters, James K. Chen
Summary: Caged morpholino oligonucleotides (cMOs) are synthetic tools that allow light-inducible gene silencing in live organisms. A new caging strategy has been developed to enhance the efficacy of cMOs in zebrafish embryos.
Article
Biochemistry & Molecular Biology
Kristie E. Darrah, Savannah Albright, Rohan Kumbhare, Michael Tsang, James K. Chen, Alexander Deiters
Summary: The structure and mechanism of the bacterial enzyme beta-lactamase, which is clinically important for antibiotic resistance, have been extensively studied. Beta-lactamase can hydrolyze the beta-lactam ring of the cephalosporin scaffold, leading to self-immolation. This study presents a circular caged morpholino oligonucleotide (cMO) activated by beta-lactamase-mediated cleavage of a cephalosporin motif, showing potential for silencing gene expression and eliciting observable phenotypes in aquatic embryos.
ACS CHEMICAL BIOLOGY
(2023)
Article
Green & Sustainable Science & Technology
Chih-Lung Lin, James K. C. Chen, Han-Hsi Ho
Summary: Smart hospitals have played a significant role in response to the COVID-19 pandemic, requiring the establishment of an evaluation system to prioritize relevant criteria and sub-criteria. Research findings highlight the importance of functionalities related to end users, while also emphasizing the crucial role of BIM in asset information management practices.
Article
Green & Sustainable Science & Technology
Jinwei Xu, Xueli Zheng, Zhiping Feng, Zhiyi Lu, Zewen Zhang, William Huang, Yanbin Li, Djordje Vuckovic, Yuanqing Li, Sheng Dai, Guangxu Chen, Kecheng Wang, Hansen Wang, James K. Chen, William Mitch, Yi Cui
Summary: The study demonstrates a method of catalytically activating H2O2 to generate hydroxyl radicals using Cu single atoms, which operates stably at pH 7.0 without the need for external energy input, providing a new approach for wastewater treatment.
NATURE SUSTAINABILITY
(2021)
Review
Biochemistry & Molecular Biology
Ukrae Cho, James K. Chen
CELL CHEMICAL BIOLOGY
(2020)
Proceedings Paper
Engineering, Electrical & Electronic
James K. C. Chen, Kuan-Chin Shu, Howard H. Y. Lee
2019 PORTLAND INTERNATIONAL CONFERENCE ON MANAGEMENT OF ENGINEERING AND TECHNOLOGY (PICMET)
(2019)
