Review
Pharmacology & Pharmacy
Lucia Sladekova, Sridhar Mani, Zdenek Dvorak
Summary: The aryl hydrocarbon receptor (AhR) is a crucial member of the helix-loop-helix transcription factors family, playing a central role in host physiology and various pathophysiologies. Activation of AhR is ligand-driven and the pharmacology of activation is dependent on the type and quantity of ligand. Therefore, understanding AhR ligands is essential for further advancements in the field. This minireview clarifies misconceptions and explores the true nature of AhR activation by discussing selected chemical classes and their qualification as true receptor ligands.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Noelia Miret, Carolina A. Pontillo, Sol Bujan, Florencia A. Chiappini, Andrea S. Randi
Summary: This literature review addresses the role of the aryl hydrocarbon receptor (AhR) and its ligands in breast cancer. The study explores the biological mechanisms of AhR agonists in interfering with breast endocrine functions and their impact on breast cancer development and progression. The findings suggest that exposure to AhR agonists stimulates pathways that promote breast cancer and contribute to tumor progression. Therefore, the evaluation and regulation of industrial and agricultural chemicals and other toxicants are essential in reducing the risk of breast cancer.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Hidekazu Maruyama, Satoshi Sakai, Laurence Dewachter, Celine Dewachter, Benoit Rondelet, Robert Naeije, Masaki Ieda
Summary: This study found that the p38MAPK/DUSP1 negative feedback loop is impaired in pulmonary arterial hypertension (PAH), leading to excessive activation of p38MAPK and hyperplasia of PA-SMCs. The IP receptor agonist MRE-269 increases DUSP1 expression and inhibits p38MAPK-mediated PA-SMC proliferation. Further elucidation of the mechanism underlying reduced DUSP1 expression would be informative for PAH treatment.
Article
Toxicology
Hyejin Park, Un-Ho Jin, Keshav Karki, Clinton Allred, Laurie A. Davidson, Robert S. Chapkin, Asuka A. Orr, Farrhin Nowshad, Arul Jayaraman, Phanourios Tamamis, Stephen Safe
Summary: Hydroxylated chalcones act as AhR agonists with structure-dependent activity, inducing CYP1A1, CYP1B1, and UGT1A1 genes in Caco2 colon cancer cells. Compounds containing 2,2'-dihydroxy substituents showed the highest AhR activation, while other hydroxychalcones exhibited lower or non-detectable AhR activity in Caco2 cells.
TOXICOLOGICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Phuc-Tan Nguyen, Yuki Nakamura, Nguyen Quoc Vuong Tran, Kayoko Ishimaru, Thuy-An Nguyen, Yoshiaki Kobayashi, Fumie Watanabe-Saito, Tohru Okuda, Nobuhiro Nakano, Atsuhito Nakao
Summary: Ethyl caffeate (EC) is a natural phenolic compound found in medicinal plants and shows anti-allergic activity by inhibiting aryl hydrocarbon receptor (AhR) signaling. EC inhibits AhR activation and downregulates AhR target gene expressions. It also inhibits mast cell activation and IL-6 production induced by AhR ligands. These findings suggest a novel mechanism for the anti-inflammatory activity of EC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Environmental Sciences
Tuan Xu, Yali Luo, Heidi Qunhui Xie, Yingjie Xia, Yunping Li, Yangsheng Chen, Zhiling Guo, Li Xu, Bin Zhao
Summary: This study investigated the effects of the aryl hydrocarbon receptor (AhR) on cell migration in human neuroblastoma cells. Through integrative analysis of mRNA and microRNA expression profiles, it was found that the mRNA-miR networks in the axon guidance pathway may play a role in dioxin-induced directional migration of human neuroblastoma cells.
ENVIRONMENT INTERNATIONAL
(2022)
Review
Biochemistry & Molecular Biology
Hyejin Park, Un-Ho Jin, Gregory Martin, Robert S. Chapkin, Laurie A. Davidson, Kyongbum Lee, Arul Jayaraman, Stephen Safe
Summary: Unsubstituted flavone can induce gene expression in Caco2 cells and acts as an AhR agonist. The addition of hydroxyl groups can determine the activity of flavones, but the affinity of mono- and dihydroxyflavones to AhR is similar and cannot accurately predict their activity. Most AhR-inactive flavones also function as AhR antagonists.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Biochemistry & Molecular Biology
Masashi Ishikawa, Masae Iwasaki, Hailin Zhao, Junichi Saito, Cong Hu, Qizhe Sun, Atsuhiro Sakamoto, Daqing Ma
Summary: Inhalational anesthetics sevoflurane and desflurane were found to inhibit glioma cell malignancy through upregulation of miRNAs and downregulation of their downstream effectors HIF-1 alpha and MMP9. Further studies are warranted to explore the implications of these findings.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Ziyue Kou, Wei Dai
Summary: Aryl hydrocarbon receptor (AHR) is a cellular protein involved in detoxification of xenobiotic compounds. Research has shown that AHR plays important roles in normal development and homeostasis, and its deficiency can lead to various developmental abnormalities.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Heidi Qunhui Xie, Yongchao Ma, Hualing Fu, Tuan Xu, Yali Luo, Yiyun Liu, Yangsheng Chen, Li Xu, Yingjie Xia, Bin Zhao
Summary: Acetylcholinesterase (AChE) plays important roles in cholinergic neurotransmission and is widely recognized as a biomarker for monitoring pollution by organophosphate and carbamate pesticides. Dioxin, a persistent organic pollutant, affects the nervous system and has been linked to neurodegenerative diseases and neurodevelopmental disorders, mainly through its impact on AChE and cholinergic dysfunctions. The aryl hydrocarbon receptor (AhR)-dependent pathway is a key research focus in studying the mechanisms of dioxin-induced AChE dysregulation.
JOURNAL OF NEUROCHEMISTRY
(2021)
Review
Cell Biology
Claudia Rejano-Gordillo, Ana Ordiales-Talavero, Ana Nacarino-Palma, Jaime M. Merino, Francisco J. Gonzalez-Rico, Pedro M. Fernandez-Salguero
Summary: The transcription factor aryl hydrocarbon receptor (AHR) is a key regulator involved in cell functions and tumor progression. It can act as either an oncogene or a tumor suppressor, depending on the specific organ, tissue and cell type. In addition to its role in cell adhesion and migration, AHR has potential as a therapeutic tool, diagnosis and prognosis marker.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Rashad Haidar, Frank Henkler, Josephine Kugler, Aline Rosin, Doris Genkinger, Peter Laux, Andreas Luch
Summary: This study found that the stable compartmentalization of activated AHR in the nucleus does not depend on interactions with DNA or ARNT, and ARNT does not play a role in the intracellular trafficking of AHR.
SCIENTIFIC REPORTS
(2021)
Article
Engineering, Environmental
Jihyun Cha, Seongjin Hong, Jiyun Gwak, Mungi Kim, Junghyun Lee, Taewoo Kim, Gi Myung Han, Sang Hee Hong, Jin Hur, John P. Giesy, Jong Seong Khim
Summary: In this study, previously unidentified aryl hydrocarbon receptor agonists were identified in the livers of black-tailed gulls from South Korea using effect-directed analysis and full-scan screening analysis. These novel agonists may pose potential toxic effects and can be bioaccumulated in air-breathing organisms such as seabirds.
JOURNAL OF HAZARDOUS MATERIALS
(2022)
Review
Pharmacology & Pharmacy
Colleen S. Curran, Jeffrey B. Kopp
Summary: The aryl hydrocarbon receptor (AHR) plays an important role in the development of chronic kidney disease (CKD) by binding various endogenous and xenobiotic ligands and regulating kidney stability, transcriptional activity, and cell signaling. AHR activity is closely associated with kidney damage and protection, with its cross-talk with estrogen, peroxisome proliferator-activated receptor-gamma, and NF-kappa B pathways contributing to the diversity of AHR responses in different forms and stages of CKD. Understanding the roles of AHR in kidney fibrosis, metabolism, and the renin-angiotensin system can provide insights into the pathogenesis and therapies of CKD.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Immunology
Xiaoyu Xi, Qinbin Ye, Danping Fan, Xiaoxue Cao, Qiong Wang, Xing Wang, Mengxiao Zhang, Yuan Xu, Cheng Xiao
Summary: Several factors, including genetic, epigenetic, and environmental factors, play important roles in the pathogenesis of rheumatoid arthritis (RA), with polycyclic aromatic hydrocarbons (PAHs) being a recently highlighted environmental factor. This review summarizes the recent progress in understanding the mechanisms of PAHs and aryl hydrocarbon receptors (AHRs) in RA, and discusses the development of therapeutic drugs targeting AHRs. Challenges and prospects of AHR application in the future are also discussed.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Mariana Bezamat, Juliana F. Souza, Fernanda M. F. Silva, Emilly G. Correa, Aluhe L. Fatturi, Joao A. Brancher, Flavia M. Carvalho, Tayla Cavallari, Lais Bertolazo, Cleber Machado-Souza, Mine Koruyucu, Merve Bayram, Andrea Racic, Benjamin M. Harrison, Yan Y. Sweat, Ariadne Letra, Deborah Studen-Pavlovich, Figen Seymen, Brad Amendt, Renata Werneck, Marcelo C. Costa, Adriana Modesto, Alexandre R. Vieira
Summary: Molar incisor hypomineralization (MIH) is an enamel condition characterized by lesions ranging in color from white to brown, with potential genetic and environmental factors playing roles in its development. IRF6 and TGFA genes may interact and contribute to predisposition of MIH. Environmental factors affecting children's development may also contribute to the development of MIH.
Article
Endocrinology & Metabolism
Liu Hong, Hongli Sun, Brad A. Amendt
Summary: miRs play a crucial role in regulating craniofacial development by controlling the expression of transcription factors and signaling molecules involved in bone formation. Understanding the mechanisms of miRs during development can be applied to regenerate and repair craniofacial genetic anomalies and bone diseases caused by injuries.
Article
Medicine, Research & Experimental
Tadkamol Krongbaramee, Min Zhu, Qingwen Qian, Zeyuan Zhang, Steven Eliason, Yi Shu, Fang Qian, Adil Akkouch, Dan Su, Brad A. Amendt, Ling Yang, Liu Hong
Summary: The study characterized miR-200c and its regulators in adipogenic differentiation, obesity, and periodontitis in obese subjects. Injection of plasmid DNA encoding miR-200c rescued miR-200c downregulation, prevented periodontal and systemic inflammation, and alleviated impaired glucose metabolism in obese mice with LPS-induced periodontitis. The upregulation of miR-200c in the gingiva presents a therapeutic approach for PiOSs, potentially attenuating systemic inflammation.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)
Article
Veterinary Sciences
Amanda Brehm, Heather Wilson-Robles, Tasha Miller, Jill Jarvis, Michael Deveau
Summary: The study demonstrated that whole lung irradiation is feasible, safe, and well tolerated in dogs with appendicular osteosarcoma. While no significant improvement in outcome was observed, further investigation is warranted to characterize the efficacy and toxicity of WLI in dogs.
VETERINARY AND COMPARATIVE ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Samuel Swearson, Aseel O. Rataan, Steven Eliason, Brad A. Amendt, Yousef Zakharia, Aliasger K. Salem, Thai Ho, Youcef M. Rustum
Summary: This study quantitated the expression levels of miR-17, -19a, -34a, -155, and -210 in different types of renal cell carcinoma cell lines and primary kidney tumors. The results showed that miR-17 and -19a were expressed at lower levels, while miR-34a, miR-155, and miR-210 were expressed at higher levels. In ccRCC cell lines with sarcomatoid differentiation, miR-34a was expressed higher than miR-210, -155, -17, and -19a. More samples are needed to confirm the statistical significance of the differences in miR expression levels in tumor biopsies. Previous studies have shown that miR-210, miR-155, and HIFs are druggable targets, and downregulation of these miRs may be a novel strategy for the treatment of advanced ccRCC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Steven Eliason, Dan Su, Flavia Pinho, Zhao Sun, Zichao Zhang, Xiao Li, Mason Sweat, Shankar R. Venugopalan, Bing He, Michael Bustin, Brad A. Amendt
Summary: The study found that HMGN2 inhibits the binding of Lef-1 protein to DNA. miR-23a and miR-23b indirectly activate Pitx2 and amelogenin expression by repressing Hmgn2 expression. By examining the expression of miR-23a and miR-23b in mouse teeth, further insights into the regulatory role of these miRs in tooth organogenesis were obtained.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biotechnology & Applied Microbiology
Matthew T. Remy, Qiong Ding, Tadkamol Krongbaramee, Jue Hu, Andres V. Mora Mata, Amanda J. Haes, Brad A. Amendt, Hongli Sun, Marisa R. Buchakjian, Liu Hong
Summary: This study developed a nanoparticle-based delivery system to sustain the release of miRNAs and improve the restoration of craniofacial bone defects. The results demonstrated that CaCO3 nanoparticles enhance bone formation in a safe manner, indicating their potential application in restoring large bone defects.
Article
Oncology
Steven Eliason, Liu Hong, Yan Sweat, Camille Chalkley, Huojun Cao, Qi Liu, Hank Qi, Hongwei Xu, Fenghuang Zhan, Brad A. Amendt
Summary: The study found that inhibition of miR-210 expression can effectively reduce the growth of colorectal cancer tumors, and direct application of the inhibitor can better inhibit tumor growth. At the same time, miR-210 inhibition also activates specific pathways to reduce tumor formation, and functions by regulating the expression of genes such as XIST and NME1.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Dan Su, Tadkamol Krongbaramee, Hongli Sun, Liu Hong, Brad A. Amendt
Summary: microRNAs, small RNA molecules, play a crucial role in regulating cellular and developmental processes, controlling gene expression pathways, and maintaining tissue homeostasis and stem cells. As potential therapeutic tools for tissue regeneration and repair, miRs hold great promise. However, their in vivo response in complex tissues and organs may differ from that in cells and cancer.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2022)
Article
Dentistry, Oral Surgery & Medicine
P. Kantaputra, A. Butali, S. Eliason, C. Chalkley, S. Nakornchai, C. Bongkochwilawan, K. Kawasaki, A. Kumchiang, C. Ngamphiw, S. Tongsima, J. R. Ketudat Cairns, B. Olsen, W. Intachai, A. Ohazama, A. S. Tucker, B. A. Amendt
Summary: This study aimed to identify the molecular etiology of dental anomalies in eight Thai patients and explore the effects of mutation on cellular functions. Clinical and radiographic examinations revealed multiple supernumerary cusps, single-cusped premolars, and reduced root number in the patients. Mutation analysis identified a heterozygous mutation in CACNA1S, which is involved in calcium signaling. Mutant protein modeling and cell culture experiments showed abnormalities in calcium flow and cell migration, suggesting a role for calcium signaling in tooth development.
Article
Multidisciplinary Sciences
Heather Wilson-Robles, Emma Warry, Tasha Miller, Jill Jarvis, Matthew K. Matsushita, Pamela Miller, Marielle Herzog, Jean-Valery H. Turatsinze, Theresa H. Kelly, S. Thomas H. Butera, Gaetan H. Michel
Summary: Currently, there is a lack of useful circulating biomarkers available in veterinary oncology for monitoring treatment response and remission in dogs with hematopoietic malignancies. This study found that plasma nucleosome concentrations can be a useful tool for monitoring treatment and disease progression in these patients.
Article
Biology
Ploy Adisornkanj, Rajit Chanprasit, Steven Eliason, Juan M. Fons, Worrachet Intachai, Sissades Tongsima, Bjorn Olsen, Stefan T. Arold, Chumpol Ngamphiw, Brad A. Amendt, Abigail S. Tucker, Piranit Kantaputra
Summary: Study identified an extremely rare mutation in the PTPN23 gene that is associated with mesiodens. This mutation was found in seven family members with mesiodens and six family members without the condition. Further research showed that the PTPN23 mutation reduces phosphatase activity, leading to the formation of mesiodens.
Article
Biochemistry & Molecular Biology
Dan Su, Steve Eliason, Zhao Sun, Fan Shao, Brad A. Amendt
Summary: Wolf-Hirschhorn syndrome (WHS) is a developmental disorder associated with oral manifestations including cleft lip and palate. The WHSC1 gene, which is deleted in every reported case of WHS, is believed to play a role in tooth development. This study reveals that the expression of Whsc1 is regulated by Pitx2, a transcription factor involved in tooth development. In addition, two microRNAs, miR-23a/b and miR-24-1/2, directly target Whsc1 and repress its expression. These findings provide new insights into the potential role of Whsc1 in tooth development and may contribute to understanding the molecular mechanism underlying dental defects in WHS.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Cell Biology
Yan Cheng, Fumou Sun, Daisy V. Alapat, Visanu Wanchai, David Mery, Wancheng Guo, Huojun Cao, Yuqi Zhu, Cody Ashby, Michael Anton Bauer, Intawat Nookaew, Eric R. Siegel, Jun Ying, Jin-Ran Chen, Dongzheng Gai, Bailu Peng, Hongwei Xu, Clyde Bailey, Samer Al Hadidi, Carolina Schinke, Sharmilan Thanendrarajan, Maurizio Zangari, Marta Chesi, P. Leif Bergsagel, Frits van Rhee, Siegfried Janz, Guido Tricot, John D. Shaughnessy, Fenghuang Zhan
Summary: The loss of NEK2 in tumor microenvironmental cells suppresses the growth of multiple myeloma. The absence of NEK2 leads to fewer inhibitory T cells and tumor-associated macrophages (TAMs). NEK2 expression in myeloid progenitor cells promotes the generation of functional TAMs. Clinically, high NEK2 expression in MM cells is associated with increased CD8+ T effector memory cells, while low NEK2 is associated with an activated T cell response. Inhibition of NEK2 upregulates PD-L1 expression.
CELL REPORTS MEDICINE
(2023)
Article
Dentistry, Oral Surgery & Medicine
B. He, V. Kram, T. Furusawa, O. Duverger, E. Y. Chu, R. Nanduri, M. Ishikawa, P. Zhang, B. A. Amendt, J. S. Lee, M. Bustin
Summary: The study suggests that HMGN proteins play a role in regulating ameloblast differentiation and enamel mineralization by modulating lineage-specific chromatin accessibility and transcription factor binding to ameloblast regulatory sites. The absence of HMGN proteins in mice leads to faster ameloblast differentiation and increased enamel deposition rate in molars and incisors.
JOURNAL OF DENTAL RESEARCH
(2023)