Article
Environmental Sciences
Severine A. Degrelle, Ioana Ferecatu, Thierry Fournier
Summary: Aryl hydrocarbon receptor (AHR) is a crucial transcription factor involved in various biological processes. Two new reporter genes have been constructed to improve the study of AHR activity, and their capability to monitor AHR activity in different cell types has been demonstrated.
ENVIRONMENT INTERNATIONAL
(2022)
Article
Biochemistry & Molecular Biology
Seung Eun Lee, Kitae Kwon, Sae Woong Oh, Se Jung Park, Eunbi Yu, Hyeyoun Kim, Seyoung Yang, Jung Yoen Park, Woo-Jae Chung, Jae Youl Cho, Jongsung Lee
Summary: The study demonstrated that resorcinol can protect against B[a]P-induced abnormal keratinocyte biology by inhibiting AhR activity and activating Nrf2-mediated antioxidant signaling pathway.
BIOMOLECULES & THERAPEUTICS
(2021)
Article
Dermatology
Mariela Kyoreva, Ying Li, Mariyah Hoosenally, Jonathan Hardman-Smart, Kirsten Morrison, Isabella Tosi, Mauro Tolaini, Guillermo Barinaga, Brigitta Stockinger, Ulrich Mrowietz, Frank O. Nestle, Catherine H. Smith, Jonathan N. Barker, Paola Di Meglio
Summary: The study suggests that CYP1A1 enzymatic activity plays a critical role in regulating beneficial AHR signaling in skin inflammation, and inhibiting CYP1A1 enzymatic activity can ameliorate skin immunopathology. Patients with psoriasis have reduced AHR pathway activation and increased CYP1A1 enzymatic activity, indicating a potential role of dysregulated AHR/CYP1A1 axis in inflammatory skin disease.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Pharmacology & Pharmacy
Jin Chen, Mingxuan Zhang, Hongmei Zou, Stanley Aniagu, Yan Jiang, Tao Chen
Summary: This study demonstrates that PM2.5 induces mitochondrial dysfunction in zebrafish embryos' hearts via the AHR-mediated cyp1a1 overexpression, leading to increased mtROS generation, mPTP opening, MMP collapse, reduced ATP levels, and decreased expression of mitochondrial proteins. Inhibition of AHR or mPTP can mitigate these effects and protect against apoptosis and heart defects. Furthermore, inhibiting mtROS generation with MitoQ and knockdown of cyp1a1, but not cyp1b1, attenuate the PM2.5-induced mtROS generation and heart defects.
Article
Genetics & Heredity
L. Sadeghi-Amiri, A. Barzegar, N. Nikbakhsh-Zati, P. Mehraban
Summary: This study analyzed the methylation status of CpG sites within the 5' regulatory region of the CYP1A1 gene and its association with gene expression in gastric cancer. The results indicated that variably methylated CpG sites near the XRE10 regulatory region of CYP1A1 are associated with gene upregulation and likely involved in gastric cancer incidence and metastasis. Methylation analysis of CpG sites around the XRE10 motif in the CYP1A1 promoter may serve as a potential marker for evaluating individual susceptibility to gastric cancer.
Review
Genetics & Heredity
N. R. Coelho, A. B. Pimpao, M. J. Correia, T. C. Rodrigues, E. C. Monteiro, J. Morello, S. A. Pereira
Summary: This review provides an overview of the pharmacodynamic and pharmacokinetic properties of AHR antagonists and CYP1A1 inhibitors in different in vivo rodent models, serving as a guide for researchers in this emerging therapeutic area targeting the AHR. It is a timely opportunity as the first AHR antagonists have recently entered the clinical stage of drug development.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Article
Biochemistry & Molecular Biology
Haisen Yin, Jianwei Zhang, Hanping Zhang, Qing Li, Hu Qiu, Kunqiao Hong, Wei Wang, Yong Xiao, Baoping Yu
Summary: Fusobacterium nucleatum (Fn) is involved in the progression of esophageal squamous cell carcinoma (ESCC) by promoting cell proliferation through the AHR/CYP1A1/AKT signaling pathway. These findings contribute to the development of therapeutic strategies for ESCC.
Article
Cell Biology
Zeinab El Amine, Jean-Francois Mauger, Pascal Imbeault
Summary: It has been found that hypoxia can partially inhibit the metabolic effects of PCB126 in human adipocytes, but hypoxia and PCB126 have different impacts on the secretion of leptin, interleukin-6, and IL-8, with no apparent crosstalk between the two factors.
Article
Toxicology
Trong Thuan Ung, Thi Thinh Nguyen, Shinan Li, Jae-Young Han, Young Do Jung
Summary: Nicotine stimulates CYP1A1 expression through transcription factors and signaling pathways, although antioxidant compounds can inhibit nicotine-induced reactive oxygen species production and CYP1A1 expression. Inhibition of NADPH oxidase activity also affects CYP1A1 expression.
TOXICOLOGY LETTERS
(2021)
Article
Medicine, Research & Experimental
Jiebin Xie, Yueshan Pang, Xiaoting Wu
Summary: Tax significantly inhibited the viability, proliferation, migration and invasion of gastric cancer cells through the AhR/CYP1A1 signaling pathway. The AhR agonist SB203580 partly abolished the inhibitory effects of Tax on gastric cancer cell viability, proliferation, migration and invasion. Additionally, Tax suppressed tumor growth in vivo, demonstrating its potential as a therapeutic strategy for gastric cancer.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2021)
Article
Toxicology
Jinwen Yuan, Xiaoming Sun, Siyan Che, Li Zhang, Zheng Ruan, Xiaomin Li, Junhua Yang
Summary: Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants that may have a negative impact on human health. The study found that BDE-209 induces apoptosis, oxidative stress, disturbances in calcium homeostasis and mitochondrial membrane potential, DNA damage, and potentially acts as a liver carcinogen. Interestingly, HepG2 cells attempt to metabolize BDE-209 through the Nrf2-mediated antioxidant pathway.
TOXICOLOGY LETTERS
(2021)
Article
Cell Biology
Hye Ji Lim, Woong Bi Jang, Vinoth Kumar Rethineswaran, Jaewoo Choi, Eun Ji Lee, Sangmi Park, Yeoreum Jeong, Jong Seong Ha, Jisoo Yun, Young Jin Choi, Young Joon Hong, Sang-Mo Kwon
Summary: StemRegenin-1 (SR-1) maintains the expression of surface markers in endothelial progenitor cells (EPCs), reduces cellular senescence, and enhances their proliferation, migration, and tube-forming capacity. SR-1 also inhibits oxidative stress-induced DNA damage and reactive oxygen species (ROS) production in EPCs by blocking aryl hydrocarbon receptor (AhR) activity. In addition, treatment with SR-1 promotes blood vessel formation in vivo.
Article
Biochemistry & Molecular Biology
Shengxian Liang, Haimei Bo, Yue Zhang, Hongcheng Zhen, Li Zhong
Summary: This study found that alizarin displays agonistic activities to the AHR receptor through activating the AHR-CYP1A1 signaling pathway in HepG2 cells, which may lead to an increased risk for cancer development.
Article
Food Science & Technology
Hyunki Cho, Ian Choi, Sang Kyum Kim, Seungyun Baik, Chang Seon Ryu
Summary: This study aimed to develop a LC-MS/MS-based assay to evaluate the induction potential of CYP1A1 following exposure to particulate matter (PM). The assay showed high selectivity for CYP1A1 and strong correlation with AhR activation and CYP1A1 mRNA levels.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Pharmacology & Pharmacy
Liyun Zhao, Liyuan Yao, Rui Chen, Jiani He, Tingting Lin, Silin Qiu, Guohua Chen, Hongfeng Chen, Sheng-Xiang Qiu
Summary: Through bioassay, the flavonoid pinostrobin was found to inhibit the replication of human coronavirus OC43 in colorectal adenocarcinoma cells. It was found that pinostrobin interfered with the metabolism of linoleic acid and arachidonic acid. Further analysis revealed that pinostrobin modulates lipid metabolism through the AHR/CYP1A1 pathway to exert its anti-coronavirus effects.
ANTIVIRAL RESEARCH
(2023)
Article
Oncology
Sabah Akhtar, Shireen Hourani, Lubna Therachiyil, Abdullah Al-Dhfyan, Abdelali Agouni, Asad Zeidan, Shahab Uddin, Hesham M. Korashy
Summary: This article summarizes the characteristics and important roles of cancer stem cells (CSCs) and their connection with environmental toxin PAHs and cytosolic receptor AhR. The review also discusses the signaling pathways related to tumorigenesis and progression that are mediated by AhR, as well as the epigenetic regulations of CSCs by the AhR/CYP1A pathway.
SEMINARS IN CANCER BIOLOGY
(2022)
Review
Cardiac & Cardiovascular Systems
Shingo Takahara, Shubham Soni, Zaid H. Maayah, Mourad Ferdaoussi, Jason R. B. Dyck
Summary: When circulating glucose levels are depleted, the heart may rely on ketone bodies as an alternative energy source, which can also suppress inflammation. Therefore, increasing circulating ketones may be beneficial for the treatment of heart failure.
CARDIOVASCULAR RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Fawaz E. Alanazi, Homood M. As Sobeai, Khalid Alhazzani, Abdullah Al-Dhfyan, Musaad A. Alshammari, Moureq Alotaibi, Khaled Al-hosaini, Hesham M. Korashy, Ali Alhoshani
Summary: This study reveals that metformin can suppress VISTA through AHR in melanoma, suggesting a new potential therapeutic strategy for treating this aggressive skin cancer.
SAUDI PHARMACEUTICAL JOURNAL
(2022)
Article
Pharmacology & Pharmacy
Ola El Atab, Crystal M. Ghantous, Nabil El-Zein, Rima Farhat, Abdelali Agouni, Hesham M. Korashy, Laiche Djouhri, Layla Kamareddine, Kazem Zibara, Asad Zeidan
Summary: This study investigates the molecular mechanisms involved in hyperglycemia-induced vascular remodeling, with a focus on the role of APN and leptin. It found that hyperglycemia increases APN synthesis but decreases APN receptor expression, and upregulates leptin expression in vascular smooth muscle cells. These changes lead to increased oxidative stress and alterations in actin cytoskeleton dynamics, facilitating vascular remodeling.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Chemistry, Physical
Hissa F. Al-Thani, Samar Shurbaji, Zain Zaki Zakaria, Maram H. Hasan, Katerina Goracinova, Hesham M. Korashy, Huseyin C. Yalcin
Summary: In this study, the use of nanoparticles to deliver the anti-cancer drug Ponatinib and reduce its cardiotoxicity was explored. The efficacy and safety of the drug-delivery system were assessed in vivo using zebrafish as an animal model. It was found that the Ponatinib-loaded nanoparticles showed no toxicity or cardiotoxicity in the zebrafish xenograft model.
Article
Biochemistry & Molecular Biology
Shubham Soni, Matthew D. Martens, Shingo Takahara, Heidi L. Silver, Zaid H. Maayah, John R. Ussher, Mourad Ferdaoussi, Jason R. B. Dyck
Summary: The study found that exogenous beta-hydroxybutyrate attenuates the inflammatory response and organ dysfunction in sepsis. Oral administration of beta-hydroxybutyrate for three days prior to lipopolysaccharide injection significantly protected mice against systemic inflammation and mitigated cardiac, renal, and liver dysfunction. These protective effects were independent of changes to enzymes involved in ketone metabolism.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Article
Oncology
Lubna Therachiyil, Ola J. Hussein, Shahab Uddin, Hesham M. Korashy
Summary: This review explores the crosstalk and interaction between the aryl hydrocarbon receptor (AhR) and cancer-related signaling pathways in gynecological malignancies. It discusses the association between exposure to environmental pollutants and cancer stem cell (CSC) enrichment in gynecological cancers, as well as the potential of targeting the AhR pathway as a novel chemotherapy for these cancers.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Abdullah Al-Dhfyan, Ayodele Alaiya, Falah Al-Mohanna, Mohamed W. Attwa, Abdullah F. AlAsmari, Saleh A. Bakheet, Hesham M. Korashy
Summary: This study investigates the crosstalk between AhR and BCL-2 in breast cancer stem cells (CSCs) and suggests a combined treatment of BCL-2 inhibitor and AhR antagonist for more effective cancer prevention and treatment.
JOURNAL OF ADVANCED RESEARCH
(2023)
Article
Chemistry, Applied
Sourour Idoudi, Yousef Hijji, Takwa Bedhiafi, Hesham M. Korashy, Shahab Uddin, Maysaloun Merhi, Said Dermime, Nashiru Billa
Summary: In this study, a successful CUR.SA conjugate has been developed and encapsulated in CM nanoparticles, showing favorable attributes for further anti-colon cancer research.
CARBOHYDRATE POLYMERS
(2022)
Review
Biochemistry & Molecular Biology
Tahseen S. Sayed, Zaid H. Maayah, Heba A. Zeidan, Abdelali Agouni, Hesham M. Korashy
Summary: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcriptional factor with diverse physiological and pathological roles. It has been found that environmental pollutants can increase the risk of diseases such as diabetes and obesity by activating AhR. Current research focuses on understanding the mechanisms of AhR in insulin secretion and glucose homeostasis, involving pathways such as gluconeogenesis, hypoxia-inducible factor, oxidative stress, and inflammation.
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2022)
Article
Chemistry, Medicinal
Hevna Dhulkifle, Tahseen S. Sayed, Hanan H. Abunada, Sara M. Abulola, Ali Alhoshani, Hesham M. Korashy, Zaid H. Maayah
Summary: Patients with sepsis are at high risk of morbidity and mortality due to multiple organ injuries caused by pathological inflammation. Acute renal injury is a significant contributor to sepsis morbidity and mortality. 6-formylindolo(3,2-b)carbazole (FICZ) has shown potential protective effects against sepsis-induced renal injury through the activation of AhR/Nrf2.
CHEMICAL RESEARCH IN TOXICOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Muhammad Ammar Zahid, Shahenda Salaheldin Abdelsalam, Hicham Raiq, Aijaz Parray, Hesham Mohamed Korashy, Asad Zeidan, Mohamed A. Elrayess, Abdelali Agouni
Summary: A timely and adequate response to stress is crucial for maintaining cell function, and disruptions in defense mechanisms against stress can lead to various pathologies. Aging and cardiovascular diseases can reduce the effectiveness of these defense mechanisms. Sestrin2 (SESN2) is a stress-inducible protein that can protect cells by increasing antioxidants, temporarily halting stressful reactions, and promoting autophagy. Maintaining sufficient levels/activity of SESN2 may prevent cardiovascular aging and disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Zaid H. H. Maayah, Mourad Ferdaoussi, Abrar Alam, Shingo Takahara, Heidi Silver, Shubham Soni, Matthew D. D. Martens, Dean T. T. Eurich, Jason R. B. Dyck
Summary: The study demonstrates that CBD can improve cardiac function and reduce renal injury induced by cytokine storm, by reducing inflammation levels both systemically and renally. This suggests a potential repurposing of CBD to reduce morbidity in patients with cytokine storm, especially in severe infections such as sepsis.
CANNABIS AND CANNABINOID RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
Shingo Takahara, Shubham Soni, Kiran Phaterpekar, Ty T. Kim, Zaid H. Maayah, Jody L. Levasseur, Heidi L. Silver, Darren H. Freed, Mourad Ferdaoussi, Jason R. B. Dyck
Summary: Recent evidence has shown that ketone bodies, especially BHB, benefit the failing heart by serving as an alternative energy source and possessing anti-inflammatory and anti-oxidative properties. Chronic supplementation of ketones improved cardiac function in mice with established heart failure, reducing cardiomyocyte hypertrophy and fibrosis. These findings suggest that ketone therapy may be a potential treatment option for heart failure.