Evolutionary history of magnoliid genomes and benzylisoquinoline alkaloid biosynthesis DOI Creative Commons
Yiheng Hu, Jinpeng Wang, Lumei Liu

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 29, 2025

Benzylisoquinoline alkaloids (BIAs) are important metabolites synthesized in early-diverging eudicots and magnoliids, yet the genetic basis of BIA biosynthesis magnoliids remains unclear. Here, we decode genomes two magnoliid species, Saruma henryi Aristolochia manshuriensis, reconstruct ancestral karyotype infer chromosomal rearrangement history following diversification. Metabolomic, transcriptomic, phylogenetic analyses reveal intermediate chemical components A. manshuriensis. Although core enzymes involved synthesis appear to be largely conserved between biosynthetic pathways seem exhibit greater flexibility. Significantly, our investigation evolutionary genes revealed that almost all were duplicated before emergence extant angiosperms, with only preferentially retaining these genes, thereby enabling BIAs groups.

Language: Английский

Emerging paradigms for target discovery of traditional medicines: A genome-wide pan-GPCR perspective DOI Creative Commons

Zenghao Bi,

Huan Li, Yuting Liang

et al.

The Innovation, Journal Year: 2025, Volume and Issue: 6(3), P. 100774 - 100774

Published: Jan. 18, 2025

Traditional medicines serve not only as an integral part of medical treatments prescribed by healthcare providers but also a fundamental reservoir for novel molecular scaffolds. However, gaps remain in our understanding the mechanisms underlying their activity. A superfamily membrane proteins, G protein-coupled receptors (GPCRs), have been demonstrated to be potential targets several compounds isolated from traditional medicines. Given that GPCRs approximately one-third all marketed drugs, they may compelling repurposing Despite this potential, research investigating activity or ligands across GPCRome, library human GPCRs, is scarce. Drawing on functional and structural knowledge presently available, review contemplates prospective trends GPCR drug discovery, proposes innovative strategies medicines, highlights ligand screening approaches identifying drug-like molecules. To discover bioactive molecules either directly bind indirectly modify function, genome-wide pan-GPCR discovery platform was designed identification components targets, evaluation pharmacological profiles. This aims aid exploration all-sided relations between GPCRome using advanced high-throughput techniques. We present various used many, including ourselves, illuminate previously unexplored aspects GPCRs.

Language: Английский

Citations

3
The Mutographs biorepository: A unique genomic resource to study cancer around the world DOI Creative Commons
Sandra Pérdomo, Behnoush Abedi‐Ardekani, Ana Carolina de Carvalho

et al.

Cell Genomics, Journal Year: 2024, Volume and Issue: 4(3), P. 100500 - 100500

Published: Feb. 6, 2024

Large-scale biorepositories and databases are essential to generate equitable, effective, sustainable advances in cancer prevention, early detection, therapy, care, surveillance. The Mutographs project has created a large genomic dataset biorepository of over 7,800 cases from 30 countries across five continents with extensive demographic, lifestyle, environmental, clinical information. Whole-genome sequencing is being finalized for 4,000 cases, the primary goal understanding causes at eight anatomic sites. Genomic, exposure, data will be publicly available through International Cancer Genome Consortium Accelerating Research Genomic Oncology platform. sample metadata constitutes legacy resource new projects collaborations aiming increase our current research efforts epidemiology globally.

Language: Английский

Citations

10
Liver Cancer: Progress and Priorities DOI
Katherine A. McGlynn, Jessica L. Petrick, John D. Groopman

et al.

Cancer Epidemiology Biomarkers & Prevention, Journal Year: 2024, Volume and Issue: 33(10), P. 1261 - 1272

Published: Oct. 2, 2024

Liver cancer, the sixth most frequently occurring cancer in world and third common cause of mortality, has wide geographical variation both incidence mortality rates. At end 20th century, rates began declining some high-rate areas increasing lower-rate areas. These trends were undoubtedly driven by shifting contributions well-established more novel risk factors. While notable strides have been made combating major factors, such as hepatitis B virus C virus, emergence metabolic conditions important drivers liver indicates that much work remains to be done prevention. As is strongly associated with economic social deprivation, research, early-diagnosis, treatment among disadvantaged populations are paramount importance.

Language: Английский

Citations

10
Possible opportunities and challenges for traditional Chinese medicine research in 2035 DOI Creative Commons
Nanqu Huang, Wendi Huang, Jingjing Wu

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: June 21, 2024

The drug development process is poised for significant transformation due to the rapid advancement of modern biological and information technologies, such as artificial intelligence (AI). As these new technologies concepts infiltrate every stage development, efficiency success rate research are expected improve substantially. Traditional Chinese medicine (TCM), a time-honored therapeutic system encompassing herbal medicine, acupuncture, qigong, will also be profoundly impacted by advancements. Over next decade, encounter both opportunities challenges it integrates with concepts. By 2035, TCM anticipated merge through more contemporary open model, providing substantial support treating broader spectrum diseases.

Language: Английский

Citations

9
Nanomedicine as potential cancer therapy via targeting dysregulated transcription factors DOI
Anas Ahmad, Summya Rashid, Anis Ahmad Chaudhary

et al.

Seminars in Cancer Biology, Journal Year: 2023, Volume and Issue: 89, P. 38 - 60

Published: Jan. 18, 2023

Language: Английский

Citations

21
Dual-template molecularly imprinted double emission proportional fluorescence sensor based on CsPbBr3 and CsPb(Br/I)3 perovskite quantum dots for visual, selective and sensitive detection of methyl eugenol and aristolochic acid A DOI

Zengcheng Du,

Yulan Li,

Chaoying Zeng

et al.

Sensors and Actuators B Chemical, Journal Year: 2024, Volume and Issue: 417, P. 136189 - 136189

Published: June 24, 2024

Language: Английский

Citations

7
Screening DNA Damage in the Rat Kidney and Liver by Untargeted DNA Adductomics DOI

Nagarjunachary Ragi,

Scott J. Walmsley,

Foster C. Jacobs

et al.

Chemical Research in Toxicology, Journal Year: 2024, Volume and Issue: 37(2), P. 340 - 360

Published: Jan. 9, 2024

Air pollution, tobacco smoke, and red meat are associated with renal cell cancer (RCC) risk in the United States Western Europe; however, chemicals that form DNA adducts initiate RCC mainly unknown. Aristolochia herbaceous plants used for medicinal purposes Asia worldwide. They a significant factor upper tract urothelial carcinoma (UTUC) to lesser extent. The aristolochic acid (AA) 8-methoxy-6-nitrophenanthro-[3,4-d]-1,3-dioxolo-5-carboxylic (AA-I), component of herbs, contributes UTUC Asian cohorts Croatia, where AA-I exposure occurs from ingesting contaminated wheat flour. adduct AA-I, 7-(2′-deoxyadenosin-N6-yl)-aristolactam I, is often detected patients UTUC, its characteristic A:T-to-T:A mutational signature oncogenes tumor suppressor genes AA-associated UTUC. Identifying parenchyma pelvis caused by other crucial gaining insights into unknown etiologies. We employed untargeted screening wide-selected ion monitoring tandem mass spectrometry (wide-SIM/MS2) nanoflow liquid chromatography/Orbitrap detect formed rat kidneys liver mixture 13 environmental, tobacco, dietary carcinogens may contribute RCC. Twenty were detected. 3-nitrobenzanthrone (3-NBA), an atmospheric pollutant, most abundant. nitrophenanthrene moieties 3-NBA undergo reduction their N-hydroxy intermediates 2′-deoxyguanosine (dG) 2′-deoxyadenosine (dA) adducts. also discovered 2′-deoxycytidine dA dG 10-methoxy-6-nitro-phenanthro-[3,4-d]-1,3-dioxolo-5-carboxylic (AA-III), isomer minor herbal extract assayed, signifying AA-III potent kidney DNA-damaging agent. roles AA-III, nitrophenanthrenes, nitroarenes damage human warrant further study. Wide-SIM/MS2 powerful scanning technology discovery etiology characterization.

Language: Английский

Citations

6
Mutational signature and prognosis in adenocarcinoma of the bladder DOI

Guoliang Yang,

Akezhouli Shahatiaili, Shihao Bai

et al.

The Journal of Pathology, Journal Year: 2024, Volume and Issue: 262(3), P. 334 - 346

Published: Jan. 5, 2024

Adenocarcinoma of the bladder is a rare urinary carcinoma with limited therapy options due to lack molecular characterization. Here, we aimed reveal mutational and transcriptomic landscapes adenocarcinoma assess any relationship prognosis. Between February 2015 June 2021, total 23 patients were enrolled. These included 16 primary adenocarcinomas seven urachal adenocarcinoma. Whole exome sequencing (16 patients), whole genome bulk RNA (RNA-seq) (19 single-cell RNA-seq (5 patients) conducted for specimens. Correlation analysis, survival t-tests also performed. Prevalent T>A substitutions observed among somatic mutations, major trinucleotide contexts 5'-CTC-3' 5'-CTG-3'. This pattern was mainly contributed by COSMIC signature 22 related chemical carcinogen exposure (probably aristolochic acid), which has not been reported in Moreover, genes copy number changes enriched KEGG term 'chemical carcinogenesis'. Transcriptomic analysis suggested high immune cell infiltration luminal-like features majority samples. Interestingly, small fraction samples an APOBEC-derived exhibited higher risk disease progression compared only carcinogen-related signature, confirming prognostic heterogeneity study presents adenocarcinoma, indicates that may be better prognosis APOBEC bladder. © 2024 The Pathological Society Great Britain Ireland.

Language: Английский

Citations

5
Aristolochic acids-hijacked p53 promotes liver cancer cell growth by inhibiting ferroptosis DOI
Chunyu Hou, Yuhong Suo, Pan Lv

et al.

Acta Pharmacologica Sinica, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

Language: Английский

Citations

5
Bioaccumulation and DNA Adduct Formation of Aristolactam I: Unmasking a Toxicological Mechanism in the Pathophysiology of Aristolochic Acid Nephropathy DOI
Chun-Kit Au,

Yat-Hing Ham,

Wan Chan

et al.

Chemical Research in Toxicology, Journal Year: 2023, Volume and Issue: 36(2), P. 322 - 329

Published: Feb. 9, 2023

Prolonged exposure to aristolochic acid (AA) through AA-containing herbal medicines or AA-tainted food is putting a large portion of the global population at risk developing renal fibrosis and tumors upper urinary tract. In an effort better understand organotropic property AA, we studied cytotoxicity, absorption, oxidative-stress inducing potential, DNA adduct formation capability aristolactam I (ALI), one major metabolites (AAI) in human cells. Despite ALI having slightly lower cytotoxicity than that AAI, analysis revealed, for first time, bioaccumulated 900 times more AAI inside cultured kidney Furthermore, induced significantly larger glutathione depletion exposed Together with ALI-DNA reasonably high abundance, results this study unmasked previously disregarded causative role tumor-targeting AA.

Language: Английский

Citations

11