Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Discov Oncol. 2024 Nov 6;15(1):624. doi: 10.1007/s12672-024-01506-y.

HPRT1: a preliminary investigation on its involvement in nasopharyngeal 
carcinoma.

Chen A(1), Wang G(2), Wang D(1), Liu R(3).

Author information:
(1)Otolaryngology, The Second Affiliated Hospital of Shandong First Medical 
University, Tai'an, 271000, China.
(2)Department of Pediatrics, The Second Affiliated Hospital of Shandong First 
Medical University, Tai'an, 271000, China.
(3)Otolaryngology, The Second Affiliated Hospital of Shandong First Medical 
University, Tai'an, 271000, China. tyfyentliu@163.com.

BACKGROUND: Accumulating evidences have stressed the association between 
hypoxanthine phosphoribosyl transferase 1 (HPRT1) overexpression and the poor 
prognosis of various cancers. Our study, herein, preliminarily investigates the 
involvement of HPRT1 in nasopharyngeal carcinoma (NPC).
METHODS: Data from TCGA were applied to read HPRT1 expression in diverse cancers 
including NPC and to predict the prognosis of NPC patients. The total RNA and 
protein from NPC cells and nasopharyngeal epithelial cells NP460 were extracted 
to quantify HPRT1 expression. Following the completion of transfection, the 
proliferation and migration of NPC cells were determined employing MTT, colony 
formation and western blot assay (the quantification on expressions of protein 
related to proliferation and migration).
RESULTS: HPRT1 was differentially expressed in diverse cancers yet particularly 
highly expressed in NPC, and high HPRT1 expression was related to the poor 
prognosis of NPC patients. Also, HPRT1 expression was higher in NPC cells and 
its silencing diminished the viability and proliferation of NPC cells and 
reduced the expressions of CyclinD1, CyclinE, Multidrug Resistance Protein 1 
(MDR1), matrix metalloproteinase (MMP)-2, and MMP-9.
CONCLUSION: This study preliminarily explored the involvement of HPRT1 in NPC 
based on some cellular assays in vitro, which may provide evidence for 
investigating the specific mechanism underlying the effects of HPRT1 in cancers.

© 2024. The Author(s).

DOI: 10.1007/s12672-024-01506-y
PMID: 39505752


2. Stem Cell Rev Rep. 2024 Nov 4. doi: 10.1007/s12015-024-10821-4. Online ahead
of  print.

Unleashing the Power of Induced Pluripotent stem Cells in in vitro Modelling of 
Lesch-Nyhan Disease.

Javed S(1), Fersini M(1), Bernardini G(2).

Author information:
(1)Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di 
Siena, via Aldo Moro 2, Siena, 53100, Italy.
(2)Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di 
Siena, via Aldo Moro 2, Siena, 53100, Italy. giulia.bernardini@unisi.it.

Lesch-Nyhan disease (LND) is a monogenic rare neurodevelopmental disorder caused 
by a deficiency in hypoxanthine-guanine phosphoribosyltransferase (HPRT), the 
key enzyme of the purines salvage pathway. Beyond its well-documented metabolic 
consequences, HPRT deficiency leads to a distinctive neurobehavioral syndrome 
characterized by motor disabilities, cognitive deficits, and self-injurious 
behavior. Although various cell and animal models have been developed to 
investigate LND pathology, none have adequately elucidated the underlying 
mechanisms of its neurological alterations. Recent advances in human pluripotent 
stem cell research and in vitro differentiation techniques have ushered in a new 
era in rare neurodevelopmental disorders research. Pluripotent stem cells, with 
their ability to propagate indefinitely and to differentiate into virtually any 
cell type, offer a valuable alternative for modeling rare diseases, allowing for 
the detection of pathological events from the earliest stages of neuronal 
network development. Furthermore, the generation of patient-derived induced 
pluripotent stem cells using reprogramming technology provides an opportunity to 
develop a disease-relevant model within the context of a patient-specific 
genome. In this review, we examine current stem cell-based models of LND and 
assess their potential as optimal models for exploring key pathological 
molecular events during neurogenesis and for the discovering novel treatment 
options. We also address the limitations, challenges, and future prospects for 
improving the use of iPSCs in LND research.

© 2024. The Author(s), under exclusive licence to Springer Science+Business 
Media, LLC, part of Springer Nature.

DOI: 10.1007/s12015-024-10821-4
PMID: 39495466


3. PLoS One. 2024 Oct 31;19(10):e0313174. doi: 10.1371/journal.pone.0313174. 
eCollection 2024.

Mutational analysis of Phanerochaete chrysosporium´s purine transporter.

Barraco-Vega M(1), Sanguinetti M(2), da Rosa G(3), Cecchetto G(4).

Author information:
(1)Microbiología, Departamento de Biociencias, Facultad de Química Universidad 
de la República, Montevideo, Uruguay.
(2)Sección Bioquímica, Facultad de Ciencias, Universidad de la República, 
Montevideo, Uruguay.
(3)Departamento de Ciencias Biológicas, CENUR-Litoral Norte, Universidad de la 
República, Montevideo, Uruguay.
(4)Microbiología, Instituto de Química Biológica, Facultad de Ciencias-Facultad 
de Química, Universidad de la República, Montevideo, Uruguay.

We present here a mutational analysis of the purine transporter from 
Phanerochaete chrysosporium (PhZ), a member of the AzgA-like subfamily within 
the Nucleobase Ascorbate Transporters family. We identified key residues that 
determine its substrate specificity and transport efficiency. Thirteen PhZ 
mutants were generated and heterologously expressed in Aspergillus nidulans. The 
growth of mutant strains in the presence of purines and toxic analogues and the 
uptake rate of radiolabelled hypoxanthine were evaluated. Results revealed that 
ten mutants showed differences in transport compared to the wild-type PhZ: six 
mutants completely lost function, two exhibited decreased transport activity, 
and two showed increased hypoxanthine uptake. Subcellular localization and 
expression level analyses indicated that the differences in transport activity 
were not due to trafficking issues to the plasma membrane or protein stability. 
A three-dimensional model of PhZ, constructed with the artificial 
intelligence-based AlphaFold2 program, suggested that critical residues for 
transport are located in transmembrane segments and an internal helix. In the 
latter, the A418 residue was identified as playing a pivotal role in transport 
efficiency despite being far from the putative substrate binding site, as mutant 
A418V showed an increased initial uptake efficiency for the transporter´s 
physiological substrates. We also report that residue L124, which lies in the 
putative substrate binding site, plays a critical role in substrate transport, 
emerging as an additional determinant in the transport mechanism of this family 
of transporters. These findings underscore the importance of specific residues 
in AzgA-like transporters and enhance our understanding of the intricate 
mechanisms governing substrate specificity and transport efficiency within this 
family.

Copyright: © 2024 Barraco-Vega et al. This is an open access article distributed 
under the terms of the Creative Commons Attribution License, which permits 
unrestricted use, distribution, and reproduction in any medium, provided the 
original author and source are credited.

DOI: 10.1371/journal.pone.0313174
PMCID: PMC11527162
PMID: 39480815 [Indexed for MEDLINE]

Conflict of interest statement: The authors have declared that no competing 
interests exist.


4. J Heart Lung Transplant. 2024 Oct 30:S1053-2498(24)01905-3. doi: 
10.1016/j.healun.2024.10.020. Online ahead of print.

The effect of rewarming ischemia on tissue transcriptome and metabolome 
signatures: a clinical observational study in lung transplantation.

Van Slambrouck J(1), Loopmans S(2), Prisciandaro E(1), Barbarossa A(1), 
Kortleven P(3), Feys S(4), Vandervelde CM(1), Jin X(5), Cenik I(6), Moermans 
K(7), Fieuws S(8), Provoost AL(1), Willems A(2), De Leyn P(1), Van Veer H(1), 
Depypere L(1), Jansen Y(1), Pirenne J(9), Neyrinck A(10), Weynand B(11), 
Vanaudenaerde B(5), Carmeliet G(7), Vos R(12), Van Raemdonck D(1), Ghesquière 
B(2), Van Weyenbergh J(13), Ceulemans LJ(14).

Author information:
(1)Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium; 
Department of Chronic Diseases and Metabolism, Laboratory of Respiratory 
Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium.
(2)Department of Cellular and Molecular Medicine, Laboratory of Applied Mass 
Spectrometry, KU Leuven, Leuven, Belgium; Center for Cancer Biology, 
Metabolomics Core Facility Leuven, VIB, Leuven, Belgium.
(3)Department of Chronic Diseases and Metabolism, Laboratory of Respiratory 
Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium; Department 
of Pharmaceutical and Pharmacological Sciences, Molecular Virology and Gene 
Therapy, KU Leuven, Leuven, Belgium.
(4)Department of Microbiology, Immunology and Transplantation, Laboratory of 
Clinical Infectious and Inflammatory Disorders, KU Leuven, Leuven, Belgium; 
Department of Medical Intensive Care, University Hospitals Leuven, Leuven, 
Belgium.
(5)Department of Chronic Diseases and Metabolism, Laboratory of Respiratory 
Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium.
(6)Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium.
(7)Department of Chronic Diseases and Metabolism, Laboratory of Clinical and 
Experimental Endocrinology, KU Leuven, Leuven, Belgium.
(8)Department of Public Health, Interuniversity Center for Biostatistics and 
Statistical Bioinformatics, KU Leuven, Leuven, Belgium.
(9)Department of Microbiology, Immunology and Transplantation, Laboratory of 
Abdominal Transplantation, KU Leuven, Leuven, Belgium; Department of Abdominal 
Transplant Surgery, University Hospitals Leuven, Leuven, Belgium.
(10)Department of Cardiovascular Sciences, Anesthesiology and Algology, KU 
Leuven, Belgium; Department of Anesthesiology, University Hospitals Leuven, 
Leuven, Belgium.
(11)Department of Pathology, University Hospitals Leuven, Leuven, Belgium; 
Department of Imaging and Pathology, Laboratory of Translational Cell & Tissue 
Research, KU Leuven, Leuven, Belgium.
(12)Department of Chronic Diseases and Metabolism, Laboratory of Respiratory 
Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium; Department 
of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium.
(13)Department of Microbiology, Immunology and Transplantation, Laboratory of 
Clinical and Epidemiological Virology, Rega Institute, KU Leuven, Leuven, 
Belgium.
(14)Department of Thoracic Surgery, University Hospitals Leuven, Leuven, 
Belgium; Department of Chronic Diseases and Metabolism, Laboratory of 
Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium. 
Electronic address: https://twitter.com/CeulemansLJ.

BACKGROUND: In lung transplantation (LuTx), various ischemic phases exist, yet 
the rewarming ischemia time (RIT) during implantation has often been overlooked. 
During RIT, lungs are deflated and exposed to the body temperature in the 
recipient's chest cavity. Our prior clinical findings demonstrated that 
prolonged RIT increases the risk of primary graft dysfunction. However, the 
molecular mechanisms of rewarming ischemic injury in this context remain 
unexplored. We aimed to characterize the rewarming ischemia phase during LuTx by 
measuring organ temperature and comparing transcriptome and metabolome profiles 
in tissue obtained at the end versus the start of implantation.
METHODS: In a clinical observational study, 34 double-LuTx with ice preservation 
were analyzed. Lung core and surface temperature (n=65 and 55 lungs) was 
measured during implantation. Biopsies (n=59 lungs) were wedged from right 
middle lobe and left lingula at start and end of implantation. Tissue 
transcriptomic and metabolomic profiling were performed.
RESULTS: Temperature increased rapidly during implantation, reaching 
core/surface temperatures of 21.5°C/25.4°C within 30min. Transcriptomics showed 
increased pro-inflammatory signaling and oxidative stress at the end of 
implantation. Upregulation of NLRP3 and NFKB1 correlated with RIT. Metabolomics 
indicated elevated levels of amino acids, hypoxanthine, uric acid, 
cysteineglutathione disulfide alongside decreased levels of glucose and 
carnitines. Arginine, tyrosine, and 1-carboxyethylleucine showed correlation 
with incremental RIT.
CONCLUSIONS: The final rewarming ischemia phase in LuTx involves rapid organ 
rewarming, accompanied by transcriptomic and metabolomic changes indicating 
pro-inflammatory signaling and disturbed cell metabolism. Limiting implantation 
time and lung cooling represent potential interventions to alleviate rewarming 
ischemic injury.

Copyright © 2024 International Society for the Heart and Lung Transplantation. 
Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.healun.2024.10.020
PMID: 39486771


5. Food Sci Nutr. 2024 Aug 20;12(10):8053-8066. doi: 10.1002/fsn3.4403.
eCollection  2024 Oct.

Luteolin ameliorates hyperuricemic nephropathy by activating urate excretion and 
Nrf2/HO-1/NQO1 antioxidant pathways in mice.

Yu H(1)(2), Huang L(3), Gui L(1)(2), Wu Z(1)(2), Luo H(1), Xu M(1), Zhang Y(1), 
Qian Y(1), Cao W(1), Liu L(1), Li F(1).

Author information:
(1)School of Pharmaceutical Sciences, Hubei Key Laboratory of Wudang Local 
Chinese Medicine Research Hubei University of Medicine Shiyan Hubei China.
(2)Institute of Biomedicine Hubei University of Medicine Shiyan Hubei China.
(3)Department of Hepatopancreatobiliary Surgery, Taihe Hospital Hubei University 
of Medicine Shiyan Hubei China.

Luteolin is a natural flavonoid, which exists in many plants, including onions, 
broccoli, carrots, peppers, celery, olive oil, and mint. Luteolin is a dietary 
flavonoid with potent uric acid-lowering and antioxidant bioactivities. To date, 
the mechanism by which luteolin alleviates hyperuricemia nephropathy (HN) still 
needs to be better defined. This study aims to evaluate the therapeutic efficacy 
of luteolin in a preclinical mouse model and in vitro. Luteolin was administered 
in the HN mice induced by the combination of potassium oxonate and hypoxanthine 
to evaluate the potential renoprotective effects in vivo. The NRK-52E cells were 
stimulated with adenosine for in vitro evaluation. Hematoxylin and eosin 
staining, biochemical analysis, immunoblotting, immunofluorescence, and 
immunohistochemistry were performed for the histopathologic and mechanistic 
investigations. The results suggest that luteolin attenuated tubular dilation 
and epithelial atrophy in the renal tissue of HN mice. Further, luteolin 
improved biochemical indicators concerning renal functions and oxidative stress 
in vivo. Mechanistically, luteolin reduced the renal expressions of KIM-1 and 
caspase-3. Luteolin activated renal SIRT1/6 cascade and its downstream 
Nrf2-mediated antioxidant pathway. Furthermore, luteolin elevated the renal 
expressions of ATP-binding cassette subfamily G isoform 2 protein (ABCG2) and 
organic anion/cation transporters. In addition, livers of luteolin-treated HN 
mice exhibited robust inhibition of xanthine oxidase. Together, our study shows 
that luteolin alleviates renal injury in the HN mice by activating urate 
excretion and Nrf2/HO-1/NQO1 antioxidant pathways and inhibiting liver xanthine 
oxidase activity. Thus, luteolin may be a potential agent for the treatment of 
HN.

© 2024 The Author(s). Food Science & Nutrition published by Wiley Periodicals 
LLC.

DOI: 10.1002/fsn3.4403
PMCID: PMC11521689
PMID: 39479625

Conflict of interest statement: All authors have no conflicts of interest.