Bile acids inhibit equilibrative adenosine transport to alter adenosine receptor signaling in cholestasis DOI Creative Commons
Arnav Joshi, Sijie Chen, Fifa Rahman

et al.

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108563 - 108563

Published: April 1, 2025

High plasma bile acid (BA) levels in individuals with cholestasis affect adenosine (Ado) receptor (AdoR) signaling, but the underlying mechanisms are unclear. Here, we investigated BA interference cellular Ado transport as a putative mechanism for altering extracellular availability AdoR signaling. Computational modeling and experimental studies revealed that equilibrative nucleoside transporter 2 (ENT2), not ENT1, is capable of translocating BAs across mammalian membrane. ENT2-mediated has low affinity, pH independent, partially sensitive to inhibition by nitrobenzylthioinosine (NBMPR). At cholestatic concentrations BAs, however, interfere Na+-independent, NBMPR-sensitive, ENTs without affecting Na+-driven, NBMPR-insensitive, concentrative transporters (CNTs). Interestingly, this ENT was largely selective Ado, minimal no impact on other purine or pyrimidine nucleosides. Xenopus oocyte-based demonstrated order ENT3≥ENT2>ENT1, which also corresponds intrinsic ability individual BAs. In silico analysis tend occupy similar spaces within translocation pores polar hydrophilic pore-lining residues determine interaction Furthermore, vivo indicated accumulation extraneously administered decreases livers mice alters Together, these findings reveal novel ENT-dependent BA‒Ado interactions may have implications dysregulation signaling liver diseases.

Language: Английский

Oxidative stress: A common pathological state in a high-risk population for osteoporosis DOI Open Access
Chi Zhang, Hao Li, Jie Li

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 163, P. 114834 - 114834

Published: May 8, 2023

Osteoporosis is becoming a major concern in the field of public health. The process bone loss insidious and does not directly induce obvious symptoms. Complications indicate an irreversible decrease mass. high-risk populations osteoporosis, including postmenopausal women, elderly men, diabetic patients obese individuals need regular mineral density testing appropriate preventive treatment. However, primary changes these are different, increasing difficulty effective treatment osteoporosis. Determining core pathogenesis osteoporosis helps improve efficiency efficacy among populations. Oxidative stress common pathological state secondary to estrogen deficiency, aging, hyperglycemia hyperlipemia. In this review, we divided oxidative into direct effect reactive oxygen species (ROS) reduction antioxidant enzyme activity discuss their roles development ROS initiated mitochondrial apoptotic signaling suppressed osteogenic marker expression weaken osteogenesis. MAPK NF-κB pathways mediated positive on osteoclast differentiation. Antioxidant enzymes only eliminate negative effects ROS, but also participate regulation metabolism. Additionally, described proinflammatory factors HIF-1α under pathophysiological inflammation hypoxia, which provided supplement stress-induced conclusion, our review showed that was population for Targeted would greatly optimize therapeutic schedule various treatments.

Language: Английский

Citations

83
Metabolic changes induced by heavy metal copper exposure in human ovarian granulosa cells DOI Creative Commons

Jiaru Lin,

Ling Wang, Mingquan Huang

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 285, P. 117078 - 117078

Published: Sept. 20, 2024

Language: Английский

Citations

28
Caffeine and Its Antioxidant Properties—It Is All about Dose and Source DOI Open Access
Bianca-Eugenia Ősz,

George Jîtcă,

Ruxandra Ștefănescu

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(21), P. 13074 - 13074

Published: Oct. 28, 2022

Caffeine is the most frequently used substance with a central nervous system stimulant effect, but its consumption often due to intake of foods and drinks that contain it (coffee, tea, chocolate, food supplements plant extracts Guarana, Mate herba, Cola nuts). Due innocuity, caffeine safe xanthine alkaloid for human in wide range doses, being stimulating lipolytic diuresis-enhancing properties, also as permitted ergogenic compound athletes. In addition mechanisms explain effects on targeted organ, there are many proposed by which this would have antioxidant effects. As such, prevents occurrence/progression certain neurodegenerative diseases well other medical conditions associated increased levels reactive oxygen or nitrogen species. However, studies assessed beneficial pure caffeine. The question, therefore, arises whether daily from drink has similar benefits, considering high content, substances could interfere action, either potentiating decreasing capacity. Natural sources combine polyphenols (phenol-carboxylic acids, catechins) known effects; however, dietary sugars artificial sweeteners can significantly reduce oxidative stress. objective review clarify modulating stress assess these source dose administered.

Language: Английский

Citations

59
Integrated microbiological and metabolomics analyses to understand the mechanism that allows modified biochar to affect the alkalinity of saline soil and winter wheat growth DOI

Manli Duan,

Rupan Yan,

Quanjiu Wang

et al.

The Science of The Total Environment, Journal Year: 2023, Volume and Issue: 866, P. 161330 - 161330

Published: Jan. 2, 2023

Language: Английский

Citations

25
Hematopoiesis Revolves Around the Primordial Evolutional Rhythm of Purinergic Signaling and Innate Immunity – A Journey to the Developmental Roots DOI Creative Commons
Mariusz Z. Ratajczak, Kamila Bujko, Katarzyna Brzeźniakiewicz‐Janus

et al.

Stem Cell Reviews and Reports, Journal Year: 2024, Volume and Issue: 20(3), P. 827 - 838

Published: Feb. 16, 2024

Abstract A cell's most significant existential task is to survive by ensuring proper metabolism, avoiding harmful stimuli, and adapting changing environments. It explains why early evolutionary primordial signals pathways remained active regulate cell tissue integrity. This requires energy supply a balanced redox state. To meet these requirements, the universal intracellular transporter purine nucleotide-adenosine triphosphate (ATP) became an important signaling molecule precursor of purinergic after being released into extracellular space. Similarly, ancient proteins involved in metabolism gave rise third protein component (C3) complement cascade (ComC), soluble arm innate immunity. These induce cytosol reactive oxygen (ROS) nitrogen species (RNS) that state cells. While low levels ROS RNS promote growth differentiation, supra-physiological concentrations can lead damage pyroptosis. balance impact immunity on organogenesis, development. Subsequently, along with evolution, new regulatory cues emerge form factors, cytokines, chemokines, bioactive lipids. However, their expression still modulated both pathways. review will focus data carry developmental hematopoiesis specification hematopoietic stem/progenitor cells (HSPCs). Moreover, recent evidence shows operate paracrine manner inside HSPCs at autocrine level. Graphical

Language: Английский

Citations

9
Metabolomics in Parkinson’s Disease and Correlation with Disease State DOI Creative Commons
Elena A. Ostrakhovitch, Kenjiro Ono, Tritia R. Yamasaki

et al.

Metabolites, Journal Year: 2025, Volume and Issue: 15(3), P. 208 - 208

Published: March 18, 2025

Changes in the level of metabolites, small molecules that are intermediates produced by metabolism or catabolism, associated with developing diseases. Metabolite signatures body fluids such as plasma, cerebrospinal fluid, urine, and saliva Parkinson’s disease. Here, we discuss alteration metabolites TCA cycle, pentose phosphate pathway, kynurenic network, redox system. We also summarize efforts many research groups to differentiate between metabolite profiles characterize PD motor progression dyskinesia, gait balance, non-motor symptoms depression cognitive decline. Understanding how changes lead may allow for identification individuals at earliest stage disease development new therapeutic strategies.

Language: Английский

Citations

1
Purine metabolism in the development of osteoporosis DOI Open Access
Keda Yang, Jie Li, Lin Tao

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 155, P. 113784 - 113784

Published: Sept. 29, 2022

Osteoporosis is a common bone metabolic disease in postmenopausal women, diabetic patients and obese characterized by an imbalance formation resorption. Current studies have conducted in-depth research on these groups revealed their respective pathogenesis treatment measures. However, the causes of osteoporosis are complex, usually combining multiple factors. Unifying same pathway that induces loss various pathological states will greatly facilitate diagnosis osteoporosis. Purine metabolism important biological process determining genetic orientation functional performance. Adequate evidence confirms widespread existence purine disorders types plays role remodeling. The aim present study was to determine changes high-risk populations with caused abnormal metabolism. Two balance maintained remodeling including osteogenesis adipogenesis osteoblasts osteoclasts. Abnormal hyperuricemia accumulation reactive oxygen species (ROS). Monosodium urate (MSU), ROS ROS-induced inflammation inhibit expression osteogenic turnover indicators promote osteoclast differentiation. ADA, ADCY, ENPP1 PDE genes involved most strongly associated Constructing network between mining core regulatory mechanism contribute revealing optimizing

Language: Английский

Citations

33
Umbilical cord mesenchymal stem cell-derived apoptotic extracellular vesicles ameliorate cutaneous wound healing in type 2 diabetic mice via macrophage pyroptosis inhibition DOI Creative Commons
Yiming Wang,

Jing Lin,

Lei Xiao

et al.

Stem Cell Research & Therapy, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 19, 2023

Delayed healing of diabetic cutaneous wounds is one the most common complications type 2 diabetes mellitus (T2DM), which can bring great distress to patients. In patients, macrophages accumulate around skin and produce NLRP3 (NOD-, LRR-, pyrin domain-containing protein 3) inflammasomes, in turn undergo pyroptosis inflammatory factors such as interleukin-1β that affect wound healing. Although our previous study revealed apoptotic extracellular vesicles (ApoEVs) produced from mesenchymal stem cells (MSCs) improve normal C57BL/6 mice, whether ApoEVs also remains unclear. Umbilical cord (UCMSCs) were cultured vitro apoptosis was induced. extracted identified used a T2DM mouse model evaluate efficacy. The inhibitory effect on macrophage verified vivo vitro, level oxidative stress assessed explore mechanism by play role. UCMSC-derived improved defect mice. Moreover, inhibited mice well under high-glucose culture conditions. addition, we demonstrated reduce levels, possible they inhibit pyroptosis. Our confirmed local application ApoEVs, products MSC apoptosis, regulate death process decreasing stress.

Language: Английский

Citations

17
Mechanism of Purinergic Regulation of Neurotransmission in Mouse Neuromuscular Junction: The Role of Redox Signaling and Lipid Rafts DOI
А. R. Giniatullin,

Kamilla A. Mukhutdinova,

Alexey M. Petrov

et al.

Neurochemical Research, Journal Year: 2024, Volume and Issue: 49(8), P. 2021 - 2037

Published: May 30, 2024

Language: Английский

Citations

7
Combined exposure to decabromodiphenyl ether and nano zero-valent iron aggravated oxidative stress and interfered with metabolism in earthworms DOI
Ying Han, Siyuan Ling,

Shuangqing Hu

et al.

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 926, P. 172033 - 172033

Published: March 27, 2024

Language: Английский

Citations

6