Exploring the Molecular Mechanisms of Tirzepatide in Alleviating Metabolic Dysfunction- Associated Fatty Liver in Mice through Integration of Metabolomics, Lipidomics, and Proteomics DOI Creative Commons
Jinliang Liang, Huanyi Liu,

Guo Lv

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 18, 2024

Abstract Clinical studies have suggested that tirzepatide may also possess hepatoprotective effects; however, the molecular mechanisms underlying this association remain unclear. In our study, we performed biochemical analyses of serum and histopathological examinations liver tissue in mice. To preliminarily explore on metabolic dysfunction-associated fatty disease (MAFLD), liquid chromatography-mass spectrometry (LC-MS) was employed for comprehensive metabolomic, lipidomic, proteomic MAFLD mice fed a high-fat diet (HFD). The results demonstrated significantly reduced levels alanine transaminase (ALT) aspartate (AST), as well hepatic triglycerides (TG) total cholesterol (TC), indicating its efficacy treating MAFLD. Further findings revealed acid uptake by downregulating Cd36 Fabp2/4, enhance mitochondrial-lysosomal function upregulating Lamp1/2. addition, promoted efflux reabsorption expression Hnf4a, Abcg5, Abcg8. These suggest exerts therapeutic effects reducing uptake, promoting excretion, enhancing function, providing theoretical basis understanding tirzepatide.

Language: Английский

Bioactive compounds from nature: Antioxidants targeting cellular transformation in response to epigenetic perturbations induced by oxidative stress DOI Open Access
Abdelhakim Bouyahya, Saad Bakrim, Sara Aboulaghras

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116432 - 116432

Published: March 22, 2024

Oxidative stress results from a persistent imbalance in oxidation levels that promotes oxidants, playing crucial role the early and sustained phases of DNA damage genomic epigenetic instability, both which are intricately linked to development tumors. The molecular pathways contributing carcinogenesis this context, particularly those related double-strand single-strand breaks DNA, serve as indicators due cancer cases, well factors instability through ectopic expressions. has been considered therapeutic target for many years, an increasing number studies have highlighted promising effectiveness natural products treatment. In regard, we present significant research on targeting oxidative using molecules underscore essential cancer. consequences stress, especially also offer prospects. use epi-drugs capable modulating reorganizing network is beginning emerge remarkably. review, emphasize close connections between tumor transformation, while highlighting substances antioxidants anti-tumoral context.

Language: Английский

Citations

17

The therapeutic role of naringenin nanoparticles on hepatocellular carcinoma DOI Creative Commons

Ayman Mahmoud Elwan,

Tarek M. Mohamed,

Doha M. Beltagy

et al.

BMC Pharmacology and Toxicology, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 3, 2025

Abstract Background Naringenin, a flavonoid compound found in citrus fruits, possesses valuable anticancer properties. However, its potential application cancer treatment is limited by poor bioavailability and pharmacokinetics at tumor sites. To address this, Naringenin nanoparticles (NARNPs) were prepared using the emulsion diffusion technique their effects investigated HepG2 cells. Methods The particle size of NARNPs was determined transmission electron microscopy scanning analysis. NARNP characterized Fourier transform infrared spectroscopy X-ray diffraction. Study cytotoxic various doses naringenin, DOX on WI38 cell lines after 24 h 48 MTT assay. Flow cytometric analysis used to study apoptotic also examined expression proteins (p53) autophagy-related genes ATG5, LC3 with NARNPs, doxorubicin, combinations Results analysis, showing mean diameters 54.96 ± 18.6 nm 31.79 6.8 nm, respectively. confirmed successful conjugation between naringenin NARNPs. an amorphous state that IC50 values as 22.32 µg/ml for 1.6 0.46 doxorubicin. showed induced late apoptosis 56.1% cells had no effect 97% viable incubation. cycle arrest Go/G1 G2/M phases results increased LC3, p53 treated concentrations enhanced doxorubicin but decreased Conclusions demonstrated effectively inhibit proliferation induce human hepatocellular carcinoma Importantly, normal cells, indicating promising therapy hepatocarcinogenesis. Combining chemotherapy drugs could present novel approach treating cancers.

Language: Английский

Citations

1

Exploring the molecular mechanisms of tirzepatide in alleviating metabolic dysfunction-associated fatty liver in mice through integration of metabolomics, lipidomics, and proteomics DOI Creative Commons
Jinliang Liang, Huanyi Liu,

Guo Lv

et al.

Lipids in Health and Disease, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 10, 2025

Clinical studies have suggested that tirzepatide may also possess hepatoprotective effects; however, the molecular mechanisms underlying this association remain unclear. In our study, we performed biochemical analyses of serum and histopathological examinations liver tissue in mice. To preliminarily explore on metabolic dysfunction-associated fatty disease (MAFLD), liquid chromatography-mass spectrometry (LC-MS) was employed for comprehensive metabolomic, lipidomic, proteomic MAFLD mice fed a high-fat diet (HFD). The results demonstrated significantly reduced levels alanine transaminase (ALT) aspartate (AST), as well hepatic triglycerides (TG) total cholesterol (TC), indicating its efficacy treating MAFLD. Further findings revealed acid uptake by downregulating Cd36 Fabp2/4, enhance mitochondrial-lysosomal function upregulating Lamp1/2. addition, promoted efflux reabsorption expression Hnf4a, Abcg5, Abcg8. These suggest exerts therapeutic effects reducing uptake, promoting excretion, enhancing function, providing theoretical basis understanding tirzepatide.

Language: Английский

Citations

1

Umbilical cord mesenchymal stem cells and lung cancer: We should be hopeful or hopeless? DOI
Reza Arefnezhad,

Maryam Helfi,

Rana Okhravijouybari

et al.

Tissue and Cell, Journal Year: 2024, Volume and Issue: 88, P. 102410 - 102410

Published: May 18, 2024

Language: Английский

Citations

6

Exploring the mechanism of rosmarinic acid in the treatment of lung adenocarcinoma based on bioinformatics methods and experimental validation DOI Creative Commons
Caicun Zhou, Zhong Ren, Lei Zhang

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 15, 2025

Rosmarinic acid (RosA) is a natural polyphenol compound that has been shown to be effective in the treatment of inflammatory disease and variety malignant tumors. However, its specific mechanism for lung adenocarcinoma (LUAD) not fully elucidated. Therefore, this study aims clarify RosA LUAD by integrating bioinformatics, network pharmacology vivo experiments, explore potential active ingredients traditional Chinese medicine treating LUAD. Firstly, was used screen targets, LUAD-related differential expressed genes (DEGs) were acquired from GEO database. The intersection regulated (RDEGs) obtained through Venn diagram. Secondly, GO KEGG enrichment analysis RDEGs performed, protein–protein interaction networks (PPIs) constructed identify visualize hub RDEGs. Then, molecular docking between further evaluation carried out using bioinformatics predictive value Finally, verified establishing xenograft model NSCLC nude mouse. Bioinformatics other showed that, compared with control group, expressions MMP-1, MMP-9, IGFBP3 PLAU tissues significantly up-regulated, PPARG FABP4 down-regulated, these had In experimental results could inhibit growth transplanted tumors mice bearing cancer cells, reduce positive expression Ki67 tumor tissue, hinder proliferation cells. Upregulated activating PPAR signaling pathway increases level ROS promotes apoptosis addition, can also MMP-9 IGFBP3, migration invasion tissue This demonstrated induce regulating proliferation, thereby exerting anti-LUAD effects. provides new insight into therapeutic avenue

Language: Английский

Citations

0

Management succinate release through SDHA by G protein-coupled receptor 91 signal, TRAP1, and SIRT3 regulation in lung cancer cells by NAR nanoparticles DOI Creative Commons
Eman M. Ragab, Abeer A. Khamis, Tarek M. Mohamed

et al.

Journal of Genetic Engineering and Biotechnology, Journal Year: 2025, Volume and Issue: 23(1), P. 100464 - 100464

Published: Feb. 11, 2025

Language: Английский

Citations

0

Specific gut microbiota and serum metabolite changes in patients with osteoarthritis DOI Creative Commons
Wendong Wang, Xincheng Liu, Nan Hao

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 14, 2025

Introduction Recent research indicated a strong link between the gut microbiota and osteoarthritis. However, complex interplay microbiota, serum metabolites, progression of osteoarthritis in affected individuals remains largely unexplored. This study aimed to investigate characteristics metabolites patients with Methods Participants either healthy knees or were enrolled categorized into control (HC) (OA) groups. Fecal blood samples collected for 16S rRNA gene sequencing, metabolomic analysis via liquid chromatography–mass spectrometry (LC-MS), integrated evaluation. Results The results showed no significant variation richness diversity two abundance Bacteroides plebeius Faecalibacterium prausnitzii was reduced OA group, both which are known their potential as next-generation probiotics human health. Metabolomic that including pyrogallol 3-hydroxybutyrate (3HB), significantly lower group. These positively impact other diseases demonstrated good diagnostic performance distinguishing from controls. Correlation revealed positive correlation 3HB. Discussion highlighted specific metabolite profiles patients, suggesting changes bacteria derived closely tied progression. underscores modifiable elements therapeutic targets prevention.

Language: Английский

Citations

0

The potential of natural herbal plants in the treatment and prevention of non-small cell lung cancer: An encounter between ferroptosis and mitophagy DOI
Yujie Yang,

Bing Jiang,

Lijuan Shi

et al.

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119555 - 119555

Published: Feb. 1, 2025

Language: Английский

Citations

0

Collagen type III resists UVB induced photoaging of HaCaT cells by regulating mTOR signaling pathway DOI

Helei Liu,

Hao Li,

Pengwei Zhao

et al.

Journal of Photochemistry and Photobiology B Biology, Journal Year: 2025, Volume and Issue: unknown, P. 113153 - 113153

Published: April 1, 2025

Language: Английский

Citations

0

Polydatin protects against leukemia by inducing apoptosis and activating autophagy via p38-MAPK pathway DOI
Wenhui Zhang, Liu Z,

Peiyuan Hao

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Language: Английский

Citations

0