Metal mixtures associate with higher amyotrophic lateral sclerosis risk and mortality independent of genetic risk and correlate to self-reported exposures: a case-control study DOI Creative Commons

Dae Gyu Jang,

John Dou, Emily J. Koubek

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 28, 2024

ABSTRACT Background The pathogenesis of amyotrophic lateral sclerosis (ALS) involves both genetic and environmental factors. This study investigates associations between metal measures in plasma urine, ALS risk survival, exposure sources. Methods Participants with without from Michigan provided urine samples for measurement via inductively coupled mass spectrometry. Odds hazard ratios each were computed using survival models. Environmental scores (ERS) created to evaluate the association mixtures source. (ALS-PGS) (metal-PGS) polygenic constructed an independent genome-wide relevant literature-selected SNPs. Results Plasma 454 294 control participants analyzed. Elevated levels individual metals, including copper, selenium, zinc, significantly associated survival. ERS representing strongly (plasma, OR=2.95, CI=2.38-3.62, p <0.001; OR=3.10, CI=2.43-3.97, <0.001) poorer HR=1.42, CI=1.24-1.63, HR=1.52, CI=1.31-1.76, <0.001). Addition ALS-PGS or metal-PGS did not alter significance metals Occupations high potential elevated ERS. Additionally, occupational non-occupational exposures measured metals. Conclusion Metals increased reduced risk, correlated exposures. These data underscore progression.

Язык: Английский

Integrating network pharmacology, molecular docking and experimental verification to reveal the mechanism of artesunate in inhibiting choroidal melanoma DOI Creative Commons

Qingyue Ma,

Yichong Liu,

Qian Zhang

и другие.

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Авг. 9, 2024

Artesunate (ART), a natural compound derived from Artemisia annua, has shown promising clinical potentials in the treatment of various tumors, but exact mechanism is unclear. Choroidal melanoma (CM) major malignant ocular tumor adults, known for its significant malignancy and poor prognosis, with limited efficacy current treatments. This study explored anti-CM effects mechanisms ART using combination network pharmacology, molecular docking experimental validation. Potential targets were screened PubChem, Swiss Target Prediction Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database Analysis Platform databases, while target genes related to CM prognosis selected Online Mendelian Inheritance Man (OMIM), GeneCards DisGeNET databases. The intersection these two groups datasets yielded involved CM. Protein-protein interaction (PPI) analysis intersecting targets, as well Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) analyses, conducted identify core critical pathways. Molecular methods performed predict binding interactions between targets. on evaluated through CCK8, colony formation, transwell, flow cytometry assays detect apoptosis, cell cycle, reactive oxygen species (ROS). Western blot (WB) investigate impact key proteins pathways associated Finally, vivo further validate subcutaneous tumors nude mice. Research that treating identified pharmacology approach. results verified strong affinity predicted indicated primarily exerted tumor-related like apoptosis. vitro confirmed significantly inhibited proliferation migration cells. was achieved by promoting apoptosis activation p53 signaling pathway, causing cycle arrest at G0/G1 phase inhibiting PI3K/AKT/mTOR pathway increasing intracellular level ROS activating NRF2/HO-1 pathway. Additionally, validated proliferation-inhibitory effect study, making initial exploration, illustrated combined vitro/in assays, potential anti-cancer inducing levels ROS. These findings suggested held therapeutic

Язык: Английский

Процитировано

4
Copper induced cytosolic escape of mitochondrial DNA and activation of cGAS-STING-NLRP3 pathway-dependent pyroptosis in C8-D1A cells DOI Creative Commons
Wei Shi, Qian Zhou, Lu Lu

и другие.

Ecotoxicology and Environmental Safety, Год журнала: 2024, Номер 285, С. 117085 - 117085

Опубликована: Сен. 24, 2024

Язык: Английский

Процитировано

4
Induction of mitophagy via ROS-dependent pathway protects copper-induced hypothalamic nerve cell injury DOI

Song Zhu,

Hongbin Wu,

Hengmin Cui

и другие.

Food and Chemical Toxicology, Год журнала: 2023, Номер 181, С. 114097 - 114097

Опубликована: Окт. 13, 2023

Язык: Английский

Процитировано

9
Yi-Qi-Huo-Xue decoction alleviates intracerebral hemorrhage injury through inhibiting neuronal autophagy of ipsilateral cortex via BDNF/TrkB pathway DOI Creative Commons
Dan Han, Xinyue Chang, Dan Xu

и другие.

Phytomedicine, Год журнала: 2024, Номер 128, С. 155438 - 155438

Опубликована: Фев. 19, 2024

Yi-Qi-Huo-Xue Decoction (YQHXD), a traditional Chinese medicine formula, has demonstrated efficacy in the clinical treatment of intracerebral hemorrhage (ICH) for over decade. Nevertheless, precise pharmacotherapeutic compounds YQHXD capable penetrating into cerebral tissue and pharmacological underpinnings remain ambiguous. The active components rat brains was analyzed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. potential targets, pathways biological progresses ameliorating ICH induced injury predicted network pharmacology. Moreover, collagenase-induced model, primary cortex neurons exposed to hemin molecular docking were applied validate mechanisms YQHXD. Eleven identified within brains. Employing Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) databases, our investigation concentrated on roles autophagy BDNF/TrkB signaling pathway context. results revealed that alleviated neurological dysfunction, brain water content, swelling, pathological caused ICH. Meanwhile, inhibited influx autophagosome vivo, regulated neuronal TrkB/BDNF both vivo vitro. Subsequently, N-acetyl serotonin (NAS), selective TrkB agonist, employed corroborate significance this process. combination NAS did not further enhance protective rats. Additionally, outcomes analysis nine exhibited regulatory effects TrkB. Ipsilateral activated 72 h after effectively resisted ICH, which related suppression ipsilateral via pathway. This study provides novel insights therapeutic context treatment.

Язык: Английский

Процитировано

3
Metal mixtures associate with higher amyotrophic lateral sclerosis risk and mortality independent of genetic risk and correlate to self-reported exposures: a case-control study DOI Creative Commons

Dae Gyu Jang,

John Dou, Emily J. Koubek

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 28, 2024

ABSTRACT Background The pathogenesis of amyotrophic lateral sclerosis (ALS) involves both genetic and environmental factors. This study investigates associations between metal measures in plasma urine, ALS risk survival, exposure sources. Methods Participants with without from Michigan provided urine samples for measurement via inductively coupled mass spectrometry. Odds hazard ratios each were computed using survival models. Environmental scores (ERS) created to evaluate the association mixtures source. (ALS-PGS) (metal-PGS) polygenic constructed an independent genome-wide relevant literature-selected SNPs. Results Plasma 454 294 control participants analyzed. Elevated levels individual metals, including copper, selenium, zinc, significantly associated survival. ERS representing strongly (plasma, OR=2.95, CI=2.38-3.62, p <0.001; OR=3.10, CI=2.43-3.97, <0.001) poorer HR=1.42, CI=1.24-1.63, HR=1.52, CI=1.31-1.76, <0.001). Addition ALS-PGS or metal-PGS did not alter significance metals Occupations high potential elevated ERS. Additionally, occupational non-occupational exposures measured metals. Conclusion Metals increased reduced risk, correlated exposures. These data underscore progression.

Язык: Английский

Процитировано

3