Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 1, 2024
Language: Английский
Journal of Human Genetics, Journal Year: 2023, Volume and Issue: 68(12), P. 823 - 833
Published: Aug. 24, 2023
Abstract Objectives Genome-wide association studies (GWAS) have successfully revealed numerous susceptibility loci for obesity. However, identifying the causal genes, pathways, and tissues/cell types responsible these associations remains a challenge, standardized analysis workflows are lacking. Additionally, due to limited treatment options obesity, there is need development of new pharmacological therapies. This study aimed address issues by performing step-wise utilization knowledgebase gene prioritization assessing potential relevance key obesity genes as therapeutic targets. Methods results First, we generated list 28,787 obesity-associated SNPs from publicly available GWAS dataset (approximately 800,000 individuals in GIANT meta-analysis). Then, prioritized 1372 with significant silico evidence against genomic transcriptomic data, including transcriptionally regulated brain transcriptome-wide studies. In further narrowing down list, selected which found be useful discovery drug seeds demonstrated lipid separately. We thus identified 74 highly interconnected enriched several biological processes that contribute energy expenditure homeostasis. Of 37 had not been reported pathophysiology Finally, drug-gene interaction analysis, detected 23 (of 74) targets 78 approved marketed drugs. Conclusions Our provide valuable insights into through data-driven approach integrates multiple up-to-date knowledgebases.
Language: Английский
Citations
11
Heliyon, Journal Year: 2025, Volume and Issue: 11(3), P. e42196 - e42196
Published: Jan. 22, 2025
Language: Английский
Citations
0
Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 61(4), P. 2249 - 2264
Published: Oct. 23, 2023
Language: Английский
Citations
8
ACS Chemical Neuroscience, Journal Year: 2023, Volume and Issue: 14(17), P. 3173 - 3182
Published: Aug. 14, 2023
Depression is a multifaceted psychiatric disorder that affects significant number of individuals worldwide, and its pathophysiology encompasses variety mechanisms, including the induction endoplasmic reticulum (ER) stress, which has been correlated with depressive-like behaviors in animal models. Yamogenin, bioactive compound derived from traditional Chinese medicine Dioscorea species, possesses diverse pharmacological properties. This investigation aimed to explore antidepressant-like effects yamogenin underlying mechanisms involved. By utilizing murine model lipopolysaccharide (LPS)-induced behavior, we demonstrated enhanced sucrose preference reduced immobility time forced swimming test. These were observed alongside attenuation ER stress through modulation PERK/eIF2α/ATF4/CHOP signaling pathway prefrontal cortex. Moreover, augmented expression antiapoptotic protein Bcl-2 while diminishing proapoptotic caspase-3. Additionally, exhibited inhibitory on microglial activation but did not elicit promotion brain-derived neurotrophic factor (BDNF) signaling. Collectively, our findings propose exerts LPS-induced mice by inhibiting activation. study contributes novel insights into potential utilization as natural antidepressant agent.
Language: Английский
Citations
6
Brain Research Bulletin, Journal Year: 2024, Volume and Issue: 211, P. 110944 - 110944
Published: April 9, 2024
Ischemic stroke is a serious cerebrovascular condition. Isobavachalcone (ISO) has been documented to exhibit an anti-inflammatory effect across variety of diseases; however, its protective impact on ischemic remains unexplored. In this study, we evaluated the influence ISO in both transient middle cerebral artery occlusion/reperfusion (tMCAO/R) rat models and oxygen-glucose deprivation/reperfusion (OGD/R) cell models. We observed that pretreatment with 50 mg/kg diminished volume brain infarction, reduced edema, ameliorated neurological deficits rats. A reduction Nissl bodies was noted tMCAO/R group, which reversed following treatment ISO. TUNEL/NeuN double staining revealed decrease TUNEL-positive cells rats treated Furthermore, suppressed expression cleaved caspase-3 BAX, while elevating BCL-2 The levels CD86 iNOS were elevated rats; conversely, enhanced CD206 Arg-1. Additionally, TNF-α, IL-6, IL-1β rats, whereas counteracted effect. also increased TGF-β IL-10 penumbra It found hindered microglial M1 polarization favored M2 polarization. Histone Deacetylase 1 (HDAC1) downstream target protein ISO, resulting decreased HDAC1 OGD/R-induced cells. Overexpression shown promote inhibit OGD/R+ISO Overall, mitigated damage by promoting attenuated injury repressing expression.
Language: Английский
Citations
2
Journal of Functional Foods, Journal Year: 2024, Volume and Issue: 117, P. 106242 - 106242
Published: May 17, 2024
Diabetes mellitus (DM) plays a causative role in memory impairment. Neuroprotective effects of tea polyphenol (TP), unique and vital functional component tea, have been widely investigated neurodegenerative diseases, but the exact mechanisms still not entirely clarified yet. Here, we conducted experiment to assess whether TP could protect aged T2DM rats from impairment its potential mechanisms. Our study revealed that was alleviated after treatment. Both vivo vitro experiments showed raised expression GLUT4, activities key enzymes glucose metabolism production ATP model group, along with elevated O-GlcNAc glycosylation reduced phosphorylation Tau. Collectively, ameliorates via modulating hippocampal uptake/metabolism glycosylation/phosphorylation Tau, which provides new insights into beneficial effect on DM-related
Language: Английский
Citations
2
Epigenetics and human health, Journal Year: 2024, Volume and Issue: unknown, P. 31 - 48
Published: Jan. 1, 2024
Language: Английский
Citations
1
Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 15
Published: Oct. 8, 2024
Background Patients with unruptured intracranial aneurysms (UIAs) often experience emotional changes and cognitive impairments. However, the specific mechanisms underlying these impairments are still not fully understood. Methods In present study, voxel-based morphometry (VBM) surface-based (SBM) were employed to investigate structural alterations in 49 patients diagnosed UIAs compared 50 healthy controls. Additionally, this study aimed analyze correlations among cortical morphological indices, cerebral blood perfusion values neuropsychological test results. Results Compared control group, UIA exhibited increased gray matter volume right anterior orbitofrontal cortex decreased left thalamus pulvinar hippocampus. Furthermore, fractal dimension was lower postcentral gyrus entorhinal cortex. The abnormal brain regions demonstrated a downward trend, which associated reduction hippocampus, elevated anxiety levels impaired executive function. Conclusion prone impairment dysregulation, accompanied by subtle local decreases flow. These findings provide new insights into potential observed patients.
Language: Английский
Citations
0
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(20), P. 11169 - 11169
Published: Oct. 17, 2024
Obesity confers risk for cardiovascular disease and vascular dementia. However, genomic alterations modulated by obesity in endothelial cells the brain their relationship to other neurovascular unit (NVU) are unknown. We performed single nuclei RNA sequencing (snRNAseq) of NVU (endothelial cells, astrocytes, microglia, neurons) from hippocampus obese (
Language: Английский
Citations
0
Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 1, 2024
Language: Английский
Citations
0