Cancer drug discovery and develogment/Cancer drug discovery and development, Journal Year: 2024, Volume and Issue: unknown, P. 95 - 127
Published: Jan. 1, 2024
Language: Английский
Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 385 - 385
Published: Feb. 23, 2024
Traumatic Brain Injury (TBI) remains a significant global health challenge, lacking effective pharmacological treatments. This shortcoming is attributed to TBI’s heterogeneous and complex pathophysiology, which includes axonal damage, mitochondrial dysfunction, oxidative stress, persistent neuroinflammation. The objective of this study analyze transcranial photobiomodulation (PBM), employs specific red near-infrared light wavelengths modulate brain functions, as promising therapy address pathophysiology in single intervention. reviews the feasibility therapy, firstly by synthesizing PBM’s cellular mechanisms with each identified pathophysiological aspect. outcomes human clinical studies are then reviewed. findings support potential for treating TBI, notwithstanding variations parameters such wavelength, power density, dose, source positioning, pulse frequencies. Emerging data indicate that these plays role outcomes. Additionally, new research into effects on electrical properties polymerization dynamics neuronal microstructures, like microtubules tubulins, provides insights future parameter optimization. In summary, PBM represents multifaceted therapeutic intervention TBI vast may be fulfilled optimizing parameters. Future should investigate parameters, possible incorporating artificial intelligence.
Language: Английский
Citations
15
Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)
Published: Jan. 24, 2025
Recent genome-wide association studies (GWASs) of several individual sleep traits have identified hundreds genetic loci, suggesting diverse mechanisms. Moreover, are moderately correlated, so together may provide a more complete picture health, while illuminating distinct domains. Here we construct novel health scores (SHSs) incorporating five core self-report measures: duration, insomnia symptoms, chronotype, snoring, and daytime sleepiness, using additive (SHS-ADD) principal components-based (SHS-PCs) approaches. GWASs these six SHSs identify 28 significant loci adjusting for multiple testing on (p < 8.3e-9), along with 341 previously reported 5e-08). The heritability the first three SHS-PCs equals or exceeds that SHS-ADD (SNP-h2 = 0.094), revealing sleep-domain-specific discoveries. Significant enrich in brain tissues metabolic neuronal pathways. Post-GWAS analyses uncover mechanisms underlying reveal connections (including potential causal links) to behavioral, psychological, cardiometabolic traits. Data-driven composite scores, combining self-reported insomnia, heritable, interpretable phenotypes GWAS discoveries elucidating regulatory
Language: Английский
Citations
1
Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 292, P. 117997 - 117997
Published: March 1, 2025
Aflatoxin B1 (AFB1), a prevalent agricultural mycotoxin, represents serious health hazard to humans and animals owing its toxic effects. Diosmetin (DIOS), naturally occurring flavonoid, has demonstrated potential hepatoprotective properties. This research seeks investigate the mechanisms by which DIOS mitigates AFB1-induced hepatotoxicity in mice. The mice were divided into four groups: control (CON), AFB1, DIOS+AFB1, DIOS. Over 28 - day period, all groups administered their respective treatments via oral gavage. CON group was given an equivalent volume of PBS, AFB1 received (0.4 mg/kg/day), DIOS+AFB1 treated with (20 mg/kg/day) combination alone. Then various experiments used evaluate hepatotoxic effects Our findings initially that induced liver injury, oxidative stress, endoplasmic reticulum (ER) apoptosis autophagy. treatment notably ameliorated damage lowering LDH MDA levels, increasing total antioxidant capacity enhancing GSH-Px, SOD CAT activities. Additionally, dampened secretion inflammatory cytokines IL-1β TNF-α, blocked NF-κB pathway. Moreover, administration lessened ER stress-mediated inhibiting mRNA protein expressions GRP78, p-PERK, p-elF2α, ATF6 ATF4, while concurrently upregulating Bcl-2 expression reducing Bax Cleaved Caspase-3 expressions. Furthermore, also found suppress levels LC3B, Beclin-1, ATG5, p62, promote AKT phosphorylation. Overall, effectively mitigated inflammation, autophagy inhibition pathway stimulation PI3K/AKT results imply may be viable therapeutic approach for prevention caused exposure.
Language: Английский
Citations
1
CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(10)
Published: Oct. 1, 2024
Huntington's disease (HD) is a devastating neurodegenerative that manifested by gradual loss of physical, cognitive, and mental abilities. As the advances, age has major impact on pathogenic signature mutant huntingtin (mHTT) protein aggregation. This review aims to explore intricate relationship between aging, mHTT toxicity, cellular senescence in HD. Scientific data interplay mHTT, HD were collected from several academic databases, including PubMed, Google Scholar, Google, ScienceDirect. The search terms employed "AGING," "HUNTINGTON'S DISEASE," "MUTANT HUNTINGTIN," "CELLULAR SENESCENCE." Additionally, gather information molecular mechanisms potential therapeutic targets, was extended include relevant such as "DNA DAMAGE," "OXIDATIVE STRESS," "AUTOPHAGY." According research, aging leads worsening pathophysiology through some processes. result accumulation, promoted, which causes DNA damage, oxidative stress, decreased autophagy, increased inflammatory responses. Pro-inflammatory cytokines other substances are released senescent cells, may worsen neuronal damage course disease. It been shown treatments directed at these pathways reduce symptoms enhance longevity experimental animals, pointing new possibility treating condition. Through their amplification harmful effects play crucial roles development Comprehending interplays creates novel opportunities for measures targeted alleviating enhancing patients' quality life.
Language: Английский
Citations
6
Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(1), P. 6 - 20
Published: Jan. 31, 2024
The endoplasmic reticulum, a key cellular organelle, regulates wide variety of activities. Endoplasmic reticulum autophagy, one the quality control systems plays pivotal role in maintaining homeostasis by controlling turnover, remodeling, and proteostasis. In this review, we briefly describe system, subsequently focus on emphasizing spatial temporal mechanisms underlying regulation autophagy according to requirements. We also summarize evidence relating how defective or abnormal contributes pathogenesis neurodegenerative diseases. summary, review highlights associated with they influence pathophysiology degenerative nerve disorders. This would help researchers understand roles regulatory reticulum-phagy
Language: Английский
Citations
5
European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: 997, P. 177469 - 177469
Published: March 5, 2025
Language: Английский
Citations
0
Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15
Published: June 19, 2024
Hederagenin (HG) is a natural pentacyclic triterpenoid that can be isolated from various medicinal herbs. By modifying the structure of HG, multiple derivatives with superior biological activities and safety profiles have been designed synthesized. Accumulating evidence has demonstrated HG its display pharmacological against cancers, inflammatory diseases, infectious metabolic fibrotic cerebrovascular neurodegenerative depression. Previous studies confirmed combat cancer by exerting cytotoxicity, inhibiting proliferation, inducing apoptosis, modulating autophagy, reversing chemotherapy resistance in cells, action targets involved mainly include STAT3, Aurora B, KIF7, PI3K/AKT, NF-κB, Nrf2/ARE, Drp1, P-gp. In addition, antagonize inflammation through production release pro-inflammatory cytokines mediators regulating inflammation-related pathways targets, such as MAPK, JAK2/STAT3, Keap1-Nrf2/HO-1, LncRNA A33/Axin2/β-catenin. Moreover, anti-pathogen, anti-metabolic disorder, anti-fibrosis, neuroprotection, anti-depression mechanisms partially elucidated. The diverse properties hold significant implications for future research development new drugs derived which lead to improved effectiveness profiles.
Language: Английский
Citations
4
BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)
Published: Jan. 6, 2025
Abstract Background Rectal cancer is a highly heterogeneous gastrointestinal tumor, and the prognosis for patients with treatment-resistant metastatic rectal remains poor. Mitophagy, type of selective autophagy that targets mitochondria, plays role in promoting or inhibiting tumors; however, importance mitophagy-related genes (MRGs) treatment unclear. Methods In this study, we used differentially expressed (DEGs) MRGs from TCGA-READ dataset to identify (MRDEGs). The mitophagy scores were then analyzed differential expression ROC. Seven module identified using weighted gene coexpression network analysis (WGCNA) approach subsequently validated merged datasets GSE87211 GSE90627. model obtained based on prognostic features, subgroups distinguished by risk score. Gene enrichment, immune infiltration immunotherapy response also evaluated. Finally, validation was carried out clinical samples, employing Immunohistochemistry (IHC). Results We demonstrated 22 between normal tissues. A constructed WGCNA Cox regression, which exhibited good diagnostic performance. four molecular markers ( MYLK , FLNC MYH11 NEXN ) as potential biomarkers first time. Moreover, our findings indicate derived are associated tumor immunity. To further validate findings, IHC analyses suggested MYH1 1 tissues lower than nontumorous Conclusion could predict might be able personalize patients.
Language: Английский
Citations
0
Journal of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 9, 2025
Autophagy is a fundamental cellular process critical for maintaining neuronal health, particularly in the context of neurodegenerative diseases such as Alzheimer's disease (AD). This review explores intricate role SNARE complex fusion autophagosomes with lysosomes, crucial step autophagic flux. Disruptions this process, often resulting from aberrant function or impaired lysosomal acidification, contribute to pathological accumulation and lysosomes observed AD. We examine composition, regulation, interacting molecules complex, emphasizing its central autophagosome-lysosome fusion. Furthermore, we discuss potential impact specific protein mutations broader implications health progression. By elucidating molecular mechanisms underlying SNARE-mediated fusion, aim highlight therapeutic targets that could restore mitigate processes characteristic
Language: Английский
Citations
0
Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)
Published: Jan. 13, 2025
Autophagy is responsible for maintaining cellular balance and ensuring survival. plays a crucial role in the development of diseases, particularly human cancers, with actions that can either promote survival or induce cell death. However, brain tumors contribute to high levels both mortality morbidity globally, resistance treatments being acquired due genetic mutations dysregulation molecular mechanisms, among other factors. Hence, having knowledge processes advancement enlightening, current review specifically examines autophagy. The discussion would focus on pathways control autophagy tumors, its dual as tumor suppressor supporter different types like glioblastoma, glioma, ependymoma, demonstrating potential treatment. mechanisms influence metastasis drug there complex interplay between responses stress hypoxia starvation. inhibit growth by promoting apoptosis. focusing could offer fresh perspectives creating successful treatments.
Language: Английский
Citations
0