Investigating the causal relationship between inflammation and multiple types of hearing loss: a multi-omics approach combining Mendelian randomization and molecular docking DOI Creative Commons

Jingqi Zhang,

Tao Guo,

Yaxin Chen

и другие.

Frontiers in Neurology, Год журнала: 2024, Номер 15

Опубликована: Ноя. 28, 2024

Background Hearing loss affects over 10% of the global population. Inflammation is a key factor in hearing caused by noise, infection, and aging, damaging various hearing-related tissues (e.g., spiral ligament, stria vascularis). Mendelian randomization (MR) can help identify potential causal relationships therapeutic targets. Methods We conducted MR analyses on 91 inflammatory proteins ( n = 14,824) genome-wide association study results for types European ancestry populations, including sensorineural (SNHL; cases 15,952, controls 196,592), sudden idiopathic (SIHL; 1,491, other (OHL; 4,157, 196,592). Additionally, with difficulty 14,654, 474,839) served as validation set. To predict protein-enriched pathways tissues, we performed enrichment analysis, functional annotation, tissue using “OmicsNet2.0” “FUMA” platforms. also combined “CoreMine” molecular docking to explore drugs targeting investigate binding efficacy. Results CCL19 was identified common risk SNHL OHL, which validated dataset. Tissue analysis revealed that SIHL-related were enriched amygdala. Multi-omics research indicated associations between neurodegenerative diseases. Molecular studies suggested Chuanxiong Rhizoma Uncariae Ramulus Cumuncis are CCL19. Conclusion This through highlighting crucial role loss. The related amygdala their diseases provide new insights into mechanisms

Язык: Английский

1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI): From an Obscure to Pivotal Member of the DOX Family of Serotonergic Psychedelic Agents – A Review DOI Creative Commons
Richard A. Glennon, Małgorzata Dukat

ACS Pharmacology & Translational Science, Год журнала: 2024, Номер 7(6), С. 1722 - 1745

Опубликована: Май 8, 2024

1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI, or DOX where X = −I) was first synthesized in 1973 a structure–activity study to explore the effect of various aryl substituents on then newly identified, and subsequently controlled, hallucinogenic agent 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM, −CH3). Over time, DOI found be serotonin (5-HT) receptor agonist using peripheral 5-HT tissue assays later, following identification multiple families central receptors, an at 5-HT2 receptors rat and, then, human brain. Today, classical hallucinogens, currently referred as serotonergic psychedelic agents, are receiving considerable attention for their potential therapeutic application neuropsychiatric disorders including treatment-resistant depression. Here, we review, historical current developments that led becoming unique, perhaps landmark, research.

Язык: Английский

Процитировано

10

Treatment-resistant depression: molecular mechanisms and management DOI Creative Commons
Mayanja Kajumba, Angelina Kakooza‐Mwesige, Noeline Nakasujja

и другие.

Molecular Biomedicine, Год журнала: 2024, Номер 5(1)

Опубликована: Окт. 17, 2024

Due to the heterogeneous nature of depression, underlying etiological mechanisms greatly differ among individuals, and there are no known subtype-specific biomarkers serve as precise targets for therapeutic efficacy. The extensive research efforts over past decades have not yielded much success, currently used first-line conventional antidepressants still ineffective close 66% patients. Most clinicians use trial-and-error treatment approaches, which seem beneficial only a fraction patients, with some eventually developing resistance. Here, we review evidence from both preclinical clinical studies on pathogenesis depression antidepressant response. We also discuss efficacy pharmacological non-pharmacological well novel emerging therapies. reveals that in response, specific, but rather involve an interplay between various neurotransmitter systems, inflammatory mediators, stress, HPA axis dysregulation, genetics, other psycho-neurophysiological factors. None current hypotheses sufficiently accounts interactional involved its etiology could partly explain limited success discovering efficacious treatment. Effective management treatment-resistant (TRD) requires targeting several mechanisms, using and/or personalized modalities, could, example, include multi-target pharmacotherapies augmentation psychotherapy approaches. Future guided by interaction provide more insights into potential etiologies TRD, precision biomarker targets, modalities.

Язык: Английский

Процитировано

4

The immunomodulatory effects of classical psychedelics: A systematic review of preclinical studies DOI Creative Commons
Zhen Xuen Brandon Low,

Wei Shen Ng,

Eugene Lim

и другие.

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Год журнала: 2024, Номер unknown, С. 111139 - 111139

Опубликована: Сен. 1, 2024

Язык: Английский

Процитировано

1

Investigating the causal relationship between inflammation and multiple types of hearing loss: a multi-omics approach combining Mendelian randomization and molecular docking DOI Creative Commons

Jingqi Zhang,

Tao Guo,

Yaxin Chen

и другие.

Frontiers in Neurology, Год журнала: 2024, Номер 15

Опубликована: Ноя. 28, 2024

Background Hearing loss affects over 10% of the global population. Inflammation is a key factor in hearing caused by noise, infection, and aging, damaging various hearing-related tissues (e.g., spiral ligament, stria vascularis). Mendelian randomization (MR) can help identify potential causal relationships therapeutic targets. Methods We conducted MR analyses on 91 inflammatory proteins ( n = 14,824) genome-wide association study results for types European ancestry populations, including sensorineural (SNHL; cases 15,952, controls 196,592), sudden idiopathic (SIHL; 1,491, other (OHL; 4,157, 196,592). Additionally, with difficulty 14,654, 474,839) served as validation set. To predict protein-enriched pathways tissues, we performed enrichment analysis, functional annotation, tissue using “OmicsNet2.0” “FUMA” platforms. also combined “CoreMine” molecular docking to explore drugs targeting investigate binding efficacy. Results CCL19 was identified common risk SNHL OHL, which validated dataset. Tissue analysis revealed that SIHL-related were enriched amygdala. Multi-omics research indicated associations between neurodegenerative diseases. Molecular studies suggested Chuanxiong Rhizoma Uncariae Ramulus Cumuncis are CCL19. Conclusion This through highlighting crucial role loss. The related amygdala their diseases provide new insights into mechanisms

Язык: Английский

Процитировано

0