The GPR39 Receptor Plays an Important Role in the Pathogenesis of Overactive Bladder and Corticosterone-Induced Depression DOI Open Access
Jan Wróbel, Paulina Iwaniak, Piotr Dobrowolski

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12630 - 12630

Published: Nov. 25, 2024

Despite the close and clinically confirmed association between depression overactive bladder, it remains unclear whether this affective disorder is a factor causing bladder or specific symptom of psychosomatic disorders. This study examined effects repeated corticosterone administration on occurrence symptoms associated with bladder. Additionally, we administering TC-G 1008, an antidepressant that selectively activates GPR39 receptor, could alleviate corticosterone-induced depression-like behavior detrusor overactivity-related changes in cystometric measurements. We also explored its potential to reverse alterations various biomarkers both conditions serum, urinary brain female rats. The (20 mg/kg/day for 14 days) yielded anticipated results, including increase duration immobility during forced swim test, parameters overactivity, decrease neurotrophins, elevation pro-inflammatory cytokine levels. Treatment 1008 (15 mg/kg/day) alleviated overactivity depression, while restoring levels biochemical markers normal ranges. antidepressants based agonists enhance kynurenic acid neuroprotective pathway. These results indicate agonist receptor might be promising future therapeutic approach treating occurs alongside depression.

Language: Английский

Psychobiotics and the Microbiota–Gut–Brain Axis: Where Do We Go from Here? DOI Creative Commons
Sylvie Binda, Annie Tremblay, Umar Iqbal

et al.

Microorganisms, Journal Year: 2024, Volume and Issue: 12(4), P. 634 - 634

Published: March 22, 2024

The bidirectional relationship between the gut microbiota and nervous system is known as microbiota-gut-brain axis (MGBA). MGBA controls complex interactions brain, enteric system, gut-associated immune neuroendocrine systems, regulating key physiological functions such response, sleep, emotions mood, food intake, intestinal functions. Psychobiotics are considered tools with potential to modulate through preventive, adjunctive, or curative approaches, but their specific mechanisms of action on many aspects health yet be characterized. This narrative review perspectives article highlights paradigms needing attention scope probiotics applications in human increases, a growing body evidence supporting systemic beneficial effects. However, there limitations overcome before establishing extent which we can incorporate management neuropsychiatric disorders. Although this uses term general manner, it remains important study at strain level most cases.

Language: Английский

Citations

7
Tryptophan Metabolism Through the Kynurenine Pathway in Glial Cells DOI Creative Commons

Deivison Silva Argolo,

Lucas Matheus Gonçalves de Oliveira, Gilles J. Guillemin

et al.

Neuroglia, Journal Year: 2025, Volume and Issue: 6(1), P. 14 - 14

Published: March 12, 2025

The central nervous system (CNS) relies on complex and dynamic interactions between neurons glial cells. Among cells, astrocytes regulate the chemical environment surrounding supply essential nutrients for brain metabolism whereas microglia, resident macrophages of CNS, play critical roles in homeostasis, defense, responses to injury. Both microglia contribute regulation excitotoxicity inflammation mediated by tryptophan (Trp) via kynurenine pathway. Trp generates several bioactive metabolites, including quinolinic acid (QUIN) kynurenic (KYNA), which have opposing effects. QUIN, produced activated acts as an agonist NMDA receptors; excessive stimulation these receptors can lead neuronal death. Conversely, KYNA, primarily 2,3-aminotransferases (KAT), receptor antagonist, conferring neuroprotection mitigating excitotoxicity. Dysregulation is implicated many neurodegenerative diseases such Alzheimer’s disease, Parkinson’s multiple sclerosis amyotrophic lateral sclerosis, well various neuropsychiatric disorders. This review examines cellular molecular mechanisms underlying highlighting unique contributions each phenotype, implications CNS pathologies, potential biomarkers therapeutic targets restoring homeostasis preventing disease progression.

Language: Английский

Citations

0
Tryptophan As a New Member of RNA‐Induced Silencing Complexes Prevents Colon Cancer Liver Metastasis DOI Creative Commons
Fangyi Xu, Yi Ren,

Yun Teng

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(31)

Published: June 20, 2024

Abstract Essential amino acids (EAA) and microRNAs (miRs) control biological activity of a cell. Whether EAA regulates the miR has never been demonstrated. Here, as proof‐of‐concept, tryptophan (Trp, an EAA) complex containing Argonaute 2 (Ago2) miRs including miR‐193a (Trp/Ago2/miR‐193a) is identified. Trp binds miR‐193a‐3p interacts with Ago2. Trp/Ago2/miR‐193a increases via enhancing RNase activity. Other miR‐103 miR‐107 in enhance by targeting same genes. Mechanistically, Trp‐binding pockets PIWI domain Ago2 to mediated This newly formed Ago2/Trp/miR‐193a‐3p more efficient than alone inhibiting expression targeted genes colon cancer liver metastasis. The findings show that through communication RNA‐induced silencing complexes (RISC), which provides basis for based therapy.

Language: Английский

Citations

4
Tryptophan metabolism-related gene CYP1B1 serves as a shared biomarker for both Parkinson’s disease and insomnia DOI Creative Commons
Xinyu Li, Wen-Kai Yu,

Jinghao Wu

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 8, 2025

Parkinson's disease (PD) and insomnia are prevalent neurological disorders, with emerging evidence implicating tryptophan (TRP) metabolism in their pathogenesis. However, the precise mechanisms by which TRP contributes to these conditions remain insufficiently elucidated. This study explores shared metabolism-related genes (TMRGs) molecular underlying PD insomnia, aiming provide insights into We analyzed datasets for (GSE100054) (GSE208668) obtained from Gene Expression Omnibus (GEO) database. TMRGs were Molecular Signatures Database (MSigDB) Genecards Tryptophan differentially expressed (TM-DEGs) identified intersecting (DEGs) datasets. Through Protein–Protein Interaction (PPI) network analysis, Support Vector Machine-Recursive Feature Elimination (SVM-RFE) , Extreme Gradient Boosting (XGBoost) machine learning, we Cytochrome P4501B1 (CYP1B1) Electron Transfer Flavoprotein Alpha (ETFA) as key hub genes. Subsequently, employed CIBERSORT single-sample gene set enrichment analysis (ssGSEA) further investigate association between peripheral immune activation inflammatory response. Additionally, interaction, Drug-mRNA, Transcription Factor (TF)-mRNA, competing endogenous RNA (ceRNA) networks centered on constructed explore regulatory potential drug interactions. Finally, validation through bioinformatics animal experiments CYP1B1 a promising biomarker associated both insomnia.

Language: Английский

Citations

0
Design, fabrication and biocompatibility assessment of a carbon cloth-integrated MoS2-CuS-GO thermoresponsive hydrogel microsystem for photothermal-triggered benvitimod delivery DOI Creative Commons
Wenting Wang, Mengyang Zhang, Xiaoxia Wang

et al.

Nano Materials Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Microbiome-based precision nutrition: Prebiotics, probiotics and postbiotics DOI

Adrián Odriozola,

Adriana González-Silvera,

Iñaki Odriozola

et al.

Advances in genetics, Journal Year: 2024, Volume and Issue: unknown, P. 237 - 310

Published: Jan. 1, 2024

Language: Английский

Citations

2
Kynurenine Pathway after Kidney Transplantation: Friend or Foe? DOI Open Access
Izabela Zakrocka, Ewa M. Urbańska, Wojciech Załuska

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 9940 - 9940

Published: Sept. 14, 2024

Kidney transplantation significantly improves the survival of patients with end-stage kidney disease (ESKD) compared to other forms replacement therapy. However, transplant recipients’ outcomes are not fully satisfactory due increased risk cardiovascular diseases, infections, and malignancies. Immune-related complications remain biggest challenge in management graft recipients. Despite broad spectrum immunosuppressive agents available more detailed methods used monitor their effectiveness, chronic allograft nephropathy remains most common cause rejection. The kynurenine (KYN) pathway is main route tryptophan (Trp) degradation, resulting production a plethora substances ambiguous properties. Conversion Trp KYN by enzyme indoleamine 2,3-dioxygenase (IDO) rate-limiting step determining formation next from pathway. IDO activity, as well subsequent metabolites pathway, highly dependent on balance between pro- anti-inflammatory conditions. Moreover, products themselves possess immunomodulating properties, e.g., modify activity control immune-related processes. were widely studied neurological disorders but recently gained attention researchers context immune-mediated diseases. Evidence that this degradation may represent peripheral tolerogenic significant implications for further fueled interest. Our review aimed present recent knowledge about role pathogenesis, diagnosis, monitoring, treatment complications.

Language: Английский

Citations

2
Indoleamine 2,3-dioxygenase (IDO1) – Can dendritic cells and monocytes expressing this moonlight enzyme change the phase of Parkinson’s Disease? DOI Creative Commons
Milene Gonçalves, Paulo Rodrigues‐Santos, Cristina Januário

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 133, P. 112062 - 112062

Published: April 22, 2024

Parkinson's Disease (PD) is the second most common neurodegenerative disease where central and peripheral immune dysfunctions have been pointed out as a critical component of susceptibility progression this disease. Dendritic cells (DCs) monocytes are key players in promoting response regulation can induce enzyme indoleamine 2,3-dioxygenase 1 (IDO1) under pro-inflammatory environments. This with catalytic signaling activity supports axis IDO1-KYN-aryl hydrocarbon receptor (AhR), disease-specific immunomodulatory effects. IDO1 rate-limiting kynurenine pathway (KP) that begins tryptophan (Trp) catabolism across pathway. The functions pathway, which extensively described cancer, forgotten so far diseases, chronic inflammatory environment underlines Despite KP PD, these mainly associated neurotoxic functions. With review, we aim to focus on properties IDO1+DCs IDO1+monocytes possible strategy balance profile PD. We also highlight importance exploring role dopaminergic therapeutics modulation possibly optimize current PD therapeutic strategies.

Language: Английский

Citations

0
Metabolic Side Effects from Antipsychotic Treatment with Clozapine Linked to Aryl Hydrocarbon Receptor (AhR) Activation DOI Creative Commons
Karin Fehsel

Biomedicines, Journal Year: 2024, Volume and Issue: 12(10), P. 2294 - 2294

Published: Oct. 10, 2024

Metabolic syndrome (MetS) is the most common adverse drug reaction from psychiatric pharmacotherapy. Neuroreceptor blockade by antipsychotic clozapine induces MetS in about 30% of patients. Similar to insulin resistance, impedes Akt kinase activation, leading intracellular glucose and glutathione depletion. Additional cystine shortage triggers tryptophan degradation kynurenine, which a well-known AhR ligand. Ligand-bound downregulates iron pool, thereby increasing risk mitochondrial dysfunction. Scavenging stabilizes transcription factor HIF-1, shifts metabolism toward transient glycolysis. Furthermore, inhibits AMPK obesity liver steatosis. Increasing uptake activation prevents dyslipidemia damage and, therefore, reduces MetS. In line with vitro results, feeding experiments rats revealed disturbed glucose-/lipid-/iron-metabolism treatment hyperglycemia hepatic deposits female steatosis anemia male animals. Decreased energy expenditure seems be cause fast weight gain first weeks treatment. patients, this due neuroleptic correlates an improvement psychotic syndromes can even used anticipate therapeutic effect

Language: Английский

Citations

0
Human and gut microbiota synergy in a metabolically active superorganism: a cardiovascular perspective DOI Creative Commons
Matteo Antonio Russo, Matteo Puccetti, Claudio Costantini

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Oct. 11, 2024

Despite significant advances in diagnosis and treatment over recent decades, cardiovascular disease (CVD) remains one of the leading causes morbidity mortality Western countries. This persistent burden is partly due to incomplete understanding fundamental pathogenic mechanisms, which limits effectiveness current therapeutic interventions. In this context, evidence highlights pivotal role immuno-inflammatory activation by gut microbiome influencing disorders, potentially opening new avenues. Indeed, while atherosclerosis has been established as a chronic inflammatory arterial wall, accumulating data suggest that immune system regulation anti-inflammatory pathways mediated microbiota metabolites play crucial range CVDs, including heart failure, pericardial disease, arrhythmias, cardiomyopathies. Of particular interest emerging how tryptophan metabolism-by both host microbiota-converges on Aryl hydrocarbon Receptor (AhR), key regulator homeostasis. review seeks enhance our inflammation CVD, with focus microbiome-derived metabolites, such indoles their derivatives, contribute cardioimmunopathology. By exploring these we aim facilitate development novel, microbiome-centered strategies for combating CVD.

Language: Английский

Citations

0