Combined Use of Intranasal Methylprednisolone and Allopregnanolone: Revisiting Anti-inflammatory and Remyelinating Treatment in a Murine Model of Multiple Sclerosis DOI Creative Commons
Ivan Nicolás Pérez‐Osorio, Alejandro Espinosa,

Camila Álvarez-Gutiérrez

et al.

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(12)

Published: Dec. 18, 2024

Multiple sclerosis (MS) is a demyelinating, neuroinflammatory, progressive disease that severely affects human health of young adults. Neuroinflammation (NI) and demyelination, as well their interactions, are key therapeutic targets to halt or slow progression. Potent steroidal anti-inflammatory drugs such methylprednisolone (MP) remyelinating neurosteroids allopregnanolone (ALLO) could be co-administered intranasally enhance efficacy by providing direct access the central nervous system (CNS).

Language: Английский

The emergence of antidepressant drugs targeting GABAA receptors: A concise review DOI Creative Commons
Xénia Gonda, Frank I. Tarazi, Péter Döme

et al.

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 228, P. 116481 - 116481

Published: Aug. 13, 2024

Depression is among the most common psychiatric illnesses, which imposes a major socioeconomic burden on patients, caregivers, and public health system. Treatment with classical antidepressants (e.g. tricyclic selective serotonine reuptake inhibitors), primarily affect monoaminergic systems has several limitations, such as delayed onset of action moderate efficacy in relatively large proportion depressed patients. Furthermore, depression highly heterogeneus, its different subtypes, including post-partum depression, involve distinct neurobiology, warranting differential approach to pharmacotherapy. Given these shortcomings, need for novel that are superior faster fully justified. The development market introduction rapid-acting accelerated recent years. Some new act through GABAergic In this review, we discuss discovery, efficacy, limitations treatment classic antidepressants. We provide detailed discussion neurotransmission, special focus GABA

Language: Английский

Citations

4
Study on the potential diagnostic value of metabolomics changes in different biological fluids for aspiration pneumonia DOI Creative Commons
Lianghui Chen, Yazhen Chen, Fengyu Lin

et al.

BMC Pulmonary Medicine, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 4, 2025

Abstract Background Aspiration pneumonia (AP) is a type of lung inflammation caused by the aspiration food, oropharyngeal secretions, or gastric contents. This condition particularly common in older adults and individuals with impaired swallowing consciousness. While diagnosis AP relies on clinical history, assessments, imaging, these methods have significant limitations, often leading to underdiagnosis misdiagnosis. Reliable biomarkers for are lacking, making early detection treatment challenging. Methods Nineteen patients diagnosed were included this study, divided into two groups: ( n = 10) non-AP 9). Biological fluid samples, including bronchoalveolar lavage (BALF), saliva, serum, sputum, urine, analyzed using non-targeted liquid chromatography tandem mass spectrometry (LC-MS/MS). Differential metabolites identified fold change analysis, statistical significance, receiver operating characteristic (ROC) curve analysis evaluate their diagnostic potential. Spearman correlation was used examine relationship between selected parameters. Results Significant metabolic differences found patients, many different across biological fluids. Dehydroepiandrosterone sulfate (DHEAS), Androstenediol-3-sulfate (ADIOLS), beta-muricholic acid as key through ROC showing consistent increasing decreasing trends BALF, serum samples. DHEAS be negatively correlated Acute Physiology Chronic Health Evaluation II (APACHE II) r − 0.619, p 0.005) BALF sample. The area under (AUC) values showed that molecules could serve effective AP. Conclusions study identifies DHEAS, ADIOLS promising AP, potential improve treatment. These findings underscore value metabolomics developing tools facilitating better management patient outcomes. Further research required validate larger cohorts explore mechanistic roles pathophysiology.

Language: Английский

Citations

0
Multiplex Immunoassay for Biomarker Profiling of Whole Blood Cell Lysates and Supernatants and Pathogen Response in Neat Whole Blood Cultures DOI Creative Commons
Irina Balan, Alejandro G. Lopez, A. Leslie Morrow

et al.

Methods and Protocols, Journal Year: 2025, Volume and Issue: 8(3), P. 46 - 46

Published: May 1, 2025

Replicating in vivo conditions is essential for understanding immune responses and measuring biomarkers blood. Sampling plasma or serum often fails to detect disease-relevant signals, possibly because these markers are sequestered cells extracellular vesicles. Furthermore, traditional whole blood cultures using external media may not accurately mimic the physiological environment of cells. To address limitations, we developed a strategy cell lysates supernatants optimize biomarker detection. Additionally, employed neat culture methods, preserving natural cellular biochemical assess sensitivity modulators, such as lipopolysaccharide (LPS). This cost-effective approach minimizes variability contamination risks. By utilizing Luminex multiplex immunoassays, profiled with higher efficiency than ELISAs. Blood samples from individuals high alcohol consumption validated our method by assessing levels before after LPS stimulation, providing insights into intracellular inflammatory pathways. enhances processes cells, demonstrating advantages lysates, supernatants, advanced assays immunological research.

Language: Английский

Citations

0
Dehydroepiandrosterone and Its Metabolite 5-Androstenediol: New Therapeutic Targets and Possibilities for Clinical Application DOI Creative Commons
Т. А. Федотчева, M. E. Uspenskaya,

Darya N. Ulchenko

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(9), P. 1186 - 1186

Published: Sept. 9, 2024

Dehydroepiandrosterone and its sulfate are the most abundant steroids in humans. The metabolism of dehydroepiandrosterone can differ significantly depending on organ or tissue subtype steroid receptors expressed it. For dehydroepiandrosterone, as a precursor all hormones, intracrine hormonal activity is inherent. This unique feature could be beneficial for medicinal application, especially local treatment various pathologies. At present, clinical use limited by Intrarosa® (Quebec city, QC, Canada) prasterone) 6.5 mg vaginal suppositories atrophy dyspareunia, while synthetic derivatives Triplex, BNN 27, Fluasterone have investigational status diseases. Here, we discuss molecular targets which open future prospects to expand indications use. Dehydroepiandrosterone, an oral drug, surmised promise osteoporosis, cachexia, sarcopenia, does 10% unguent skin muscle regeneration. Also, 5-androstenediol, metabolite promising candidate acute radiation syndrome immunostimulating agent during radiopharmaceutical therapy. design synthesis new 5-androstenediol with increased bioavailability may lead appearance highly effective cytoprotectors pharmaceutical market. argumentations applications these novel insights into their mechanisms action discussed.

Language: Английский

Citations

2
Peripartum buprenorphine and oxycodone exposure impair maternal behavior and increase neuroinflammation in the brains of new mother rats DOI
Courtney Dye, Andrew I. Webb,

Martha P. Fankhauser

et al.

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

Citations

2
Neurosteroid [3α,5α]-3-Hydroxy-pregnan-20-one Enhances the CX3CL1-CX3CR1 Pathway in the Brain of Alcohol-Preferring Rats with Sex-Specificity DOI Creative Commons
Irina Balan, Adelina Grusca, Samantha Lucenell Chéry

et al.

Life, Journal Year: 2024, Volume and Issue: 14(7), P. 860 - 860

Published: July 9, 2024

This study investigates the impact of allopregnanolone ([3α,5α]3-hydroxypregnan-20-one or 3α,5α-tetrahydroprogesterone (3α,5α-THP); 10 mg/kg, IP) on fractalkine/CX3-C motif chemokine ligand 1 (CX3CL1) levels, associated signaling components, and markers for microglial astrocytic cells in nucleus accumbens (NAc) male female alcohol-preferring (P) rats. Previous research suggested that 3α,5α-THP enhances anti-inflammatory interleukin-10 (IL-10) cytokine production brains P rats, with no similar effect observed females. reveals elevates CX3CL1 levels by 16% NAc significant changes males. The increase induced was females across multiple brain regions, including NAc, amygdala, hypothalamus, midbrain, while noted Additionally, rats treated exhibited notable increases receptor (CX3CR1; 48%) transforming growth factor-beta (TGF-β1; 24%) along heightened activation (phosphorylation) signal transducer activator transcription (STAT1; 85%) NAc. Conversely, alterations were Furthermore, decreased glial fibrillary acidic protein (GFAP) 19% both rat without affecting ionized calcium-binding adaptor molecule (IBA1) transmembrane 119 (TMEM119). These findings indicate CX3CL1/CX3CR1 pathway but not males, primarily influencing astrocyte reactivity, activation.

Language: Английский

Citations

1
Neurosteroids in Glioma: A Novel Therapeutic Concept DOI Creative Commons

Ava Hogan,

Melike Mut

Life, Journal Year: 2024, Volume and Issue: 14(8), P. 975 - 975

Published: Aug. 2, 2024

Glioma, a diverse group of brain and spinal cord tumors arising from glial cells, is characterized by varying degrees malignancy, with some types exhibiting highly aggressive behavior, rapid proliferation, invasive growth patterns, posing significant therapeutic challenges. This review delves into the complex interactions between glioma neurotransmitters, neurosteroids, emphasizing their potential as targets. Key like glutamate gamma-aminobutyric acid (GABA), play crucial roles in growth, invasion, treatment response. examines involvement neurosteroids biology explores innovative strategies targeting these systems. It encompasses biosynthesis mechanisms gliomas spatial distribution neurosteroid synthesis gliomas, role ion channels, hormonal influences, enzyme modulation, neuroimmune system progression. Additionally, it highlights to modulate pathways for benefit.

Language: Английский

Citations

1
Novel Inhibitory Actions of Neuroactive Steroid [3α,5α]-3-Hydroxypregnan-20-One on Toll-like Receptor 4-Dependent Neuroimmune Signaling DOI Creative Commons
Alejandro G. Lopez, Venkat R. Chirasani, Irina Balan

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(11), P. 1441 - 1441

Published: Nov. 13, 2024

The endogenous neurosteroid (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP) modulates inflammatory and neuroinflammatory signaling through toll-like receptors (TLRs) in human mouse macrophages, blood cells alcohol-preferring (P) rat brains. Although it is recognized that 3α,5α-THP inhibits TLR4 activation by blocking interactions with MD2 MyD88, the comprehensive molecular mechanisms remain to be elucidated. This study explores additional sites, including TIRAP binding which pivotal for MyD88 myddosome formation, as well LPS TLR4:MD2 complex. Both male female P rats (n = 8/group) received intraperitoneal administration of (15 mg/kg; 30 min) or a vehicle control, their hippocampi were analyzed using immunoprecipitation immunoblotting techniques. significantly reduces levels mediators IL-1β HMGB1, confirming its anti-inflammatory actions. We found binds TLR4, IRAK4, IRAK1, TIRAP. Notably, MyD88-TIRAP (Males: −31 ± 9%, t-test, p < 0.005; Females: −53 15%, 0.005), without altering IRAK4 baseline expression these proteins. Additionally, docking dynamic analysis revealed sites on complex, targeting hydrophobic pocket usually occupied Lipid A LPS. Surface plasmon resonance (SPR) assays validated disrupts (Kd 4.36 5.7 μM) an inhibition constant (Ki) 4.5 1.65 nM. These findings indicate mediator production involves critical protein-lipid protein-protein at key activation, shedding light action underscoring therapeutic potential against TLR4-driven inflammation.

Language: Английский

Citations

0
Combined Use of Intranasal Methylprednisolone and Allopregnanolone: Revisiting Anti-inflammatory and Remyelinating Treatment in a Murine Model of Multiple Sclerosis DOI Creative Commons
Ivan Nicolás Pérez‐Osorio, Alejandro Espinosa,

Camila Álvarez-Gutiérrez

et al.

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(12)

Published: Dec. 18, 2024

Multiple sclerosis (MS) is a demyelinating, neuroinflammatory, progressive disease that severely affects human health of young adults. Neuroinflammation (NI) and demyelination, as well their interactions, are key therapeutic targets to halt or slow progression. Potent steroidal anti-inflammatory drugs such methylprednisolone (MP) remyelinating neurosteroids allopregnanolone (ALLO) could be co-administered intranasally enhance efficacy by providing direct access the central nervous system (CNS).

Language: Английский

Citations

0