Pharmacological Reports最新文献

Background: The gut microbiome has been increasingly recognized for its potential role in schizophrenia through gut-brain interactions involving immune, neural, and metabolic pathways. This pilot study evaluated the impact of fecal microbiota transplantation (FMT) on the abundance and variability of selected fungal and archaeal species in the gut microbiota in the rat model of schizophrenia.

Methods: Sprague-Dawley rats using as a prenatal methylazoxymethanol acetate (MAM-E17) model of schizophrenia underwent FMT or placebo. Fecal DNA was extracted and analyzed via quantitative Real-Time PCR (qPCR) to quantify selected fungi (Candida tropicalis, Malassezia spp., Cryptococcus neoformans) and archaea (Methanobrevibacter smithii, Methanosphaera stadtmanae) before and after intervention RESULTS: A slightly higher prevalence of C. tropicalis was noted in MAM-exposed rats compared to healthy controls (19% vs. 10%). Post-FMT, C. tropicalis colonization increased to nearly 100% across all groups, irrespective of transplantation source, indicating natural microbiome maturation rather than FMT effect. Malassezia spp. were commonly present before treatment, with their abundance significantly declining after both FMT and placebo administration, suggesting procedural impacts rather than specific FMT effects. C. neoformans and methanogenic archaea were absent.

Conclusions: Overall, the results suggest that FMT has limited impact on gut fungal populations, possibly due to the developmental stage of microbiome maturation or procedural interventions. The absence of archaea underscores the complexity of the microbiome's role in neurodevelopmental disorders, highlighting the necessity for continued research into microbial influences on schizophrenia pathophysiology.

Background: Serum canrenone concentrations have so far only been measured in patients with acute heart failure or heart failure with preserved ejection fraction. The results of these studies showed that low or undetectable canrenone concentrations could contribute to the lack of pharmacological effect of spironolactone, while patients with detectable canrenone concentrations had significantly higher potassium concentrations. However, no detailed information on serum canrenone concentrations in patients with heart failure with reduced ejection fraction (HFrEF) has been published to date. The aim of the study was to determine serum canrenone concentrations in samples collected from patients with HFrEF during routine medical care and correlate them with selected clinical parameters such as left ventricular ejection fraction (LVEF), systolic and diastolic blood pressure, and the levels of N-terminal pro-B-type natriuretic peptide, serum potassium, liver enzymes, and renal function markers.

Methods: This cross-sectional study analyzed data from 64 patients treated for HFrEF with oral spironolactone. Patients were recruited from the Cardiology Outpatient Clinic of the University Hospital, Ostrava, Czech Republic. Blood samples were collected in an outpatient setting from each patient between November 2022 and October 2023 as part of a routine examination to determine steady-state serum canrenone concentrations.

Results: Serum canrenone concentrations ranged from 5.0 to 336.2 µg/L. A correlation was observed between canrenone concentration and both the daily spironolactone dose and dose per kilogram of body weight. However, wide inter-individual variability was observed in canrenone concentrations achieved after administering the same dose of spironolactone and in the concentration-to-dose ratio. Patients with LVEF < 30% used the same dose per day and kilogram of body weight as patients with LVEF ≥ 30% but achieved significantly higher canrenone concentrations. A correlation was observed between canrenone and serum urea, creatinine, and potassium concentrations. An inverse correlation was observed between diastolic blood pressure and dose per kilogram of body weight.

Conclusions: Wide inter-individual variability in the minimum serum concentrations of canrenone was observed after the same dose of spironolactone was administered. Patients with impaired renal and/or myocardial function were found to be at a higher risk of canrenone accumulation, leading to increased serum potassium concentrations.

Anxiety and depressive disorders constitute a public health concern with a high negative impact on patients' quality of life. These disorders are among the prevalent neuropsychiatric conditions significantly contributing to the global burden. Although the precise mechanisms underlying the development of anxiety- and depressive-like behaviors remain incompletely understood, increasing evidence indicates that these disorders arise from complex and multifactorial processes involving dysfunction across multiple body organs. The gut microbiota (GM) seem to play certain role in developing of these conditions, as supported by studies demonstrating its influence on brain function and behavior. Indeed, several studies have recently reported that alterations in GM composition and function are linked with immune system dysregulation (inflammation/neuroinflammation) and subsequently influence brain pathways and systems, including neurotransmitters, the hypothalamic-pituitary-adrenal axis (HPA), and neurotrophic factors. Also, therapeutic agents targeting gut dysbiosis (GD) have yielded significant results. This review summarizes the role of GM in the pathophysiology of anxiety and depressive behaviors, its interaction with some psychotropic drugs, and its potential use as a therapeutic target for these conditions.Clinical trial number: Not applicable.

The intricate interplay between the brain and gut, often referred to as the gut-brain axis, has emerged as a cornerstone of health and disease. This bidirectional communication network, mediated by neural, hormonal, immune, and microbial signals, plays a pivotal role in maintaining homeostasis and influencing both neurological and gastrointestinal functions. Dysregulation of the gut-brain axis is implicated in various neurological and gastrointestinal disorders, highlighting the need to explore novel therapeutic strategies targeting this axis. Uridine, an endogenous pyrimidine nucleoside that is also obtained through dietary sources, has recently gained increasing attention for its neuroprotective and gut-modulating properties. Known for its critical role in RNA synthesis, membrane phospholipid production, and neurotransmitter regulation, uridine has demonstrated potential in enhancing synaptic plasticity, reducing inflammation, and supporting neuronal survival. Emerging evidence also suggests that uridine may influence gut health by promoting epithelial integrity, modulating the gut microbiota, and reducing intestinal inflammation. Given the interconnected nature of the gut and brain, uridine's dual actions present a compelling opportunity to explore its role in modulating the gut-brain axis as a means of achieving neuroprotection. This review aims to provide a comprehensive overview of the effect of uridine on brain and gut health, with a particular focus on its potential to influence the gut-brain axis.

Background: Separation and encapsulation provide a practical and effective strategy for the targeted delivery of bioactive components in formulation technologies. This study aimed to develop an inorganic Pickering-mediated formulation, Solcumin™, for food-derived tetrahydrocurcumin (THC), and to evaluate its long-term storage stability and in vitro bioactivity.

Methods: In this study, we investigated the application of inorganic Pickering-mediated techniques to encapsulate food-derived bioactive compounds. Solcumin™ was industrially produced and subjected to physicochemical analysis, stability testing in distilled water over 8 weeks at 25 °C, and in vitro bioactivity assessment, including antioxidant (DPPH, ABTS), cytotoxicity (HDFn cells), and anti-inflammatory (NO, IL-6) assays.

Results: Solcumin™ contained 11.5% tetrahydrocurcumin (THC) and exhibited excellent stability in distilled water, retaining 85% of its initial THC content after 8 weeks of storage at 25°C, while effectively preventing leaching and oxidation. Furthermore, Solcumin™ demonstrated notable anti-inflammatory activity, inhibiting nitric oxide (NO) production by approximately 89.11% and reducing interleukin-6 (IL-6) expression in a dose-dependent manner. It also exhibited antioxidant activity, as indicated by radical scavenging activity in both 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays at a concentration of 100 µg/mL.

Conclusions: To the best of our knowledge, this is the first study to report the development of biomineralization-based Solcumin™ and evaluate its in vitro bioactivity.

Background: The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of the cellular antioxidant response, playing an important role in protecting neurons from ischemic injury. The hippocampus exhibits region-specific vulnerability to ischemia, with CA1 neurons being highly susceptible, while CA2-3 and dentate gyrus (DG) neurons demonstrate greater resistance. Our previous work revealed higher basal and post-ischemia/reperfusion (I/R) Nrf2 activity in the resistant CA2-3,DG region compared to CA1. This study aimed to identify potential Nrf2-regulated genes that contribute to this regional neuroprotection in a gerbil model of global cerebral ischemia.

Methods: We used a combined computational and experimental approach. By utilizing the mouse Hipposeq database and Nrf2 target gene lists from the GSEA Molecular Signatures Database, we identified 15 candidate genes with predicted roles in the CA2-3,DG stress response. Quantitative real time-PCR and Western blot analysis were then used to validate expression patterns in the gerbil hippocampus following I/R.

Results: The analysis confirmed distinct expression patterns. Although some genes, including MPP3, RET, and SHISA2, showed higher basal expression in CA2-3,DG, they were unexpectedly downregulated after I/R. In contrast, others, such as AIFM2, BRIP1, and CAMK1, were specifically upregulated in this region. Furthermore, some (GPC1) showed delayed upregulation or showed altered protein levels despite unchanged mRNA expression (FZD7, STC2).

Conclusions: These results emphasize the regional and time-dependent regulation of gene expression in the hippocampus after I/R. The identified up- and downregulated genes represent novel molecular targets whose pharmacological modulation could enhance endogenous neuroprotective pathways, revealing new therapeutic avenues for stroke.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease leading to permanent damage to the central and peripheral motor neurons. Currently, there is no effective treatment for ALS, and therapy focuses solely on slowing the progression of the disease. Recent studies show that gut microbiota plays an important role in the development of neurodegenerative diseases. Altered gut microbiota has also been found in ALS. These changes have prompted the search for alternative forms of ALS treatment, focusing on changing the microbial composition of the gut. It has been noted that diet, probiotics, prebiotics and vitamins can all influence the course of ALS. Another interesting issue is fecal microbiota transplantation, which is already used in the treatment of certain intestinal diseases and could potentially be useful in the treatment of ALS. This review summarizes current knowledge on the impact of gut microbiota on the neurodegenerative process in ALS, with particular emphasis on the role of diet and probiotics. It also discusses potential mechanisms and highlights future research directions in this emerging field.