NPY5R

Cardiac dysfunction is commonly observed in patients with subarachnoid haemorrhage (SAH). However, the specific timeline of cardiac remodelling and the underlying mechanisms responsible for this effect following SAH remain unknown. This study aims to explore the impact of SAH on cardiac dysfunction and its potential mechanisms over time.

In Protocol 1, we investigated cardiac function and potential mechanisms in a Sprague-Dawley rat model of SAH at six time points (baseline and Days 1, 3, 7, 14, and 28) while exploring the underlying mechanisms. Our assessments included the haemodynamic profile, echocardiography, and the concentrations of plasma biomarkers at various time points post-SAH. We determined neuropeptide Y (NPY) 1-5 receptor protein expression levels through western blotting. In Protocol 2, we administered an NPY1 receptor antagonist to evaluate the effects of cardiac dysfunction induced by SAH on Day 3. In Protocol 1, SAH gradually provoked cardiac systolic dysfunction during the acute phase, reaching its peak on Day 3 without concurrent alterations in wall thickness. However, no significant changes were observed from Days 14 to 28 compared with Day 0. The changes in cardiac dysfunction were consistent with myocardial injury, inflammatory biomarkers, and NPY levels. SAH resulted in a heightened heart rate and systolic blood pressure, correlating with elevated epinephrine and norepinephrine levels. In Protocol 2, the administration of the NPY1 receptor antagonist effectively ameliorated cardiac dysfunction.

SAH induces transient cardiac dysfunction in the acute phase, and the underlying mechanisms for this response involve the NPY-NPY1 receptor pathway, otherwise known as catecholamines.

N⁶ -methyladenosine (m⁶ A) is the most prevalent epigenetic modification on eukaryotic messenger RNAs. Recent studies have focused on elucidating the key role of m⁶ A modification patterns in tumor progression. However, the relationship between m⁶ A and transcriptional regulation remains elusive. Nanopore technology enables the quantification of m⁶ A levels at each genomic site. In this study, a pair of tumor tissues and adjacent normal tissues from clear cell renal cell carcinoma (ccRCC) surgical samples were collected for Nanopore direct RNA sequencing. We identified 9644 genes displaying anomalous m⁶ A modifications, with 5343 genes upregulated and 4301 genes downregulated. Among these, 5224 genes were regarded as dysregulated genes, encompassing abnormal regulation of both m⁶ A modification and RNA expression. Gene Set Enrichment Analysis revealed an enrichment of these genes in pathways related to renal system progress and fatty acid metabolic progress. Furthermore, the χ² test demonstrated a significant association between the levels of m⁶ A in dysregulated genes and their transcriptional expression levels. Additionally, we identified four obesity-associated genes (FTO, LEPR, ADIPOR2, and NPY5R) among the dysregulated genes. Further analyses using public databases revealed that these four genes were all related to the prognosis and diagnosis of ccRCC. This study introduced the novel approach of employing conjoint analysis of m⁶ A modification and RNA expression based on Nanopore sequencing to explore potential disease-related genes. Our work demonstrates the feasibility of the application of Nanopore sequencing technology in RNA epigenetic regulation research and identifies new potential therapeutic targets for ccRCC.

In several studies, the regulatory role of the neuropeptide W (NPW) system in food intake has been demonstrated. Considering the lack of avian studies in this field, the current research was conducted to evaluate the effects of intracerebroventricular (ICV) infusion of NPW and its interferences with corticotropin, melanocortin, and neuropeptide Y (NPY) receptors on meal consumption and feeding behaviors of broilers. In the first experiment, birds were injected with NPW (0.75, 1.5, and 3 nmol) in addition to saline. In the second experiment, saline, CRF1 receptor antagonist (NBI35965, 30 μg), NPW (3 nmol), and simultaneous injections of NBI35965 and NPW were performed. Experiments 3-8 were identical to experiment 2, except that CRF2 receptor antagonist (K41498, 30 μg), MC3/MC4 receptor antagonist (SHU9119, 0.5 nmol), MC4 receptor antagonist (HS024, 0.5 nmol), NPY1 receptor antagonist (BMS193885, 1.25 nmol), NPY2 receptor antagonist (CYM9484, 1.25 nmol), and NPY5 receptor (antagonist L-152,804, 1.25 nmol) were administrated instead of NBI35965. After that, cumulative feed intake and feeding behavior were monitored for 2 h and 30 min after injections, respectively. Following the infusion of NPW (1.5 and 3 nmol), there was a significant stimulation of meal consumption in chickens (P < 0.05). Concomitant injection of NBI35965 and K41498 with NPW enhanced the appetite-increasing effect of NPW (P < 0.05); while BMS193885 suppressed this effect of NPW (P < 0.05). Injection of SHU9119, HS024, CYM9484, and L-152804 with NPW at the same time, had no significant effect on NPW-induced hyperphagia (P > 0.05). NPW also significantly decreased the standing period and the number of jumps, steps, and exploratory pecks, and led to an increase in sitting period and feeding pecks (P < 0.05). Based on the observations, it seems that NPW-induced hyperphagia could be mediated through CRF1, CRF2, and NPY1 receptors in neonatal broilers.