Search Results (161)

Objective: To investigate the effects of oat fiber on animal constipation and elucidate its underlying mechanisms. Methods: Male BALB/c mice were randomly allocated into five groups: control group (CON), model control group (MODEL), low dose group (LOW), middle dose group (MIDDLE), high dose group (HIGH). Constipation was induced in the mice by intragastric administration of loperamide. Subsequently, the mice (except those in the CON and MODEL groups) were administered oat fiber intragastrically for 21 consecutive days. Results: Compared with the MODEL group, oat fiber significantly increased the number of fecal pellets, fecal wet weight, and fecal water content (p < 0.05), shortened the time to first black stool excretion (p < 0.05), and enhanced the small intestinal propulsion rate in constipated mice. Additionally, oat fiber significantly upregulated motilin (MTL) and gastrin (GAS) levels (p < 0.05), while downregulating vasoactive intestinal peptide (VIP) and somatostatin (SS) levels (p < 0.05). It also significantly reduced the transcription level of Aquaporin 8 (AQP8) (p < 0.05), effectively alleviating intestinal mucosal injury and immune inflammation. The relative expression levels of TNF-α and IL-1β were significantly decreased in the oat fiber group (p < 0.05). Gut microbiota analysis revealed that oat fiber increased both the abundance and diversity of gut microbiota in constipated mice. Specifically, oat fiber was found to enhance the relative abundance of Firmicutes while reducing that of Bacteroidetes. At the genus level, it promoted the proliferation of Lachnospiraceae_NK4A136_group and Roseburia. Conclusions: Oat fiber alleviates constipation in mice by modulating gastrointestinal regulatory peptides, gut microbiota, aquaporin and mitigating intestinal barrier damage and immune-inflammatory responses. Full article

Microglial cells, the resident immune cells of the central nervous system (CNS), are essential for maintaining CNS homeostasis. Dysregulation of microglial function is implicated in the pathogenesis of various neurodegenerative diseases. Vasoactive intestinal polypeptide receptors 1 and 2 (VPAC1 and VPAC2) are G-protein-coupled receptors (GPCRs) expressed by microglia, with their primary ligands being pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP). However, the specific roles of VPAC-type receptors in microglial regulation remain poorly understood. In this study, we generated VPAC1^+/− and VPAC2^+/− BV2 microglial cell lines using CRISPR-Cas9 gene editing and conducted a series of biological and molecular assays to elucidate the functions of these receptors. Our findings demonstrated that both mutant cell lines exhibited a polarized phenotype and increased migratory activity. VPAC1^+/− cells showed enhanced survivability and baseline activation of the unfolded protein response (UPR), a protective mechanism triggered by endoplasmic reticulum (ER) stress, whereas this response appeared impaired in VPAC2^+/− cells. In contrast, under lipopolysaccharide (LPS)-induced inflammatory conditions, UPR activation was impaired in VPAC1^+/− cells but restored in VPAC2^+/− cells, resulting in improved survival of VPAC2^+/− cells, whereas VPAC1^+/− cells exhibited reduced resilience. Overall, our findings suggest that VPAC1 and VPAC2 receptors play distinct yet complementary roles in BV2 microglia. VPAC2 is critical for regulating survival, ER stress responses, and polarization under basal conditions, while VPAC1 is essential for adaptive responses to inflammatory stimuli such as LPS. These insights advance our understanding of microglial receptor signaling and may inform therapeutic strategies targeting microglial dysfunction in neurodegenerative diseases. Full article

This study aimed to investigate the potential role of the vasoactive intestinal peptide receptor-1 (VIPR-1) gene polymorphisms and haplotypes in influencing egg production performance and egg quality parameters in laying-type quail. Genomic DNA was extracted from 150 quail across three strains: Chinese yellow (CY, n = 50), Beijing white (BW, n = 50), and Korean (KO, n = 50). We designed two pairs of primers and initiated PCR amplification, after which the amplified products were sent to a testing company for purification. Sanger sequencing was employed to identify single nucleotide polymorphisms (SNPs) within the VIPR-1 gene. Two SNP sites were selected for genotyping; g.1603402T>G was analyzed using PCR-RFLP with the BsrD I enzyme, while g.1614884A>G was genotyped using the HpyCH4 IV enzyme. The association results revealed that the g.1603402T>G site showed significant association with egg shell thickness (EST) in the BW strain (p < 0.05). There were no significant associations between these two loci and the remaining egg quality traits in the BW and KO strains (p > 0.05). Differences in egg quality and laying performance among haplotype combinations were not significant (p > 0.05). In conclusion, the VIPR-1 gene, with its identified polymorphisms and haplotypes, has potential as a molecular marker that could improve egg shell thickness in BW quail. Full article

Inhibin (INH) plays a key role in the regulation of the reproductive performance of geese. It inhibits follicle-stimulating hormone (FSH) secretion from the anterior pituitary gland to regulate spermatogenesis. Immunization against INH in male geese leads to the production of antibodies to neutralize the INH activity that enhances testicular function and gonadotropin production. The objectives of the present research were to elaborate on the effects of inhibin (INH) immunization on testicular histology, plasma LH, pituitary PRL mRNA, and hypothalamic VIP mRNA expressions in Yangzhou ganders. A total of 60 birds were selected and divided into control (CON) and INH-immunized (INH-immunized) groups, having 30 in each group. In this experiment, the ganders were immunized with INH three times, and birds in the CON group were inoculated with bovine serum albumin (BSA). The analyzed data revealed that immunization against inhibin had no significant effects on improving the plasma concentration of LH hormone; however, significant effects were observed on the germ cell line, hypothalamic VIP mRNA, and pituitary PRL mRNA expressions. It is concluded that INH (INH) immunization is an effective tool to improve reproductive efficiency in Yangzhou ganders; however, INH immunization may harm pituitary PRL mRNA and hypothalamic mRNA expressions and LH plasma concentration. Seasonality played a vital impact on the hypothalamus–pituitary–gonadal (HPG) axis. Full article

Background/Objectives: The incidence, timing, and predictors of hemodynamic and respiratory deterioration in patients with high-risk or intermediate-high-risk pulmonary embolism (PE) undergoing pulmonary mechanical thrombectomy (PMT) remain poorly understood. This hemodynamic and respiratory instability can lead to modifications in the anesthetic management. This study investigates these key factors and quantifies the 30-day mortality following thrombectomy. Methods: A retrospective study was conducted on 98 patients aged ≥18 years who underwent PMT. Patients were categorized based on the occurrence of cardiac arrest (CA). Results: Of the 98 patients, 34 had high-risk PE, 62 intermediate/high-risk, and 2 low risk. There were 27 cases of CA, 17 pre- and 10 intra-PMT. An SBP < 90 mmHg increases the risk of CA by 33 (p < 0.001); men have an 8-fold higher risk than women (p = 0.004); SpO₂ <90% by 6 (p = 0.012); and pre-existing respiratory conditions increase the risk by 4 (p = 0.047)). N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were 8206 ± 11660.86 and 2388.50 ± 5683.71 pg/mL (p = 0.035) in patients with and without CA, respectively. During PMT, 14% of patients required increased vasoactive drug use, and 38.77% were intubated, including 12 who required ECMO support. Sedation was administered in 64.3% of patients, while general anesthesia was used in 38.8%, with a preemptive indication in 23.5%. The survival rate of patients without CA before and/or during PMT was 96%. Conclusions: While PMT was successfully performed in all patients, hemodynamic and respiratory instability remained a significant concern. More than 10% of patients experienced severe hemodynamic instability, primarily during thrombus extraction, requiring conversion from sedation to general anesthesia. Male sex, pre-existing respiratory disease, SpO₂ < 90%, and SBP < 90 mmHg were associated with an increased risk of CA. Additionally, elevated NT-proBNP levels were linked to a higher incidence of CA. Full article

Introduction: Acute cardiorenal syndrome (ACRS) is a common complication of acute heart failure (AHF), leading to worse outcomes and therapeutic challenges. This study aimed to identify clinical parameters associated with ACRS and evaluate its impact on prognosis in hospitalized AHF patients. Methods: This prospective observational study included patients hospitalized for AHF at the Venizelio Cardiology Department from February to November 2023. Demographic characteristics, comorbidities, medications, laboratory and echocardiographic parameters, hospital stay, and in-hospital mortality were recorded. Patients with incomplete data or end-stage chronic kidney disease (CKD) were excluded. Survivors were followed for six months to assess renal function changes, readmissions, initiation of renal replacement therapy (RRT), and mortality. ACRS was defined as a serum creatinine increase of ≥0.3 mg/dL or ≥1.5 times baseline. Results: Among 218 hospitalized AHF patients, 112 (51.3%) developed ACRS. These patients were older, had higher CKD prevalence, worse New York Heart Association (NYHA) functional class, lower hemoglobin, and higher N-terminal Pro-B-type Natriuretic peptide (NT-proBNP) levels. Multivariate analysis identified CKD stage (OR 2.30, 95% CI 1.64–3.23, p < 0.001) and creatinine change on admission (OR 3.53, 95% CI 2.02–6.18, p < 0.001) as independent predictors of ACRS. ACRS was associated with higher in-hospital mortality, longer hospital stays, increased vasoactive medication use, worsening renal function, and higher six-month all-cause readmission and mortality rates. Conclusions: ACRS is a frequent and severe complication in AHF. CKD stage and creatinine on admission are key predictors. Early recognition for risk stratification and individualized management are crucial to improving outcomes in this high-risk population. Full article

Patients infected with SARS-CoV-2 may develop mild respiratory symptoms but also Acute Respiratory Distress Syndrome (ARDS). Additionally, severe systemic inflammation contributes to morbidity and mortality. The SARS-CoV-2 virus enters the cell by binding to the angiotensin-converting enzyme 2 (ACE2) receptor, followed by cleavage by transmembrane serine protease 2 (TMPRSS2). Vasoactive intestinal peptide (VIP) is known for its immune-modulating effects by suppressing the release of pro-inflammatory cytokines and enhancing regulatory T-cells. Furthermore, it has been tested in SARS-CoV-2-related clinical trials. We set out to investigate its role in the setting of SARS-CoV-2 infection in vitro. Epithelial cells (CaCo-2) were stimulated with SARS-CoV-2 spike protein, treated with native VIP and analyzed to investigate the mRNA and surface expression of ACE2 and TMPRSS2, the enzyme activity of TMPRSS2 and the infection rate by a SARS-CoV-2 pseudovirus. VIP downregulated ACE2 and TMPRSS2 mRNA and surface expression. Beyond these direct effects, VIP mediates the shedding of surface-expressed ACE2 and TMPRSS2 via upregulation of a sheddase protease (ADAM10). Functionally, these dual mechanisms of VIP-mediated downregulation of proteins involved in SARS-CoV-2 cell entry resulted in a reduced infection rate by the SARS-CoV-2 pseudovirus. These data imply that VIP hampers viral entry mechanisms based on SARS-CoV-2 and the linkage to ADAM10 may stimulate research in other indications beyond SARS-CoV-2. Full article

Background: Patent ductus arteriosus (PDA) in preterm infants presents a significant challenge in neonatal care, marked by ongoing debates about its definition, diagnosis, treatment options, and effects on patient outcomes. Plasma biomarkers assess mediators involved in PDA closure and hemodynamic responses, assisting in identifying newborns at higher risk of developing potentially serious neonatal conditions. The purpose of this review was to investigate the relationship between PDA and various plasma biomarkers used to evaluate and diagnose ductal patency during perinatal life, as outlined in the relevant literature. Methods: We conducted an electronic search of the National Library of Medicine (MEDLINE)/PubMed and Web of Science for relevant studies published up to December 2024, including prospective, retrospective, cohort, and cross-sectional studies, as well as reviews and meta-analyses. The keywords used in the search included “preterm infant”, “persistent ductus arteriosus”, “patent ductus arteriosus”, “PDA”, “neonatal biomarkers”, “cardiac biomarkers”, and “vasoactive biomarkers”. Results: Out of the 813 identified articles, 85 were included in our review of cardiac biomarkers: Natriuretic peptides (NPs), Cardiac troponin T (cTnT), vasoactive biomarkers (Mid-regional pro-adrenomedullin (MR-proADM), Endothelin-1 (ET-1), Copeptin, and Isoprostanes (IPs)), and inflammatory biomarkers (Interleukin-6 (IL-6), IL-8, IL-10, Growth Differentiation Factor 15 (GDF-15), Monocyte Chemoattractant Protein-1 (MCP-1/CCL2), Macrophage Inflammatory Protein-1α (MIP-1α/CCL3)) in relation to PDA. Conclusions: Even if research shows a strong correlation between specific biomarkers and echocardiographic parameters in patients with PDA, clinical judgment must take these evaluations into account, particularly when determining whether to treat a PDA. Future research should focus on investigating new biomarkers associated with the underlying mechanisms of perinatal ductus arteriosus dynamics in preterm infants. Full article

Rosacea is a common chronic inflammatory condition primarily affecting middle-aged women. It presents with flushing, erythema, telangiectasia, papules, pustules, phymatous changes, and ocular involvement. Although typically grouped into four subtypes—erythematotelangiectatic, papulopustular, ocular, and phymatous—overlapping features often favor a phenotypic diagnostic approach. Neurogenic rosacea (NR) has emerged as a distinct subgroup featuring distinguishing features such as peripheral facial erythema, severe burning and stinging sensations, and resistance to standard rosacea therapies. Recent insights into the pathophysiology of NR propose neural dysregulation as the main driver of the condition. Specifically, the activation of TRP channels at cutaneous sensory nerve endings in the dermis triggers the release of vasoactive peptides, driving neuroinflammation and resulting in burning and stinging. Additionally, there is a marked association with neuropsychiatric comorbidities, which would further mediate the pathogenesis of the condition. In line with this pathophysiological model, NR often fails to respond to conventional rosacea treatments. Instead, patients benefit more from antidepressants and neuroleptic agents that help modulate neuronal activity and alleviate symptoms. This review explores and summarizes the scientific evidence regarding the new insights on disease pathogenesis, clinical manifestations, and proposed treatments for NR. Full article

Lactiplantibacillus plantarun HFY11 (LP-HFY11) is a newly discovered microbial strain. This study was the first to investigate the preventive effect of LP-HFY11 on compound diphenoxylate induced constipation in mice by measuring intestinal contents, serum, and small intestinal tissue indexes. In mice suffering from constipation, LP-HFY11 could prevent the reduction in fecal weight, particle count, and water content. The constipated mice that ingested a high LP-HFY11 dose (LP-HFY11H) expelled the first black stool faster than the model group and the drug lactulose-treated group, but they were slower than the normal group. Furthermore, the small intestine in the LP-HFY11H group had a greater propulsion rate of activated charcoal than that in the model and lactulose groups, but the propulsion rate was still lower than that in the normal group. According to hematoxylin–eosin (H&E) staining, LP-HFY11H was more effective than lactulose at reducing intestinal villi breaking and constipation-induced harm to the small intestine. Simultaneously, compared with the model group, the LP-HFY11H group had markedly increased serum levels of motilin (MTL), endothelin-1 (ET-1), vasoactive intestinal peptide (VIP), and acetylcholinesterase (AchE). Transient receptor potential vanilloid 1 (TRPV1) expression was only higher than in the normal group, but the mRNA expression of c-Kit, stem cell factor (SCF), and glial cell line-derived neurotrophic factor (GDNF) was all higher in the small intestine in the LP-HFY11H group than in the model and lactulose groups, according to the results of quantitative polymerase chain reaction (qPCR) experiments. Analysis of microbial mRNA in the small intestinal contents of the constipated mice further validated the capacity of LP-HFY11 to decrease the abundance of Firmicutes and increase the abundance of Bacteroidetes, Bifidobacteria, and Lactobacillus. This revealed that LP-HFY11, which produced better results than the drug lactulose, can control the gut microbiota of constipated mice and successfully cure constipation. LP-HFY11 has the potential to be used as a probiotic in the treatment of constipation. It has good application prospects in the food industry and biopharma. Full article

Endothelial dysfunction mediated by elevated levels of autoantibodies against vasoactive peptides occurring after COVID-19 infection is proposed as a possible pathomechanism for orthostatic intolerance in long COVID patients. This case-control study comprised 100 long COVID patients from our prospective POSTCOV registry and three control groups, each consisting of 20 individuals (Asymptomatic post-COVID group; Healthy group = pan-negative for antispike protein of SARS-CoV-2; Vaccinated healthy group = no history of COVID-19 and vaccinated). Autoantibodies towards muscarinic acetylcholine receptor M3, endothelin type A receptor (ETAR), beta-2 adrenergic receptor (Beta-2 AR), angiotensin II receptor 1 and angiotensin 1-7 (Ang1-7) concentrations were measured by enzyme-linked immunosorbent assay in long COVID patients and controls. Orthostatic intolerance was defined as inappropriate sinus tachycardia, postural tachycardia, orthostatic hypotonia and other dysautonomia symptoms, such as dizziness or blurred vision (n = 38 long COVID patients). Autoantibody concentrations were compared with routine laboratory parameters and quality of life questionnaires (EQ-5D). The concentration of ETAR autoantibodies were significantly higher in long COVID, Asymptomatic and Vaccinated groups compared to the antispike protein pan-negative Healthy group. A trend towards higher plasma levels of Beta-2 AR and Ang1-7 was measured in long COVID patients, not related to presence of orthostatic intolerance. ETAR autoantibody concentration showed significant positive correlation with the EQ-5D item “Problems in performing usual activities”. Full article

The interaction between the neuroendocrine system and the immune system plays a key role in the onset and progression of various diseases. Neuropeptides, recognized as common biochemical mediators of communication between these systems, are receiving increasing attention because of their potential therapeutic applications in immune-related disorders. Additionally, many neuropeptides share significant similarities with antimicrobial peptides (AMPs), and evidence shows that these antimicrobial neuropeptides are directly involved in innate immunity. This review examines 10 antimicrobial neuropeptides, including pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), α-melanocyte stimulating hormone (α-MSH), ghrelin, adrenomedullin (AM), neuropeptide Y (NPY), urocortin II (UCN II), calcitonin gene-related peptide (CGRP), substance P (SP), and catestatin (CST). Their expression characteristics and the immunomodulatory mechanisms mediated by their specific receptors are summarized, along with potential drugs targeting these receptors. Future studies should focus on further investigating antimicrobial neuropeptides and advancing the development of related drugs in preclinical and/or clinical studies to improve the treatment of immune-related diseases. Full article

Background/Objectives: Sensitivity to ocular irritation varies among individuals, being influenced by clinical, subjective, and biochemical factors. This study aimed to evaluate individual variability in ocular irritation sensitivity, focusing on clinical parameters, pain perception, and tear neuromediator profiles. Methods: Sixty female participants aged 20–40 were classified into high-sensitivity and low-sensitivity groups based on their response to an irritant (Tween20). Clinical assessments included the ocular surface disease index (OSDI), tear break-up time (TBUT), Schirmer test, and corneal touch threshold measured with the Cochet–Bonnet esthesiometer. Pain sensitivity was assessed using the pain sensitivity questionnaire (PSQ), and tear neuromediators were quantified in tear samples before and after stimulation. The concentrations of calcitonin gene-related peptide (CGRP), nerve growth factor, neuropeptide Y, vasoactive intestinal peptide (VIP), and substance P were measured using an enzyme-linked immune sorbent assay (ELISA). Results: The high-sensitivity group exhibited significantly higher OSDI scores (p = 0.038). No significant differences were observed in TBUT, corneal staining scores, or Schirmer’s test results. The PSQ results revealed that the high-sensitivity group had lower total and moderate pain scores (p = 0.037 and p = 0.040, respectively). An analysis of the tear neuromediator showed elevated baseline CGRP levels (p = 0.017) and a significant post-stimulation increase in substance P (p = 0.021) in the high-sensitivity group. Conclusions: These findings emphasize the value of combining clinical, subjective, and biochemical measures to understand sensitivity to ocular irritation. This comprehensive approach may guide the development of safer cosmetic formulations and improve safety assessment protocols. Full article

Constipation is a prevalent global health issue that greatly affects human well-being. However, many existing treatments are associated with side effects, necessitating the development of alternative approaches. In this study, a balanced fatty acid red pine seed direct-drinking oil (SFA:MUFA:PUFA = 1.14:1.08:1, n − 6:n − 3 = 4.17:1) was formulated using red pine seed oil as the base oil, blended with coconut oil, rice bran oil, and camellia oil. The study investigated the effects and mechanisms of this red pine seed direct-drinking oil in alleviating constipation in mice. Results showed that, compared to normal mice, constipated mice exhibited symptoms of dry stools, difficulty defecating, abnormal neurotransmitter levels, oxidative stress, and colonic tissue damage. Additionally, the protein expression levels of occludin and claudin-1 were reduced by 86.11% and 25.00%, respectively (p < 0.05), while mRNA expression levels decreased by 70.80% and 59.00% (p < 0.05). Red pine seed direct-drinking oil intake improved defecation, reduced serum levels of vasoactive intestinal peptide (VIP), endothelin-1 (ET-1), and nitric oxide (NO), and increased substance P (SP) levels. Furthermore, it also significantly elevated serum levels of superoxide dismutase (SOD) and catalase (CAT) (p < 0.05), alleviated colonic tissue damage, and upregulated the protein and mRNA expression levels of occludin and claudin-1 (p < 0.05). These findings suggest that red pine seed direct-drinking oil alleviates constipation in mice by enhancing intestinal motility, regulating serum neurotransmitters, mitigating oxidative stress, repairing intestinal barrier damage, and increasing tight junction protein expression. This study represents the first use of red pine seed direct-drinking oil to alleviate constipation in mice, providing a novel approach to improving symptoms in individuals with constipation. Full article

Astrocytes, vital support cells in the central nervous system (CNS), are crucial for maintaining neuronal health. In neurodegenerative diseases such as Alzheimer’s disease (AD), astrocytes play a key role in clearing toxic amyloid-β (Aβ) peptides. Aβ, a potent neuroinflammatory trigger, stimulates astrocytes to release excessive glutamate and inflammatory factors, exacerbating neuronal dysfunction and death. Recent studies underscore the role of Rho GTPases—particularly RhoA, Rac1, and Cdc42—in regulating Aβ clearance and neuroinflammation. These key regulators of cytoskeletal dynamics and intracellular signaling pathways function independently through distinct mechanisms but may converge to modulate inflammatory responses. Their influence on astrocyte structure and function extends to regulating endothelin-converting enzyme (ECE) activity, which modulates vasoactive peptides such as endothelin-1 (ET-1). Through these processes, Rho GTPases impact vascular permeability and neuroinflammation, contributing to AD pathogenesis by affecting both Aβ clearance and cerebrovascular interactions. Understanding the interplay between Rho GTPases and the cerebrovascular system provides fresh insights into AD pathogenesis. Targeting Rho GTPase signaling pathways in astrocytes could offer a promising therapeutic approach to mitigate neuroinflammation, enhance Aβ clearance, and slow disease progression, ultimately improving cognitive outcomes in AD patients. Full article