Search Results (133)

Serotonin (5-hydroxytryptamine) is a key neurotransmitter involved in gastrointestinal and central nervous system functions. Given that approximately 90% of serotonin is synthesized in the gut, dietary interventions targeting the gut microbiota have emerged as promising strategies to modulate serotonin homeostasis. Kefir, a fermented milk beverage rich in probiotics and bioactive compounds, has been suggested to influence gut–brain axis signaling, yet its effects in the pediatric period remain insufficiently characterized. This study aimed to investigate the impact of kefir supplementation on serotonin biosynthesis, receptor expression, and metabolic pathways in a pediatric rat model, focusing on molecular markers across brain, jejunum, and serum tissues. Sixteen male Wistar rats (four weeks old) were divided into kefir and control groups. The kefir group received daily oral gavage of kefir (1 mL/100 g) for eight weeks, while controls received saline. Gene and protein expression levels of serotonergic markers (5-HT, TPH1, TPH2, SLC6A4, VMAT2, 5-HTR2B, 5-HTR3A, and 5-HTR4) were analyzed using quantitative PCR, ELISA, and Western blotting. Serotonin turnover was assessed via 5-HIAA levels. Kefir supplementation significantly increased 5-HT and TPH1 expression in both brain and jejunum tissues. In the brain, kefir elevated TPH2 and upregulated 5-HTR3A and 5-HTR2B, while reducing 5-HIAA levels, suggesting decreased serotonin degradation. In the jejunum, 5-HTR4 expression was markedly increased. Serum analyses revealed reduced TPH1/TPH2 expression but elevated 5-HTR4 levels, indicating systemic modulation of serotonergic signaling. Kefir exerts multifaceted effects on the serotonergic system in pediatric rats by enhancing serotonin biosynthesis, modulating receptor expression, and reducing serotonin turnover. These findings highlight kefir as a potential psychobiotic capable of influencing the gut–brain axis during early life, with implications for pediatric neurodevelopment and mental health. Further research, including clinical trials, is warranted to confirm its translational potential. Full article

Serotonin (5-hydroxytryptamine—5-HT) is an important neurotransmitter that exerts a remarkably large array of biological roles in the central nervous system and at the body level. It is involved in generating emotions, being a natural mood stabilizer; it reduces depression, anxiety, modulates sleep, and has many other effects. It is also involved in fetal and postnatal brain development. This variety of biological effects, particularly in the central nervous system, with influence on behavior and cognitive functions, relies on a large number of pre- and postsynaptic serotonin receptor (5-HTR) isoforms spread throughout the brain. They can be grouped in seven large families and include over 18 subtypes, identified based on gene sequences, expression patterns, and pharmacological responses. While in vertebrates these receptors have been properly characterized and described, their correspondents in invertebrates have been far less explored, despite the assumption that they may have similar properties to those described in vertebrates. This paper summarizes the current knowledge in several important areas that together define the entire scope of serotonin receptor research, with a particular emphasis on the role of serotonergic central pathways and circuitry in thermoregulation and correlations with neurologic and psychiatric pathology. Full article

Introduction: Chronic spontaneous urticaria (CSU), vitiligo, and Hashimoto’s thyroiditis (HT) frequently co-occur in the same patients, suggesting a shared autoimmune pathogenesis. These conditions are increasingly recognized as components of polyautoimmunity, with overlapping clinical, immunological, and pathogenetic features. Among the proposed common mechanisms, vitamin D deficiency and oxidative stress (OS) have emerged as key contributors. We aimed to explore the shared immunopathogenic pathways linking these conditions, with a focus on the interplay between vitamin D status and redox imbalance. Methods: An extensive narrative review of the current literature regarding the associations among CSU, vitiligo, and HT, focusing on the role of vitamin D status, OS, and nitrosative stress, and shared immunological pathways was conducted. Discussion: Vitamin D deficiency was consistently observed across all three conditions and is associated with increased disease activity and poorer clinical outcomes. Several polymorphisms in the vitamin D receptor (VDR) and binding protein genes correlate with disease susceptibility. OS and nitrosative stress markers, such as malondialdehyde (MDA) and nitric oxide (NO) metabolites, are elevated in patients with CSU, vitiligo, and HT, and are linked to tissue-specific immune activation, apoptosis, and loss of self-tolerance. Evidence suggests that vitamin D and antioxidant supplementation may provide clinical benefit. In vitiligo, narrowband ultraviolet B (NB-UVB) phototherapy not only promotes repigmentation through melanocyte stimulation but also reduces ROS production and modulates local immune responses. Conclusions: The coexistence of CSU, vitiligo, and HT reflects a broader systemic autoimmune tendency, with vitamin D deficiency and redox imbalance serving as potential unifying mechanisms. Routine assessment of vitamin D levels and OS parameters may enhance diagnostic precision and inform therapeutic strategies. Antioxidant-based interventions represent promising avenues in the integrated management of autoimmune skin and endocrine disorders. Full article

Familial hypercholesterolemia leads to the early development of cardiovascular diseases at a young age due to the prolonged exposure of the arterial vessel wall to high concentrations of atherogenic lipids. Serotonin plays a significant role in the development and progression of atherosclerotic processes. Monoamine has a damaging effect on the vascular wall, stimulates the proliferation of vascular smooth muscle cells and fibroblasts, and participates in platelet activation and aggregation. The aim of the work was the demonstration of the importance of serotonin, transporters, and receptors in the pathogenesis of atherosclerotic plaque formation. The study was performed on immature mice of the C57BL/6JGpt-Ldlr^em1Cd82/Gpt (Ldlr^+/−) line (main group) and C57BL/6 mice of comparable age and sex demographics (control group). Morphological manifestations of early signs of atherosclerosis (pre-lipid stage and lipoidosis stage, which were confirmed by Sudan III staining) in the gene-modified mice’s aorta were determined. Morphological changes in the aorta correlated with changes in the left ventricle of the heart, where lipid content also increased. No atherosclerotic changes in the control-group mice were detected. A statistically significant increase in the expression of the membrane serotonin transporter and 5HT2A and 5HT2B receptors in both the aorta and left ventricle was also found in the animals of the main group. Serotonin and its receptors and transporter may become new therapeutic targets for the treatment and prevention of atherosclerotic vascular lesion progression in children and adults. Full article

Background: Depression is one of the most prevalent mental health disorders worldwide, affecting a significant proportion of the global population. Its etiology is complex and influenced by the interaction of environmental factors and genetic variations. In Mexico, it has been reported that 41.3% of the population exhibits depressive symptoms. Previous studies have suggested that susceptibility to depression may be associated with the C-1019G (rs6295) polymorphism in the serotonin 1A (5-HT1A) receptor gene. Objective: In this study, we aimed to evaluate the association between the C-1019G polymorphism and depressive symptoms in a rural Mexican population. Methods: Using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP), we examined the effect of C-1019G on depression symptoms, as evaluated by the Beck Depression Inventory. Data were obtained from 83 volunteers; individuals with depressive symptoms and those with a healthy mood were compared. Results: The results showed that the homozygous C/C genotype was found significantly more frequently in the control group than in individuals with depressive symptoms, particularly among men, and is thus associated with a decreased risk of depressive symptomatology. Conclusions: The C/C genotype could protect against susceptibility to developing depressive symptoms in a rural population in Mexico. Full article

The 5-HT_1A and 5-HT₇ receptors play a key role in regulating cognitive processes and have been widely linked to the pathophysiology of depression, anxiety, and schizophrenia—disorders often associated with memory impairment. Recently, interest has grown in understanding how the coexpression of these receptors contributes to cognitive decline. This review explores the individual roles of 5-HT_1A and 5-HT₇ receptors, as well as their coexpression, in memory regulation. The heterodimerization of these receptors at both pre- and postsynaptic levels, along with their colocalization in serotonergic, glutamatergic, GABAergic, and dopaminergic neurons, adds to the complexity of this interaction and may help explain the paradoxical effects of selective serotonergic drugs (agonists and antagonists). These findings underscore the need for further research into the 5-HT_1A and 5-HT₇ receptor relationship in cognitive decline through diverse approaches, including targeted gene silencing, electrophysiology, and cell culture studies. Full article

Global climate change presents a significant challenge to aquatic ecosystems, with ectothermic fish being particularly sensitive to temperature fluctuations. The brain plays a crucial role in perceiving, regulating, and adapting to thermal changes, and its response to heat stress is crucial for survival. However, the molecular mechanisms underlying heat stress and acclimation in fish brains remain poorly understood. This study aimed to investigate the adaptive mechanisms of Hong Kong catfish (Clarias fuscus) brains under heat acclimation and acute heat stress using transcriptome analysis. Fish were divided into two groups: a normal temperature group (NT, 26 °C for 90 days) and a heat-acclimated group (HT, 34 °C for 90 days), followed by acute heat stress (34 °C for 72 h) and recovery (26 °C for 72 h). Heat acclimation improved C. fuscus tolerance to acute heat stress, with faster gene responses and stronger neuroprotection. Key pathways enriched included cell adhesion and ECM-receptor interactions during recovery. Apoptosis regulation was balanced, with the HT group upregulating anti-apoptotic genes to mitigate neuronal cell death. Additionally, the lysosome–phagosome pathway was activated during recovery, facilitating the transport of lysosomal enzymes and the clearance of damaged cellular components, aiding neuronal repair. Ribosome biogenesis was suppressed under heat stress to conserve energy, but this suppression was less pronounced in the HT group. In summary, heat acclimation enhances neural protection in C. fuscus brains by promoting neuronal repair, suppressing apoptosis, and activating lysosomal pathways, thereby improving tolerance to acute heat stress. These findings offer a molecular basis for breeding heat-tolerant fish species in aquaculture, and deepen our understanding of thermal adaptation in aquatic animals amid global climate change. Full article

Hashimoto’s thyroiditis (HT) is an autoimmune disorder of the thyroid gland characterized by chronic inflammation, which in most cases results in hypothyroidism. The melatonin receptor MTNR1B is sporadically expressed in the thyroid gland. It modulates immune responses, and alterations in the melatonin–MTNR1B receptor signaling pathway may play a role in developing autoimmune diseases. Obesity worsens the severity and progression of some autoimmune diseases and reduces treatment efficacy. This study aimed to investigate the association of MTNR1B gene polymorphisms (rs10830963, rs1387153, and rs4753426) with HT with regards to the body mass index (BMI). Patients with HT were categorized into normal weight BMI ≤ 25 kg/m² and overweight/obese BMI > 25 kg/m² groups. This study included 115 patients with a clinical-, ultrasound-, and laboratory-confirmed diagnosis of HT (64 normal-weight patients and 51 overweight/obese patients) with a mean age of 43 ± 12 years. The results showed that specific MTNR1B polymorphisms are associated with obesity in HT patients. BMI was found to be associated with the rs10830963 polymorphism, and the G allele and GG genotype of the rs10830963 polymorphism were more common in overweight/obese HT patients. Furthermore, the results suggest that genetic factors associated with BMI play a role in developing HT and open new possibilities for personalized treatment approaches. Full article

Serotonin (5-HT), dopamine (DA), and norepinephrine (NE) are key monoamine neurotransmitters regulating behaviors, mood, and cognition. 5-HT affects early brain development, and its dysfunction induces brain vulnerability to stress, raising the risk of depression, anxiety, and autism in adulthood. These neurotransmitters are synthesized from tryptophan and tyrosine via hydroxylation and decarboxylation, and are metabolized by monoamine oxidase (MAO). This review aims to summarize the current findings on the role of dietary phytochemicals in modulating monoamine neurotransmitter biosynthesis, metabolism, and function, with an emphasis on their potential therapeutic applications in neuropsychiatric disorders. Phytochemicals exert antioxidant, neurotrophic, and neurohormonal activities, regulate gene expression, and induce epigenetic modifications. Phytoestrogens activate the estrogen receptors or estrogen-responsive elements of the promoter of target genes, enhance transcription of tryptophan hydroxylase and tyrosine hydroxylase, while inhibiting that of MAO. These compounds also influence the interaction between genetic and environmental factors, potentially reversing dysregulated neurotransmission and the brain architecture associated with neuropsychiatric conditions. Despite promising preclinical findings, clinical applications of phytochemicals remain challenging. Advances in nanotechnology and targeted delivery systems offer potential solutions to enhance clinical efficacy. This review discusses mechanisms, challenges, and strategies, underscoring the need for further research to advance phytochemical-based interventions for neuropsychiatric diseases. Full article

Although it has been shown that the tumor extracellular matrix (ECM) may sustain the cancer stem cell (CSC) niche, its role in the modulation of CSC properties remains poorly characterized. To elucidate this, paired tumor and adjacent normal mucosa, derived from colon cancer patients’ surgical resections, were decellularized and recellularized with two distinct colon cancer cells, HT-29 or HCT-15. Methods: The matrix impact on cancer stem cell marker expression was evaluated by flow cytometry and qRT-PCR, while transforming growth factor-β (TGF-β) secretion and matrix metalloprotease (MMP) activity were quantified by ELISA and zymography. Results: In contrast to their paired normal counterparts, the tumor decellularized matrices enhanced HT-29 expression of the pluripotency and stemness genes NANOG (p = 0.0117), SOX2 (p = 0.0156), and OCT4 (p = 0.0312) and of the epithelial-to-mesenchymal transition (EMT)-associated transcription factor SNAI1 (p = 0.0156). Notably, no significant differences were found in the expression of SLUG or TGFB on HT-29 or of the six transcripts on HCT-15 cells. HT-29 mRNA alterations were followed by enhanced expression of the stemness-associated receptors cluster of differentiation 44 (CD44), CD133, and CD166 (p = 0.0078), the secretion of TGF-β (p = 0.0286), and MMP-2 (p = 0.0081) and MMP-9 (p = 0.0402) proteolysis. To infer the clinical relevance of these findings, we assessed cohort databases and evidenced that patients expressing higher levels of the four stemness-associated genes (NANOG/SOX2/OCT4/SNAI1) had worse overall survival. This study demonstrates that normal and tumor matrices harbor different stemness potential and suggest patient-derived decellularized matrices as an excellent three-dimensional (3D) model to unveil stemness signatures, appointing candidates for future therapeutic strategies. Full article

Background: Chronic migraine (CM) is a common complex nervous system disease, often accompanied by symptoms of the digestive tract that interact with each other, leading to prolonged and difficult-to-cure migraines. These symptoms are associated with abnormalities in 5-HT and its receptors. Wuzhuyu decoction (WZYD) is a traditional Chinese medicine prescription commonly used in clinics to treat CM; it relieves gastrointestinal symptoms, such as nausea and vomiting; however, its mechanism is still unclear. Investigating the differences in the role of WZYD compared to existing drugs targeting 5-HT receptors in the treatment of CM not only helps elucidate its pathogenesis but also provides possibilities for the development of new therapeutic approaches. Methods: An inflammation soup (IS)-induced CM male rat model was established. Based on a preliminary experiment, the target of WZYD in treating CM was determined by network pharmacology, and verified by molecular docking. ELISA, immunofluorescence, western blot, and real-time quantitative polymerase chain reaction (RT-qPCR) were used to evaluate the expression levels of CM-related indicators (5-HT, calcitonin gene-related peptide (CGRP), and c-Fos) to ensure the successful establishment of the CM model and the effectiveness of the drug. On this basis, the protein expression levels of 5-HT1A/3A receptors and their cAMP-response element binding protein (CREB) signaling pathway were detected by western blot and immunohistochemistry. The role of 5-HT1A/3A receptors in the treatment of CM by WZYD was validated using a 5-HT1A receptor antagonist (WAY 100635) and a 5-HT3A receptor agonist (SR 57227). Results: The results showed that WZYD increased the expression of 5-HT in the brain, decreased the expression of CGRP, c-Fos, ionized calcium-binding adapter molecule 1 (Iba1), and relieved CM. At the same time, WZYD also increased the expression of the 5-HT1A receptor and decreased the expression of the 5-HT3A receptor in the brain and colon of CM rats. Subsequently, WZYD further exerted its brain-gut integrated therapeutic effects by regulating the CREB signaling pathway mediated by 5-HT1A/3A receptors in the brain and colon of CM rats. Conclusions: WZYD not only regulates neurotransmitters in the brain and colon at the same time, but also specifically regulates 5-HT1A/3A receptors in the brain and colon, which explains the characteristics and advantages of WZYD from a new perspective. While effectively relieving headache symptoms, it also improves related gastrointestinal symptoms, which is more conducive to the treatment of CM. Full article

Objectives: This study aims to show the distribution of angiotensin-converting enzyme (ACE) rs1799752 (I>D) gene insertion/deletion (I/D) polymorphism and angiotensin II receptor type 1 (AGTR1) rs5186 (A>C) gene polymorphism in adolescents with hypertension (HT) and type 1 diabetes (T1D), as well as its association with hypertension and the diurnal variation of mean blood pressure (dipping phenomenon). Methods: A cross-sectional study was conducted involving 118 adolescents diagnosed with T1D who underwent clinical and laboratory investigations, genetic analyses, and 24 h ambulatory blood pressure monitoring. The genotype frequencies were compared between adolescents with HT and those with normal blood pressure. Additionally, the genotype frequencies were compared between dippers and non-dippers. Results: Patients with HT were more likely to be female and exhibited significantly poorer glycemic control and higher triglycerides, along with increased body mass index and daily insulin dosage. The prevalence of ACE rs1799752 genotypes in the hypertensive group was 20% II, 66.7% ID, and 13.3% DD, which did not significantly differ from the normal blood pressure group with 29.1% II, 53.4% ID, and 17.5% DD (p = 0.625). The prevalence of AGTR1 rs5186 genotypes in the hypertensive group was 53.3% AC, 40% AA, and 6.7% CC, which also did not significantly differ from the normal blood pressure group with 39.8% AC, 52.4% AA, and 7.8% CC (p = 0.608). A total of 46% of the patients exhibited non-dipping phenomena. The prevalence of non-dippers among the ACE genotypes was 13% DD, 33.3% II, and 53.7% ID (p = 0.369), while for the AGTR1 genotypes, it was 50% AA, 42.6% AC, and 7.4% CC (p = 0.976). Conclusions: Our results indicate that in our adolescents with T1D, clinical and metabolic factors such as higher body mass index, triglycerides, suboptimal glycemic control, and female gender are more indicative of the development of hypertension than ACE and AGTR1 gene polymorphisms. A potential reason for this finding could be the young age of the patients or the relatively small size of the study group. Future research involving larger sample sizes is needed to further investigate the genetic predisposition for the development of hypertension. Full article

Background: Resistance to thyroid hormones (RTH) is a rare, genetically determined disease characterised by reduced tissue sensitivity to thyroid hormones (THs). It is caused by mutations in genes encoding the receptors for thyroid hormones, α (THRα) or β (THRβ), the distribution of which varies between tissues. Therefore, patients present with elevated TH levels with unsuppressed TSH levels, and symptoms of both hypothyroidism and hyperthyroidism may be present. Methods: Hence, we report the case of a boy with a complex, cyanotic, congenital heart defect who was also diagnosed with TH resistance syndrome. Results: Because of the clinical features of hyperthyroidism in preparation for cardiac surgery, thiamazole was administered, resulting in the normalisation of TH effects on the α-receptor for HTs. Due to the effectiveness of the proposed treatment, it was further introduced before the further stages of cardiac surgeries. Conclusions: The management of RTH is a constant challenge for clinicians and must be individualised. Full article

Chronic stress poses threats to the physical and psychological well-being of dogs. Resveratrol (Res) is a polyphenol with antidepressant properties and has rarely been studied in dogs. This study aimed to investigate the stress-relieving effects and underlying mechanism of Res in dogs. Dogs were fed a basal diet supplemented with Res for 35 days. The fecal microbiota of the dogs was cultured with Res in vitro. The results show that Res improved the stress-related behaviors and increased the serum levels of 5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF), immunoglobulin A, and antioxidant capacity in dogs. Res downregulated the hormones of the hypothalamic–pituitary–adrenal axis. The abundance of butyric-producing bacteria, like Blautia, increased, while the growth of Fusobacterium related to gut inflammation was inhibited in the Res group. A higher content of fecal butyric acid was observed in the Res group. The metabolome indicated that Res increased the fecal and serum levels of tryptophan (Trp) and decreased the consumption of Trp by microorganisms. A chronic unpredictable mild stress mouse model was established, and Res was administered for 35 days. The results show that Res ameliorated the stress-related behavior and increased the levels of Trp and 5-HT in the whole brains of mice. The relative mRNA expression of genes associated with the tight junction protein, aryl hydrocarbon receptor, and Trp transporters in the colon were upregulated. In conclusion, Res could ameliorate canine stress by increasing 5-HT, BDNF, and the antioxidant capacity and improving the immune function and stress response, which was attributed to the role of Res in the restructuring of gut microbiota and the modulation of tryptophan metabolism. Full article

Hypertension is associated with alterations in the composition and diversity of the intestinal microbiota. Indeed, supplementation with probiotics and prebiotics has shown promising results in modulating the gut microbiota and improving cardiovascular health. However, there are no studies regarding the possible beneficial effects of postbiotics on cardiovascular function and particularly on hypertension-induced cardiovascular alterations. Thus, the aim of this study was to analyze the effect of supplementation with the heat-treated Bifidobacterium animalis subsp. lactis CECT 8145 strain (BPL1™ HT), a postbiotic developed by the company ADM-Biopolis, on cardiovascular alterations induced by angiotensin II (AngII) infusion in mice. For this purpose, three groups of C57BL/6J male mice were used: (i) mice infused with saline (control); (ii) mice infused with AngII for 4 weeks (AngII); and (iii) mice supplemented with BPL1™ HT in the drinking water (1010 cells/animal/day) for 8 weeks and infused with AngII for the last 4 weeks (AngII + BPL1™ HT). AngII infusion was associated with heart hypertrophy, hypertension, endothelial dysfunction, and overexpression of proinflammatory cytokines in aortic tissue. BPL1™ HT supplementation reduced systolic blood pressure and attenuated AngII-induced endothelial dysfunction in aortic segments. Moreover, mice supplemented with BPL1™ HT showed a decreased gene expression of the proinflammatory cytokine interleukin 6 (Il-6) and the prooxidant enzymes NADPH oxidases 1 (Nox-1) and 4 (Nox-4), as well as an overexpression of AngII receptor 2 (At2r) and interleukin 10 (Il-10) in arterial tissue. In the heart, BPL1™ HT supplementation increased myocardial contractility and prevented ischemia–reperfusion-induced cardiomyocyte apoptosis. In conclusion, supplementation with the postbiotic BPL1™ HT prevents endothelial dysfunction, lowers blood pressure, and has cardioprotective effects in an experimental model of hypertension induced by AngII infusion in mice. Full article