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β-Alanine (BA) is one of the most widely used sport supplements, due to its capacity to improve high-intensity exercise performance by increasing muscle carnosine (MCarn) content, and consequently, the buffering capacity of the muscle. BA is also available in a variety of animal foods, but little is currently known about the influence of dietary BA intake on MCarn. The aim of the current study was to compile a detailed summary of available data on the BA content of commonly consumed foods, and to explore whether associations could be detected between self-reported dietary BA intake and skeletal MCarn in a group of 60 healthy, active, omnivorous men and women. Dietary BA intake was assessed via 3-day food records, and MCarn content assessed by high-performance liquid chromatography. A series of univariate and multivariate linear regression models were used to explore associations between estimated dietary BA and MCarn. No evidence of associations between dietary BA intake and MCarn were identified, with effect sizes close to zero calculated from models accounting for key demographic variables (f² ≤ 0.02 for all analyses). These findings suggest that capacity to increase MCarn via dietary strategies may be limited, and that supplementation may be required to induce increases of the magnitude required to improve performance. [ABSTRACT FROM AUTHOR]

Rationale: Atmospheric pressure matrix‐assisted laser desorption/ionization (AP‐MALDI) mass spectrometry has enabled the untargeted analysis and imaging of neuropeptides and proteins in biological tissues under ambient conditions. Sensitivity in AP‐MALDI can be improved by using sample‐specific preparation methods. Methods: A comprehensive and detailed optimization strategy including instrument parameters, matrix spraying and sample tissue washing pretreatment was implemented to enhance the sensitivity and coverage of neuropeptides in mouse pituitary tissues by commercial AP‐MALDI mass spectrometry imaging (MSI). Results: The sensitivity of a commercial AP‐MALDI system for endogenous neuropeptides in mouse pituitary was enhanced by up to 15.2‐fold by shortening the transmission gap from the sample plate to the inlet, attaching copper adhesive tape to an indium tin oxide‐coated glass slide, optimizing the matrix spray solvent and using sample tissue washing pretreatment. Following careful optimization, the distributions of nine endogenous neuropeptides were successfully visualized in the pituitary. Furthermore, the quantitative capability of AP‐MALDI for neuropeptides was evaluated and the concentrations of neuropeptides oxytocin and vasopressin in the pituitary posterior lobe were increased approximately twofold under hypertonic saline stress. Conclusion: Mouse pituitary neuropeptides have emerged as important signaling molecules due to their role in stress response. This work indicates the potential of modified AP‐MALDI as a promising AP MSI method for in situ visualization and quantification of neuropeptides in complex biological tissues. [ABSTRACT FROM AUTHOR]

Background: Monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway have shown good efficacy in migraine prophylaxis. However, a subset of patients does not respond to the first mAb treatment and switches among the available mAbs. The goal of this study is to characterize the switching pattern of migraine patients treated with anti-CGRP(-receptor, -R) mAbs, and to describe the headache burden of those who did not switch, switched once, and switched twice. Methods: This study used real world data from the NeuroTransData Cohort, a registry of migraine patients treated at outpatient neurology clinics across Germany. Patients who had received at least one anti-CGRP(-R) mAb were included. Headache diaries were collected at baseline and during treatment, along with quality of life measures every three months. Results were summarized for the subgroups of patients who did not switch and those with one and two switches. Results: Of the 655 eligible patients, 479 did not switch, 135 switched once, 35 twice, and 6 three or more times. The ≥ 50% response rates for monthly migraine days were 64.7%, 50.7%, and 25.0% for the no switch, one switch, and two switches groups in their last treatment cycles, respectively. Quality of life measures improved for the no switch and one switch groups, but not for the two switches group. Conclusion: Patients who switched among anti-CGRP(-R) mAbs during the course of their treatment still benefited overall but to a lesser extent than those who did not switch. Treatment response in patients who switched twice was markedly lower compared to the no switch and one switch subgroup. [ABSTRACT FROM AUTHOR]

The endogenous opioid neuropeptide Beta-endorphin is produced in the pituitary gland and stored in vesicles, it is an analgesic and relieves pain. The natural compound morphine is widely used as a painkiller and is much more potent than any other first-line and second-line pain management however it is only used in emergencies because it results in addiction, thus sometimes results in drug tolerance. Therefore, a healthy lifestyle and healthy practices like exercises, laughter, and meditation can elevate beta-endorphin release and help in pain management, improving mental and heart health. Natural compounds like curcumin, capsaicin can boost beta-endorphin synthesis in peripheral sites and overcome stress and improve mental health. This paper reflects on the role of exercise in pain management and how regular laughter can enlighten the mood and help the individual overcome depression, anxiety, and stress. This paper also reflects light on the natural substances that can boost beta-endorphin in the body as well as the compounds that prevent the beta-endorphin release, how body fluids can be used to detect the presence of beta-endorphin level, and methods to detect it. The available standard laboratory methods are not very specific for beta-endorphin. The future approach of biosensors for beta-endorphin can improve the sensitivity and selectivity for beta-endorphin. • Role of physical activities in boosting Beta-endorphin. • Natural compounds that can boost Beta-endorphin. • Relation between exercise, laughter with heart health. • Standard laboratory techniques for beta-endorphin detection. • Future advancement for beta-endorphin detection. [ABSTRACT FROM AUTHOR]

Blood–brain barrier (BBB) peptide-shuttles (BBBpS) are able to translocate the BBB and reach the brain. Despite the importance of brain targeting in pharmacology, BBBpS are poorly characterized. Currently, their development relies on the empiric assumption that cell-penetrating peptides (CPPs), with proven ability to traverse lipid membranes, will likewise behave as a BBBpS. The relationship between CPPs/BBBpS remains elusive and, to the best of our knowledge, has not hitherto been subject to thorough experimental scrutiny. In this work, we have identified/quantified the main physicochemical properties of BBBpS and then searched for CPPs with these properties, hence potential BBBpS. The specific features found for BBBpS are: (i) small size, (ii) none or few aromatic residues, (iii) hydrophobic, and (iv) slight cationic nature. Then, we selected the 10 scoring best in an ordinary least squares analysis, and tested them in vitro and in vivo. Overall, we identified the molecular determinants for brain targeting by peptides, devised a methodology that can be used to assist in the design of peptides with potential brain penetration from amino acid residue sequences, and found four new BBBpS within the CPP library. [ABSTRACT FROM AUTHOR]

Simple Summary: As the precursor of pepsin, Pepsinogen C (PGC) is the final product of the maturation and differentiation of gastric mucosa cells. The latest bioinformatics analysis found that PGC may play a little-known role in the carcinogenic process, but there is no relevant experimental evidence to prove the effect of PGC on the biological function of cancer cells. In our research, we found PGC may act as a tumor suppressor in the development and metastasis of gastric cancer. PGC can downregulate its interacting protein IQGAP1 and inhibit the Rho-GTPase pathway, thereby participating in the inhibition of gastric cancer cell migration and invasion. Thus, PGC has the potential to be a new therapeutic target for gastric cancer. Aim: This study systematically explored the biological effects and mechanisms of PGC on gastric cancer (GC) cells in vitro and in vivo. Method: The critical biological roles of PGC in GC were assessed via EdU staining, Hoechst staining, flow cytometry, mouse models, CCK-8, wound healing, transwell, and sphere-forming assays. The interaction study with IQ-domain GTPase-activating protein 1 (IQGAP1) was used by Liquid chromatography-mass spectrometry co-immunoprecipitation, immunofluorescence staining, CHX-chase assay, MG132 assay, and qRT-PCR. Results: PGC inhibited the proliferation, viability, epithelial–mesenchymal transition, migration, invasion, and stemness of GC cells and promoted GC cell differentiation. PGC suppressed subcutaneous tumor growth and peritoneal dissemination in vivo. The interaction study found PGC inhibits GC cell migration and invasion by downregulating IQGAP1 protein and IQGAP1-mediated Rho-GTPase signaling suppression. In addition, PGC disrupts the stability of the IQGAP1 protein, promoting its degradation and significantly shortening its half-life. Moreover, the expression levels of PGC and IQGAP1 in GC tissues were significantly negatively correlated. Conclusion: PGC may act as a tumor suppressor in the development and metastasis of GC. PGC can downregulate its interacting protein IQGAP1 and inhibit the Rho-GTPase pathway, thereby participating in the inhibition of GC cell migration and invasion. [ABSTRACT FROM AUTHOR]

The vertebrate sense of taste allows rapid assessment of the nutritional quality and potential presence of harmful substances prior to ingestion. Among the five basic taste qualities, salty, sour, sweet, umami, and bitter, bitterness is associated with the presence of putative toxic substances and elicits rejection behaviors in a wide range of animals including humans. However, not all bitter substances are harmful, some are thought to be health-beneficial and nutritious. Among those compound classes that elicit a bitter taste although being non-toxic and partly even essential for humans are bitter peptides and l-amino acids. Using functional heterologous expression assays, we observed that the 5 dominant human bitter taste receptors responsive to bitter peptides and amino acids are activated by bile acids, which are notorious for their extreme bitterness. We further demonstrate that the cross-reactivity of bitter taste receptors for these two different compound classes is evolutionary conserved and can be traced back to the amphibian lineage. Moreover, we show that the cross-detection by some receptors relies on "structural mimicry" between the very bitter peptide l-Trp-Trp-Trp and bile acids, whereas other receptors exhibit a phylogenetic conservation of this trait. As some bile acid-sensitive bitter taste receptor genes fulfill dual-roles in gustatory and non-gustatory systems, we suggest that the phylogenetic conservation of the rather surprising cross-detection of the two substance classes could rely on a gene-sharing-like mechanism in which the non-gustatory function accounts for the bitter taste response to amino acids and peptides. [ABSTRACT FROM AUTHOR]

Background: Chronic migraine (CM) is a debilitating neurofunctional disorder primarily affecting females, characterized by central sensitization. Central sensitization refers to the enhanced response to sensory stimulation, which involves changes in neuronal excitability, synaptic plasticity, and neurotransmitter release. Environmental enrichment (EE) can increase the movement, exploration, socialization and other behaviors of mice. EE has shown promising effects in various neurological disorders, but its impact on CM and the underlying mechanism remains poorly understood. Therefore, the purpose of this study was to determine whether EE has the potential to serve as a cost-effective intervention strategy for CM. Methods: A mouse CM model was successfully established by repeated administration of nitroglycerin (NTG). We selected adult female mice around 8 weeks old, exposed them to EE for 2 months, and then induced the CM model. Nociceptive threshold tests were measured using Von Frey filaments and a hot plate. The expression of c-Fos, calcitonin gene-related peptide (CGRP) and inflammatory response were measured using WB and immunofluorescence to evaluate central sensitization. RNA sequencing was used to find differentially expressed genes and signaling pathways. Finally, the expression of the target differential gene was investigated. Results: Repeated administration of NTG can induce hyperalgesia in female mice and increase the expression of c-Fos and CGRP in the trigeminal nucleus caudalis (TNC). Early exposure of mice to EE reduced NTG-induced hyperalgesia in CM mice. WB and immunofluorescence revealed that EE inhibited the overexpression of c-Fos and CGRP in the TNC of CM mice and alleviated the inflammatory response of microglia activation. RNA sequencing analysis identified that several central sensitization-related signaling pathways were altered by EE. VGluT1, a key gene involved in behavior, internal stimulus response, and ion channel activity, was found to be downregulated in mice exposed to EE. Conclusion: EE can significantly ameliorate hyperalgesia in the NTG-induced CM model. The mechanisms may be to modulate central sensitization by reducing the expression of CGRP, attenuating the inflammatory response, and downregulating the expression of VGluT1, etc., suggesting that EE can serve as an effective preventive strategy for CM. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic systemic inflammatory cutaneous disease. Where the immune system plays an important role in its pathogenesis, with key inflammatory intercellular signalling peptides and proteins including IL‐17 and IL‐23. The psychoneurological system also figures prominently in development of psoriasis. There is a high prevalence of comorbidity between psoriasis and mental health disorders such as depression, anxiety and mania. Patients with psoriasis often suffer from pathological pain in the lesions, and their neurological accidents could improve the lesions in innervated areas. The immune system and the psychoneurological system interact closely in the pathogenesis of psoriasis. Patients with psoriasis exhibit abnormal levels of neuropeptides both in circulating and localized lesion, acting as immunomodulators involved in the inflammatory response. Moreover, receptors for inflammatory factors are expressed in both peripheral and central nervous systems (CNSs), suggesting that nervous system can receive and be influenced by signals from immune system. Key inflammatory intercellular signalling peptides and proteins in psoriasis, such as IL‐17 and IL‐23, can be involved in sensory signalling and may affect synaptic plasticity and the blood–brain barrier of CNS through the circulation. This review provides an overview of the multiple effects on the peripheral and CNS under conditions of systemic inflammation in psoriasis, providing a framework and inspiration for in‐depth studies of neuroimmunomodulation in psoriasis. [ABSTRACT FROM AUTHOR]

This article examines the involvement of the brain-derived neurotrophic factor (BDNF) in the control of nociception and pain. BDNF, a neurotrophin known for its essential role in neuronal survival and plasticity, has garnered significant attention for its potential implications as a modulator of synaptic transmission. This comprehensive review aims to provide insights into the multifaceted interactions between BDNF and pain pathways, encompassing both physiological and pathological pain conditions. I delve into the molecular mechanisms underlying BDNF's involvement in pain processing and discuss potential therapeutic applications of BDNF and its mimetics in managing pain. Furthermore, I highlight recent advancements and challenges in translating BDNF-related research into clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: An optimal internal response to feeding state is critical for survival and development in insects. Part of this response originates in the insect midgut, which detects the nutritional status of incoming food and sends relevant signals to other organs via hormones. Starvation leads to changes in insect behaviors, such as food-seeking, and physiology, such as modifying nutrient usage to save energy for survival. Therefore, in this study, proteomics was used on fed and starved tobacco hornworm (Manduca sexta) caterpillar digestive tracts to characterize how the midgut responds to starvation. Several processes were modified by starvation, including digestive enzymes and metabolic functions. Additionally, gut-produced neuropeptide hormones were detected, and some changed in abundance in starved insects, particularly neuropeptide F1, which suggests that the dynamics of neuropeptide F1 are tied to feeding state. Overall, this study provides a foundation for understanding the gut response, particularly the dynamics of neuropeptide hormones, to starvation and provides multiple targets for future work. Starvation is a complex physiological state that induces changes in protein expression to ensure survival. The insect midgut is sensitive to changes in dietary content as it is at the forefront of communicating information about incoming nutrients to the body via hormones. Therefore, a DIA proteomics approach was used to examine starvation physiology and, specifically, the role of midgut neuropeptide hormones in a representative lepidopteran, Manduca sexta. Proteomes were generated from midguts of M. sexta fourth-instar caterpillars, starved for 24 h and 48 h, and compared to fed controls. A total of 3047 proteins were identified, and 854 of these were significantly different in abundance. KEGG analysis revealed that metabolism pathways were less abundant in starved caterpillars, but oxidative phosphorylation proteins were more abundant. In addition, six neuropeptides or related signaling cascade proteins were detected. Particularly, neuropeptide F1 (NPF1) was significantly higher in abundance in starved larvae. A change in juvenile hormone-degrading enzymes was also detected during starvation. Overall, our results provide an exploration of the midgut response to starvation in M. sexta and validate DIA proteomics as a useful tool for quantifying insect midgut neuropeptide hormones. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated whether repeated high-intensity interval exercise (HIIE) influences plasma oxytocin (OT) concentration in healthy men, and, given that OT is mainly synthesized in the hypothalamus, we assessed the concentration difference between the arterial (OTART) versus the internal jugular venous OT concentration (OTIJV). Additionally, we hypothesized that an increase in cerebral OT release and the circulating concentration would be augmentedby repeated HIIE. Methods: Fourteen healthy men (age = 24 ± 2 yr; mean± SD) performed two identical bouts of HIIE. These HIIE bouts included a warm-up at 50%-60% maximal workload (Wmax) for 5 min followed by four bouts of exercise at 80%-90% Wmax for 4 min interspersed by exercise at 50%-60% Wmax for 3 min. The HIIE bouts were separated by 60 min of rest. OT was evaluated in blood through radial artery and internal jugular vein catheterization. Results: Both HIIE bouts increased both OTART (median [IQR], from 3.9 [3.4-5.4] to 5.3 [4.4-6.3] ng⋅mL-1 in the first HIIE, P < 0.01) and OTIJV (from 4.6 [3.4-4.8] to 5.9 [4.3-8.2] ng⋅mL-1, P < 0.01), but OTART-IJV was unaffected (from -0.24 [-1.16 to 1.08] to 0.04 [-0.88 to 0.78] ng⋅mL-1, P = 1.00). The increased OT levels were similar in the first and second HIIE bouts (OTART P = 0.25, OTIJV P = 0.36). Conclusions: Despite no change in the cerebral OT release via the internal jugular vein, circulating OT increases during HIIE regardless of the accumulated exercise volume, indicating that OT may play role as one of the exerkines. [ABSTRACT FROM AUTHOR]

Objective: We conducted a systematic review and meta‐analysis to explore the relationship between blood pituitary adenylate cyclase‐activating polypeptide (PACAP) levels and migraine. Background: PACAP is involved in the onset of migraine, but the results from clinical studies on PACAP level variations across different periods of migraine are conflicting. Methods: We systematically searched for observational studies that reported PACAP levels in people with migraine and non‐migraine controls published in English from the PubMed, Web of Science, and Ovid electronic databases, or in Chinese from the Chinese National Knowledge Infrastructure and the WanFang Med database. The Newcastle–Ottawa Quality Assessment Scale was used to assess the quality of the included studies. The quality of evidence for each outcome was assessed according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines. Results: Of the 514 identified studies, 8 were eligible for inclusion. There was a "very low" level of evidence suggesting that the PACAP level is negatively correlated with migraine disease duration in adults with migraine (summary r = −0.35, 95% confidence interval [CI] −0.49 to −0.22) and that the PACAP is higher in people with migraine during the ictal period than in the interictal period (standardized mean difference = 0.41, 95% CI 0.17 to 0.66) for both adults and children with migraine. Adult patients with episodic migraine (weighted mean difference [WMD] = −9.58 pg/mL, 95% CI −13.41 to −5.75 pg/mL) or chronic migraine (WMD = −10.93 pg/mL, 95% CI −15.57 to −6.29 pg/mL) had lower blood PACAP levels than non‐migraine controls during the interictal period, supported by a "low" or "very low" quality of evidence, respectively, according to the GRADE rules. Conclusion: There is a very low certainty of evidence suggesting that the PACAP level is negatively correlated with migraine disease duration of adults with migraine and it varies greatly among different periods of migraine of both adults and children with migraine. Plain Language Summary: Pituitary adenylate cyclase‐activating polypeptide (PACAP) is thought to be involved in migraine attacks, but studies looking at the relationship between PACAP levels and migraine have not shown consistent results. We reviewed and summarized data from studies that looked at PACAP levels and migraine to clarify this relationship. Our study showed that PACAP levels were lower in people who have a longer history of migraine, which might mean that PACAP could be important for treating migraine; however, more research will be needed to find out whether this is true. [ABSTRACT FROM AUTHOR]

Introduction: Neuropeptides regulate vital physiological processes in multicellular organisms, including growth, reproduction, metamorphosis, and feeding. Recent transcriptome analyses have revealed neuropeptide genes with potential roles in vertebrate and invertebrate growth and reproduction. Among these genes, haliotid growth-associated peptide (HGAP) was identified as a novel gene in abalone. Methods: This study focused on HGAP in Pacific abalone (Haliotis discus hannai), where the complete cDNA sequence named Hdh-HGAP was identified and characterized. Samples from different experiments, such as metamorphosis, juvenile abalone growth, gonad development stages, muscle remodeling, and starvation, were collected for mRNA expression analysis. Results: The sequence spans 552 bp, encoding 96 amino acids with a molecular weight of 10.96 kDa. Expression analysis revealed that Hdh-HGAP exhibited higher levels in muscle tissue. Notably, during metamorphosis, Hdh-HGAP exhibited greater expression in the trochophore, veliger, and juvenile stages than in the cell division stages. Regarding growth patterns, Hdh-HGAP was highly expressed during rapid growth compared to stunted, minimal, and normal growth. In gonadal development, Hdh-HGAP mRNA reached its highest expression level during the ripening stage, indicating a potential role in gonadal cell proliferation and maturation. The in vivo effects of GnRH on gonad development and the expression of the Hdh-HGAP neuropeptide indicate its involvement in regulating reproduction in Pacific abalone. While tissue remodeling is primarily governed by immune genes, Hdh-HGAP was also upregulated during muscle tissue remodeling. Conversely, Hdh-HGAP was downregulated during prolonged starvation. Conclusion: This study marks the first comprehensive exploration of the Hdh-HGAP neuropeptide gene in Pacific abalone, shedding light on its involvement in growth, reproduction, metamorphosis, tissue remodeling, and response to starvation, although regulatory mechanisms are mostly unknown. [ABSTRACT FROM AUTHOR]

Skin-innervating sensory neurons recognize a diverse array of exogenous and endogenous stimuli, including pathogens, allergens, tissue-derived alarmins, and immune-derived cytokines. Neuropeptides derived from sensory neurons signal to immune cells in the skin to promote or dampen innate immune responses to external insults. Sensory neurons influence the mode and magnitude of antigen-specific adaptive cutaneous immune responses by altering dendritic cell activation, migration, and priming of naïve T cells. Dendritic cell populations in mouse skin and skin-draining lymph nodes express mRNAs of numerous neuropeptide receptor genes, presenting ample opportunities for future investigation into neuronal control of cutaneous immunity. Skin-innervating sensory neurons detect noxious stimuli and release neuropeptides to control and shape mammalian innate and adaptive immune responses to external insults. Peripheral sensory neurons recognize diverse noxious stimuli, including microbial products and allergens traditionally thought to be targets of the mammalian immune system. Activation of sensory neurons by these stimuli leads to pain and itch responses as well as the release of neuropeptides that interact with their cognate receptors expressed on immune cells, such as dendritic cells (DCs). Neuronal control of immune cell function through neuropeptide release not only affects local inflammatory responses but can impact adaptive immune responses through downstream effects on T cell priming. Numerous neuropeptide receptors are expressed by DCs but only a few have been characterized, presenting opportunities for further investigation of the pathways by which cutaneous neuroimmune interactions modulate host immunity. [ABSTRACT FROM AUTHOR]

Agouti-related protein (Agrp) is an orexigenic peptide hormone found in fish and other vertebrates. Understanding appetite regulation is important for improving production performance in aquaculture systems. However, information on appetite-related hormones in yellowtail is still fragmentary. In this study, two distinct agrpgenes (i.e., agrp1 and agrp2) were cloned from the yellowtail brain. Brain distribution and response of the agrp genes to fasting, along with other candidate orexigenic peptide hormone-related genes including neuropeptide Y (npy) and melanin-concentrating hormones (mch1 and mch2), were studied. The highest expression level of those genes was observed in the hypothalamus, except for npy. After fasting, agrp1 and npy increased significantly in the hypothalamus, whereas agrp2 in the olfactory bulb and cerebellum decreased significantly. After feeding with a fishmeal (FM)-based diet and addition of a fishmeal soluble fraction (FMS), hypothalamic agrp1, agrp2, mch1, and mch2 increased, whereas hypothalamic npy decreased significantly. From the fasting experiment, agrp1 and npy may function as orexigenic hormones in yellowtail; however, the function of other hormones warrants further research. Expression of all the analyzed appetite-related hormonal genes might respond to the smell/taste of fishmeal through sensory organs. Furthermore, npy and agrp1 may enhance appetite through different mechanisms in yellowtail. [ABSTRACT FROM AUTHOR]

Background: Itch is the most common symptom of atopic dermatitis (AD) and significantly decreases the quality of life. Skin microbiome is involved in AD pathogenesis, whereas its role in the regulation of itch remains elusive. In this study, we aimed to investigate the effects of skin microbial metabolite propionate on acute and chronic pruritus and to explore the mechanism. Methods: Using various mouse models of itch, the roles of propionate were explored by behavioral tests and histopathology/immunofluorescent analysis. Primary‐cultured dorsal root ganglion neurons and HEK293 cells expressing recombinant human TRP channels were utilized for in vitro calcium imaging/in vivo miniature two‐photon imaging in combination with electrophysiology and molecular docking approaches for investigation of the mechanism. Results: Propionate significantly alleviated itch and alloknesis in various mouse models of pruritus and AD and decreased the density of intraepidermal nerve fibers. Propionate reduced the responsiveness of dorsal root ganglion neurons to pruritogens in vitro, attenuated the hyper‐excitability in sensory neurons in MC903‐induced AD model, and inhibited capsaicin‐evoked hTRPV1 currents (IC50 = 20.08 ± 1.11 μM) via interacting with the vanilloid binding site. Propionate also decreased the secretion of calcitonin gene‐related peptide by nerves in MC903‐induced AD mouse model, which further attenuated itch and skin inflammation. Conclusion: Our study revealed a protective effect of propionate against persistent itch through direct modulation of sensory TRP channels and neuropeptide production in neurons. Regulation of itch via the skin microbiome might be a novel strategy for the treatment of AD. [ABSTRACT FROM AUTHOR]

Peptidoglycan (PG), an essential component of the cell envelope unique to the bacterial kingdom, is the target of several widely used antibiotics and continues to be an attractive candidate for development of novel antimicrobials. PG is a covalently closed macromolecule surrounding the plasma membrane that forms a unique mesh-like polymer conferred by crosslinking of glycan strands through short peptides. Bacteria encode several specialized enzymes for the formation and hydrolysis of the PG, enabling its remodeling in response to cellular requirement and environmental growth conditions. Peptide crosslinks are the load-bearing bonds of PG, and enzymes that cleave the crosslinks are mediators of PG plasticity. Crosslink-specific endopeptidases play a fundamental role in cell wall expansion and emerge as promising targets for novel antimicrobials. Peptidoglycan (PG) is a protective mesh-like polymer in bacterial cell walls that enables their survival in almost every ecological niche. PG is formed by crosslinking of several glycan strands through short peptides, conferring a characteristic structure and elasticity, distinguishing it from other polymeric exoskeletons. The significance of PG crosslink formation has been known for decades, as some of the most widely used antibiotics, namely β-lactams, target the enzymes that catalyze this step. However, the importance of crosslink hydrolysis in PG biology remained largely underappreciated. Recent advances demonstrate the functions of crosslink cleavage in diverse physiological processes, including an indispensable role in PG expansion during the cell cycle, thereby making crosslink cleaving enzymes an untapped target for novel drugs. Here, we elaborate on the fundamental roles of crosslink-specific endopeptidases and their regulation across the bacterial kingdom. [ABSTRACT FROM AUTHOR]

BACKGROUND: Non‐nutritive sweeteners (NNS) are commonly used in sweetened foods and beverages; however their role in metabolic regulation is still not clear. In this experiment, we used guinea pigs as an animal model to study the effect of NNS on body growth and intestinal health by modifying gut microbiota and hypothalamus‐related proteins. RESULTS: For a 28‐day feeding experiment a total of 40 guinea pigs were randomly divided into four groups, one control (CN) group and three treatments, in which three NNS were added to the diet: rebaudioside A (RA, 330 mg kg−1), sodium saccharin (SS, 800 mg kg−1), and sucralose (TGS, 167 mg kg−1), respectively. The TGS group exhibited significantly reduced food consumption in comparison with the CN group (P < 0.05) whereas the RA group showed increased food consumption in comparison with the CN group (P < 0.05). Notably, Taste receptor type 1 subunit 2 (T1R2) expression in the hypothalamus was significantly higher in the RA group than in the CN group (P < 0.05). The mRNA expressions of appetite‐stimulated genes arouti‐related neuropeptide (AGRP), neuropeptide Y (NPY), and thyroid stimulating hormone (TSHB) were significantly higher than those in the CN group (P < 0.05) but mRNA expressions of appetite‐suppressed genes tryptophan hydroxylase 2(THP2) were significantly lower in the TGS group (P < 0.05). Furthermore, NNS in the guinea pig diets (RA, SS, TGS) significantly increased the relative abundance of Muribaculaceae but decreased the relative abundance of Clostridia_vadin BB60 in comparison with the CN group (P < 0.05). We also found that dietary supplementation with RA also significantly altered the relative abundance of Lactobacillus. CONCLUSION: Our finding confirmed that dietary supplementation with RA and TGS affected body growth and intestinal health by modulating hypothalamic RNA profiles and ileum microbiota, suggesting that NNS should be included in guinea‐pig feeding. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Neuropeptides are endogenous active substances within the central and peripheral nervous systems that play important roles in a wide range of brain functions, including metabolism, food intake, social behavior, reproduction, learning, sleep, and wakefulness. This article reviews recent advances in the involvement of neuropeptides in vascular dementia. Neuropeptides are present in the brain as chemical signals and last for nearly 50 years. Peptide hormones are chemical signals of the endocrine system. Thus, neuropeptides are the most diverse class of signaling molecules in the brain, involving the genomes of many mammals, encoding neuropeptide precursors and many bioactive neuropeptides. Here the aim is to describe the recent advances in classical neuropeptides, as well as putative neuropeptides from other families, in the control of or as diagnostic tools for vascular dementia. Additionally, its molecular mechanisms are described to explore new avenues of treatment and early diagnosis, as there is increasing evidence that dysregulation of vascular processes is associated with different pathological conditions. [ABSTRACT FROM AUTHOR]

Background: Neuropeptides play a critical role in regulating pain and inflammation. Despite accumulating evidence has further uncovered the novel functions and mechanisms of different neuropeptides in orofacial pain sensation and transmission, there is deficient systematic description of neuropeptides' pain modulation in the orofacial region, especially in the trigeminal system. Objectives: The present review aims to summarise several key neuropeptides and gain a better understanding of their major regulatory roles in orofacial inflammation and pain. Methods: We review and summarise current studies related to calcitonin gene‐related peptide (CGRP), substance P (SP), opioid peptide (OP), galanin (GAL) and other neuropeptides' functions and mechanisms as well as promising targets for orofacial pain control. Results: A number of neuropeptides are clearly expressed in the trigeminal sensory system and have critical functions in the transduction and pathogenesis of orofacial pain. The functions, possible cellular and molecular mechanisms have been introduced and discussed. Neuropeptides and their agonists or antagonists which are widely studied to be potential treatment options of orofacial pain has been evaluated. Conclusions: Various neuropeptides play important but distinct (pro‐nociceptive or analgesic) roles in orofacial pain with different mechanisms. In summary, CGRP, SP, NPY, NKA, HK‐1, VIP mainly play proinflammatory and pro‐nociceptive effects while OP, GAL, OXT, OrxA mainly have inhibitory effects on orofacial pain. [ABSTRACT FROM AUTHOR]

Purpose: The retina contains a number of vasoactive neuropeptides and corresponding receptors, but the role of these neuropeptides for tone regulation of retinal arterioles has not been studied in detail. Methods: Porcine arterioles with preserved perivascular retinal tissue were mounted in a wire myograph, and the tone was measured after the addition of increasing concentrations of bradykinin, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), substance P (SP), calcitonin gene‐related peptide (CGRP) and brain natriuretic peptide (BNP). The experiments were performed during inhibition of the synthesis of nitric oxide (NO), prostaglandins and dopamine and were repeated after removal of the perivascular retinal tissue. Results: Bradykinin, VIP and CGRP induced significant concentration‐dependent dilatation and NPY significant concentration‐dependent contraction of the arterioles in the presence of perivascular retinal tissue (p < 0.03 for all comparisons) but not on isolated arterioles. BNP and SP had no effect on vascular tone. The NOS inhibitor L‐NAME reduced bradykinin‐ and VIP‐induced relaxation (p < 0.001 for both comparisons), whereas none of the other inhibitors influenced the vasoactive effects of the studied neuropeptides. Conclusion: The effects of neuropeptides on the tone of retinal arterioles depend on the perivascular retinal tissue and may involve effects other than those mediated by nitric oxide, prostaglandins and adrenergic compounds. Investigation of the mechanisms underlying the vasoactive effect of neuropeptides may be important for understanding and treating retinal diseases where disturbances in retinal flow regulation are involved in the disease pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Calcitonin gene-related peptide (CGRP) is the most promising candidate to become the first migraine biomarker. However, literature shows clashing results and suggests a methodological source for such discrepancies. We aimed to investigate some of these methodological factors to evaluate the actual role of CGRP as biomarker. Methods: Previous to the experimental part, we performed a literature review of articles measuring CGRP in migraine patients. Using our 399 bio-bank sera samples, we performed a series of experiments to test the validity of different ELISA kits employed, time of sample processing, long-term storage, sampling in rest or after moderate exercise. Analysis of in-house data was performed to analyse average levels of the peptide and the effect of sex and age. Results: Literature review shows the high variability in terms of study design, determination methods, results and conclusions obtained by studies including CGRP determinations in migraine patients. CGRP measurements depends on the method and specific kit employed, also on the isoform detected, showing completely different ranges of concentrations. Alpha-CGRP and beta-CGRP had median with IQR levels of 37.5 (28.2–54.4) and 4.6 (2.4–6.4)pg/mL, respectively. CGRP content is preserved in serum within the 24 first hours when samples are stored at 4°C after clotting and immediate centrifugation. Storages at -80°C of more than 6 months result in a decrease in CGRP levels. Moderate exercise prior to blood extraction does not modulate the concentration of the peptide. Age positively correlates with beta-CGRP content and men have higher alpha-CGRP levels than women. Conclusions: We present valuable information for CGRP measurements in serum. ELISA kit suitability should be tested prior to the experiments. Alpha and beta-CGRP levels should be analysed separately as they can show different behaviours even within the same condition. Samples can be processed in a 24-h window if they have been kept in 4°C and should not be stored for more than 6 months at -80°C before assayed. Patients do not need to rest before the blood extraction unless they have performed a high-endurance exercise. For comparative studies, sex and age should be accounted for as these parameters can impact CGRP concentrations. [ABSTRACT FROM AUTHOR]

Sexual dimorphism has been revealed for many neurological disorders including chronic pain. Prelicinal studies and post-mortem analyses from male and female human donors reveal sexual dimorphism of nociceptors at transcript, protein and functional levels suggesting different mechanisms that may promote pain in men and women. Migraine is a common female-prevalent neurological disorder that is characterized by painful and debilitating headache. Prolactin is a neurohormone that circulates at higher levels in females and that has been implicated clinically in migraine. Prolactin sensitizes sensory neurons from female mice, non-human primates and humans revealing a female-selective pain mechanism that is conserved evolutionarily and likely translationally relevant. Prolactin produces female-selective migraine-like pain behaviors in rodents and enhances the release of calcitonin gene-related peptide (CGRP), a neurotransmitter that is causal in promoting migraine in many patients. CGRP, like prolactin, produces female-selective migraine-like pain behaviors. Consistent with these observations, publicly available clinical data indicate that small molecule CGRP-receptor antagonists are preferentially effective in treatment of acute migraine therapy in women. Collectively, these observations support the conclusion of qualitative sex differences promoting migraine pain providing the opportunity to tailor therapies based on patient sex for improved outcomes. Additionally, patient sex should be considered in design of clinical trials for migraine as well as for pain and reassessment of past trials may be warranted. [ABSTRACT FROM AUTHOR]

Oxytocin is a neuropeptide associated with both psychological and somatic processes like parturition and social bonding. Although oxytocin homologs have been identified in many species, the evolutionary timeline of the entire oxytocin signaling gene pathway has yet to be described. Using protein sequence similarity searches, microsynteny, and phylostratigraphy, we assigned the genes supporting the oxytocin pathway to different phylostrata based on when we found they likely arose in evolution. We show that the majority (64%) of genes in the pathway are 'modern'. Most of the modern genes evolved around the emergence of vertebrates or jawed vertebrates (540 - 530 million years ago, 'mya'), including OXTR, OXT and CD38. Of those, 45% were under positive selection at some point during vertebrate evolution. We also found that 18% of the genes in the oxytocin pathway are 'ancient', meaning their emergence dates back to cellular organisms and opisthokonta (3500–1100 mya). The remaining genes (18%) that evolved after ancient and before modern genes were classified as 'medium-aged'. Functional analyses revealed that, in humans, medium-aged oxytocin pathway genes are highly expressed in contractile organs, while modern genes in the oxytocin pathway are primarily expressed in the brain and muscle tissue. A study on the evolution of the oxytocin system illustrates the varied role of this neuropeptide in physiology and behavior [ABSTRACT FROM AUTHOR]

Background: Migraine is a complex neurological disorder with significant heterogeneity in its clinical presentation and molecular mechanisms. Calcitonin gene-related peptide (CGRP) has emerged as a key player in migraine pathophysiology, but challenges remain in its utilization as a biomarker. This study aimed to investigate salivary CGRP levels during migraine attacks across the frequency spectrum and explore associations with clinical variables. Methods: A prospective longitudinal pilot study was conducted, recruiting migraine patients from an outpatient headache clinic. Salivary CGRP levels were measured at interictal, onset, post-2 h of onset and end-of-attack. Using generalized linear mixed models, we explored the effect of CGRP changes over the attack in presence of depressive symptoms (DS), acute attack treatment, and after three-months of erenumab treatment. Finally, patients were classified and compared according to their CGRP phenotype. Results: A total of 44 migraine patients were included (90.9% women), with 80 migraine attacks analyzed. Salivary CGRP levels increased at the onset of migraine attacks. We observed statistically significant interactions between DS and both the linear (Est. [SE]: 19.4 [5.8], p = 0.001) and quadratic terms of time (-19.1 [6.0], p = 0.002). Additionally, a significant three-way interaction within the use of acute treated attack (linear-term: -18.5 [6.2], p = 0.005; quadratic-term: 19.2 [6.8], p = 0.005) was also found. Molecular phenotyping revealed that 72.7% (32/44) of patients presented only CGRP-dependent attacks, while 27.3% (12/44) presented non-CGRP-dependent migraine attacks. Patients with only CGRP-dependent attacks were associated with younger age, shorter disease evolution time, a higher proportion of aura, and fewer monthly headache days (p < 0.05). Exploratory analysis of erenumab treatment effects did not result in changes in CGRP levels during migraine attacks. Conclusions: Our study underscores the dynamic nature of migraine at a molecular level and emphasizes the importance of integrating clinical variables, such as depressive symptoms, in understanding its pathophysiology. The identification of distinct migraine subtypes based on CGRP dependence suggests potential opportunities for personalized treatment approaches. [ABSTRACT FROM AUTHOR]

Endometriosis is a chronic gynecological syndrome characterized by endometrial cell invasion of the extra‐uterine milieu, pelvic pain and infertility. Treatment relies on either symptomatic drugs or hormonal therapies, even though the mechanism involved in the onset of endometriosis is yet to be elucidated. The signaling of sphingolipid sphingosine 1‐phosphate (S1P) is profoundly dysregulated in endometriosis. Indeed, sphingosine kinase (SK)1, one of the two isoenzymes responsible for S1P biosynthesis, and S1P1, S1P3 and S1P5, three of its five specific receptors, are more highly expressed in endometriotic lesions compared to healthy endometrium. Recently, missense coding variants of the gene encoding the receptor 1 for neuropeptide S (NPS) have been robustly associated with endometriosis in humans. This study aimed to characterize the biological effect of NPS in endometriotic epithelial cells and the possible involvement of the S1P signaling axis in its action. NPS was found to potently induce cell invasion and actin cytoskeletal remodeling. Of note, the NPS‐induced invasive phenotype was dependent on SK1 and SK2 as well as on S1P1 and S1P3, given that the biological action of the neuropeptide was fully prevented when one of the two biosynthetic enzymes or one of the two selective receptors was inhibited or silenced. Furthermore, the RhoA/Rho kinase pathway, downstream to S1P receptor signaling, was found to be critically implicated in invasion and cytoskeletal remodeling elicited by NPS. These findings provide new information to the understanding of the molecular mechanisms implicated in endometriosis pathogenesis, establishing the rationale for non‐hormonal therapeutic targets for its treatment. [ABSTRACT FROM AUTHOR]

Influenza A virus (IAV) is a common respiratory pathogen and a global cause of significant and often severe morbidity. Although inflammatory immune responses to IAV infections are well described, little is known about how neuroimmune processes contribute to IAV pathogenesis. In the present study, we employed surgical, genetic, and pharmacological approaches to manipulate pulmonary vagal sensory neuron innervation and activity in the lungs to explore potential crosstalk between pulmonary sensory neurons and immune processes. Intranasal inoculation of mice with H1N1 strains of IAV resulted in stereotypical antiviral lung inflammation and tissue pathology, changes in breathing, loss of body weight and other clinical signs of severe IAV disease. Unilateral cervical vagotomy and genetic ablation of pulmonary vagal sensory neurons had a moderate effect on the pulmonary inflammation induced by IAV infection, but significantly worsened clinical disease presentation. Inhibition of pulmonary vagal sensory neuron activity via inhalation of the charged sodium channel blocker, QX-314, resulted in a moderate decrease in lung pathology, but again this was accompanied by a paradoxical worsening of clinical signs. Notably, vagal sensory ganglia neuroinflammation was induced by IAV infection and this was significantly potentiated by QX-314 administration. This vagal ganglia hyperinflammation was characterized by alterations in IAV-induced host defense gene expression, increased neuropeptide gene and protein expression, and an increase in the number of inflammatory cells present within the ganglia. These data suggest that pulmonary vagal sensory neurons play a role in the regulation of the inflammatory process during IAV infection and suggest that vagal neuroinflammation may be an important contributor to IAV pathogenesis and clinical presentation. Targeting these pathways could offer therapeutic opportunities to treat IAV-induced morbidity and mortality. Author summary: Influenza viruses are a common respiratory pathogen that represent a constant and pervasive threat to human health. Although the inflammatory and immune responses to influenza viral infections are well described, little is known about the role the nervous system plays in the formation and progression of disease. The lungs receive a rich supply of sensory nerve fibers from the vagus nerve. These nerves are critical for protecting the lungs against harmful stimuli and play an important defence role against pathogens, including viruses. Here we use several complex animal models to demonstrate the impact lung sensory neurons have on influenza viral infection and disease outcome. We demonstrate that ablation of lung sensory neurons and inhibition of their neural activity significantly worsens the clinical outcome in mice infected with influenza virus, however with only a moderate impact on lung pathology. Interestingly, when the activity of these neurons is inhibited during influenza viral infection, this drives a hyper neuroinflammatory response within the vagal sensory ganglia, where their cell bodies are located. Our work provides new insights into how these lung sensory neurons are involved in influenza viral infections and may offer therapeutic opportunities to treat influenza-induced morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background: Autonomic nervous system (ANS) testing has aided in our ability to evaluate autonomic dysfunction in migraine patients. We reviewed the literature in multiple databases which investigate ANS function in migraine patients and healthy subjects. Methods: This systematic review and meta-analysis examined the respective deep breathing, Valsalva manoeuvre, orthostatic and isometric challenge results, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analyses of Observational Studies in Epidemiology (MOOSE) statements. Results: Seven articles met all inclusion criteria. Fixed-effects meta-analysis showed migraine patients (n = 424), collectively, had lower interictal autonomic test results compared with healthy controls (n = 268). In detail, this was true for the standardized mean difference (g) of deep breathing (g= -0.32; 95% confidence interval (CI) -0.48, -0.16), orthostatic challenge (g= -0.28; 95% CI -0.44, -0.13) and isometric challenge (g= -0.55; 95% CI -0.71, -0.39) and for the difference of means (MD) of the Valsalva ratio (MD = -0.17; 95% CI -0.23, -0.10). Conclusions: Interictal ANS dysfunction can be identified in migraine patients when compared to healthy controls. These findings indicate the importance to evaluate ANS function in migraine patients - especially, as migraine-specific prophylactic therapies (such as anti-calcitonin gene-related peptide (CGRP) antibodies) may affect the function of the ANS. [ABSTRACT FROM AUTHOR]

Anxiety among nursing students documented during the COVID-19 pandemic reflected their fear of contracting infections, adhering to the mandatory use of masks in public, engaging in the new experience of distance learning, having financial problems, and so on. The purpose of this study was to examine the mediating role of emotional intelligence (EI) on nursing students' coping strategies and anxiety during the pandemic. This cross-sectional correlational study was conducted in a university in Jordan. An online survey was used to obtain data from a sample of 282 nursing students who had returned to on-campus learning during the summer semester of 2019/2020. The survey held four parts: (a) questions about sociodemographics, (b) the General Anxiety Disorder-7 (GAD-7) scale, (c) the Trait Emotional Intelligence Questionnaire-Short Form (TEIQue-SF), and (d) the Brief-Coping Behavior Questionnaire (Brief-COPE). The results showed that EI had a fully mediating role in the relationship between problem-focused coping strategies and anxiety, and it partially mediated the emotion-focused and avoidant/dysfunctional coping strategies and anxiety relationships. Nursing students who used the problem-focused coping strategies had high levels of EI, and with increasing levels of EI, anxiety levels decreased. Promoting the development of EI among nursing students would enable them to manage their emotions effectively and control their anxiety, particularly in new circumstances such as those that occurred during the COVID 19 pandemic. [ABSTRACT FROM AUTHOR]

Lysophosphatidic acid (LPA) is a bioactive phospholipid that plays a crucial role in cardiovascular diseases. Here, we question whether LPA contributes to myocardial ischemia/reperfusion (I/R) injury by acting on transient receptor potential vanilloid 1 (TRPV1) in spinal cord. By ligating the left coronary artery to establish an in vivo I/R mouse model, we observed a 1.57-fold increase in LPA level in the cerebrospinal fluid (CSF). The I/R-elevated CSF LPA levels were reduced by HA130, an LPA synthesis inhibitor, compared to vehicle treatment (4.74 ± 0.34 vs. 6.46 ± 0.94 μg/mL, p = 0.0014). Myocardial infarct size was reduced by HA130 treatment compared to the vehicle group (26 ± 8% vs. 46 ± 8%, p = 0.0001). To block the interaction of LPA with TRPV1 at the K710 site, we generated a K710N knock-in mouse model. The TRPV1K710N mice were resistant to LPA-induced myocardial injury, showing a smaller infarct size relative to TRPV1WT mice (28 ± 4% vs. 60 ± 7%, p < 0.0001). Additionally, a sequence-specific TRPV1 peptide targeting the K710 region produced similar protective effects against LPA-induced myocardial injury. Blocking the K710 region through K710N mutation or TRPV1 peptide resulted in reduced neuropeptides release and decreased activity of cardiac sensory neurons, leading to a decrease in cardiac norepinephrine concentration and the restoration of intramyocardial pro-survival signaling, namely protein kinase B/extracellular regulated kinase/glycogen synthase kinase-3β pathway. These findings suggest that the elevation of CSF LPA is strongly associated with myocardial I/R injury. Moreover, inhibiting the interaction of LPA with TRPV1 by blocking the K710 region uncovers a novel strategy for preventing myocardial ischemic injury. [ABSTRACT FROM AUTHOR]

Background: Galangin, commonly employed in traditional Chinese medicine for its diverse medicinal properties, exhibits potential in treating inflammatory pain. Nevertheless, its mechanism of action remains unclear. Methods: Mice were randomly divided into 4 groups for 7 days: a normal control group, a galangin-treated (25 and 50 mg/kg), and a positive control celecoxib (20 mg/kg). Analgesic and anti-inflammatory effects were evaluated using a hot plate test, acetic acid-induced writhing test, acetic acid-induced vascular permeability test, formalininduced paw licking test, and carrageenan-induced paw swelling test. The interplay between galangin, transient receptor potential vanilloid 1 (TRPV1), NF-κB, COX-2, and TNF-α proteins was evaluated via molecular docking. COX-2, PGE2, IL-1β, IL-6, and TNF-α levels in serum were measured using ELISA after capsaicin administration (200 nmol/L). TRPV1 expression in the dorsal root ganglion was analyzed by Western blot. The quantities of substance P (SP) and calcitonin gene-related peptide (CGRP) were assessed using qPCR. Results: Galangin reduced hot plate-induced licking latency, acetic acid-induced contortions, carrageenantriggered foot inflammation, and capillary permeability in mice. It exhibited favorable affinity towards TRPV1, NF-κB, COX-2, and TNF-α, resulting in decreased levels of COX-2, PGE2, IL-1β, IL-6, and TNF-α in serum following capsaicin stimulation. Galangin effectively suppressed the upregulation of TRPV1 protein and associated receptor neuropeptides CGRP and SP mRNA, while concurrently inhibiting the expression of NF-κB, TNF-α, COX-2, and PGE2 mRNA. Conclusions: Galangin exerts its anti-inflammatory pain effects by inhibiting TRPV1 activation and regulating COX-2, NF-κB/TNF-α expression, providing evidence for the use of galangin in the management of inflammatory pain. [ABSTRACT FROM AUTHOR]

Epilepsy is a widespread neurological disorder. Many neurotransmitters, neuropeptides and neuromodulators have a significant role in the epileptic activity. Apelin-13 and cannabinoid CB1 receptor agonist and antagonist have an effect in the penicillin model of epilepsy. The relationship between apelin and epilepsy, and the apelin-cannabinoid relationship in epilepsy is still not well understood. Thus, this study focuses on the relationship between apelin-13 and CB1 receptor in experimental model of epilepsy. Penicillin injection was given intracortically (i.c.) for the development of epileptic seizures. Ninety-one male Wistar rats were divided into 13 groups. CB1 receptor agonist ACEA (7.5 µg, intracerebroventricularly, icv) and antagonist AM-251 (0.25 µg and 0.125 µg, icv) were administered to three different groups, two different doses of apelin-13 (5 µg and 15 µg, icv) were applied and the interactions between these five groups of substances were evaluated. Both apelin-13 (15 µg) and AM-251 (0.25 µg) raised the spike frequency of epileptiform activity separately. Application of apelin-13 + AM-251 also increased the spike frequency of epileptiform activity beginning in the 30 min after apelin-13 application. When the non-effective dose of AM-251 and the effective dose of apelin-13 were administered together, epileptic activity increased in the 20 min. ACEA reduced the epileptiform activity starting in the 50th min. apelin-13 and ACEA administration in effective doses decreased epileptiform activity. The non-effective doses of AM-251, apelin-13 and effective dose of ACEA decreased the epileptiform activity in the 50 min. Application of non-effective doses of apelin and AM-251 together does not induce any additional proconvulsant activity, and CB1 receptor agonist, ACEA reversed the proconvulsant activity of apelin-13. These results suggest that they utilize different receptors to begin their own effects by increasing intracellular Ca2+ in epilepsy. Considering that apelin-13 is an endogenous substance known for its neuroprotective properties, the proconvulsant effect of apelin-13 in the presented study is remarkable. [ABSTRACT FROM AUTHOR]

Objectives: Fibroblast activating protein (FAP) is associated with various organ fibrosis. However, the expression and molecular function of FAP in oral submucous fibrosis (OSF) is still unclear. Materials and Methods: The high‐performance liquid chromatography was used to detect the presence of alkaloids in areca nut extract (ANE). Real‐time qPCR, Western blot, and Immunohistochemistry assay were used to analyze the expression of FAP mRNA or protein in OSF and normal oral tissue. A chi‐squared test analyzed the relationship between FAP protein expression and clinicopathological data of OSF patients. CCK‐8, Wound‐healing, and Transwell migration assay were employed to assess the effect of the proliferation and migration ability of hOMF cells with FAP overexpression or knockdown. The expression level of a‐SMA, FSP1, and P13K–Akt signaling pathways‐related protein in hOMF cells transfected with FAP overexpression or knockdown plasmid was verified by western blot assay. Results: The four specific areca alkaloids (Arecoline, Guvacine, Arecaidine, and Guvacoline) were successfully detected in the ANE. The viability of hOMF cells was significantly improved in the 50 μg/mL ANE group and was inhibited in the 5 and 50 mg/mL ANE groups. The expression of FAP was upregulated in OSF tissues, and hOMF cells treated with 50 μg/mL ANE and was related to pathology grade, clinical stage, and history of chewing betel nut. Additionally, FAP may promote the proliferation, migration, and activation of hOMF cells through the P13K–Akt signaling pathway. Conclusions: This study found that ANE had a bidirectional effect on the viability of hOMF cells, and the FAP gene was a potential therapeutic target in OSF. [ABSTRACT FROM AUTHOR]

The hypothalamic molecular processes participate in the regulation of the neuro-immune-endocrine system, including hormone, metabolite, chemokine circulation, and corresponding physiological and behavioral responses. RNA-sequencing profiles were analyzed to understand the effect of juvenile immune and metabolic distress 100 days after virally elicited maternal immune activation during gestation in pigs. Over 1,300 genes exhibited significant additive or interacting effects of gestational immune activation, juvenile distress, and sex. One-third of these genes presented multiple effects, emphasizing the complex interplay of these factors. Key functional categories enriched among affected genes included sensory perception of pain, steroidogenesis, prolactin, neuropeptide, and inflammatory signaling. These categories underscore the intricate relationship between gestational immune activation during gestation, distress, and the response of hypothalamic pathways to insults. These effects were sex-dependent for many genes, such as Prdm12, Oprd1, Isg20, Prl, Oxt, and Vip. The prevalence of differentially expressed genes annotated to proinflammatory and cell cycle processes suggests potential implications for synaptic plasticity and neuronal survival. The gene profiles affected by immune activation, distress, and sex pointed to the action of transcription factors SHOX2, STAT1, and REST. These findings underscore the importance of considering sex and postnatal challenges when studying causes of neurodevelopmental disorders and highlight the complexity of the "two-hit" hypothesis in understanding their etiology. Our study furthers the understanding of the intricate molecular responses in the hypothalamus to gestational immune activation and subsequent distress, shedding light on the sex-specific effects and the potential long-lasting consequences on pain perception, neuroendocrine regulation, and inflammatory processes. NEW & NOTEWORTHY:The interaction of infection during gestation and insults later in life influences the molecular mechanisms in the hypothalamus that participate in pain sensation. The response of the hypothalamic transcriptome varies between sexes and can also affect synapses and immune signals. The findings from this study assist in the identification of agonists or antagonists that can guide pretranslational studies to ameliorate the effects of gestational insults interacting with postnatal challenges on physiological or behavioral disorders. [ABSTRACT FROM AUTHOR]

Since 1975, the incidence of obesity has increased to epidemic proportions, and the number of patients with obesity has quadrupled. Obesity is a major risk factor for developing other serious diseases, such as type 2 diabetes mellitus, hypertension, and cardiovascular diseases. Recent epidemiologic studies have defined obesity as a risk factor for the development of neurodegenerative diseases, such as Alzheimer's disease (AD) and other types of dementia. Despite all these serious comorbidities associated with obesity, there is still a lack of effective antiobesity treatment. Promising candidates for the treatment of obesity are anorexigenic neuropeptides, which are peptides produced by neurons in brain areas implicated in food intake regulation, such as the hypothalamus or the brainstem. These peptides efficiently reduce food intake and body weight. Moreover, because of the proven interconnection between obesity and the risk of developing AD, the potential neuroprotective effects of these two agents in animal models of neurodegeneration have been examined. The objective of this review was to explore anorexigenic neuropeptides produced and acting within the brain, emphasizing their potential not only for the treatment of obesity but also for the treatment of neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Peptides play an essential role in plant development and immunity. Filipendula ulmaria, belonging to the Rosaceae family, is a medicinal plant which exhibits valuable pharmacological properties. F. ulmaria extracts in vitro inhibit the growth of a variety of plant and human pathogens. The role of peptides in defense against pathogens in F. ulmaria remains unknown. The objective of this study was to explore the repertoire of antimicrobial (AMPs) and defense-related signaling peptide genes expressed by F. ulmaria in response to infection with Bipolaris sorokiniana using RNA-seq. Transcriptomes of healthy and infected plants at two time points were sequenced on the Illumina HiSeq500 platform and de novo assembled. A total of 84 peptide genes encoding novel putative AMPs and signaling peptides were predicted in F. ulmaria transcriptomes. They belong to known, as well as new, peptide families. Transcriptional profiling in response to infection disclosed complex expression patterns of peptide genes and identified both up- and down-regulated genes in each family. Among the differentially expressed genes, the vast majority were down-regulated, suggesting suppression of the immune response by the fungus. The expression of 13 peptide genes was up-regulated, indicating their possible involvement in triggering defense response. After functional studies, the encoded peptides can be used in the development of novel biofungicides and resistance inducers. [ABSTRACT FROM AUTHOR]

Introduction: The perception of hunger is a complex physiological process that requires precise coordination between the central and peripheral tissues. Methods: In this study, tilapia fasted for 24 h was chosen to establish a hunger model to study the mechanism of homeostasis recovery under the joint regulation of the central nervous system (CNS) and peripheral tissues. Results: The gastric and intestinal contents of tilapia were predominantly depleted after a fasting period of 9 h and 24 h, respectively. The serum glucose level significantly decreased at the 9-h and 24-h fasting, respectively, and the glucokinase-dependent glucosensing mechanism in the liver was identified as well as the significant activation of phospho-AMPK. However, fasting for 24 h did not activate glucosensing mechanisms and AMPK signaling pathways in the hypothalamus. On the other hand, significant reductions were observed in the mRNA levels of the lipid synthesis-related genes fas and accα, and the serum triglyceride levels as well. The mRNA levels of npy, agrp, pomc, and cart in the hypothalamus fluctuated during the fasting period without significant differences. With in situ hybridization npy signals upregulated in the ventral zone of posterior periventricular nucleus after 24-h fasting, pomc signals enhanced in the lateral tuberal nucleus. Based on the serum metabolomic analysis, the levels of branched-chain amino acids, butyrate, and short-chain acylcarnitine decreased, while those of medium- and long-chain acylcarnitine increased. Conclusion: Fasting for 24 h resulted in changes in npy and pomc signals within the hypothalamus and triggered the glucosensing mechanism in the liver of tilapia. This study is beneficial for elucidating the response of neuropeptides in the CNS to the changes of nutritional factors when hungry. [ABSTRACT FROM AUTHOR]

Objective: Based upon similarities between the urge to move and sensory discomfort of restless legs syndrome (RLS) and properties of melanocortin hormones, including their incitement of movement and hyperalgesia, we assessed plasma and cerebrospinal fluid (CSF) α‐melanocyte‐stimulating hormone (α‐MSH) and β‐endorphin in RLS patients and controls. Methods: Forty‐two untreated moderate‐to‐severe RLS patients and 44 matched controls underwent venipuncture at 19:00, 20:30, and 22:00; 37 RLS and 36 controls had lumbar puncture at 21:30. CSF and plasma were analyzed for pro‐opiomelanocortin (POMC), adrenocorticotropin hormone (ACTH), α‐MSH, β‐MSH, and β‐endorphin by immunoassay. RLS severity was assessed by International RLS Study Group Severity Scale. Results: RLS participants were 52.7 ± 12.0 years old, 61.9% were women, 21.4% had painful RLS, and RLS severity was 24.8 ± 9.0. Controls had similar age and sex. Plasma ACTH, α‐MSH, and β‐endorphin were similar between groups. Plasma POMC was significantly greater in RLS than controls (17.0 ± 11.5 vs 12.7 ± 6.1fmol/ml, p = 0.048). CSF ACTH was similar between groups. CSF β‐MSH was significantly higher in painful than nonpainful RLS or controls (48.2 ± 24.8 vs 32.1 ± 14.8 vs 32.6 ± 15.2pg/ml, analysis of variance [ANOVA] p = 0.03). CSF α‐MSH was higher in RLS than controls (34.2 ± 40.9 vs 20.3 ± 11.0pg/ml, p = 0.062). CSF β‐EDP was lowest in painful RLS, intermediate in nonpainful RLS, and highest in controls (8.0 ± 3.4 vs 10.8 ± 3.1 vs 12.3 ± 5.0pg/ml, ANOVA p = 0.049). The ratio of the sum of CSF α‐ and β‐MSH to CSF β‐endorphin was highest, intermediate, and lowest in painful RLS, nonpainful RLS, and controls (p = 0.007). Interpretation: CSF β‐MSH is increased and CSF β‐endorphin decreased in RLS patients with painful symptoms. ANN NEUROL 2024;95:688–699 [ABSTRACT FROM AUTHOR]

The midbrain dopamine system is a sophisticated hub that integrates diverse inputs to control multiple physiological functions, including locomotion, motivation, cognition, reward, as well as maternal and reproductive behaviors. Dopamine is a neurotransmitter that binds to G-protein-coupled receptors. Dopamine also works together with other neurotransmitters and various neuropeptides to maintain the balance of synaptic functions. The dysfunction of the dopamine system leads to several conditions, including Parkinson's disease, Huntington's disease, major depression, schizophrenia, and drug addiction. The ventral tegmental area (VTA) has been identified as an important relay nucleus that modulates homeostatic plasticity in the midbrain dopamine system. Due to the complexity of synaptic transmissions and input–output connections in the VTA, the structure and function of this crucial brain region are still not fully understood. In this review article, we mainly focus on the cell types, neurotransmitters, neuropeptides, ion channels, receptors, and neural circuits of the VTA dopamine system, with the hope of obtaining new insight into the formation and function of this vital brain region. [ABSTRACT FROM AUTHOR]

Mythimna separata is a notorious phytophagous pest which poses serious threats to cereal crops owing to the gluttony of the larvae. Because short neuropeptide F (sNPF) and its receptor sNPFR are involved in a diversity of physiological functions, especially in functions related to feeding in insects, it is a molecular target for pest control. Herein, an sNPF and 2 sNPFRs were identified and cloned from M. separata. Bioinformatics analysis revealed that the sNPF and its receptors had a highly conserved RLRFamide C‐terminus and 7 transmembrane domains, respectively. The sNPF and its receptor genes were distributed across larval periods and tissues, but 2 receptors had distinct expression patterns. The starvation‐induced assay elucidated that sNPF and sNPFR expression levels were downregulated under food deprivation and recovered with subsequent re‐feeding. RNA interference knockdown of sNPF, sNPFR1, and sNPFR2 by injection of double‐stranded RNA into larvae not only suppressed food consumption and increased body size and weight, but also led to decrease of glycogen and total lipid contents, and increase of trehalose compared with double‐stranded green fluorescent protein injection. Furthermore, molecular docking was performed on the interaction mode between sNPFR protein and its ligand sNPF based on the 3‐dimensional models constructed by AlphaFold; the results indicated that both receptors were presumably activated by the mature peptide sNPF‐2. These results revealed that sNPF signaling played a considerably vital role in the feeding regulation of M. separata and represents a potential control target for this pest. [ABSTRACT FROM AUTHOR]

Neurogenic inflammation is involved in the development and progression of respiratory inflammatory diseases. However, its role in community-acquired pneumonia (CAP) remains unclear. We therefore aimed to investigate plasma levels of neurogenic inflammation-related neuropeptides, calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY), and procalcitonin (PCT) in pediatric patients with CAP and to assess their diagnostic value in viral and bacterial/mixed pneumonia. A total of 124 pediatric patients with CAP (1 month-18 years old) and 56 healthy children of similar ages were prospectively enrolled. The patients were classified as viral (n = 99) and bacterial/mixed (n = 25) pneumonia. Plasma levels of the peptides were quantified by ELISA. ROC analysis was performed to evaluate possible diagnostic value of the peptides. While plasma levels of CGRP, VIP and PCT were significantly higher in patients with CAP than in the control group, respectively, NPY levels were significantly lower. Moreover, plasma levels of all neuropeptides and PCT were significantly higher in bacterial pneumonia patients compared to viral pneumonia patients. ROC analysis revealed that CGRP, SP and NPY had a diagnostic value in distinguishing viral and bacterial/mixed pneumonia. Conclusions: Our findings suggest that these neuropeptides may be implicated in pediatric CAP. CGRP, SP and NPY together may be a promising candidate in distinguishing viral and bacterial/mixed pneumonia, however, for this, further studies are needed. What is Known: • Neurogenic inflammation contributes to the development and progression of respiratory inflammatory diseases such as chronic obstructive pulmonary disease and bronchial asthma. What is New: • Plasma levels of neurogenic inflammation related neuropeptides calcitonin gene-related peptide, substance P, vasoactive intestinal peptide and neuropeptide Y are changed in pediatric community-acquired pneumonia. Calcitonin gene-related peptide, substance P and neuropeptide Y are promising candidates in distinguishing viral and bacterial/mixed pneumonia. [ABSTRACT FROM AUTHOR]

Lysine acetylation is a reversible, dynamic protein modification regulated by lysine acetyltransferases and deacetylases. However, in Basidiomycetes, the extent of lysine acetylation of nonhistone proteins remains largely unknown. Recently, we identified the deacetylase Gl sirt1 as a key regulator of the biosynthesis of ganoderic acid (GA), a key secondary metabolite of Ganoderma lucidum. To gain insight into the characteristics, extent, and biological function of Glsirt1 -mediated lysine acetylation in G. lucidum , we aimed to identify additional Gl sirt1 substrates via comparison of acetylomes between wild-type (WT) and Glsirt1 -silenced mutants. A large amount of Gl sirt1-dependent lysine acetylation occurs in G. lucidum according to the results of this omics analysis, involving energy metabolism, protein synthesis, the stress response and other pathways. Our results suggest that Gl CAT is a direct target of Gl sirt1 and that the deacetylation of Gl CAT by Gl sirt1 reduces catalase activity, thereby leading to the accumulation of intracellular reactive oxygen species (ROS) and positively regulating the biosynthesis of GA. Our findings provide evidence for the involvement of nonhistone lysine acetylation in the biological processes of G. lucidum and help elucidate the involvement of important ROS signaling molecules in regulating physiological and biochemical processes in this organism. In conclusion, this proteomic analysis reveals a striking breadth of cellular processes affected by lysine acetylation and provides new nodes of intervention in the biosynthesis of secondary metabolites in G. lucidum. [Display omitted] • Glsirt1-mediated deacetylation is involved in regulating ROS accumulation. • GlCAT is a direct target of Glsirt1. • The deacetylation of GlCAT by Glsirt1 reduces its activity. [ABSTRACT FROM AUTHOR]

It has been 50 years since the suprachiasmatic nucleus (SCN) was first identified as the central circadian clock and 25 years since the last overview of developments in the field was published in the Journal of Biological Rhythms. Here, we explore new mechanisms and concepts that have emerged in the subsequent 25 years. Since 1997, methodological developments, such as luminescent and fluorescent reporter techniques, have revealed intricate relationships between cellular and network-level mechanisms. In particular, specific neuropeptides such as arginine vasopressin, vasoactive intestinal peptide, and gastrin-releasing peptide have been identified as key players in the synchronization of cellular circadian rhythms within the SCN. The discovery of multiple oscillators governing behavioral and physiological rhythms has significantly advanced our understanding of the circadian clock. The interaction between neurons and glial cells has been found to play a crucial role in regulating these circadian rhythms within the SCN. Furthermore, the properties of the SCN network vary across ontogenetic stages. The application of cell type–specific genetic manipulations has revealed components of the functional input-output system of the SCN and their correlation with physiological functions. This review concludes with the high-risk effort of identifying open questions and challenges that lie ahead. [ABSTRACT FROM AUTHOR]

Obesity, a worldwide epidemic, leads to various metabolic disorders threatening human health. In response to stress or fasting, glucocorticoid (GC) levels are elevated to promote food intake. This involves GC-induced expression of the orexigenic neuropeptides in agouti-related protein (AgRP) neurons of the hypothalamic arcuate nucleus (ARC) via the GC receptor (GR). Here, we report a selective GR modulator (SGRM) that suppresses GR-induced transcription of genes with non-classical glucocorticoid response elements (GREs) such as Agrp-GRE, but not with classical GREs, and via this way may serve as a novel anti-obesity agent. We have identified a novel SGRM, 2-O-trans-p-coumaroylalphitolic acid (Zj7), a triterpenoid extracted from the Ziziphus jujube plant, that selectively suppresses GR transcriptional activity in Agrp-GRE without affecting classical GREs. Zj7 reduces the expression of orexigenic genes in the ARC and exerts a significant anorexigenic effect with weight loss in both high fat diet-induced obese and genetically obese db/db mouse models. Transcriptome analysis showed that Zj7 represses the expression of a group of orexigenic genes including Agrp and Npy induced by the synthetic GR ligand dexamethasone (Dex) in the hypothalamus. Taken together, Zj7, as a selective GR modulator, showed beneficial metabolic activities, in part by suppressing GR activity in non-classical GREs in orexigenic genes. This study demonstrates that a potential anorexigenic molecule may allow GRE-specific inhibition of GR transcriptional activity, which is a promising approach for the treatment of metabolic disorders. [ABSTRACT FROM AUTHOR]

Food security is important for the ever-growing global population. Soybean, Glycine max (L.) Merr., is cultivated worldwide providing a key source of food, protein and oil. Hence, it is imperative to maintain or to increase its yield under different conditions including challenges caused by abiotic and biotic stresses. In recent years, the soybean pod-sucking stinkbug Riptortus pedestris has emerged as an important agricultural insect pest in East, South and Southeast Asia. Here, we present a genomics resource for R. pedestris including its genome assembly, messenger RNA (mRNA) and microRNA (miRNA) transcriptomes at different developmental stages and from different organs. As insect hormone biosynthesis genes (genes involved in metamorphosis) and their regulators such as miRNAs are potential targets for pest control, we analyzed the sesquiterpenoid (juvenile) and ecdysteroid (molting) hormone biosynthesis pathway genes including their miRNAs and relevant neuropeptides. Temporal gene expression changes of these insect hormone biosynthesis pathways were observed at different developmental stages. Similarly, a diet-specific response in gene expression was also observed in both head and salivary glands. Furthermore, we observed that microRNAs (bantam, miR-14, miR-316, and miR-263) of R. pedestris fed with different types of soybeans were differentially expressed in the salivary glands indicating a diet-specific response. Interestingly, the opposite arms of miR-281 (-5p and -3p), a miRNA involved in regulating development, were predicted to target Hmgs genes of R. pedestris and soybean, respectively. These observations among others highlight stinkbug's responses as a function of its interaction with soybean. In brief, the results of this study not only present salient findings that could be of potential use in pest management and mitigation but also provide an invaluable resource for R. pedestris as an insect model to facilitate studies on plant-pest interactions. [ABSTRACT FROM AUTHOR]

Background: Migraine stands as a prevalent primary headache disorder, with prior research highlighting the significant involvement of oxidative stress and inflammatory pathways in its pathogenesis and chronicity. Existing evidence indicates the capacity of Dl-3-n-butylphthalide (NBP) to mitigate oxidative stress and inflammation, thereby conferring neuroprotective benefits in many central nervous system diseases. However, the specific therapeutic implications of NBP in the context of migraine remain to be elucidated. Methods: We established a C57BL/6 mouse model of chronic migraine (CM) using recurrent intraperitoneal injections of nitroglycerin (NTG, 10 mg/kg), and prophylactic treatment was simulated by administering NBP (30 mg/kg, 60 mg/kg, 120 mg/kg) by gavage prior to each NTG injection. Mechanical threshold was assessed using von Frey fibers, and photophobia and anxious behaviours were assessed using a light/dark box and elevated plus maze. Expression of c-Fos, calcitonin gene-related peptide (CGRP), Nucleus factor erythroid 2-related factor 2 (Nrf2) and related pathway proteins in the spinal trigeminal nucleus caudalis (SP5C) were detected by Western blotting (WB) or immunofluorescence (IF). The expression of IL-1β, IL-6, TNF-α, Superoxide dismutase (SOD) and malondialdehyde (MDA) in SP5C and CGRP in plasma were detected by ELISA. A reactive oxygen species (ROS) probe was used to detect the expression of ROS in the SP5C. Results: At the end of the modelling period, chronic migraine mice showed significantly reduced mechanical nociceptive thresholds, as well as photophobic and anxious behaviours. Pretreatment with NBP attenuated nociceptive sensitization, photophobia, and anxiety in the model mice, reduced expression levels of c-Fos and CGRP in the SP5C and activated Nrf2 and its downstream proteins HO-1 and NQO-1. By measuring the associated cytokines, we also found that NBP reduced levels of oxidative stress and inflammation. Most importantly, the therapeutic effect of NBP was significantly reduced after the administration of ML385 to inhibit Nrf2. Conclusions: Our data suggest that NBP may alleviate migraine by activating the Nrf2 pathway to reduce oxidative stress and inflammation in migraine mouse models, confirming that it may be a potential drug for the treatment of migraine. [ABSTRACT FROM AUTHOR]

Objective: Emotions play an important role in consumers' perception of a sensory experience. The objective of this work was to investigate the ability of basic skin care formulas (i.e. without interference of odour, colour and packaging) and pillar ingredients (i.e. emollients and rheology modifiers) to elicit emotions. Another objective was to track, as claimed by neurocosmetics, the possible effect of formulas to trigger emotions from their direct biochemical effects on the skin. Methods: Standard methodologies were mobilized, combining subjective and behavioural parameters (i.e. verbatim, prosody and gesture). Sense and Story methodology based on a collection of metaphoric verbatim was conducted after an induction phase. In addition, an experimental electrophysiological real‐time visualization method was tried as a first experience in cosmetics. Finally, the ability of formulations with emotional benefits to modulate the release of neuropeptides by sensory neurons was evaluated on a 3D human model (epidermis co‐cultured with sensory neurons). Results: Skin care formulas were shown to play a role in emotional potential and the types of emotion generated, while changing one ingredient mostly acted on the intensity of the emotions. Verbatim provided contrasted answers depending on the protocol, highlighting the interest of non‐verbal approaches to detect subtle effects. The in vitro model substantiated physiological effects of skin care formulas with emotional potential on human skin sensory neuron activity. Conclusion: Emotions were impacted by the change in ingredients and were better captured through non‐verbal methods. [ABSTRACT FROM AUTHOR]

The article focuses on the impaired glymphatic and meningeal lymphatic functions observed in patients with chronic migraine, as revealed by magnetic resonance imaging (MRI) techniques. Topics discussed include the methodology used to assess glymphatic and lymphatic function in migraine patients, the comparison between chronic and episodic migraine, and the potential implications of these findings for migraine pathophysiology and treatment strategies.

Depression is the most prevalent psychiatric disorder worldwide. Although numerous antidepressant treatments are available, there is a serious clinical concern due to their severe side effects and the fact that some depressed patients are resistant to them. Lithium is the drug of choice for bipolar depression and has been used as adjunct therapy with other groups of antidepressants. The present study aims to investigate the effect of lithium augmentation with cerebrolysin on the neurochemical, behavioral and histopathological alterations induced in the reserpine model of depression. The animals were divided into control and reserpine-induced model of depression. The model animals were further divided into rat model of depression, rat model treated with lithium, rat model treated with cerebrolysin and rat model treated with a combination of lithium and cerebrolysin. Treatment with lithium, cerebrolysin, or their combination alleviated most of the changes in behavior, oxidative stress parameters, acetylcholinesterase and monoamines in the cortex and hippocampus of the reserpine-induced model of depression. It also improved the alterations in brain-derived neurotrophic factor (BDNF) and histopathology induced by reserpine. The augmentation of lithium with cerebrolysin showed a clear beneficial effect in the present model of depression suggesting the use of cerebrolysin as an adjuvant in antidepressant treatment. [ABSTRACT FROM AUTHOR]