Neuroendocrine Pathways Research Articles

Structure of an LGR dimer - an evolutionary predecessor of glycoprotein hormone receptors.

The glycoprotein hormones of humans, produced in the pituitary and acting through receptors in the gonads to support reproduction and in the thyroid gland for metabolism, have co-evolved from invertebrate counterparts 1,2 . These hormones are heterodimeric cystine-knot proteins; and their receptors bind the cognate hormone at an extracellular domain and transmit the signal of this binding through a transmembrane domain that interacts with a heterotrimeric G protein. Structures determined for the human receptors as isolated for cryogenic electron microscopy (cryo-EM) are all monomeric 3-6 despite compelling evidence for their functioning as dimers 7-10 . Here we describe the cryo-EM structure of the homologous receptor from a neuroendocrine pathway that promotes growth in a nematode 11 . This structure is an asymmetric dimer that can be activated by the hormone from that worm 12 , and it shares features especially like those of the thyroid stimulating hormone receptor (TSHR). When studied in the context of the human homologs, this dimer provides a structural explanation for the transactivation evident from functional complementation of binding-deficient and signaling-deficient receptors 7 , for the negative cooperativity in hormone action that is manifest in the 1:2 asymmetry of primary TSH:TSHR complexes 8,9 , and for switches in G-protein usage that occur as 2:2 complexes form 9,10 .

Hotspots and development trends of gut microbiota in atopic dermatitis: A bibliometric analysis from 1988 to 2024.

Atopic dermatitis (AD) is a prevalent inflammatory skin condition that commonly occurs in children. More and more scientific evidence suggests that gut microbiota plays an important role in the pathogenesis of AD, whereas there is no article providing a comprehensive summary and analysis. We aimed to analyze documents on AD and gut microbiota and identify hotspots and development trends in this field. Articles and reviews in the field of AD and gut microbiota from January 1, 1988 to October 20, 2024 were obtained from the Web of Science Core Collection database. Biblioshiny was utilized for evaluating and visualizing the core authors, journals, countries, documents, trend topics, and hotspots in this field. Among 1672 documents, it indicated that the number of annual publications generally increased. The United States had the highest production, impact, and international collaboration. Journal of Allergy and Clinical Immunology was the journal of the maximum publications. Based on keyword co-occurrence and clustering analysis, "stratum-corneum lipids," "probiotics," "prebiotics," "fecal microbiota transplantation," "phage therapy," "short chain fatty-acids," "biologic therapy," and "skin inflammation" represented current trend topics. The pathological and molecular mechanisms and associated therapeutic methods for AD and gut microbiota were the research hotspots. The incorporation of microbiota-based therapies alongside conventional treatments can contribute to better clinical outcomes. We highlighted that gut microbiota may exacerbate symptoms of AD through various aspects, including immunity, metabolites, and neuroendocrine pathways. More efforts are required to investigate the safety and efficacy of gut microbial management methods for the prevention and treatment of AD.

Integrated Analysis of Neuroendocrine and Neurotransmission Pathways Following Developmental Atrazine Exposure in Zebrafish.

Atrazine is an endocrine-disrupting herbicide, with exposure impacting adverse outcomes along multiple endocrine pathways. This study investigated the neuroendocrine system as the central target of atrazine toxicity, examining effects of early developmental exposures on neurohormones and genes associated with kisspeptin, hypothalamic, pituitary, and dopamine systems. Zebrafish were exposed to 0, 0.3, 3, or 30 ppb (µg/L) atrazine during two developmental time windows. For neurohormone assessments, exposure was ceased at the end of embryogenesis (72 h post-fertilization, hpf) and analyzed immediately or grown to 0.5, 2, or 2.5 years post-fertilization (ypf). Gene expression was measured immediately after 1-72 hpf or 72-120 hpf exposure. Estradiol decreased in the 0.3 and 30 ppb groups in 0.5 ypf female brains, while dopamine decreased in the same treatment groups at 72 hpf. Increases were also observed in 2.5 ypf female brains (3 ppb) for estradiol and in 2 ypf female and male brains (3 and 30 ppb) for dopamine. Gene expression alterations occurred for the follicle-stimulating hormone (fsh) at 72 hpf and the growth hormone (gh1) at 72 and 120 hpf. Overall, results indicated that developmental atrazine exposure has immediate and long-term sex-specific effects on neurohormonal systems.

SMO theory: A comprehensive review of oxytocin secretion via serotonin and melatonin pathways

The secretion of oxytocin, a neuropeptide critical for social bonding, emotional regulation, and reproductive processes, is influenced by complex neuroendocrine pathways. Among these, the serotonin and melatonin pathways have garnered significant attention for their roles in modulating oxytocin release. The Serotonin-Melatonin-Oxytocin (SMO) Theory proposes a synergistic interaction between these neurotransmitters and hormones, with serotonin acting as a precursor to melatonin and both regulating oxytocin secretion through circadian rhythms and neurochemical signaling. This review provides a comprehensive analysis of current research on the serotonin and melatonin pathways in relation to oxytocin release. We explore the molecular mechanisms involved, the influence of circadian rhythms, and the broader physiological and behavioral implications of the SMO pathway. Additionally, the review discusses how dysregulation of this system may contribute to mood disorders, stress responses, and social behavior abnormalities. By integrating findings from neurobiology, chronobiology, and endocrinology, this paper aims to provide a holistic understanding of the SMO pathway and its critical role in oxytocin secretion.

Navigating the Role and Approach of Gut Microbiota in Addressing Alzheimer's Disease Pathogenesis

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid beta plaques and tau protein neurofibrillary tangles, leading to cognitive decline. The lack of effective treatments compounds the significant human and financial burdens AD poses. Despite extensive research, the exact mechanisms of the disease remain elusive. Recent studies have shown promise in using anti-Aβ antibodies to reduce amyloid accumulation and slow dementia progression. However, diversifying therapeutic strategies is crucial for making meaningful progress. In recent years, research has increasingly focused on the microbiota-gut-brain axis in AD. Mounting evidence suggests that changes in gut microbiota composition are linked to AD progression, implicating various pathways. Dysregulation of microbiota taxa can trigger systemic inflammation by increasing gut permeability, ultimately leading to neural damage and neurodegeneration. Poor dietary habits and aging exacerbate gut dysbiosis, worsening AD pathology. However, investigations in this area are still in their early stages, with many aspects awaiting exploration and understanding. A thorough comprehension of the complex interactions within the microbiota-AD relationship is essential for refining therapeutic approaches. Interventions targeting gut microbiota, such as dietary adjustments, probiotics, and faecal microbiota transplantation, offer potential as therapeutics. This review highlights the detrimental role of gut dysbiosis in AD, offering insights into enhancing therapeutic avenues for the disease. Graphical abstract: The bidirectional interaction between the brain and the gut through neuroendocrine, immune, and metabolic pathways. Created with BioRender.com

PTSD Increases Risk for Hypertension Development Through PVN Activation and Vascular Dysfunction in Sprague Dawley Rats.

This study investigates the impact of single prolonged stress (SPS), a model of post-traumatic stress disorder (PTSD), on cardiovascular responses, hypothalamic paraventricular nucleus (PVN) activity, and vascular function to elucidate the mechanisms linking traumatic stress to hypertension. Although SPS did not directly cause chronic hypertension in male Sprague Dawley (SD) rats, it induced acute but transient increases in blood pressure and heart rate and significantly altered the expression of hypertension-associated genes, such as vasopressin, angiotensin II type 1 receptor (AT1R), and FOSL1 in the PVN. Notably, mitochondrial reactive oxygen species (mtROS) were predominantly elevated in the pre-autonomic regions of the PVN, colocalizing with AT1R- and FOSL1-expressing cells, suggesting that oxidative stress may amplify sympathetic activation and stress responses. SPS also increased mRNA levels of pro-inflammatory cytokines (TNFα and IL1β) and inducible nitric oxide synthase (iNOS) in the aorta, and impaired vascular reactivity to vasoconstrictor and vasodilator stimuli, reflecting compromised vascular function. These findings suggest that SPS-sensitize neuroendocrine, autonomic, and vascular pathways create a state of cardiovascular vulnerability that could predispose individuals to hypertension when exposed to additional stressors. Understanding these mechanisms provides critical insights into the pathophysiology of stress-related cardiovascular disorders and underscores the need for targeted therapeutic interventions that address oxidative stress and modulate altered PVN pathways to mitigate the cardiovascular impact of PTSD and related conditions.

Investigating Neuroendocrine Regulation in Physiological Processes: Advancements in Techniques, Challenges and Future Direction for Human Health

Neuroendocrine regulation plays a pivotal role in orchestrating various physiological processes in organisms. The neuroendocrine system is a complex, multifaceted process that acts as a resource distributor in the body, monitoring and regulating a variety of physiological functions like metabolism, reproduction, stress response, and immunity by using complicated signaling pathways and sophisticated feedback mechanisms that use hormones, neurotransmitters, and neural circuits. This study aims to investigate the intricate mechanisms by which neuroendocrine signals modulate physiological functions. Adjuvant neuroendocrine strategies such as the use of neurotransmitters, hormones, pharmacotherapy, surgical intervention, and emerging technologies play an invaluable role in alleviating symptoms and improving outlooks for people suffering from these conditions. Through a comprehensive review of current literature, we explore the role of neuroendocrine pathways in regulating processes such as metabolism, reproduction, stress response, and immune function. We highlight the involvement of key neuroendocrine factors such as hormones, neuropeptides, and neurotransmitters in modulating these physiological processes. Additionally, authors discuss emerging research avenues and potential clinical implications of understanding neuroendocrine regulation in health and disease.

Is depression a neuroendocrine disease?

Depression, according to the World Health Organization, stands as one of the most impactful disabilities worldwide. Its toll reaches beyond mood and thought, extending into physical health risks like coronary artery disease, diabetes, osteoporosis, and stroke, leading to a lifespan reduction of approximately 7 to 10 years in those affected. This paper explores the view of depression as a neuroendocrine disorder, especially focusing on the subtype of melancholic depression. Structural and functional disruptions in brain areas—such as the prefrontal cortex and hippocampus—reveal a misalignment in the stress response system that might drive depressive symptoms. Specifically, the roles of corticotropin-releasing hormone, norepinephrine hyperactivity, glucocorticoid levels, and inflammation-related mechanisms are investigated here. These insights point to promising new treatments targeting these neuroendocrine pathways that may enhance therapeutic responses.

Insomnia symptoms predict systemic inflammation in women, but not in men with inflammatory bowel disease.

Insomnia has been suggested as a potential modulator of systemic inflammation. However, few studies have examined the longitudinal association between insomnia and inflammation as well as the role of sex differences, despite accumulating evidence of the vulnerability of women to immune consequences of disturbed sleep. In this study, we tested the association between self-reported insomnia symptoms and serum C-reactive protein, a marker of systemic inflammation, at 1-year follow-up, in 54 outpatients with inflammatory bowel disease (52.81 ± 16.09, 40.7% women). Insomnia symptoms were measured using the Insomnia Severity Index. After controlling for baseline inflammation and health variables, longitudinal moderated regression analysis showed that baseline insomnia symptoms predicted C-reactive protein levels at follow-up in women (β = 0.416, p = 0.014), but not in men (β = -0.179, p = 0.212). Results were not influenced by sex differences in insomnia severity or C-reactive protein levels. This study suggests insomnia symptoms may partially influence systemic inflammation in women with inflammatory bowel disease. Sex-specific psychological, immune and neuroendocrine pathways linking sleep to inflammation should be further elucidated.

Understanding the influence of Manasika Bhavas on Stanya Kshaya: A Conceptual Study

Breast milk stands as the foremost source of nutrition in every individual's early life. According to Ayurveda, Stanya is considered an Upadhatu of Rasa and is pivotal for the nourishment and development of infants. Ayurveda defines decreased breast milk or lactation insufficiency as Stanya Kshaya, primarily attributed to emotions like anger, grief, and excessive affection, alongside dietary influences. Psychological factors such as emotional stress, anxiety, and maternal health also significantly impact milk production, necessitating both psychological and medical interventions. Any disruption in Agni affects Ahara Rasa, leading to disturbances in Rasa Dhatu, thereby affecting Stanya. Psychological aspects play a crucial role in the proper formation of Ahara Rasa. The significance of Manasika Bhavas lies in their advocacy of Soumanasya as a primary treatment for Ksheerajanana. This paper explores the correlation between psychological well-being and lactation outcomes, drawing on both contemporary psychological research and traditional Ayurvedic principles. Psychological stress, anxiety, depression, and maternal bonding are examined as key factors affecting hormonal balance and neuroendocrine pathways involved in lactation. Understanding these influences is crucial for holistic approaches to maternal health and breastfeeding support. The integration of psychological interventions alongside conventional medical treatments could enhance maternal lactation success rates and overall maternal-infant health outcomes. Thus, managing Stanya Kshaya requires thorough consideration of both psychological factors and dietary practices.

The epigenetic effects of glucocorticoids, sex hormones and vitamin D as steroidal hormones in rheumatic musculoskeletal diseases.

Chronic rheumatological diseases are multifactorial conditions in which both the neuroendocrine hormone pathway, including cortisol, sex hormones and active vitamin D3 (calcitriol), all deriving from cholesterol, and the epigenetic modifications that they cause play an important role. In fact, epigenetics modulates the function of the DNA of immune cells, through three main mechanisms: DNA methylation, modifications to the histones that make up chromatin and production of non-coding RNAs (microRNA - miRNA). In this narrative review, the main data regarding the epigenetic modifications induced by cortisol, 17β-oestradiol, progesterone, testosterone and calcitriol on immune cells were collected, discussing how these can interfere in the predisposition and course of chronic rheumatological diseases (i.e. rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis). An ever-increasing number of miRNAs have been identified, which are produced by neuroendocrine hormones and can influence the inflammatory-fibrotic response at various levels. Concerning the involvements of the neuro-endocrine-immunology within the pathophysiology of rheumatic diseases, the epigenetic effects induced by steroid hormones must be taken into consideration to evaluate their impact on the progression of the single condition and even inside the single patient.

Role of urea to creatinine ratio in the prediction of outcomes in chronic heart failure

Abstract Background Renal function predicts events in chronic heart failure (HF). Urea to creatinine ratio (UCR) is a simple and cheap biomarker which correlates with neuroendocrine pathways. Objectives Evaluate the prognostic role of UCR in patients with chronic HF. Methodology 86 patients with chronic HF from an academic hospital were included (with reduced, mildly reduced or improved left ventricular ejection fraction). UCR was calculated at baseline, and patients were followed for a median of 360 (interquartile range 180-472) days. We plotted ROC curves for NT-proBNP and UCR and evaluated two scenarios using the Kaplan-Meier curve to determine the event-free survival. We grouped patients into four subgroups: a) UCR and NT-proBNP below the cut-off; b) UCR above and NT-proBNP below; c) UCR below and NT-proBNP above; and d) both above the cut-off. A second scenario was analysed, grouped as follows: a) UCR and NT-proBNP below; b) at least one of them above the cut-off; and c) both above the cutoff. The primary endpoint was cardiovascular death or HF hospitalisation. The level of significance was 5%. Results The mean age was 66.1±12.1y, and 60.5% were male. There were 28 events in the follow-up (32.5%). The ROC curve for UCR had an AUC of 0.75 (CI 0.64-0.86; p=0.0002) for a cut-off of 43.8 (sensitivity of 75% and specificity of 70.7%). The AUC for NT-proBNP was 0.64 (0.51-0.77; p=0.043) for a cut-off of 2010 pg/mL (sensitivity of 64.3% and specificity of 65.5%). In the Cox regression model, the UCR was the only independent predictor with HR of 1.06 per 1 unit increase (1.03-1.10; p=0.0002). UCR above cut-off (as a categorical variable) was the only independent predictor, with HR 5.34 (2.26-12.6; p=0.0001). Kaplan-Meier curves in Figures 1 and 2 show the UCR performance associated with NT-proBNP. Conclusions UCR is a simple and cheap biomarker that has been shown to have predictive power, probably due to persistent neuroendocrine activation in patients with low volume. In this population, elevated UCR added risk even in patients with low levels of NT-proBNP.

Autonomic nervous system responses to hypo- and hyperglycemia in type 2 diabetes and prediabetes.

Previous research points to a role of the brain in the regulation of glucose and pathogenesis of type 2 diabetes (T2D) via modulation of counter-regulatory hormone secretion and activity in the autonomic nervous system (ANS). The aim of this study was to investigate glucose-dependent responses of catecholamines and ANS activity in individuals with T2D, prediabetes (PD), and normoglycemia (NG). Cross-sectional. Individuals with T2D (n = 19, 7 men, HbA1c 49 mmol/mol), PD (n = 18, 8 men), and NG (n = 17, 3 men) underwent 1 stepwise hyperinsulinemic-euglycemic-hypoglycemic and 1 hyperglycemic clamp with repeated measurements of catecholamines, symptoms, heart rate variability (HRV), and hemodynamics. The hypoglycemic response of adrenaline was augmented in T2D and PD vs NG (both P < .05), and there was a strong association with insulin resistance (P < .05 for M-value). In relation to achieved glucose levels in both clamps, noradrenaline exhibited a steeper rise during hypoglycemia in T2D vs NG and PD (both P < .05). There were trends toward more marked autonomic hypoglycemic symptoms in T2D vs PD and NG. By contrast, insulin resistance was associated with attenuated responses of heart rate and HRV indices PLF and PHF at the target glucose plateau of 2.7 mmol/L (P < .05), independent of BMI and HbA1c. Alterations in glucose-dependent responses of counter-regulatory hormones and the ANS appear before, and probably contribute to, the onset of T2D. Together with other reported alterations in neuroendocrine pathways, the findings suggest that a maladaptation of the brain's responses to glucose fluctuations is important in T2D progression.

RETRACTION: Basic Fibroblast Growth Factor Accelerates Matrix Degradation via a Neuro-endocrine Pathway in Human Adult Articular Chondrocytes.

H.-J. Im, X. Li, P. Muddasani, G.-H. Kim, F. Davis, J. Rangan, C. B. Forsyth, M. Ellman, and E. J. Thonar, "Basic Fibroblast Growth Factor Accelerates Matrix Degradation via a Neuro-endocrine Pathway in Human Adult Articular Chondrocytes," Journal of Cellular Physiology 215, no. 2 (2008): 452-463, https://doi.org/10.1002/jcp.21317. The above article, published online on 24 October 2007 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Robert Heath; and Wiley Periodicals LLC. The retraction has occurred due to concerns related to the data presented in the article raised by the Office of Research Compliance at Rush University Medical Center following an investigation jointly conducted by Rush University and the Jesse Brown Veterans Affairs Medical Center (JBVAMC). Specifically, image elements of the experimental data in Figure 6 A were found to have been used by the same author(s) for publication elsewhere in a different scientific context. The corresponding author, Dr. Hee-Jeong Im Sampen, has been informed of the decision to retract but did not agree with it, as she is confident that any errors in the publication do not impact the reliability of the paper's findings. She also advised the editors that she stands ready to cooperate fully to make any necessary corrections. However, the article is retracted as the editors lost trust in the accuracy of the data and consider the conclusions invalid.

Associations of pre- and postnatal per- and polyfluoroalkyl substance exposure with adolescents' eating behaviors.

Per- and polyfluoroalkyl substances (PFAS), persistent environmental chemicals, may act as obesogens by interacting with neuroendocrine pathways regulating energy homeostasis and satiety signals influencing adolescent eating behaviors. In 211 HOME Study adolescents (Cincinnati, OH; recruited 2003-2006), we measured PFAS concentrations in serum collected during pregnancy, at delivery, and at ages 3, 8, and 12 years. Caregivers completed the Child Eating Behavior Questionnaire (CEBQ) at age 12, and we calculated food approach and food avoidance scores. Using quantile-based g-computation, we estimated covariate-adjusted associations between a mixture of four gestational PFAS and CEBQ scores. We identified high (n = 76, 36%) and low (n = 135, 64%) longitudinal PFAS mixture exposure profiles between delivery and age 12 years using latent profile analysis and related these to CEBQ scores. We examined whether child sex or physical activity modified these associations. We observed no association of gestational PFAS mixture with food approach or food avoidance scores. Children in the higher longitudinal PFAS mixture profile had slightly higher food approach scores (β: 0.47, 95% CI: -0.27, 1.23) and similar food avoidance scores (β: -0.15, 95% CI: -0.75, 0.46) compared with children in the lower profile. We found some evidence that higher physical activity favorably modified the association between longitudinal PFAS mixture profiles and emotional overeating (interaction P value = 0.13). Child sex did not consistently modify any associations. Serum PFAS concentrations were not consistently linked to adolescent eating behaviors in this study, suggesting alternative pathways, such as metabolic rate, may underlie previously observed associations between PFAS exposure and childhood obesity.

Targeting MCH Neuroendocrine Circuit in Lateral Hypothalamus to Protect Against Skeletal Senescence.

Neuroendocrine regulation is essential for maintaining metabolic homeostasis. However, whether neuroendocrine pathway influence bone metabolism and skeletal senescence is unelucidated. Here, a central neuroendocrine circuit is identified that directly controls osteogenesis. Using virus based tracing, this study is identified that melanin concentrating hormone (MCH) expressing neurons in the lateral hypothalamus (LH) are connected to the bone. Chemogenetic activation of MCH neurons in the LH induces osteogenesis, whereas inhibiting these neurons reduces osteogenesis. Meanwhile, MCH is released into the circulation upon chemogenetic activation of these neurons. Single cell sequencing reveals that blocking MCH neurons in the LH diminishes osteogenic differentiation of bone marrow stromal cells (BMSCs) and induces senescence. Mechanistically, MCH promotes BMSC differentiation by activating MCHR1 via PKA signaling, and activating MCHR1 by MCH agonists attenuate skeletal senescence in mice. By elucidating a brain-bone connection that autonomously enhances osteogenesis, these findings uncover the neuroendocrinological mechanisms governing bone mass regulation and protect against skeletal senescence.

Exploring the pathogenesis of insomnia and acupuncture intervention strategies based on the microbiota-gut-brain axis.

Insomnia is a common sleep disorder observed in clinical settings, with a globally rising prevalence rate. It not only impairs sleep quality and daytime functioning but also contributes to a range of physiological and psychological conditions, often co-occurring with somatic and mental disorders. Currently, the pathophysiology of this condition is not fully understood. Treatment primarily involves symptomatic management with benzodiazepine receptor agonists, melatonin and its receptor agonists, sedative antidepressants, atypical antipsychotics, and orexin receptor antagonists. However, due to the adverse side effects of these drugs, including dependency, addiction, and tolerance, there is an urgent need for safer, more effective, and environmentally friendly treatment methods. In recent years, research on the microbiota-gut-brain axis has received significant attention and is expected to be key in uncovering the pathogenesis of insomnia. Acupuncture stimulates acupoints, activating the body's intrinsic regulatory abilities and exerting multi-pathway, multi-target regulatory effects. A substantial body of evidence-based research indicates that acupuncture is effective in treating insomnia. However, the unclear mechanisms of its action have limited its further clinical application in insomnia treatment. Therefore, this study aims to elucidate the pathogenesis of insomnia from the perspective of the microbiota-gut-brain axis by examining metabolic, neuro-endocrine, autonomic nervous, and immune pathways. Additionally, this study discusses the comprehensive application of acupuncture in treating insomnia, aiming to provide new strategies for its treatment.

Photoneuroendocrine, circadian and seasonal systems: from photoneuroendocrinology to circadian biology and medicine.

This contribution highlights the scientific development of two intertwined disciplines, photoneuroendocrinology and circadian biology. Photoneuroendocrinology has focused on nonvisual photoreceptors that translate light stimuli into neuroendocrine signals and serve rhythm entrainment. Nonvisual photoreceptors first described in the pineal complex and brain of nonmammalian species are luminance detectors. In the pineal, they control the formation of melatonin, the highly conserved hormone of darkness which is synthesized night by night. Pinealocytes endowed with both photoreceptive and neuroendocrine capacities function as "photoneuroendocrine cells." In adult mammals, nonvisual photoreceptors controlling pineal melatonin biosynthesis and pupillary reflexes are absent from the pineal and brain and occur only in the inner layer of the retina. Encephalic photoreceptors regulate seasonal rhythms, such as the reproductive cycle. They are concentrated in circumventricular organs, the lateral septal organ and the paraventricular organ, and represent cerebrospinal fluid contacting neurons. Nonvisual photoreceptors employ different photopigments such as melanopsin, pinopsin, parapinopsin, neuropsin, and vertebrate ancient opsin. After identification of clock genes and molecular clockwork, circadian biology became cutting-edge research with a focus on rhythm generation. Molecular clockworks tick in every nucleated cell and, as shown in mammals, they drive the expression of more than 3000 genes and are of overall importance for regulation of cell proliferation and metabolism. The mammalian circadian system is hierarchically organized; the central rhythm generator is located in the suprachiasmatic nuclei which entrain peripheral circadian oscillators via multiple neuronal and neuroendocrine pathways. Disrupted molecular clockworks may cause various diseases, and investigations of this interplay will establish a new discipline: circadian medicine.

Impact of Perioperative Lidocaine on Neutrophil Extracellular Trapping and Serum Cytokines in Robot-Assisted Radical Prostatectomy: Randomized Controlled Study.

Background and Objective: This randomized controlled trial investigated the influence of perioperative lidocaine administration on the postoperative inflammatory response in patients undergoing robot-assisted radical prostatectomy, with the results having potential implications for postoperative recovery and cancer recurrence via neutrophil extracellular trapping (NETosis). Materials and Methods: In total, 58 patients with localized prostate cancer were randomly assigned to receive an intravenous infusion of 2% lidocaine or a saline placebo intraoperatively. Serum levels of interleukin (IL)-6, IL-10, and IL-17, tumor necrosis factor(TNF)-α, interferon(IFN)-γ, neutrophil elastase (NE), citrullinated histone3 (CitH3), and myeloperoxidase (MPO) were determined preoperatively and at 24 h postoperatively. Biochemical recurrence (BCR) was assessed over a follow-up period of 2 years. Results: The lidocaine group showed a significant change in MPO, a greater reduction in IL-10 level, and a smaller increase in the NE level compared to the placebo group, suggesting a modulatory effect of lidocaine on certain anti-inflammatory and neuroendocrine pathways. No significant difference in the BCR rate was observed between the two groups. Conclusions: Perioperative lidocaine administration selectively modulates certain inflammatory and neuroendocrine responses after robot-assisted radical prostatectomy surgery, potentially influencing recovery outcomes. These findings highlight the need for further investigations of the role of lidocaine in Enhanced Recovery After Surgery protocols, particularly in oncologic surgeries.

Obesity and the gut microbiota: implications of neuroendocrine and immune signaling.

Obesity is a major health challenge due to its high prevalence and associated comorbidities. The excessive intake of a diet rich in fat and sugars leads to a persistent imbalance between energy intake and energy expenditure, which increases adiposity. Here, we provide an update on relevant diet-microbe-host interactions contributing to or protecting from obesity. In particular, we focus on how unhealthy diets shape the gut microbiota and thus impact crucial intestinal neuroendocrine and immune system functions. We describe how these interactions promote dysfunction in gut-to-brain neuroendocrine pathways involved in food intake control and postprandial metabolism and elevate the intestinal proinflammatory tone, promoting obesity and metabolic complications. In addition, we provide examples of how this knowledge may inspire microbiome-based interventions, such as fecal microbiota transplants, probiotics, and biotherapeutics, to effectively combat obesity-related disorders. We also discuss the current limitations and gaps in knowledge of gut microbiota research in obesity.