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There is no consensus on the optimal surgical technique for allergic rhinitis (AR). Furthermore, the appropriateness of surgical intervention in children and older individuals remains debatable. This study aimed to analyze trends and patterns in the surgical management of AR in Japan, focusing on parasympathetic neurectomy. Using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), we conducted a comprehensive review of procedures performed between April 2014 and March 2022. In addition, a cross-sectional survey targeting otolaryngologists across Japan was conducted to gather insights into surgical preferences and practices. The NDB data showed an increasing trend in neurectomies, with the most frequent age group being 25–29 years; the procedure was also performed in pediatric and older patients. The survey among otolaryngologists indicated that 58.2 % of surgeons preferred peripheral branch neurectomy of the posterior nasal nerve. The findings of this study also indicated a cautious approach toward conducting these procedures in children, with 51.2 % of surgeons considering patients less than 18 years of age unsuitable for the procedure. This study highlighted a shift toward simple and minimally invasive surgical methods, such as peripheral branch neurectomy, in Japan. However, further research is needed to understand the long-term outcomes and refine the surgical techniques. The findings of this study also emphasized the need for age-specific considerations when treating pediatric and older patients with AR. [ABSTRACT FROM AUTHOR]

Many researchers have focused on the role of the autonomic nervous system in the tumor microenvironment. Autonomic nerves include the sympathetic and parasympathetic nerves, which are known to induce cancer growth and metastasis. However, in salivary duct carcinoma (SDC), a rare and highly malignant tumor, the issue should be investigated from both biological and therapeutic perspectives. We explored the clinicopathological and prognostic implications of the autonomic nerves in 129 SDCs. Immunohistochemistry was performed to determine the nature of each nerve using antibodies against S100, tyrosine hydroxylase (TH) as a sympathetic marker, and vesicular acetylcholine transporter (VAChT) as a parasympathetic marker. The area of each marker-positive nerve was digitized and evaluated quantitatively. Double immunofluorescence for TH and VAChT was performed in selected cases. The expression of the secreted neurotrophins was also examined. S100-positive nerves were present in the cancer tissue in 94 of 129 cases (72.9%). Among them, TH-positive sympathetic nerves and/or VAChT-positive parasympathetic nerves were identified in 92 cases (97.9%), and 59 cases (62.8%) had TH/VAChT-co-expressing nerves. Double immunofluorescence revealed a mosaic pattern of sympathetic and parasympathetic fibers in co-expressing nerve bundles. The presence of autonomic nerves, regardless of their area, was significantly associated with aggressive histological features, advanced T/N classification, and a poor prognosis, with shorter disease-free and overall survival. There was an association between some tumor immune microenvironment-related markers and the autonomic nerve status, but not the latter and the secreted neurotrophin expression. This study suggests that autonomic nerves might play a role in the progression of SDC. [ABSTRACT FROM AUTHOR]

During the urine storage phase, tonically contracting urethral musculature would have a higher energy consumption than bladder muscle that develops phasic contractions. However, ischaemic dysfunction is less prevalent in the urethra than in the bladder, suggesting that urethral vasculature has intrinsic properties ensuring an adequate blood supply. Diameter changes in rat or mouse urethral arterioles were measured using a video‐tracking system. Intercellular Ca2+ dynamics in arteriolar smooth muscle (SMCs) and endothelial cells were visualised using NG2‐ and parvalbumin‐GCaMP6 mice, respectively. Fluorescence immunohistochemistry was used to visualise the perivascular innervation. In rat urethral arterioles, sympathetic vasoconstrictions were predominantly suppressed by α,β‐methylene ATP (10 μM) but not prazosin (1 μM). Tadalafil (100 nM), a PDE5 inhibitor, diminished the vasoconstrictions in a manner reversed by N‐ω‐propyl‐l‐arginine hydrochloride (l‐NPA, 1 μM), a neuronal NO synthesis (nNOS) inhibitor. Vesicular acetylcholine transporter immunoreactive perivascular nerve fibres co‐expressing nNOS were intertwined with tyrosine hydroxylase immunoreactive sympathetic nerve fibres. In phenylephrine (1 μM) pre‐constricted rat or mouse urethral arterioles, nerve‐evoked vasodilatations or transient SMC Ca2+ reductions were largely diminished by l‐nitroarginine (l‐NA, 10 μM), a broad‐spectrum NOS inhibitor, but not by l‐NPA. The CGRP receptor antagonist BIBN‐4096 (1 μM) shortened the vasodilatory responses, while atropine (1 μM) abolished the l‐NA‐resistant transient vasodilatory responses. Nerve‐evoked endothelial Ca2+ transients were abolished by atropine plus guanethidine (10 μM), indicating its neurotransmitter origin and absence of non‐adrenergic non‐cholinergic endothelial NO release. In urethral arterioles, NO released from parasympathetic nerves counteracts sympathetic vasoconstrictions pre‐ and post‐synaptically to restrict arteriolar contractility. Key points: Despite a higher energy consumption of the urethral musculature than the bladder detrusor muscle, ischaemic dysfunction of the urethra is less prevalent than that of the bladder.In the urethral arterioles, sympathetic vasoconstrictions are predominately mediated by ATP, not noradrenaline.NO released from parasympathetic nerves counteracts sympathetic vasoconstrictions by its pre‐synaptic inhibition of sympathetic transmission as well as post‐synaptic arteriolar smooth muscle relaxation.Acetylcholine released from parasympathetic nerves contributes to endothelium‐dependent, transient vasodilatations, while CGRP released from sensory nerves prolongs NO‐mediated vasodilatations.PDE5 inhibitors could be beneficial to maintain and/or improve urethral blood supply and in turn the volume and contractility of urethral musculature. [ABSTRACT FROM AUTHOR]

Background: Endoscopic vidian neurectomy is expected to provide good therapeutic relief in patients with allergic rhinitis (AR) being refractory to medication therapy or conservative surgery. However, the evidence bases for its benefit remain debatable. In this study, we conducted a systematic review and meta‐analysis to clarify the therapeutic role of various forms of vidian neurectomy in refractory AR. Method: Preferred Reporting Items for Systematic Reviews and Meta‐analyses guidelines were used to conduct a systematic review of primary studies that reported original patient data for endoscopic vidian neurectomy (EVN) and vidian‐branch neurectomy, which includes selective vidian neurectomy (SVN) and posterior nasal neurectomy (PNN). The primary outcome was patient‐reported outcome measures (PROMs), including the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and Visual Analog Scale (VAS), to assess an improvement in nasal symptom severity and quality of patient's life. The incidence of surgical complications and other objective outcomes were considered secondary outcomes. Results: This review included 24 clinical studies involving 1677 patients with refractory AR, of which 510 patients in six studies had combined chronic rhinosinusitis with nasal polyps (CRSwNP) and 95 patients in one study had combined asthma. Postoperative PROMs were significantly better than preoperatively in almost all patients who underwent vidianp (RQLQ: standardized mean difference [SMD] = 2.66, 95% confidence interval [CI] = 2.40–2.92, p < 0.001; VAS: SMD = 5.15, 95% CI = 4.29–6.02, p < 0.001) or vidian‐branch neurectomy (RQLQ in PNN: SMD = 3.29, 95% CI = 2.45–4.13, p < 0.001; VAS in PNN: SMD = 4.38, 95% CI = 3.41–5.34, p < 0.001), and were generally better than in the conservative treatment group. Dividing with 18 months as the cutoff point, a subgroup analysis of the follow‐up period was conducted, and the results showed that both long‐term and short‐term postoperative patients had considerably reduced symptoms compared to the preoperative period. The two surgical procedures, SVN and PNN, attributed to vidian‐branch neurectomy have extremely few complications. However, EVN is more likely to cause dry eyes and palatal numbness, with no other serious complications. In patients with AR and CRSwNP, vidian or selective vidian neurectomy combined with functional endoscopic sinus surgery (FESS) is more effective than conventional FESS (RQLQ: SMD = 2.17, 95% CI = 1.66–2.69, p < 0.001; VAS: SMD = 6.42, 95% CI = 4.78–8.06, p < 0.001). For patients who have both AR and asthma, SVN with pharyngeal branch excision is a potential treatment option. Conclusion: EVN and vidian‐branch neurectomy (including SVN and PNN) are effective treatments, but the former has a higher risk of complications. Additionally, vidian‐branch neurectomy with FESS is beneficial for patients with mixed CRSwNP. SVN is a potential approach for patients with coexisting AR and asthma. [ABSTRACT FROM AUTHOR]

Airway nerves regulate vital airway functions including bronchoconstriction, cough, and control of respiration. Dysregulation of airway nerves underlies the development and manifestations of airway diseases such as chronic cough, where sensitization of neural pathways leads to excessive cough triggering. Nerves are heterogeneous in both expression and function. Recent advances in confocal imaging and in targeted genetic manipulation of airway nerves have expanded our ability to visualize neural organization, study neuro-immune interactions, and selectively modulate nerve activation. As a result, we have an unprecedented ability to quantitatively assess neural remodeling and its role in the development of airway disease. This review highlights our existing understanding of neural heterogeneity and how advances in methodology have illuminated airway nerve morphology and function in health and disease. [ABSTRACT FROM AUTHOR]

This retrospective cross-sectional study aimed to investigate the association between autonomic parameters measured using the Kiritsu-Meijin device and visual-field defects in patients with open-angle glaucoma. A total of 79 eyes of 42 patients with open-angle glaucoma were enrolled in this study. Kiritsu-Meijin testing comprised three phases: sitting, standing, and sitting again (2 min, 2 min, and 1 min, respectively). Continuous electrocardiograms were recorded for five minutes. Autonomic parameters were extracted from the resulting data and analyzed, including activity, balance, reaction, switchover, and recovery; these are five representative parameters derived from Kiritsu-Meijin testing. Correlations between these parameters and mean deviation from Humphrey visual field testing were determined. Additionally, we used a linear mixed-effects model to observe sectoral differences in the relationship between total deviation and the Kiritsu-Meijin parameters. In this study, we focused on superior, central, and inferior total deviations. Significant positive correlations were observed between activity, balance, and recovery and mean deviation values (β = 0.29–0.38, p <.05). The β value between activity and inferior total deviation was higher than that between activity and superior total deviation (β = 0.22, p <.05). Balance did not show any sectoral differences (p >.05). Recovery was more strongly associated with central to inferior total deviation than superior total deviation (β = 0.17–0.25, p <.05). Our findings suggest that in patients with open-angle glaucoma, lower activity and recovery are associated with more severe central and/or inferior visual field defects in the superior quadrant. These results imply that measurements of autonomic function made with the Kiritsu-Meijin device may have clinical utility in the management of glaucoma. [ABSTRACT FROM AUTHOR]

Abstract Recent research underscores the significance of the nervous system in tumor progression. Nonetheless, understanding the intricate roles of nerves in gastric tumorigenesis remains limited. Our study aims to elucidate nerve alterations, associated key genes, and signaling pathways during gastric tumorigenesis. We enroll 257 patients with gastric precancerous lesions (GPLs) from four national cohorts. Utilizing immunohistochemistry and digital analysis, we quantified the densities of sympathetic and parasympathetic nerves, as well as Schwann cells in patient slides. We collected three mRNA expression profiles of GPL samples from the gene expression omnibus database and assessed them for nerve expression signatures, differentially expressed genes, enriched pathways, and the immune microenvironment. Parasympathetic nerve and Schwann cell densities display a progressive increase, while sympathetic nerve exhibits an inverse trend along the precancerous spectrums. Notably, CD8+ T cells, natural killer cells, and antigen‐presenting cells (APC) co‐inhibition decrease, while epithelial‐mesenchymal transition increases significantly from early to late premalignancy. Several key nerve‐regulating genes (NTRK3, MYBL2, NRP1, BCL2, CCND1, VEGFA, PLXNA2, ADRB2), and pathways (mitogen‐activated protein kinase [MAPK]/ERK, PI3K/AKT, Wnt) emerge as potential contributors to precancerous progression. Our study reveals a dynamic relationship between sympathetic and parasympathetic nerves, characterized by a gradual increase in parasympathetic nerve and Schwann cell density, contrasting with an inverse trend in sympathetic nerve across precancerous spectrums. Targeting the interaction between tumor cells and nerves, including sympathetic and parasympathetic nerves, has emerged as a promising strategy for the prevention and treatment of gastric cancer.

ObjectiveBiliary innervation is considered important in regulating the function of bile ducts, whereas the role of innervation in the hepatobiliary system of patients with biliary atresia (BA) remains unknown. This current study aims to investigate the role of innervation in biliary remnants and analyze the relationship between the innervation and prognosis of BA after surgery.MethodsEighty-seven patients with type III BA who underwent the Kasai procedure were consecutively enrolled from January 2017 to September 2020. Innervation and ductules in remnants were examined by pathologists. Liver function, onset of cholangitis, jaundice clearance, and survival with the native liver were recorded. Patients were followed up for 24 months. The relationship between innervation and prognosis was analyzed.ResultsIn total, 67 patients had bile drainage postoperatively, and 21 biliary remnants contained neuronal plexuses where there was no neuron but nerve fiber bundles. Acetylcholinesterase staining was positive in all plexuses. In patients with bile drainage, those with plexuses had improved postoperative liver function, significantly better jaundice clearance 3 or 6 months postoperatively (50.0% vs. 19.1%, or 90.0% vs. 63.8%, respectively), fewer episodes of early cholangitis (10.0% vs. 34.0%), and better survival (80.0% vs. 61.7%) compared to those without. In addition, a larger area of plexuses was associated with a larger area of ductules (R2 = 0.786, p = 0.000), less frequent (p = 0.000) and later cholangitis onset (p = 0.012), and better jaundice clearance (p = 0.063).ConclusionsIncreased cholinergic innervation in biliary remnants may help reduce the onset of cholangitis and lead to better and earlier jaundice clearance. Thus, it improves the postoperative prognosis of patients with BA.

Type 1 diabetes (T1D) is an autoimmune disease with a shortage of islet β cells. To date, the etiology of T1D remains elusive. Increasing clinical evidence and animal studies demonstrate that autoimmune cells are directed against the nervous system of pancreatic islets, contributing to the development of T1D. Therefore, it highlights the necessity to explore novel clinical approaches to fundamentally correct the T1D autoimmunity not only focusing on islet β cells but also on protecting the islet nervous system. This allows the restoration of the integrity of islet innervation and the normal islet β-cell function. To address these issues, we developed a novel technology designated the Stem Cell Educator TM therapy, based on immune education by human cord-blood-derived multipotent stem cells (CB-SC). International amulticenter clinical trials demonstrated its clinical safety and efficacy to treat T1D and other autoimmune diseases. Stem Cell Educator TM therapy may have the potential to revolutionize the treatment of T1D, without the safety and ethical concerns associated with conventional immune and/or stem cell-based therapies. [ABSTRACT FROM AUTHOR]

The autonomic nervous system (ANS) is a diffuse network that regulates physiological systems to maintain body homeostasis by integrating inputs from the internal and external environment, including the sympathetic, parasympathetic, and enteric nervous systems (ENS). Recent evidence suggests that ANS is one of the key neural pathways for acupuncture signal transduction, which has attracted worldwide attention in the acupuncture field. Here, we reviewed the basic and clinical research published in PubMed over the past 20 years on the effects of acupuncture on ANS regulation and homeostasis maintenance. It was found that acupuncture effectively alleviates ANS dysfunction-associated symptoms in its indications, such as migraine, depression, insomnia, functional dyspepsia, functional constipation. Acupuncture stimulation on some specific acupoints activates sensory nerve fibers, the spinal cord, and the brain. Using information integration and efferents from a complex network of autonomic nuclei of the brain, such as the insular cortex (IC), prefrontal cortex, anterior cingulate cortex (ACC), amygdala (AMG), hypothalamus, periaqueductal gray (PAG), nucleus tractus solitarius (NTS), ventrolateral medulla (VLM), nucleus ambiguus (AMB), acupuncture alleviates visceral dysfunction, inflammation via efferent autonomic nerves, and relieves pain and pain affect. The modulating pattern of sympathetic and parasympathetic nerves is associated with acupuncture stimulation on specific acupoints, intervention parameters, and disease models, and the relationships among them require further exploration. In conclusion, ANS is one of the therapeutic targets for acupuncture and mediates acupuncture's actions, which restores homeostasis. A systemic study is needed to determine the rules and mechanisms underlying the effects of acupoint stimulation on corresponding organs mediated by specific central nervous networks and the efferent ANS. [ABSTRACT FROM AUTHOR]

Objectives: Although many studies have shown that acupuncture can improve sleep quality, there is no clear evidence by objective physiological measures. The authors investigated the effects of acupuncture on the autonomic indices of heart rate variability (HRV) during sleep. Design: The authors applied true acupuncture and sham-site stimulations in 10 healthy adult males (mean ± standard deviation age, 40 ± 9 years) and compared autonomic nerve indices of HRV during each sleep stage in a crossover design. The sleep stages were estimated by the combined analysis of an HRV maker of non-rapid eye movement (REM) sleep (HRV sleep index [Hsi]) and actigraphic body movement. Results: Heart rate was lower (true vs. sham acupuncture, mean ± standard error of the mean, 60.9 ± 1.8 vs. 61.7 ± 1.7 bpm, p < 0.0001) and the power of low-frequency and high-frequency components of HRV was higher (35.6 ± 2.0 vs. 34.7 ± 2.0 msec, p = 0.04 and 26.7 ± 3.2 vs. 25.8 ± 3.2 msec, p < 0.0001, respectively) after the true acupuncture compared with the sham-site stimulation throughout sleep. During non-REM sleep, heart rate was lower (59.6 ± 1.8 vs. 60.1 ± 1.8 bpm, p = 0.0004) and the power of low-frequency and high-frequency components were higher (27.7 ± 1.8 vs. 26.1 ± 1.8 msec p = 0.0004 and 28.4 ± 3.5 vs. 27.7 ± 3.5 msec, p = 0.004) after the true acupuncture than the sham-site stimulation. Whereas during REM sleep, there was no significant difference in either HRV indices between them, while heart rate was lower after the true acupuncture than the sham-site stimulation (60.8 ± 1.6 vs. 61.7 ± 1.6 bpm, p < 0.0001). Conclusions: Acupuncture increases parasympathetic HRV indices during sleep, especially during the non-REM stage. [ABSTRACT FROM AUTHOR]

Many researchers have focused on the role of the autonomic nervous system in the tumor microenvironment. Autonomic nerves include the sympathetic and parasympathetic nerves, which are known to induce cancer growth and metastasis. However, in salivary duct carcinoma (SDC), a rare and highly malignant tumor, the issue should be investigated from both biological and therapeutic perspectives. We explored the clinicopathological and prognostic implications of the autonomic nerves in 129 SDCs. Immunohistochemistry was performed to determine the nature of each nerve using antibodies against S100, tyrosine hydroxylase (TH) as a sympathetic marker, and vesicular acetylcholine transporter (VAChT) as a parasympathetic marker. The area of each marker-positive nerve was digitized and evaluated quantitatively. Double immunofluorescence for TH and VAChT was performed in selected cases. The expression of the secreted neurotrophins was also examined. S100-positive nerves were present in the cancer tissue in 94 of 129 cases (72.9%). Among them, TH-positive sympathetic nerves and/or VAChT-positive parasympathetic nerves were identified in 92 cases (97.9%), and 59 cases (62.8%) had TH/VAChT-co-expressing nerves. Double immunofluorescence revealed a mosaic pattern of sympathetic and parasympathetic fibers in co-expressing nerve bundles. The presence of autonomic nerves, regardless of their area, was significantly associated with aggressive histological features, advanced T/N classification, and a poor prognosis, with shorter disease-free and overall survival. There was an association between some tumor immune microenvironment-related markers and the autonomic nerve status, but not the latter and the secreted neurotrophin expression. This study suggests that autonomic nerves might play a role in the progression of SDC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The technique of organ transplantation is well established and after transplantation the patient might be faced with the problem of nerve regeneration of the transplanted organ. Transplanted organs are innervated by the sympathetic, parasympathetic, and visceral sensory plexuses, but there is a lack of clarity regarding the neural influences on the heart, liver and kidneys and the mechanisms of their innervation. Although there has been considerable recent work exploring the potential mechanisms of nerve regeneration in organ transplantation, there remains much that is unknown about the heterogeneity and individual variability in the reinnervation of organ transplantation. The widespread availability of radioactive nerve tracers has also made a significant contribution to organ transplantation and has helped to investigate nerve recovery after transplantation, as well as providing a direction for future organ transplantation research. In this review we focused on neural tracer imaging techniques in humans and provide some conceptual insights into theories that can effectively support our choice of radionuclide tracers. This also facilitates the development of nuclear medicine techniques and promotes the development of modern medical technologies and computer tools. We described the knowledge of neural regeneration after heart transplantation, liver transplantation and kidney transplantation and apply them to various imaging techniques to quantify the uptake of radionuclide tracers to assess the prognosis of organ transplantation. We noted that the aim of this review is both to provide clinicians and nuclear medicine researchers with theories and insights into nerve regeneration in organ transplantation and to advance imaging techniques and radiotracers as a major step forward in clinical research. Moreover, we aimed to further promote the clinical and research applications of imaging techniques and provide clinicians and research technology developers with the theory and knowledge of the nerve.

Purpose: The present study attempted to explore the effects of different tempos of piano music on heart rate and autonomous nervous system during the recovery period after high‐intensity exercise. In addition, the study analyzed the influence of different tempos on the recovery period of athletes to devise methods for accelerating fatigue recovery through piano music. Method: A total of 57 college students majoring in physical education were selected as experimental subjects and were divided into three groups, namely Lento group (n = 20), Moderato group (n = 20), and Allegretto group (n = 20; only 17 students completed the experiment). Results: Under the same high‐intensity exercise regimen, the three groups did not differ significantly in the body composition, high‐intensity exercise ability, and time‐domain variation indices, namely heart rate (HR), heart rate variability index parameters (p >.05). The time‐domain variation analysis in the recovery period revealed significant differences in HR frequency domain indices among the groups exposed to different rhythms (p <.05). Conclusion: Moderate‐tempo piano music was the most effective in facilitating HR and autonomic nervous system recovery during the recovery period. [ABSTRACT FROM AUTHOR]

Aims and objectives: The present study investigated whether morning or afternoon activity is more effective at increasing the high‐frequency (HF) index, a parasympathetic index, in patients with cardiovascular risk factors. Background: A decreased HF index, a heart rate variability (HRV) parameter, is a well‐established marker of poor cardiovascular prognosis. Because blood pressure and sympathetic tone are higher in the morning, physical activity and exercise in the afternoon has been recommended for patients with cardiovascular diseases. However, there have been no reports concerning the superior effects of afternoon exercise on parasympathetic activity and sleep. Design: This observational study was a post hoc comparison. Methods: Patients' physical activity was measured for 1 month to determine their habits. Patients' HF index was measured by 24‐h Holter electrocardiography. The study enrolled 56 patients. Each patient's morning step count (before lunch) and afternoon step count (between lunch and dinner) were compared. We adhered to the STROBE guidelines in the present study. Results: Thirty‐one patients took more steps in the morning, and 25 patients took more steps in the afternoon. The present study showed that those who took more steps in the afternoon had a significantly higher HF index during the first hour after sleep onset and during sleep than those who took more steps in the morning (p =.003,.047). Conclusions: The present study showed that those who took more steps in the afternoon had a significantly higher HF index during the first hour after sleep onset and a higher HF index during sleep than those who took more steps in the morning. Relevance to clinical practice: Exercise in the afternoon may improve the prognosis in patients with cardiovascular disease by not only preventing excessive blood pressure, afterload, and sympathetic tone but also positively influencing the parasympathetic system and sleep. [ABSTRACT FROM AUTHOR]

Background: Acetylcholine (ACh) and norepinephrine (NE) are representative neurotransmitters of parasympathetic and sympathetic nerves, respectively, that antagonize each other to coregulate internal body functions. This also includes the control of different kinds of hormone secretion from pancreatic islets. However, the molecular mechanisms have not been fully elucidated, and whether innervation in islets is abnormal in diabetes mellitus also remains unclear. Methods and results: Immunofluorescence colocalization and islet perfusion were performed and the results demonstrated that ACh/NE and their receptors were highly expressed in islet and rapidly regulated different hormones secretion. Phosphorylation is considered an important posttranslational modification in islet innervation and it was identified by quantitative proteomic and phosphoproteomic analyses in this study. The phosphorylated islet proteins were found involved in many biological and pathological processes, such as synaptic signalling transduction, calcium channel opening and insulin signalling pathway. Then, the kinases were predicted by motif analysis and further screened and verified by kinase‐specific siRNAs in different islet cell lines (αTC1‐6, Min6 and TGP52). After functional verification, Ksr2 and Pkacb were considered the key kinases of ACh and NE in insulin secretion, and Cadps, Mlxipl and Pdcd4 were the substrates of these kinases measured by immunofluorescence co‐staining. Then, the decreased expression of receptors, kinases and substrates of ACh and NE were found in diabetic mice and the aberrant rhythm in insulin secretion could be improved by combined interventions on key receptors (M3 (pilocarpine) or α2a (guanfacine)) and kinases (Ksr2 or Pkacb). Conclusions: Abnormal innervation was closely associated with the degree of islet dysfunction in diabetic mice and the aberrant rhythm in insulin secretion could be ameliorated significantly after intervention with key receptors and kinases in the early stage of diabetes mellitus, which may provide a promising therapeutic strategy for diabetes mellitus in the future. [ABSTRACT FROM AUTHOR]

Abstract Purpose The present study attempted to explore the effects of different tempos of piano music on heart rate and autonomous nervous system during the recovery period after high‐intensity exercise. In addition, the study analyzed the influence of different tempos on the recovery period of athletes to devise methods for accelerating fatigue recovery through piano music. Method A total of 57 college students majoring in physical education were selected as experimental subjects and were divided into three groups, namely Lento group (n = 20), Moderato group (n = 20), and Allegretto group (n = 20; only 17 students completed the experiment). Results Under the same high‐intensity exercise regimen, the three groups did not differ significantly in the body composition, high‐intensity exercise ability, and time‐domain variation indices, namely heart rate (HR), heart rate variability index parameters (p > .05). The time‐domain variation analysis in the recovery period revealed significant differences in HR frequency domain indices among the groups exposed to different rhythms (p

Abstract Background Acetylcholine (ACh) and norepinephrine (NE) are representative neurotransmitters of parasympathetic and sympathetic nerves, respectively, that antagonize each other to coregulate internal body functions. This also includes the control of different kinds of hormone secretion from pancreatic islets. However, the molecular mechanisms have not been fully elucidated, and whether innervation in islets is abnormal in diabetes mellitus also remains unclear. Methods and results Immunofluorescence colocalization and islet perfusion were performed and the results demonstrated that ACh/NE and their receptors were highly expressed in islet and rapidly regulated different hormones secretion. Phosphorylation is considered an important posttranslational modification in islet innervation and it was identified by quantitative proteomic and phosphoproteomic analyses in this study. The phosphorylated islet proteins were found involved in many biological and pathological processes, such as synaptic signalling transduction, calcium channel opening and insulin signalling pathway. Then, the kinases were predicted by motif analysis and further screened and verified by kinase‐specific siRNAs in different islet cell lines (αTC1‐6, Min6 and TGP52). After functional verification, Ksr2 and Pkacb were considered the key kinases of ACh and NE in insulin secretion, and Cadps, Mlxipl and Pdcd4 were the substrates of these kinases measured by immunofluorescence co‐staining. Then, the decreased expression of receptors, kinases and substrates of ACh and NE were found in diabetic mice and the aberrant rhythm in insulin secretion could be improved by combined interventions on key receptors (M3 (pilocarpine) or α2a (guanfacine)) and kinases (Ksr2 or Pkacb). Conclusions Abnormal innervation was closely associated with the degree of islet dysfunction in diabetic mice and the aberrant rhythm in insulin secretion could be ameliorated significantly after intervention with key receptors and kinases in the early stage of diabetes mellitus, which may provide a promising therapeutic strategy for diabetes mellitus in the future.

Type 1 diabetes (T1D) is an autoimmune disease with a shortage of islet β cells. To date, the etiology of T1D remains elusive. Increasing clinical evidence and animal studies demonstrate that autoimmune cells are directed against the nervous system of pancreatic islets, contributing to the development of T1D. Therefore, it highlights the necessity to explore novel clinical approaches to fundamentally correct the T1D autoimmunity not only focusing on islet β cells but also on protecting the islet nervous system. This allows the restoration of the integrity of islet innervation and the normal islet β-cell function. To address these issues, we developed a novel technology designated the Stem Cell Educator TM therapy, based on immune education by human cord-blood-derived multipotent stem cells (CB-SC). International amulticenter clinical trials demonstrated its clinical safety and efficacy to treat T1D and other autoimmune diseases. Stem Cell Educator TM therapy may have the potential to revolutionize the treatment of T1D, without the safety and ethical concerns associated with conventional immune and/or stem cell-based therapies.

Test anxiety is a widespread and primarily detrimental emotion in learning and achievement settings. This research aimed to explore the autonomic nervous system (ANS) response patterns of test-anxious individuals in response to evaluative stress. By presenting a standard interview task, an evaluative scenario was effectively induced. Heart rate variability (HRV), a biomarker that can accurately reflect the ANS activity, was used to reflect the physiological responses of 48 high test-anxious subjects and 49 low test-anxious subjects. Results indicate that: (1) both groups show a significantly increased emotional arousal in the evaluative scenario; (2) high test-anxious individuals show a significantly decreased emotional pleasantness in the evaluative scenario, whereas low test-anxious individuals show no significant changes; (3) both groups show a significantly increased low-frequency HRV; (4) high test-anxious individuals show a significantly decreased high-frequency HRV and root mean square of successive heartbeat interval differences (RMSSD), whereas low test-anxious individuals remain stable. These findings suggest that high test-anxious individuals display an increased sympathetic nervous system (SNS) activity and a decreased parasympathetic nervous system (PNS) activity in response to evaluative stress, while low-anxious individuals display an increased SNS activity and a stable PNS activity in response to evaluative stress. [ABSTRACT FROM AUTHOR]

Test anxiety is a widespread and primarily detrimental emotion in learning and achievement settings. This research aimed to explore the autonomic nervous system (ANS) response patterns of test-anxious individuals in response to evaluative stress. By presenting a standard interview task, an evaluative scenario was effectively induced. Heart rate variability (HRV), a biomarker that can accurately reflect the ANS activity, was used to reflect the physiological responses of 48 high test-anxious subjects and 49 low test-anxious subjects. Results indicate that: (1) both groups show a significantly increased emotional arousal in the evaluative scenario; (2) high test-anxious individuals show a significantly decreased emotional pleasantness in the evaluative scenario, whereas low test-anxious individuals show no significant changes; (3) both groups show a significantly increased low-frequency HRV; (4) high test-anxious individuals show a significantly decreased high-frequency HRV and root mean square of successive heartbeat interval differences (RMSSD), whereas low test-anxious individuals remain stable. These findings suggest that high test-anxious individuals display an increased sympathetic nervous system (SNS) activity and a decreased parasympathetic nervous system (PNS) activity in response to evaluative stress, while low-anxious individuals display an increased SNS activity and a stable PNS activity in response to evaluative stress.

Various effects have been observed when a slimy fluid is held in palmar skin. The observed effects include friction control of the skin and cleansing and moisturizing of the skin. However, few reports exist regarding the changes in the emotional state of persons when a slimy fluid is held in their palmar skin, even though the viscosity properties of the fluid affect emotional changes. Thus, this study investigates the emotional changes due to holding slimy fluid in the palmar skin by evaluating heart rate variability (HRV) and sensibility. Newtonian and non-Newtonian fluids, with viscosities ranging from 0.01 to 100 Pa·s, were prepared. Eight male subjects in their 20s soaked their palms in the slimy fluid without seeing it. At the room temperature of 25 °C, the subjects moved their palms freely for 1 min. They were allowed to rub their palms together. During the experiments, the HRV was recorded. A frequency analysis was performed for estimating autonomic nerve activity. After holding the fluid, the subjects were asked to provide feedback through the semantic differential method. Significant changes in autonomic nerve activations were observed when the subjects soaked their palms in the slimy fluid. The high viscosity Newtonian fluid reduced the parasympathetic nervous system activity. These changes in the psychophysiological indexes influenced the feelings of the subjects ascertained according to the semantic differential method. A relationship between the characteristic of the slimy fluid and a psychophysiological index can improve the efficiency when developing products exposed to human skin.

Purpose: The autonomic nervous system, consisting of sympathetic and parasympathetic/vagal nerves, is known to control the functions of any organ, maintaining whole-body homeostasis under physiological conditions. Recently, there has been increasing evidence linking sympathetic and parasympathetic/vagal nerves to cancers. The present review aimed to summarize recent developments from studies addressing the relationship between sympathetic and parasympathetic/vagal nerves and cancer behavior. Methods: Literature review. Results: Human and animal studies have revealed that sympathetic and parasympathetic/vagal nerves innervate the cancer microenvironment and alter cancer behavior. The sympathetic nerves have cancer-promoting effects on prostate cancer, breast cancer, and melanoma. On the other hand, while the parasympathetic/vagal nerves have cancer-promoting effects on prostate, gastric, and colorectal cancers, they have cancer-suppressing effects on breast and pancreatic cancers. These neural effects may be mediated by β-adrenergic or muscarinic receptors and can be explained by changes in cancer cell behavior, angiogenesis, tumor-associated macrophages, and adaptive antitumor immunity. Conclusions: Sympathetic nerves innervating the tumor microenvironment promote cancer progression and are related to stress-induced cancer behavior. The parasympathetic/vagal nerves have variable (promoting or suppressing) effects on different cancer types. Approaches directed toward the sympathetic and parasympathetic/vagal nerves can be developed as a new cancer therapy. In addition to existing pharmacological, surgical, and electrical approaches, a recently developed virus vector-based genetic local neuroengineering technology is a powerful approach that selectively manipulates specific types of nerve fibers innervating the cancer microenvironment and leads to the suppression of cancer progression. This technology will enable the creation of "cancer neural therapy" individually tailored to different cancer types. [ABSTRACT FROM AUTHOR]

Purpose: Patients with various and indefinite symptoms in the whole body occasionally have coincident with stiffness or tenderness of the cervical muscles. This prospective case series examined the effect of local modulation of the cervical muscles in patients with cervical disorders reporting indefinite whole-body symptoms.Methods: A total of 1863 hospitalized patients with cervical disorders accompanying three or more indefinite whole-body symptoms, who were resistant to outpatient care, were enrolled in this study for 12 years. All patients underwent daily physical therapies to the cervical muscles during hospitalization. Self-rated records on the medical interview sheets documenting 30 representative symptoms including cervical/shoulder pain or stiffness and 28 representative indefinite whole-body symptoms at admission and discharge were compared across the population.Results: The number of symptoms decreased significantly with the local modulation of the cervical muscles during hospitalization. All of the 28 indefinite whole-body symptoms at admission showed recovery rates greater than 50% at discharge. The mean number of symptoms decreased significantly from 17.8 at admission to 7.4 at discharge (p < 0.0001). The percentages of patients reporting 10 or more symptoms were 91.1% and 29.3% at admission and discharge, respectively. Moreover, 8.2% of patients reported no residual symptoms at discharge.Conclusion: Cervical muscle lesions may contribute to indefinite whole-body symptoms, possibly through dysfunction of the parasympathetic nervous system in the muscles. Local modulation of cervical muscles could lead to a breakthrough in the management of patients with indefinite whole-body symptoms.Trial Registration Id: UMIN000035445. These slides can be retrieved under Electronic Supplementary Material. [ABSTRACT FROM AUTHOR]

Accumulating evidence has demonstrated a significant relationship between prefrontal lobe and hypertension. Elevated blood pressure is usually associated with a prefrontal hemodynamic abnormality. However, the detailed process is still unclear. In this study, we designed a startle protocol and tested the response of the cerebral cortex and cardiovascular system in young normotensive subjects with a family history of hypertension (FH+). Additionally, the cold forehead test (CFT) was performed in hypertensive subjects. In total, 40 young normotensive subjects (21 with FH+ and 19 without a family history of hypertension (FH-)) and 49 middle-aged subjects (21 normotensives (NT) and 28 hypertensives (HT)) were recruited. Our results showed that the magnitude of startle-evoked alpha oscillation at the parasympathetic-related prefrontal cortex (FP1 and FP2) in the FH+ group was significantly smaller than in the FH- group. Acute bradycardia (RRI increase) was observed in FH- subjects but disappeared in the FH+ group. The coupling between instant cardiac acute response (increased RRI) and prefrontal arousal (magnitude of evoked oscillation) was significantly weakened in the FH+ group compared with the FH- group. Furthermore, the decrease in HR induced by parasympathetic outflow during CFT was absent in HT subjects. Hence, we concluded that the impairment of parasympathetic outflow derived from the prefrontal lobe occurs in both healthy young offspring of hypertensive and hypertensive patients. [ABSTRACT FROM AUTHOR]

Diarrhea is a gastrointestinal symptom associated with systemic anaphylaxis and could be induced by increased colonic motility. We determined colonic motility and expulsion by measuring the intracolonic pressure (ICP) and expelled fluid weight in anesthetized rats during anaphylactic hypotension. Substantial systemic hypotension occurred in every sensitized rat after antigen injection. One min after antigen injection, ICP began to increase and remained elevated for 5 min, which was revealed to represent tonic contraction by the video-recording procedure, and was accompanied by increased colonic fluid expulsion. Parasympathectomy composed of subdiaphragmatic vagotomy combined with pelvic nerve transection reduced the duration of the tonic contraction, but not expelled colonic fluid. Furthermore, denervation of afferent parasympathetic nerves produced essentially the same effect as parasympathectomy. Sympathectomy did not significantly change any parameters. In conclusion, the colonic motility during anaphylactic hypotension is characterized by 5-min lasting tonic contraction which is associated with increased colonic fluid expulsion and is involved by parasympathetic nerves, especially their afferents, but not sympathetic nerves, in anesthetized rats. [ABSTRACT FROM AUTHOR]

Objective: Biliary innervation is considered important in regulating the function of bile ducts, whereas the role of innervation in the hepatobiliary system of patients with biliary atresia (BA) remains unknown. This current study aims to investigate the role of innervation in biliary remnants and analyze the relationship between the innervation and prognosis of BA after surgery., Methods: Eighty-seven patients with type III BA who underwent the Kasai procedure were consecutively enrolled from January 2017 to September 2020. Innervation and ductules in remnants were examined by pathologists. Liver function, onset of cholangitis, jaundice clearance, and survival with the native liver were recorded. Patients were followed up for 24 months. The relationship between innervation and prognosis was analyzed., Results: In total, 67 patients had bile drainage postoperatively, and 21 biliary remnants contained neuronal plexuses where there was no neuron but nerve fiber bundles. Acetylcholinesterase staining was positive in all plexuses. In patients with bile drainage, those with plexuses had improved postoperative liver function, significantly better jaundice clearance 3 or 6 months postoperatively (50.0% vs. 19.1%, or 90.0% vs. 63.8%, respectively), fewer episodes of early cholangitis (10.0% vs. 34.0%), and better survival (80.0% vs. 61.7%) compared to those without. In addition, a larger area of plexuses was associated with a larger area of ductules ( R 2  = 0.786, p  = 0.000), less frequent ( p  = 0.000) and later cholangitis onset ( p  = 0.012), and better jaundice clearance ( p  = 0.063)., Conclusions: Increased cholinergic innervation in biliary remnants may help reduce the onset of cholangitis and lead to better and earlier jaundice clearance. Thus, it improves the postoperative prognosis of patients with BA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Yang, Chen, Wang, Su, Liu, Abudusalamu, Li, He, Wang, Xiong and Feng.)

First bite syndrome (FBS)is characterized by sharp pain in the parotid region at the first bite of a meal which gradually decreases as mastication continues, and is thought to be caused by sympathetic nerve damage. When FBS occurs with no history suggestive of nerve damage, it is classified as idiopathic. A case of idiopathic FBS that was treated effectively with Rikkosan is presented. The patient was an 81-year-old woman who developed sharp pain in the left parotid region with the first bite of every meal in November 2015. With no specific findings, the initial diagnosis was trigeminal neuralgia, but carbamazepine was ineffective. In February 2016, temporomandibular disorder was diagnosed as the cause of masticatory muscle pain and was treated with splinting and loxoprofen sodium, but this was also ineffective. In June 2016, a panoramic radiograph, plain craniocervical magnetic resonance imaging, and blood tests were all negative. Idiopathic FBS was diagnosed and treated by gargling and swallowing Rikkosan before meals and eating bitter or sweet foods first, followed by salty or sour foods. The FBS improved, and after 1 week, she had days with no pain. Rikkosan was discontinued after a month leading to immediate recurrence. The patient was instructed to use half the dose of Rikkosan, which was effective with no side effects. In October 2016, the patient started gargling with Rikkosan. In March 2017, the Rikkosan was discontinued and the dietary strategy was continued with no further recurrence. In this case, idiopathic FBS improved with Rikkosan treatment. [ABSTRACT FROM AUTHOR]

Systemic anaphylaxis is a life-threatening and allergic reaction that affects various organs. We previously reported that, in the stomach, gastric vasoconstriction occurring at the late phase (15–55 min after injection of ovalbumin antigen) was observed in anesthetized rats sensitized with ovalbumin. In addition, anaphylaxis enhances gastric motility and delays emptying. However, the role of extrinsic autonomic nervous system on antigen-induced gastric alterations was not known. Thus, using the same rat anaphylaxis model, we aimed to determine the changes in the efferent and afferent autonomic nerve activities in the stomach during anaphylactic hypotension. The findings showed that injection of ovalbumin antigen caused substantial systemic hypotension in all sensitized rats. The efferent gastric sympathetic nerve activity (efGSNA), but not the efferent vagal nerve activity, increased only at the early phase (1–10 min after injection of ovalbumin antigen) and showed baroreceptor reflex, as evidenced by a stimulatory response to sodium nitroprusside-induced hypotension. In general, excitation of ef-GSNA could induce pylorus sphincter contraction and gastric vasoconstriction. In the present study, we found that sympathectomy attenuated the anaphylaxis-induced decrease in gastric flux but not the increase in gastric vascular resistance. Thus, the increase in ef-GSNA may cause anaphylactic pylorus sphincter contraction but not anaphylactic gastric vasoconstriction. On the other hand, the afferent gastric vagal nerve activity, but not the afferent sympathetic nerve activity, increased during the early phase of anaphylactic hypotension. However, vagotomy produced no effects on the anaphylactic gastric dysfunction. In conclusion, the gastric sympathetic nerves partly modulate stomach function during systemic anaphylaxis. [ABSTRACT FROM AUTHOR]

The parasympathetic salivatory nuclei are located in the medulla oblongata, which are under descending control from higher centers of the brain, such as the cerebral cortex, hypothalamus and limbic system. Therefore, the suppression of salivary flow under stress conditions is due to inhibition in the salivatory nuclei. In addition to this mechanistic effect, the results of experimental studies suggest the existence of an inhibitory effect of the sympathetic nervous system on parasympathetic-stimulated salivary secretion from the salivary gland. In this paper, the suppressive mechanism of salivary secretion is discussed. [ABSTRACT FROM AUTHOR]

Highlights • C1 neurons are involved in the anti-inflammatory response. • Sympathoexcitation is required for anti-inflammatory response via C1 neurons. • C1 neurons are involved in the cholinergic anti-inflammatory pathway. Abstract Neuroimmune communication, the connection between the autonomic regulatory pathway and immune cells, has been implicated in the regulation of immune function and inflammation. The role of afferents (vagal afferent and somatic sensory nerves) and efferents (autonomic nervous and hypothalamic-pituitary-adrenal systems) in the inflammatory reflex has been well studied; however, the central pathway remains unknown. C1 neurons include both catecholaminergic and glutamatergic neurons, which are located in the rostral ventrolateral medulla. C1 neurons project to the spinal cord, dorsal motor nucleus of the vagus, and hypothalamus to regulate the sympathetic, parasympathetic, and hypothalamic-pituitary-adrenal systems, respectively. Because C1 neurons respond to stressors, including inflammation, hypotension, hypoxia, and hypoglycemia, it is believed that the autonomic regulatory pathway, via C1 neurons, contributes to the maintenance of physiological homeostasis. Recently, selective neural manipulation has revealed that C1 neurons participate in restraint stress-induced anti-inflammation, and protection against acute kidney injury has been attributed to stress-induced sympathoexcitation through C1 neurons. We focus here on the role of C1 neurons, which act as mediators between afferents and efferents, in the anti-inflammatory pathway. [ABSTRACT FROM AUTHOR]

Abstract: Airway eosinophils are increased in asthma and are especially abundant around airway nerves. Nerves control bronchoconstiction and in asthma, airway hyperreactivity (where airways contract excessively to inhaled stimuli) develops when eosinophils alter both parasympathetic and sensory nerve function. Eosinophils release major basic protein, which is an antagonist of inhibitory M2 muscarinic receptors on parasympathetic nerves. Loss of M2 receptor inhibition potentiates parasympathetic nerve‐mediated bronchoconstriction. Eosinophils also increase sensory nerve responsiveness by lowering neurons’ activation threshold, stimulating nerve growth, and altering neuropeptide expression. Since sensory nerves activate parasympathetic nerves via a central neuronal reflex, eosinophils’ effects on both sensory and parasympathetic nerves potentiate bronchoconstriction. This review explores recent insights into mechanisms and effects of eosinophil and airway nerve interactions in asthma. [ABSTRACT FROM AUTHOR]

The autonomic nervous system affects the gustatory responses in animals. Frog glossopharyngeal nerve (GPN) contains the parasympathetic nerve. We checked the effects of electrical stimulation (ES) of the parasympathetic nerves on the gustatory neural responses. The gustatory neural impulses of the GPNs were recorded using bipolar AgCl wires under normal blood circulation and integrated with a time constant of 1 s. Electrical stimuli were applied to the proximal side of the GPN with a pair of AgCl wires. The parasympathetic nerves of the GPN were strongly stimulated for 10 s with 6 V at 30 Hz before taste stimulation. The integrated neural responses to 0.5 M NaCl, 2.5 mM CaCl2, water, and 1 M sucrose were enhanced to 130-140% of the controls. On the other hand, the responses for 1 mM Q-HCl and 0.3 mM acetic acid were not changed by the preceding applied ES. After hexamethonium (a blocker of nicotinic ACh receptor) was intravenously injected, ES of the parasympathetic nerve did not modulate the responses for all six taste stimuli. The mechanism for enhancement of the gustatory neural responses is discussed. [ABSTRACT FROM AUTHOR]

Key points: The contribution of HCN4 pacemaker channels in the autonomic regulation of the sino‐atrial node (SAN) has been a matter of debate. The transgenic overexpression of HCN4 did not induce tachycardia, but reduced heart rate variability, while the conditional knockdown of HCN4 gave rise to sinus arrhythmia. The response of the SAN to β‐adrenergic stimulation was not affected by overexpression or knockdown of HCN4 channels. When HCN4 channels were knocked down, the parasympathetic response examined by cervical vagus nerve stimulation (CVNS) was enhanced; the CVNS induced complete sinus pause. The overexpression of HCN4 attenuated bradycardia induced by CVNS only during β‐adrenergic stimulation. We concluded that HCN4 pacemaker channels stabilize the spontaneous firing by attenuating the parasympathetic response of the SAN. Abstract: The heart rate is dynamically controlled by the sympathetic and parasympathetic nervous systems that regulate the sinoatrial node (SAN). HCN4 pacemaker channels are the well‐known causative molecule of congenital sick sinus syndrome. Although HCN4 channels are activated by cAMP, the sympathetic response of the SAN was preserved in patients carrying loss‐of‐function mutations of the HCN4 gene. In order to clarify the contribution of HCN4 channels in the autonomic regulation of the SAN, we developed novel gain‐of‐function mutant mice in which the expression level of HCN4 channels could be reversibly changed from zero to ∼3 times that in wild‐type mice, using tetracycline transactivator and the tetracycline responsive element. We recorded telemetric ECGs in freely moving conscious mice and analysed the heart rate variability. We also evaluated the response of the SAN to cervical vagus nerve stimulation (CVNS). The conditional overexpression of HCN4 did not induce tachycardia, but reduced heart rate variability. The HCN4 overexpression also attenuated bradycardia induced by the CVNS only during the β‐adrenergic stimulation. In contrast, the knockdown of HCN4 gave rise to sinus arrhythmia, and enhanced the parasympathetic response; complete sinus pause was induced by the CVNS. In vitro, we compared the effects of acetylcholine on the spontaneous action potentials of single pacemaker cells, and found that similar phenotypic changes were induced by genetic manipulation of HCN4 expression both in the presence and absence of β‐adrenergic stimulation. Our study suggests that HCN4 channels attenuate the vagal response of the SAN, and thereby stabilize the spontaneous firing of the SAN. [ABSTRACT FROM AUTHOR]

Although fasting induces hepatic triglyceride (TG) accumulation in both rodents and humans, little is known about the underlying mechanism. Because parasympathetic nervous system activity tends to attenuate the secretion of very-low-density-lipoprotein-triglyceride (VLDL-TG) and increase TG stores in the liver, and serum cholinesterase activity is elevated in fatty liver disease, the inhibition of the parasympathetic neurotransmitter acetylcholinesterase (AChE) may have some influence on hepatic lipid metabolism. To assess the influence of AChE inhibition on lipid metabolism, the effect of physostigmine, an AChE inhibitor, on fasting-induced increase in liver TG was investigated in mice. In comparison with ad libitum-fed mice, 30 h fasting increased liver TG accumulation accompanied by a downregulation of sterol regulatory element-binding protein 1 (SREBP-1) and liver-fatty acid binding-protein (L-FABP). Physostigmine promoted the 30 h fasting-induced increase in liver TG levels in a dose-dependent manner, accompanied by a significant fall in plasma insulin levels, without a fall in plasma TG. Furthermore, physostigmine significantly attenuated the fasting-induced decrease of both mRNA and protein levels of SREBP-1 and L-FABP, and increased IRS-2 protein levels in the liver. The muscarinic receptor antagonist atropine blocked these effects of physostigmine on liver TG, serum insulin, and hepatic protein levels of SREBP-1 and L-FABP. These results demonstrate that AChE inhibition facilitated fasting-induced TG accumulation with up regulation of the hepatic L-FABP and SREBP-1 in mice, at least in part via the activation of muscarinic acetylcholine receptors. Our studies highlight the crucial role of parasympathetic regulation in fasting-induced TG accumulation, and may be an important source of information on the mechanism of hepatic disorders of lipid metabolism.

Purpose: To describe and discuss the normal anatomy and function of enteric neurons in the esophagus of aged individuals. Method: We examined ganglion cells in esophagus specimens obtained from 15 elderly cadavers without any macroscopic pathology in the mediastinum and abdomen. Neuronal nitric oxide synthase and vasoactive intestinal polypeptide were used as parasympathetic nerve markers, and tyrosine hydroxylase as a sympathetic nerve marker. Results: The thoracic and abdominal esophagus contained a well-developed myenteric nerve plexus (S100 protein-positive area) in the intermuscular layer: 0.02-0.03 mm per 1-mm length of the circular esophageal wall. The cervical esophagus usually contained no ganglion cells. The number of parasympathetic ganglion cells was maximal in the upper or middle thoracic esophagus (mean 18-23 cells per section), whereas sympathetic cells were considerably less numerous at any sites (mean 1-3 cells). Conclusion: In comparison with previous data from elderly cadavers, the esophagus carried much fewer ganglion cells than the intestine and colon; sympathetic cells were particular less numerous. Esophageal smooth muscle exhibits a unique mode of peristalsis characterized by a rebound contraction with a long latency after stimulation. This type of peristalsis appears to be regulated by inhibitory, nNOS-positive nerves with a sparse distribution, which seems to account for the long-span peristalsis unique to the esophagus. The extreme sparsity of ganglion cells in the cervical esophagus suggests that enteric neuron-integrated peristalsis, like that in the intestine and colon, is unlikely. Surgical treatment of the esophagus is likely to change or impair these unique features. [ABSTRACT FROM AUTHOR]

The pathological changes of parasympathetic nerve are considered as an independent prognostic factor of the survival rate of patients with chronic liver disease. The non-selective muscarinic acetylcholine receptors (mAchR) agonists and antagonists can affect the proliferation of hepatocytes and hepatic stellate cells, but the subtypes of mAchR expressions in HCs are still uncertain. Here, we investigate the expression of mAchR in hepatic fibrosis on rats. 3 ml/kg 40% carbon tetrachloride (CCL4) was given to induce hepatic fibrosis on rats and the hepatocytes were isolated. Compared to the normal state, the expression levels of m1, 3, 5 in fibrotic liver tissues or hepatocytes were obviously increased, while m2, 4 decreased. 10 μM pilocarpine or 10 μM acetylcholine could increase the alanine aminotransferase (ALT), hydroxyproline (Hyp), collagen I, III in the hepatocytes, and decreased albumin (ALB). They also changed the expressions of mAchR similarly as the fibrotic hepatocytes and livers. However, atropine could ameliorate the state of fibrotic hepatocytes. These data indicate that mAchR played an important role in the regulation of hepatic fibrosis process. Targeting mAchR would have therapeutic potential for hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Inappropriate sympathetic activation is closely associated with the development and progression of hypertension. Renal denervation (RDN) is a neuromodulation therapy performed using an intraarterial catheter in patients with hypertension. Recent randomized sham-operated controlled trials have shown that RDN has significant antihypertensive effects that last for at least 3 years. Based on this evidence, RDN is nearly ready for general clinical application. On the other hand, there are remaining issues to be addressed, including elucidation of the precise antihypertensive mechanisms of RDN, the appropriate endpoint of RDN during the procedure, and the association between reinnervation after RDN and the long-term effects of RDN. This mini review focuses on studies implicating anatomy of the renal nerves, which consist of afferent or efferent and sympathetic or parasympathetic nerves, the response of blood pressure to renal nerve stimulation, and reinnervation of renal nerves after RDN. A comprehensive understanding of the anatomical and functional aspects of the renal nerves and the antihypertensive mechanisms of RDN, including its long-term effects, will enhance our ability to incorporate RDN into strategies to treat hypertension in clinical practice. This mini review focuses on studies implicating anatomy of the renal nerves, which consist of afferent or efferent and sympathetic or parasympathetic nerves, the response of blood pressure to renal nerve stimulation, and reinnervation of renal nerves after renal denervation. Whether the ablation site is sympathetic dominant or parasympathetic dominant, and afferent dominant or efferent dominant, would in turn determine the final output of renal denervation. BP: blood pressure., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)