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World Journal of Gastrointestinal... Dec 2023Rapid regeneration of the residual liver is one of the key determinants of successful partial hepatectomy (PHx). At present, there is a lack of recognized safe,...
BACKGROUND
Rapid regeneration of the residual liver is one of the key determinants of successful partial hepatectomy (PHx). At present, there is a lack of recognized safe, effective, and stable drugs to promote liver regeneration. It has been reported that vagus nerve signaling is beneficial to liver regeneration, but the potential mechanism at play here is not fully understood.
AIM
To explore the effect and mechanism of hepatic vagus nerve in liver regeneration after PHx.
METHODS
A PHx plus hepatic vagotomy (Hv) mouse model was established. The effect of Hv on liver regeneration after PHx was determined by comparing the liver regeneration levels of the PHx-Hv group and the PHx-sham group mice. In order to further investigate the role of interleukin (IL)-22 in liver regeneration inhibition mediated by Hv, the levels of IL-22 in the PHx-Hv group and the PHx-sham group was measured. The degree of liver injury in the PHx-Hv group and the PHx-sham group mice was detected to determine the role of the hepatic vagus nerve in liver injury after PHx.
RESULTS
Compared to control-group mice, Hv mice showed severe liver injury and weakened liver regeneration after PHx. Further research found that Hv downregulates the production of IL-22 induced by PHx and blocks activation of the signal transducer and activator of transcription 3 (STAT3) pathway then reduces the expression of various mitogenic and anti-apoptotic proteins after PHx. Exogenous IL-22 reverses the inhibition of liver regeneration induced by Hv and alleviates liver injury, while treatment with IL-22 binding protein (an inhibitor of IL-22 signaling) reduce the concentration of IL-22 induced by PHx, inhibits the activation of the STAT3 signaling pathway in the liver after PHx, thereby hindering liver regeneration and aggravating liver injury in PHx-sham mice.
CONCLUSION
Hv attenuates liver regeneration after hepatectomy, and the mechanism may be related to the fact that Hv downregulates the production of IL-22, then blocks activation of the STAT3 pathway.
PubMed: 38222006
DOI: 10.4240/wjgs.v15.i12.2866 -
FASEB Journal : Official Publication of... Jan 2024Mastitis is the most frequent disease of cows and has well-recognized detrimental effects on animal wellbeing and dairy farm profitability. With the advent of the...
Mastitis is the most frequent disease of cows and has well-recognized detrimental effects on animal wellbeing and dairy farm profitability. With the advent of the postantibiotic era, alternative antibiotic agents, especially probiotics, have received increasing attention in the treatment of mastitis. Based on research showing that Lactobacillus reuteri (L. reuteri) has anti-inflammatory effects, this study explored the protective effects and mechanisms of L. reuteri against mastitis induced by Staphylococcus aureus (S. aureus) in mice. First, mice with S. aureus-induced mastitis were orally administered L. reuteri, and the inflammatory response in the mammary gland was observed. The results showed that L. reuteri significantly inhibited S. aureus-induced mastitis. Moreover, the concentration of oxytocin (OT) and protein expression of oxytocin receptor (OTR) were measured, and inhibition of OTR or vagotomy reversed the protective effect of L. reuteri or its culture supernatant (LCS) on S. aureus-induced mastitis. In addition, in mouse mammary epithelial cells (MMECs), OT inhibited the inflammation induced by S. aureus by inhibiting the protein expression of OTR. It was suggested that L. reuteri protected against S. aureus-induced mastitis by releasing OT. Furthermore, microbiological analysis showed that the composition of the microbiota was altered, and the relative abundance of Lactobacillus was significantly increased in gut and mammary gland after treatment with L. reuteri or LCS. In conclusion, our study found the L. reuteri inhibited the mastitis-induced by S. aureus via promoting the release of OT, and treatment with L. reuteri increased the abundance of Lactobacillus in both gut and mammary gland.
Topics: Female; Humans; Animals; Cattle; Mice; Oxytocin; Gastrointestinal Microbiome; Limosilactobacillus reuteri; Staphylococcus aureus; Mastitis; Receptors, Oxytocin; Lactobacillus; Staphylococcal Infections
PubMed: 38197892
DOI: 10.1096/fj.202301961R -
ACG Case Reports Journal Jan 2024is a known cause of peptic ulcers, but it has not been reported to cause strictures in children. We present the case of a previously healthy 12-year-old boy with sudden...
is a known cause of peptic ulcers, but it has not been reported to cause strictures in children. We present the case of a previously healthy 12-year-old boy with sudden onset of abdominal pain and vomiting, positive stool antigen testing, and esophagogastroduodenoscopy revealing a gastroduodenal stricture causing gastric outlet obstruction. Because of medically refractory disease, he ultimately required laparoscopic truncal vagotomy with open pyloroplasty. This is an unusually severe presentation and may warrant being on the differential of pediatric gastrointestinal strictures as well as further discussion on other long-term implications.
PubMed: 38162007
DOI: 10.14309/crj.0000000000001227 -
Pharmaceuticals (Basel, Switzerland) Dec 2023Purine nucleosides (adenosine) and nucleotides such as adenosine mono/di/triphosphate (AMP/ADP/ATP) may produce complex cardiovascular responses. For example,...
Purine nucleosides (adenosine) and nucleotides such as adenosine mono/di/triphosphate (AMP/ADP/ATP) may produce complex cardiovascular responses. For example, adenosine-5'-(β-thio)-diphosphate (ADPβS; a stable synthetic analogue of ADP) can induce vasodilatation/vasodepressor responses by endothelium-dependent and independent mechanisms involving purinergic P2Y receptors; however, the specific subtypes participating in these responses remain unknown. Therefore, this study investigated the receptor subtypes mediating the blood pressure changes induced by intravenous bolus of ADPβS in male Wistar rats in the absence and presence of central mechanisms with the antagonists MRS2500 (P2Y), PSB0739 (P2Y), and MRS2211 (P2Y). For this purpose, 120 rats were divided into 60 anaesthetised rats and 60 pithed rats, and further subdivided into four groups ( = 30 each), namely: (a) anaesthetised rats, (b) anaesthetised rats with bilateral vagotomy, (c) pithed rats, and (d) pithed rats continuously infused (intravenously) with methoxamine (an α-adrenergic agonist that restores systemic vascular tone). We observed, in all four groups, that the immediate decreases in diastolic blood pressure produced by ADPβS were exclusively mediated by peripheral activation of P2Y receptors. Nevertheless, the subsequent increases in systolic blood pressure elicited by ADPβS in pithed rats infused with methoxamine probably involved peripheral activation of P2Y, P2Y, and P2Y receptors.
PubMed: 38139810
DOI: 10.3390/ph16121683 -
International Journal of Surgery... Mar 2024Chronic cough is common after lobectomy. Vagus nerves are part of the cough reflex. Accordingly, transection of the pulmonary branches of vagus nerve may prevent chronic... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Chronic cough is common after lobectomy. Vagus nerves are part of the cough reflex. Accordingly, transection of the pulmonary branches of vagus nerve may prevent chronic cough. And there are no clear recommendations on the management of the pulmonary branches of vagus in any thoracic surgery guidelines.
METHODS
This is a single-center, randomized controlled trial. Adult patients undergoing elective video-assisted thoracoscopic lobectomy and lymphadenectomy were randomized at a 1:1 ratio to undergo a sham procedure (control group) or transection of the pulmonary branches of the vagus nerve that innervate the bronchial stump plus the caudal-most large pulmonary branch of the vagus nerve. The primary outcome was the rate of chronic cough, as assessed at 3 months after surgery in the intent-to-treat population.
RESULTS
Between 1 February 2020 and 1 August 2020, 116 patients (59.6±10.1 years of age; 45 men) were randomized (58 in each group). All patients received designated intervention. The rate of chronic cough at 3 months was 19.0% (11/58) in the vagotomy group versus 41.4% (24/58) in the control group (OR=0.332, 95% CI: 0.143-0.767; P =0.009). In the 108 patients with 2-year assessment, the rate of persistent cough was 12.7% (7/55) in the control and 1.9% (1/53) in the vagotomy group ( P =0.032). The two groups did not differ in postoperative complications and key measures of pulmonary function, for example, maximal voluntary ventilation, diffusing capacity of the lungs for carbon monoxide, and forced expiratory volume.
CONCLUSION
Transecting the pulmonary branches of vagus nerve that innervate the bronchial stump plus the caudal-most large pulmonary branch decreased the rate of chronic cough without affecting pulmonary function in patients undergoing video-assisted lobectomy and lymphadenectomy.
Topics: Adult; Humans; Male; Chronic Cough; Lung; Lung Neoplasms; Pneumonectomy; Thoracic Surgery, Video-Assisted; Vagus Nerve; Vagus Nerve Injuries; Female; Middle Aged; Aged
PubMed: 38116674
DOI: 10.1097/JS9.0000000000001017 -
BioRxiv : the Preprint Server For... Dec 2023Circadian desynchrony induced by shiftwork or jetlag is detrimental to metabolic health, but how synchronous/desynchronous signals are transmitted among tissues is...
UNLABELLED
Circadian desynchrony induced by shiftwork or jetlag is detrimental to metabolic health, but how synchronous/desynchronous signals are transmitted among tissues is unknown. Here we report that liver molecular clock dysfunction is signaled to the brain via the hepatic vagal afferent nerve (HVAN), leading to altered food intake patterns that are corrected by ablation of the HVAN. Hepatic branch vagotomy also prevents food intake disruptions induced by high-fat diet feeding and reduces body weight gain. Our findings reveal a previously unrecognized homeostatic feedback signal that relies on synchrony between the liver and the brain to control circadian food intake patterns. This identifies the hepatic vagus nerve as a therapeutic target for obesity in the setting of chrono-disruption.
ONE SENTENCE SUMMARY
The hepatic vagal afferent nerve signals internal circadian desynchrony between the brain and liver to induce maladaptive food intake patterns.
PubMed: 38077098
DOI: 10.1101/2023.11.30.568080 -
IEEE Transactions on Ultrasonics,... Feb 2024Cardiac dysfunction is a severe complication that is associated with an increased risk of mortality in multiple diseases. Cardioprotection solution that has been...
Cardiac dysfunction is a severe complication that is associated with an increased risk of mortality in multiple diseases. Cardioprotection solution that has been researched is the electrical stimulation of the vagus nerve to exert cardio protection. This method has been shown to reduce the systemic inflammatory response and maintain the immune homeostasis of the heart. However, the invasive procedure of electrode implantation poses a risk of nerve or fiber damage. Here, we propose transthoracic ultrasound stimulation (US) of the vagus nerve to alleviate cardiac dysfunction caused by lipopolysaccharide (LPS). We developed a noninvasive transthoracic US system and exposed anesthetized mice to ultrasound protocol or sham stimulation 24 h after LPS treatment. Results showed that daily heart targeting US for 4 days significantly increased left ventricular systolic function ( p = 0.01) and improved ejection fraction ( p = 0.03) and shortening fraction ( p = 0.04). Furthermore, US significantly reduced inflammation cytokines, including IL-6 ( p = 0.03) and IL- 1β ( p = 0.04). In addition, cervical vagotomy abrogated the effect of US, suggesting the involvement of the vagus nerve's anti-inflammatory effect. Finally, the same ultrasound treatment but for a longer period (14 days) also significantly increased cardiac function in naturally aged mice. Collectively, these findings suggest the potential of transthoracic US as a possible novel noninvasive approach in the context of cardiac dysfunction with reduced systolic function and provide new targets for rehabilitation of peripheral organ function.
Topics: Mice; Animals; Lipopolysaccharides; Vagus Nerve; Heart; Cytokines; Heart Diseases
PubMed: 38064323
DOI: 10.1109/TUFFC.2023.3341248 -
JCI Insight Dec 2023Epidemiological and histopathological findings have raised the possibility that misfolded α-synuclein protein might spread from the gut to the brain and increase the...
Epidemiological and histopathological findings have raised the possibility that misfolded α-synuclein protein might spread from the gut to the brain and increase the risk of Parkinson's disease. Although past experimental studies in mouse models have relied on gut injections of exogenous recombinant α-synuclein fibrils to study gut-to-brain α-synuclein transfer, the possible origins of misfolded α-synuclein within the gut have remained elusive. We recently demonstrated that sensory cells of intestinal mucosa express α-synuclein. Here, we employed mouse intestinal organoids expressing human α-synuclein to observe the transfer of α-synuclein protein from epithelial cells in organoids to cocultured nodose neurons devoid of α-synuclein. In mice expressing human α-synuclein, but no mouse α-synuclein, α-synuclein fibril-templating activity emerged in α-synuclein-seeded fibril aggregation assays in intestine, vagus nerve, and dorsal motor nucleus. In newly engineered transgenic mice that restrict pathological human α-synuclein expression to intestinal epithelial cells, α-synuclein fibril-templating activity transfered to the vagus nerve and dorsal motor nucleus. Subdiaphragmatic vagotomy prior to induction of α-synuclein expression in intestinal epithelial cells effectively protected the hindbrain from emergence of α-synuclein fibril-templating activity. Overall, these findings highlight a potential non-neuronal source of fibrillar α-synuclein protein that might arise in gut mucosal cells.
Topics: Animals; Humans; Mice; alpha-Synuclein; Brain; Neurons; Parkinson Disease; Vagus Nerve; Gastric Mucosa
PubMed: 38063197
DOI: 10.1172/jci.insight.172192 -
International Immunopharmacology Jan 2024Susceptibility to secondary infection often increases after primary infection. Secondary infections can lead to more severe inflammatory injuries; however, the...
INTRODUCTION
Susceptibility to secondary infection often increases after primary infection. Secondary infections can lead to more severe inflammatory injuries; however, the underlying mechanisms are not yet fully elucidated.
OBJECTIVE
To investigate whether esketamine treatment immediately after primary lipopolysaccharide (LPS) exposure could alleviate cognitive impairment caused by secondary infection.
METHODS
Mice were injected intraperitoneally (IP) with LPS (5 mg/kg) 10 days apart. Esketamine (10, 15, or 30 mg/kg) was administered IP immediately after the primary LPS injection. Splenectomy or subdiaphragmatic vagotomy (SDV) was performed 7 days before secondary LPS exposure or broad-spectrum antibiotic administration.
RESULTS
Splenomegaly was observed after the primary LPS injection on Days 3 and 10. Splenomegaly was attenuated by treatment with 30 mg/kg esketamine. Esketamine treatment prevented increased plasma proinflammatory cytokines levels and cognitive dysfunction induced by secondary LPS exposure. Mice that underwent splenectomy or SDV had lower proinflammatory cytokines levels, higher hippocampal brain-derived neurotrophic factor (BDNF) levels, and improved cognitive function 1 day after secondary infection, which was not further improved by esketamine. Fecal microbiota transplantation (FMT) from endotoxic mice treated with esketamine attenuated hippocampal BDNF downregulation and cognitive dysfunction only in pseudo germ-free (PGF) mice without splenectomy. FMT with fecal suspensions from esketamine-treated endotoxic mice abrogated splenomegaly only in PGF mice without SDV. Blocking BDNF signaling blocked esketamine's ameliorating effects on secondary LPS exposure-induced cognitive dysfunction.
CONCLUSION
The intestinal flora/subdiaphragmatic vagus nerve/spleen axis-mediated hippocampal BDNF downregulation significantly affected secondary LPS-induced systemic inflammation and cognitive dysfunction. Esketamine preserves cognitive function via this mechanism.
Topics: Mice; Animals; Lipopolysaccharides; Spleen; Brain-Derived Neurotrophic Factor; Splenomegaly; Gastrointestinal Microbiome; Coinfection; Vagus Nerve; Cytokines; Cognitive Dysfunction
PubMed: 38016344
DOI: 10.1016/j.intimp.2023.111284 -
Arteriosclerosis, Thrombosis, and... Jan 2024The gut hormone GLP-2 (glucagon-like peptide-2) plays important roles in lipid handling in the intestine. During postabsorptive stage, it releases preformed chylomicrons...
BACKGROUND
The gut hormone GLP-2 (glucagon-like peptide-2) plays important roles in lipid handling in the intestine. During postabsorptive stage, it releases preformed chylomicrons stored in the intestine, the underlying mechanisms of which are not well understood. Previous studies implicate the involvement of neural pathways in GLP-2's actions on lipid absorption in the intestine, but the role of such mechanisms in releasing postabsorptive lipid storage has not been established.
METHODS
Here, in mesenteric lymph duct cannulated rats, we directly tested whether gut-brain neural communication mediates GLP-2's effects on postabsorptive lipid mobilization in the intestine. We performed total subdiaphragmatic vagotomy to disrupt the gut-brain neural communication and analyzed lipid output 5 hours after a lipid load in response to intraperitoneal GLP-2 or saline.
RESULTS
Peripheral GLP-2 administration led to increased lymph lipid output and activation of proopiomelanocortin neurons in the arcuate nucleus of hypothalamus. Disruption of gut-brain neural communication via vagotomy blunted GLP-2's effects on promoting lipid release in the intestine.
CONCLUSIONS
These results, for the first time, demonstrate a novel mechanism in which postabsorptive mobilization of intestinal lipid storage by GLP-2 enlists a gut-brain neural pathway.
Topics: Rats; Animals; Glucagon-Like Peptide 2; Chylomicrons; Brain; Neural Pathways; Intestines
PubMed: 37970717
DOI: 10.1161/ATVBAHA.123.320032