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Microbiome Jul 2020In a pilot study, we found that feces transplantation from elderly individuals to mice significantly caused cognitive impairment. Paenalcaligenes hominis and Escherichia...
BACKGROUND
In a pilot study, we found that feces transplantation from elderly individuals to mice significantly caused cognitive impairment. Paenalcaligenes hominis and Escherichia coli are increasingly detected in the feces of elderly adults and aged mice. Therefore, we isolated Paenalcaligenes hominis and Escherichia coli from the feces of elderly individuals and aged mice and examined their effects on the occurrence of age-related degenerative cognitive impairment and colonic inflammation in mice.
RESULTS
The transplantation of feces collected from elderly people and aged mice caused significantly more severe cognitive impairment in transplanted young mice than those from young adults and mice. Oral gavage of Paenalcaligenes hominis caused strong cognitive impairment and colitis in specific pathogen-free (SPF) and germ-free mice. Escherichia coli also induced cognitive impairment and colitis in SPF mice. Oral gavage of Paenalcaligenes hominis, its extracellular vesicles (EVs), and/or lipopolysaccharide caused cognitive impairment and colitis in mice. However, celiac vagotomy significantly inhibited the occurrence of cognitive impairment, but not colitis, in mice exposed to Paenalcaligenes hominis or its EVs, whereas its lipopolysaccharide or Escherichia coli had no such effects. Vagotomy also inhibited the infiltration of EVs into the hippocampus.
CONCLUSIONS
Paenalcaligenes hominis, particularly its EVs, can cause cognitive function-impaired disorders, such as Alzheimer's disease, and its EVs may penetrate the brain through the blood as well as the vagus nerve. Video Abstract.
Topics: Aging; Alcaligenaceae; Animals; Cognitive Dysfunction; Colitis; Escherichia coli; Extracellular Vesicles; Fecal Microbiota Transplantation; Feces; Female; Gastrointestinal Microbiome; Humans; Intestines; Male; Mice; Mice, Inbred C57BL; Middle Aged; Pilot Projects; Risk Factors; Vagotomy; Vagus Nerve; Young Adult
PubMed: 32669127
DOI: 10.1186/s40168-020-00881-2 -
BMJ Open Sep 2023Benign gastric outlet obstruction (BGOO) severely impacts the quality of life of patients. The main treatment methods for BGOO include surgery and endoscopy, but both...
Exploring the safety and efficacy of stomach-partitioning gastrojejunostomy with distal selective vagotomy versus conventional gastrojejunostomy with highly selective vagotomy for treating benign gastric outlet obstruction: study protocol for a randomised controlled trial.
INTRODUCTION
Benign gastric outlet obstruction (BGOO) severely impacts the quality of life of patients. The main treatment methods for BGOO include surgery and endoscopy, but both have significant drawbacks. Therefore, this study aims to explore the safety and efficacy of a new technique, to develop a new option for treating BGOO.
METHODS AND ANALYSIS
This is an ongoing prospective, single-centre, single-blind randomised controlled trial. The study will be conducted from January 2022 to December 2025, and 50 patients will be enrolled. The participants will be randomly assigned in a 1:1 ratio to either the experimental (stomach-partitioning gastrojejunostomy with distal selective vagotomy) or control groups (conventional gastrojejunostomy with highly selective vagotomy). We will collect baseline characteristics, laboratory tests, auxiliary examinations, operation, postoperative conditions and follow-up data. Follow-up will last for 3 years. The main outcome is the incidence of delayed gastric emptying within 30 days after surgery. Secondary outcomes include the efficacy indicator (consisting of serum gastrin level, pepsinogen level, 13C breath test, gastrointestinal quality of life index, operation time, blood loss and postoperative recovery), a safety evaluation index (consisting of complications and mortality within 30 days after surgery) and follow-up data (consisting of the incidence of primary ulcer progression in 3 years after surgery, and the gastroscopy results in 1 and 3 years after surgery).
ETHICS AND DISSEMINATION
This study was approved by the Ethics Committee of Beijing Friendship Hospital, Capital Medical University (no. 2021-P2-274-02). The study conformed to the provisions of the Declaration of Helsinki (as revised in 2013). Written informed consent will be obtained prior to study enrolment. The results of this study will be published in peer-reviewed publications.
TRIAL REGISTRATION NUMBER
ChiCTR2100052197.
Topics: Humans; Vagotomy, Proximal Gastric; Gastric Bypass; Prospective Studies; Quality of Life; Single-Blind Method; Vagotomy; Gastric Outlet Obstruction; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 37770279
DOI: 10.1136/bmjopen-2022-070735 -
International Journal of Biological... 2024It had been shown that selective cardiac vagal activation holds great potential for heart regeneration. Optogenetics has clinical translation potential as a novel means...
It had been shown that selective cardiac vagal activation holds great potential for heart regeneration. Optogenetics has clinical translation potential as a novel means of modulating targeted neurons. This study aimed to investigate whether cardiac vagal activation via optogenetics could improve heart regenerative repair after myocardial infarction (MI) and to identify the underlying mechanism. We used an adeno-associated virus (AAV) as the vector to deliver ChR2, a light-sensitive protein, to the left nodose ganglion (LNG). To assess the effects of the cardiac vagus nerve on cardiomyocyte (CM) proliferation and myocardial regeneration the light-emitting diode illumination (470 nm) was applied for optogenetic stimulation to perform the gain-of-function experiment and the vagotomy was used as a loss-of-function assay. Finally, sequencing data and molecular biology experiments were analyzed to determine the possible mechanisms by which the cardiac vagus nerve affects myocardial regenerative repair after MI. Absence of cardiac surface vagus nerve after MI was more common in adult hearts with low proliferative capacity, causing a poor prognosis. Gain- and loss-of-function experiments further demonstrated that optogenetic stimulation of the cardiac vagus nerve positively regulated cardiomyocyte (CM) proliferation and myocardial regeneration . More importantly, optogenetic stimulation attenuated ventricular remodeling and improved cardiac function after MI. Further analysis of sequencing results and flow cytometry revealed that cardiac vagal stimulation activated the IL-10/STAT3 pathway and promoted the polarization of cardiac macrophages to the M2 type, resulting in beneficial cardiac regenerative repair after MI. Targeting the cardiac vagus nerve by optogenetic stimulation induced macrophage M2 polarization by activating the IL-10/STAT3 signaling pathway, which obviously optimized the regenerative microenvironment and then improved cardiac function after MI.
Topics: Adult; Humans; Interleukin-10; Optogenetics; Myocardial Infarction; Vagus Nerve; Myocytes, Cardiac
PubMed: 38617528
DOI: 10.7150/ijbs.89883 -
Biomedicine & Pharmacotherapy =... Jun 2023Previous studies proved the benefits of electroacupuncture (EA) on heart in ischemia reperfusion injury and chronic heart failure. However, the role of EA on...
PURPOSE
Previous studies proved the benefits of electroacupuncture (EA) on heart in ischemia reperfusion injury and chronic heart failure. However, the role of EA on sepsis-induced cardiac dysfunction has rarely been elucidated before. In this study, we aimed to investigate the effects of EA on cardiac dysfunction in a rat model of sepsis and to speculate the underlying mechanisms.
METHODS
Sepsis was induced by cecum ligation and puncture in anesthetized rats. EA at the acupoint "Neiguan (PC6)" was applied 0.5 h after the induction of sepsis for 20 min. Heart rate variability was obtained immediately after EA to evaluate autonomic balance. Echocardiography was performed at 6 h and 24 h after sepsis induction in vivo. Measurements of hemodynamics, blood gases, cytokines and biochemistry were collected at 24 h. Cardiac tissue underwent immunofluorescence staining to determine the expression of α7 nicotinic acetylcholine receptor (α7nAChR) on macrophages.
RESULTS
EA increased vagus nerve activity, prevented the development of hyperlactatemia, attenuated the decline of left ventricle ejection fraction, suppressed systemic and cardiac inflammation and alleviated the histopathological manifestations of heart in sepsis rats. Furthermore, the cardiac tissue from EA treated rats showed increased expressions of α7nAChR on macrophages. The cardio-protective and anti-inflammatory effects of EA were partly or completely prevented in rats with vagotomy.
CONCLUSION
EA at PC6 attenuates left ventricle dysfunction and decreases inflammation in sepsis-induced cardiac dysfunction. The cardio-protective effects of EA are mediated through vagus nerve mediated cholinergic pathway.
Topics: Rats; Animals; Rats, Sprague-Dawley; alpha7 Nicotinic Acetylcholine Receptor; Electroacupuncture; Vagus Nerve; Inflammation; Heart Diseases; Punctures; Cecum; Sepsis
PubMed: 36996679
DOI: 10.1016/j.biopha.2023.114600 -
Nutrients May 2023During esophagectomy, the vagus nerve is transected, which may add to the development of postoperative complications. The vagus nerve has been shown to attenuate...
During esophagectomy, the vagus nerve is transected, which may add to the development of postoperative complications. The vagus nerve has been shown to attenuate inflammation and can be activated by a high-fat nutrition via the release of acetylcholine. This binds to α7 nicotinic acetylcholine receptors (α7nAChR) and inhibits α7nAChR-expressing inflammatory cells. This study investigates the role of the vagus nerve and the effect of high-fat nutrition on lipopolysaccharide (LPS)-induced lung injury in rats. Firstly, 48 rats were randomized in 4 groups as follows: sham (sparing vagus nerve), abdominal (selective) vagotomy, cervical vagotomy and cervical vagotomy with an α7nAChR-agonist. Secondly, 24 rats were randomized in 3 groups as follows: sham, sham with an α7nAChR-antagonist and cervical vagotomy with an α7nAChR-antagonist. Finally, 24 rats were randomized in 3 groups as follows: fasting, high-fat nutrition before sham and high-fat nutrition before selective vagotomy. Abdominal (selective) vagotomy did not impact histopathological lung injury (LIS) compared with the control (sham) group ( > 0.999). There was a trend in aggravation of LIS after cervical vagotomy ( = 0.051), even after an α7nAChR-agonist ( = 0.090). Cervical vagotomy with an α7nAChR-antagonist aggravated lung injury ( = 0.004). Furthermore, cervical vagotomy increased macrophages in bronchoalveolar lavage (BAL) fluid and negatively impacted pulmonary function. Other inflammatory cells, TNF-α and IL-6, in the BALF and serum were unaffected. High-fat nutrition reduced LIS after sham ( = 0.012) and selective vagotomy ( = 0.002) compared to fasting. vagotomy. This study underlines the role of the vagus nerve in lung injury and shows that vagus nerve stimulation using high-fat nutrition is effective in reducing lung injury, even after selective vagotomy.
Topics: Rats; Animals; Lipopolysaccharides; alpha7 Nicotinic Acetylcholine Receptor; Vagus Nerve; Vagotomy; Acute Lung Injury
PubMed: 37242210
DOI: 10.3390/nu15102327 -
BMJ Open Gastroenterology 2020In 2013, peptic ulcer disease (PUD) caused over 300 000 deaths globally. Low-income and middle-income countries are disproportionately affected. However, there is... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
In 2013, peptic ulcer disease (PUD) caused over 300 000 deaths globally. Low-income and middle-income countries are disproportionately affected. However, there is limited information regarding risk factors of perioperative mortality rates in these countries.
OBJECTIVE
To assess perioperative mortality rates from complicated PUD in Africa and associated risk factors.
DESIGN
We performed a systematic review and a random-effect meta-analysis of literature describing surgical management of complicated PUD in Africa. We used subgroup analysis and meta-regression analyses to investigate sources of variations in the mortality rates and to assess the risk factors contributing to mortality.
RESULTS
From 95 published reports, 10 037 patients underwent surgery for complicated PUD. The majority of the ulcers (78%) were duodenal, followed by gastric (14%). Forty-one per cent of operations were for perforation, 22% for obstruction and 9% for bleeding. The operations consisted of vagotomy (38%), primary repair (34%), resection and reconstruction (12%), and drainage procedures (6%). The overall PUD mortality rate was 6.6% (95% CI 5.4% to 8.1%). It increased to 9.7% (95% CI 7.1 to 13.0) when we limited the analysis to studies published after the year 2000. The correlation was higher between perforated PUD and mortality rates (r=0.41, p<0.0001) than for bleeding PUD and mortality rates (r=0.32, p=0.001). Non-significant differences in mortality rates existed between sub-Saharan Africa (SSA) and North Africa and within SSA.
CONCLUSION
Perioperative mortality rates from complicated PUD in Africa are substantially high and could be increasing over time, and there are possible regional differences.
Topics: Africa South of the Sahara; Humans; Peptic Ulcer; Peptic Ulcer Hemorrhage; Peptic Ulcer Perforation; Risk Factors
PubMed: 32128227
DOI: 10.1136/bmjgast-2019-000350 -
Obesity Surgery Jul 2022Evidences about the gut microbiota role in weight loss after bariatric surgery (BS) are growing. The objective of this study was to observe the changes of gut microbiota...
PURPOSE
Evidences about the gut microbiota role in weight loss after bariatric surgery (BS) are growing. The objective of this study was to observe the changes of gut microbiota after sleeve gastrectomy (SG) and SG plus truncal vagotomy (SG-TV) and identify specific microbes that may contribute to the improvement of obesity after surgeries.
MATERIALS AND METHODS
Forty high-fat diet-induced obesity (DIO) mice were randomized to SG, SG-TV, or sham operation (SH) groups. Body weight (BW) and fast blood glucose (FBG) were measured before and 1, 2, 4, 8, and 12 weeks post-operatively. Fecal samples were collected before and at post-operative week 12 and profiled using 16S rRNA relative and absolute quantitative sequencing.
RESULTS
After the surgery, the SG and SG-TV surgeries significantly reduce BW and FBG levels compared with SH, and the SG-TV achieved better effects than SG. A decreasing trend in alpha diversity of gut microbiota and significant changes in taxonomic composition were observed after surgeries. Then, we identified a set of microbes and pathways significantly different in abundance after BS. The genus Parabacteroides and one pathway (polyketide sugar unit biosynthesis) increased in SG-TV group specially, which was also negatively correlated with BW and FBG.
CONCLUSION
SG and SG-TV indeed achieve effects of weight loss, but TV could enhance the efficacy of SG. The identified different microbes and pathways, like Parabacteroides, polyketide sugar unit biosynthesis, may partly mediate the beneficial effects of BS, and thus possibly contribute to the development of novel bacteria-based therapeutic approaches.
Topics: Animals; Bariatric Surgery; Gastrectomy; Mice; Obesity; Obesity, Morbid; Polyketides; RNA, Ribosomal, 16S; Sugars; Vagotomy, Truncal; Weight Loss
PubMed: 35546385
DOI: 10.1007/s11695-022-06017-9 -
The Journal of Physiology May 2023Brief repeated fetal hypoxaemia during labour can trigger intrapartum decelerations of the fetal heart rate (FHR) via the peripheral chemoreflex or the direct effects of...
Brief repeated fetal hypoxaemia during labour can trigger intrapartum decelerations of the fetal heart rate (FHR) via the peripheral chemoreflex or the direct effects of myocardial hypoxia, but the relative contribution of these two mechanisms and how this balance changes with evolving fetal compromise remain unknown. In the present study, chronically instrumented near-term fetal sheep received surgical vagotomy (n = 8) or sham vagotomy (control, n = 11) to disable the peripheral chemoreflex and unmask myocardial hypoxia. One-minute complete umbilical cord occlusions (UCOs) were performed every 2.5 min for 4 h or until arterial pressure fell below 20 mmHg. Hypotension and severe acidaemia developed progressively after 65.7 ± 7.2 UCOs in control fetuses and 49.5 ± 7.8 UCOs after vagotomy. Vagotomy was associated with faster development of metabolic acidaemia and faster impairment of arterial pressure during UCOs without impairing centralization of blood flow or neurophysiological adaptation to UCOs. During the first half of the UCO series, before severe hypotension developed, vagotomy was associated with a marked increase in FHR during UCOs. After the onset of evolving severe hypotension, FHR fell faster in control fetuses during the first 20 s of UCOs, but FHR during the final 40 s of UCOs became progressively more similar between groups, with no difference in the nadir of decelerations. In conclusion, FHR decelerations were initiated and sustained by the peripheral chemoreflex at a time when fetuses were able to maintain arterial pressure. After the onset of evolving hypotension and acidaemia, the peripheral chemoreflex continued to initiate decelerations, but myocardial hypoxia became progressively more important in sustaining and deepening decelerations. KEY POINTS: Brief repeated hypoxaemia during labour can trigger fetal heart rate decelerations by either the peripheral chemoreflex or myocardial hypoxia, but how this balance changes with fetal compromise is unknown. Reflex control of fetal heart rate was disabled by vagotomy to unmask the effects of myocardial hypoxia in chronically instrumented fetal sheep. Fetuses were then subjected to repeated brief hypoxaemia consistent with the rates of uterine contractions during labour. We show that the peripheral chemoreflex controls brief decelerations in their entirety at a time when fetuses were able to maintain normal or increased arterial pressure. The peripheral chemoreflex still initiated decelerations even after the onset of evolving hypotension and acidaemia, but myocardial hypoxia made an increasing contribution to sustain and deepen decelerations.
Topics: Female; Sheep; Pregnancy; Animals; Humans; Deceleration; Heart Rate, Fetal; Umbilical Cord; Fetus; Hypoxia; Myocardial Ischemia; Acidosis; Hypotension; Fetal Hypoxia
PubMed: 37017488
DOI: 10.1113/JP284286 -
Journal of Neuroinflammation Dec 2021Atrial natriuretic peptide (ANP) secreted from atrial myocytes is shown to possess anti-inflammatory, anti-oxidant and immunomodulatory effects. The aim of this study is...
BACKGROUND
Atrial natriuretic peptide (ANP) secreted from atrial myocytes is shown to possess anti-inflammatory, anti-oxidant and immunomodulatory effects. The aim of this study is to assess the effect of ANP on bacterial lipopolysaccharide (LPS)-induced endotoxemia-derived neuroinflammation and cognitive impairment.
METHODS
LPS (5 mg/kg) was given intraperitoneally to mice. Recombinant human ANP (rhANP) (1.0 mg/kg) was injected intravenously 24 h before and/or 10 min after LPS injection. Subdiaphragmatic vagotomy (SDV) was performed 14 days before LPS injection or 28 days before fecal microbiota transplantation (FMT). ANA-12 (0.5 mg/kg) was administrated intraperitoneally 30 min prior to rhANP treatment.
RESULTS
LPS (5.0 mg/kg) induced remarkable splenomegaly and an increase in the plasma cytokines at 24 h after LPS injection. There were positive correlations between spleen weight and plasma cytokines levels. LPS also led to increased protein levels of ionized calcium-binding adaptor molecule (iba)-1, cytokines and inducible nitric oxide synthase (iNOS) in the hippocampus. LPS impaired the natural and learned behavior, as demonstrated by an increase in the latency to eat the food in the buried food test and a decrease in the number of entries and duration in the novel arm in the Y maze test. Combined prophylactic and therapeutic treatment with rhANP reversed LPS-induced splenomegaly, hippocampal and peripheral inflammation as well as cognitive impairment. However, rhANP could not further enhance the protective effects of SDV on hippocampal and peripheral inflammation. We further found that PGF mice transplanted with fecal bacteria from rhANP-treated endotoxemia mice alleviated the decreased protein levels of hippocampal polyclonal phosphorylated tyrosine kinase receptor B (p-TrkB), brain-derived neurotrophic factor (BDNF) and cognitive impairment, which was abolished by SDV. Moreover, TrkB/BDNF signaling inhibitor ANA-12 abolished the improving effects of rhANP on LPS-induced cognitive impairment.
CONCLUSIONS
Our results suggest that rhANP could mitigate LPS-induced hippocampal inflammation and cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota-brain axis.
Topics: Animals; Atrial Natriuretic Factor; Brain-Gut Axis; Cognitive Dysfunction; Endotoxins; Feces; Gastrointestinal Microbiome; Inflammation Mediators; Injections, Intraperitoneal; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Neuroinflammatory Diseases; Recombinant Proteins; Vagotomy; Vagus Nerve
PubMed: 34949194
DOI: 10.1186/s12974-021-02356-z -
Frontiers in Cardiovascular Medicine 2022Following acute myocardial infarction (MI), irreversible damage to the myocardium can only be reduced by shortening the duration between symptom onset and...
BACKGROUND
Following acute myocardial infarction (MI), irreversible damage to the myocardium can only be reduced by shortening the duration between symptom onset and revascularization. While systemic hypothermia has shown promising results in slowing pre-revascularization myocardial damage, it is resource intensive and not conducive to prehospital initiation. We hypothesized that topical neck cooling (NC), an easily implemented therapy for en route transfer to definitive therapy, could similarly attenuate myocardial ischemia-reperfusion injury (IRI).
METHODS
Using an mouse model of myocardial IRI, moderate systemic hypothermia or NC was applied following left coronary artery (LCA) occlusion and subsequent reperfusion, at early, late, and post-reperfusion intervals. Vagotomy was performed after late NC in an additional group. Hearts were harvested to measure infarct size.
RESULTS
Both hypothermia treatments equally attenuated myocardial infarct size by 60% compared to control. The infarct-sparing effect of NC was temperature-dependent and timing-dependent. Vagotomy at the gastroesophageal junction abolished the infarct-sparing effect of late NC. Cardiac perfusate isolated following ischemia had significantly reduced cardiac troponin T, HMGB1, cell-free DNA, and interferon α and β levels after NC.
CONCLUSIONS
Topical neck cooling attenuates myocardial IRI in a vagus nerve-dependent manner, with an effect comparable to that of systemic hypothermia. NC attenuated infarct size when applied during ischemia, with earlier initiation resulting in superior infarct sparing. This novel therapy exerts a cardioprotective effect without requiring significant change in core temperature and may be a promising practical strategy to attenuate myocardial damage while patients await definitive revascularization.
PubMed: 35837603
DOI: 10.3389/fcvm.2022.893837