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International Journal of Molecular... Jun 2024Cannabinoids and their receptors play a significant role in the regulation of gastrointestinal (GIT) peristalsis and intestinal barrier permeability. This review... (Review)
Review
Cannabinoids and their receptors play a significant role in the regulation of gastrointestinal (GIT) peristalsis and intestinal barrier permeability. This review critically evaluates current knowledge about the mechanisms of action and biological effects of endocannabinoids and phytocannabinoids on GIT functions and the potential therapeutic applications of these compounds. The results of ex vivo and in vivo preclinical data indicate that cannabinoids can both inhibit and stimulate gut peristalsis, depending on various factors. Endocannabinoids affect peristalsis in a cannabinoid (CB) receptor-specific manner; however, there is also an important interaction between them and the transient receptor potential cation channel subfamily V member 1 (TRPV1) system. Phytocannabinoids such as Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) impact gut motility mainly through the CB1 receptor. They were also found to improve intestinal barrier integrity, mainly through CB1 receptor stimulation but also via protein kinase A (PKA), mitogen-associated protein kinase (MAPK), and adenylyl cyclase signaling pathways, as well as by influencing the expression of tight junction (TJ) proteins. The anti-inflammatory effects of cannabinoids in GIT disorders are postulated to occur by the lowering of inflammatory factors such as myeloperoxidase (MPO) activity and regulation of cytokine levels. In conclusion, there is a prospect of utilizing cannabinoids as components of therapy for GIT disorders.
Topics: Humans; Cannabinoids; Gastrointestinal Motility; Animals; Gastrointestinal Diseases; Permeability; Intestinal Mucosa; Endocannabinoids
PubMed: 38928387
DOI: 10.3390/ijms25126682 -
International Journal of Developmental... Jun 2024Stigma maydis polysaccharide (SMPS) has regulatory effect on the intestinal microflora and promotes gastrointestinal peristalsis. Children with autism spectrum disorder...
Stigma maydis polysaccharide (SMPS) has regulatory effect on the intestinal microflora and promotes gastrointestinal peristalsis. Children with autism spectrum disorder (ASD) often experience gastrointestinal problems and dysbiosis in their gut microbiota. Our previous study revealed that SMPS interventions had an impact on the gut microbiota of valproic acid (VPA)-induced autism model rats. However, the effects of SMPS on the behavior and gut function of autism model rats remain poorly understood. Therefore, we gave different doses of SMPS intervention in the early stage of autism model rats to observe their developmental conditions and behavior performances. Through histological evaluation and real-time polymerase chain reaction (PCR), integrity of the intestinal structure and the expression of tight junction-related gene Zo-1 and Occludin were detected. The results indicated that SMPS intervention improved the physical development, learning and memory impairment, and social performance of autism model rats. Meanwhile, SMPS promoted intestinal peristalsis and restored the integrity of the intestinal structure, reduced the number of inflammatory cells, and increased the expression of the Zo-1 and Occludin genes. Furthermore, the expression levels of neurotransmitters (substance P, enkephalin, vasoactive intestinal peptide, and 5-hydroxytryptamine) in the hippocampal tissues were altered after SMPS treatment. In conclusion, SMPS could ameliorate ASD-like phenotypes and gut problems in autism model rats. Collectively, these results provide new evidence for the relationship between the gut-brain axis and ASD and suggest a novel therapeutic target for ASD treatment.
PubMed: 38923604
DOI: 10.1002/jdn.10354 -
Biomedical Chromatography : BMC Jun 2024Abnormal relaxation and contraction of intestinal smooth muscle can cause various intestinal diseases. Diarrhea is a common and important public health problem worldwide...
Revealing the material basis and mechanism for the inhibition of intestinal peristalsis by Zingiber officinale Roscoe through integrated metabolomics, serum pharmacochemistry, and network pharmacology.
Abnormal relaxation and contraction of intestinal smooth muscle can cause various intestinal diseases. Diarrhea is a common and important public health problem worldwide in epidemiology. Zingiber officinale Roscoe (fresh ginger) has been found to treat diarrhea, but the material basis and mechanism of action that inhibits intestinal peristalsis remain unclear. Metabolomics and serum pharmacology were used to identify differential metabolites, metabolic pathways, and pharmacodynamic substances, and were then combined with network pharmacology to explore the potential targets of ginger that inhibit intestinal peristalsis during diarrhea treatment, and the targets identified were verified using molecular docking and molecular dynamic simulation. We found that 25 active components of ginger (the six most relevant components), 35 potential key targets (three core targets), 40 differential metabolites (four key metabolites), and four major metabolic pathways were involved in the process by which ginger inhibits intestinal peristalsis during diarrhea treatment. This study reveals the complex mechanism of action and pharmacodynamic material basis of ginger in the inhibition of intestinal peristalsis, and this information helps in the development of new Chinese medicine to treat diarrhea and lays the foundation for the clinical application of ginger.
PubMed: 38922712
DOI: 10.1002/bmc.5932 -
American Journal of Physiology.... Jun 2024The stomach's ability to store, mix, propel, and empty its content requires highly coordinated motor functions. However, current diagnostic tools cannot simultaneously...
BACKGROUND
The stomach's ability to store, mix, propel, and empty its content requires highly coordinated motor functions. However, current diagnostic tools cannot simultaneously assess these motor processes. This study aimed to use magnetic resonance imaging (MRI) to map multifaceted gastric motor functions, including accommodation, tonic and peristaltic contractions, and emptying, through a single non-invasive experiment for both humans and rats.
METHODS
Ten humans and ten Sprague-Dawley rats consumed MRI-visible semi-solid meals and underwent MRI scans. We used a surface model to analyze MRI data, capturing the deformation of the stomach wall upon ingestion or during digestion. We inferred muscle activity, mapped motor processes, parcellated the stomach into functional regions, and revealed cross-species distinctions.
RESULTS
In humans, both the fundus and antrum distended post-meal, followed by sustained tonic contractions to regulate intragastric pressure. Peristaltic contractions initiate from the distal fundus, including three concurrent wavefronts oscillating at 3.3 cycles per minute (cpm) and traveling at 1.7 to 2.9 mm/s. These motor functions facilitate linear gastric emptying with a 61-min half-time. In contrast, rats exhibited peristalsis from the mid-corpus, showing two wavefronts oscillating at 5 cpm and traveling at 0.3 to 0.9 mm/s. For both species, motility features allowed functional parcellation of the stomach along a mid-corpus division.
CONCLUSIONS
This study maps region- and species-specific gastric motor functions. We demonstrate the value of MRI with surface modeling in understanding gastric physiology and its potential to become a new standard for clinical and preclinical investigations of gastric disorders at both individual and group levels.
PubMed: 38915290
DOI: 10.1152/ajpgi.00045.2024 -
Pediatric Research Jun 2024Necrotizing enterocolitis (NEC) is an often-lethal disease of the premature infant intestinal tract, exacerbated by significant diagnostic difficulties. In NEC, the...
BACKGROUND
Necrotizing enterocolitis (NEC) is an often-lethal disease of the premature infant intestinal tract, exacerbated by significant diagnostic difficulties. In NEC, the intestine exhibits hypoperfusion and dysmotility, contributing to disease pathogenesis. However, these features cannot be accurately and quantitively assessed with current imaging modalities. We have previously demonstrated the ability of photoacoustic imaging (PAI) to non-invasively assess intestinal tissue oxygenation and motility in a healthy neonatal rat model.
METHODS
In this first-in-disease application, we evaluated NEC using PAI to assess intestinal health biomarkers in an experimental model of NEC. NEC was induced in neonatal rats from birth to 4-days. Healthy breastfed (BF) and NEC rat pups were imaged at 2- and 4-days.
RESULTS
Intestinal tissue oxygen saturation was measured with PAI, and NEC pups showed significant decreases at 2- and 4-days. Ultrasound and PAI cine recordings were used to capture intestinal peristalsis and contrast agent transit within the intestine. Intestinal motility, assessed using computational intestinal deformation analysis, demonstrated significant reductions in both early and established NEC. NEC damage was confirmed with histology and dysmotility was confirmed by small intestinal transit assay.
CONCLUSION
This preclinical study presents PAI as an emerging diagnostic imaging modality for intestinal disease assessment in premature infants.
IMPACT
Necrotizing enterocolitis (NEC) is a devastating intestinal disease affecting premature infants with significant mortality. NEC presents significant clinical diagnostic difficulties, with limited diagnostic confidence complicating timely and effective interventional efforts. This study is an important foundational first-in-disease preclinical study that establishes the utility for PAI to detect changes in intestinal tissue oxygenation and intestinal motility with NEC disease induction and progression. This study demonstrates the feasibility and exceptional promise for the use of PAI to non-invasively assess oxygenation and motility in the healthy and diseased infant intestine.
PubMed: 38914761
DOI: 10.1038/s41390-024-03358-2 -
Bioactive Materials Oct 2024For gastrointestinal anastomosis, metallic biodegradable staples have a broad application potential. However, both magnesium and zinc alloys have relatively low strength...
For gastrointestinal anastomosis, metallic biodegradable staples have a broad application potential. However, both magnesium and zinc alloys have relatively low strength to withstand the repeated peristalsis of the gastrointestinal tract. In this study, we developed a novel kind of biodegradable high-nitrogen iron (HN-Fe) alloy wires (0.23 mm), which were fabricated into the staples. The tensile results showed that the ultimate tensile strength and elongation of HN-Fe wires were 1023.2 MPa and 51.0 %, respectively, which was much higher than those of other biodegradable wires. The degradation rate of HN-Fe wires was slightly higher than that of pure Fe wires. After 28 days of immersion, the tensile strength of HN-Fe wires remained not less than 240 MPa, meeting the clinical requirements. Furthermore, sixteen rabbits were enrolled to conduct a comparison experiment using HN-Fe and clinical Ti staples for gastroanastomosis. After 6 months of implantation, a homogeneous degradation product layer on HN-Fe staples was observed and no fracture occurred. The degradation rate of HN-Fe staples was significantly higher than that , and they were expected to be completely degraded in 2 years. Meanwhile, both benign cutting and closure performance of HN-Fe staples ensured that all the animals did not experience hemorrhage and anastomotic fistula during the observation. The anastomosis site healed without histopathological change, inflammatory reaction and abnormal blood routine and biochemistry, demonstrating good biocompatibility of HN-Fe staples. Thereby, the favorable performance makes the HN-Fe staples developed in this work a promising candidate for gastrointestinal anastomosis.
PubMed: 38910967
DOI: 10.1016/j.bioactmat.2024.06.005 -
Food & Function Jun 2024AR495 is a widely used probiotic for the treatment of various digestive diseases, including irritable bowel syndrome (IBS). However, the specific mechanisms of AR495...
AR495 is a widely used probiotic for the treatment of various digestive diseases, including irritable bowel syndrome (IBS). However, the specific mechanisms of AR495 in alleviating IBS remain unclear. Abnormal intestinal tryptophan metabolism can cause disordered immune responses, gastrointestinal peristalsis, digestion and sensation, which is closely related to IBS pathogenesis. The aim of this study is to explore the effects and mechanisms of AR495 in regulating tryptophan metabolism. Primarily, tryptophan and its related metabolites in patients with IBS and healthy people were analyzed, and an IBS rat model of acetic acid enema plus restraint stress was established to explore the alleviation pathway of AR495 in tryptophan metabolism. It was found that the 5-HT pathway was significantly changed, and the 5-HTP and 5-HT metabolites were significantly increased in the feces of patients with IBS, which were consistent with the results obtained for the IBS rat model. Maladjusted 5-HT could increase intestinal peristalsis and lead to an increase in the fecal water content and shapeless stool in rats. On the contrary, these two metabolites could be restored to normal levels intragastric administration of AR495. Further study of the metabolic pathway showed that AR495 could effectively reduce the abundance of 5-HT by inhibiting the expression of enterochromaffin cells rather than promoting its decomposition. In addition, the results showed that AR495 did not affect the expression of SERT. To sum up, AR495 could restore the normal levels of 5-HT by inhibiting the abnormal proliferation of enterochromaffin cells and the excessive activation of TPH1 to inhibit the intestinal peristalsis in IBS. These findings provide insights for the use of probiotics in the treatment of IBS and other diarrheal diseases.
PubMed: 38899520
DOI: 10.1039/d4fo01087f -
The Journal of Pediatrics Jun 2024To examine the biomarkers of pharyngoesophageal swallowing during oral feeding sessions in infants undergoing pH-impedance testing and determine if swallow frequencies...
OBJECTIVE
To examine the biomarkers of pharyngoesophageal swallowing during oral feeding sessions in infants undergoing pH-impedance testing and determine if swallow frequencies are distinct between oral- and partially oral-fed infants.
STUDY DESIGN
One oral feeding session was performed in 40 infants during pH-impedance studies and measurements included swallowing frequency, multiple swallow rate, air and liquid swallow rates, esophageal swallow clearance time (ESCT), and gastroesophageal reflux (GER) characteristics. Linear and mixed statistical models were applied to examine the swallowing markers and outcomes.
RESULTS
Infants (30.2 ± 4.4 weeks birth gestation) were evaluated at 41.2 ± 0.4 weeks postmenstrual age (PMA). Overall, 10,675 swallows were analyzed during the oral feeding sessions (19.3 ± 5.4 min per infant) and GER events were noted (2.5 ± 0.3 per study). Twenty-four-hour acid reflux index (ARI) was 9.5 ± 2.0%. Differences were noted in oral- and partially oral-fed infants for: volume consumption (p<0.01), consumption rate (p<0.01), and length of hospital stay in days (p<0.01). Infants with ARI >7% had greater frequency of swallows (p=0.01). The oral-fed group had greater ARI (12.7 ± 3.3%, p=0.05).
CONCLUSIONS
Oropharyngeal swallowing regulatory characteristics decrease over the feeding duration and were different between ARI >7% vs ≤7%. Although GER is less in infants who are partially oral-fed, the neonates with increased acid exposure achieved greater oral intakes and shorter hospitalizations, despite the presence of comorbidities. Pharyngoesophageal stimulation as during consistent feeding or GER events can activate peristaltic responses and rhythms, which may be contributory to the findings.
PubMed: 38897379
DOI: 10.1016/j.jpeds.2024.114154 -
The Journal of Obstetrics and... Jun 2024Detecting ureteral injury-a serious intraoperative and postoperative complication of hysterectomy-is a high level of difficulty if ureteral malformations are not...
A case of a blind-ending right ureter first identified intraoperatively during total laparoscopic hysterectomy for uterine adenomyosis and fibroids in a woman with severe ipsilateral kidney hypoplasia.
Detecting ureteral injury-a serious intraoperative and postoperative complication of hysterectomy-is a high level of difficulty if ureteral malformations are not identified preoperatively. A 39-year-old Japanese woman underwent total laparoscopic hysterectomy for uterine adenomyosis. During surgery, ureteral peristalsis was absent on the right side, whereas the left ureter was visible under the peritoneum. Transabdominal ultrasonography failed to locate the right kidney, with cystoscopy showing no flow from the right ureteral orifice. The ureteral tunnel was identified by tracing the vascular path of the internal iliac and uterine arteries, confirming that the corded tissue was the right ureter. Postoperative contrast-enhanced CT revealed severe right kidney atrophy with no contrast effect or connected ureter. Based on intraoperative laparoscopy and postoperative examination, a diagnosis of a unilateral ureteral scar with a proximal blind end and ipsilateral renal dysgenesis was established, marking the first reported instance of endoscopic visualization of this anomaly. In addition to normal pelvic anatomy, surgeons must consider embryological abnormalities to prevent intraoperative complications.
PubMed: 38884165
DOI: 10.1111/jog.15992 -
Journal of Mathematical Biology Jun 2024In this paper, we introduce the numerical strategy for mixed uncertainty propagation based on probability and Dempster-Shafer theories, and apply it to the computational...
In this paper, we introduce the numerical strategy for mixed uncertainty propagation based on probability and Dempster-Shafer theories, and apply it to the computational model of peristalsis in a heart-pumping system. Specifically, the stochastic uncertainty in the system is represented with random variables while epistemic uncertainty is represented using non-probabilistic uncertain variables with belief functions. The mixed uncertainty is propagated through the system, resulting in the uncertainty in the chosen quantities of interest (QoI, such as flow volume, cost of transport and work). With the introduced numerical method, the uncertainty in the statistics of QoIs will be represented using belief functions. With three representative probability distributions consistent with the belief structure, global sensitivity analysis has also been implemented to identify important uncertain factors and the results have been compared between different peristalsis models. To reduce the computational cost, physics constrained generalized polynomial chaos method is adopted to construct cheaper surrogates as approximations for the full simulation.
Topics: Peristalsis; Uncertainty; Computer Simulation; Humans; Models, Cardiovascular; Stochastic Processes; Mathematical Concepts; Animals; Heart; Models, Biological; Nonlinear Dynamics
PubMed: 38879850
DOI: 10.1007/s00285-024-02116-6