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Experimental and Therapeutic Medicine Nov 2019Changes in the levels of serum oxidative stress indexes, gastrointestinal hormones and inflammatory factors in children with different severity of reflux esophagitis...
Changes in the levels of serum oxidative stress indexes, gastrointestinal hormones and inflammatory factors in children with different severity of reflux esophagitis (RE) were detected. Sixty child patients diagnosed with gastroesophageal reflux disease (GERD) via gastroscopy were selected and divided into non-erosive reflux disease group (NERD group, n=12) and RE group (n=48) according to whether there was esophageal mucosal injury. In RE group, the patients were further divided into grade I RE group (n=15), grade II RE group (n=18) and grade III RE group (n=15) based on the severity of mucosal injury. None of the child patients took PPI and domperidone within 2 weeks before enrollment. The content of malondialdehyde (MDA) and total superoxide dismutase (T-SOD) in the esophageal mucosa was detected. The changes in the levels of serum vasoactive intestinal peptide (VIP), motilin, interleukin-1β (IL-1β), IL-8 and tumor necrosis factor-α (TNF-α) were determined. The DeMeester score was the highest in grade III RE group, followed by grade II RE group, grade I RE group and NERD group (P<0.05). The content of MDA in the esophageal mucosa was higher in RE group than that in NERD group, and the T-SOD activity declined with the increased severity of injury (P<0.05). In the three RE groups, the level of plasma VIP was significantly higher, while the motilin level was remarkably lower than those in NERD group (P<0.05). With the increased severity of disease, the expression levels of serum IL-1β, IL-8 and TNF-α in RE group were gradually raised (P<0.05). RE patients have strong oxidative stress and inflammatory response, an increased level of serum VIP, a regulator of gastrointestinal motility, and a decreased level of motilin. Controlling the changes in the above factors using effective treatment means can improve the development of GERD.
PubMed: 31602227
DOI: 10.3892/etm.2019.7978 -
Ocular Immunology and Inflammation 2022In this study, we investigated the presence of motilin receptors (MR) in adnexal tissue including the human main lacrimal gland.
INTRODUCTION
In this study, we investigated the presence of motilin receptors (MR) in adnexal tissue including the human main lacrimal gland.
METHOD
17 adnexal human specimens comprising of 11 isolated human main lacrimal gland specimens, four full-thickness human eyelid excisions and two exenterations containing full-thickness eyelid and portions of the main lacrimal gland were immunolabelled with a rabbit polyclonal human MR antibody.
RESULTS
Our results demonstrated that all main lacrimal gland specimens (13/13, 100%) were positive for MR expression with a predominance (10/13 (77%) of grade 1+ punctate distribution. Motilin receptors were not found in eccrine glands, cutaneous sebaceous glands, glands of Zeis or glands of Moll (0/6, 0%). We also confirmed MR expression in the accessory lacrimal gland tissue.
CONCLUSION
In summary, we discovered the MR receptor in the lacrimal and accessory lacrimal gland - the significance of which, in the lacrimal gland, remains unclear - but motilin may play a role in the muscarinic control of aqueous tear secretion.
Topics: Lacrimal Apparatus; Motilin; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide; Humans
PubMed: 33974477
DOI: 10.1080/09273948.2021.1903937 -
Veterinary Sciences Oct 2021To reduce the circulation path of the output current of traditional electroacupuncture (TEA) process in the body, a simple single-acupoint electroacupuncture (SEA) frame...
To reduce the circulation path of the output current of traditional electroacupuncture (TEA) process in the body, a simple single-acupoint electroacupuncture (SEA) frame was designed and the acupuncture effect of SEA was evaluated through Hou-san-li (ST-36) and Qian-san-li (LI-10) acupoints. Forty-two healthy New Zealand rabbits were randomly divided into seven groups and underwent acupuncture for 20 min in an awake state. Blood samples aseptically collected from the ear vein 3 h before acupuncture and 0, 3, 6, 9, 12 and 24 h after acupuncture were used for the detection of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase MB (CK-MB) and motilin (MTL) in serum. The simple SEA frame was developed successfully, and the acupuncture results showed that the serum AST and ALT levels were significantly higher at 3 h after TEA with high frequency ( < 0.01) compared with the control group. Regarding serum CK-MB levels, no significant differences were found after SEA or TEA stimulation ( > 0.05). Serum MTL levels were significantly increased at 0 h after SEA and TEA ( < 0.05), but there were no significant differences at other time points after SEA and TEA treatment ( > 0.05). SEA not only maintains the effect of TEA but also shortens the circulation loop of the electroacupuncture (EA) current in the body, which effectively avoids body injury.
PubMed: 34679047
DOI: 10.3390/vetsci8100217 -
Journal of Cellular and Molecular... Apr 2021In this study, we aimed to investigate the role of circORC2 in modulating miR-19a and its downstream signalling during the pathogenesis of STC. In this study, three...
In this study, we aimed to investigate the role of circORC2 in modulating miR-19a and its downstream signalling during the pathogenesis of STC. In this study, three groups of patients, that is healthy control (HC) group, normal transit constipation (NTC) group (N = 42) and slow transit constipation (STC) group, were, respectively, recruited. RT-PCR and Western blot analysis were exploited to investigate the changes in the expression levels of miR-19a and circORC2 in these patients, so as to establish a circORC2/miR-19a signalling pathway. The basic information of the patients showed no significant differences among different patient groups. Compared with the HC group, concentrations of neurotensin (NST) and motilin (MLN) were both significantly reduced in the NTC and STC groups, especially in the STC group. Also, miR-19a level was highest, whereas circORC2 level was lowest in the STC group. Furthermore, circORC2 was validated to sponge the expression of miR-19a, and the transfection of circORC2 reduced the expression of miR-19a. Meanwhile, MLN and NST mRNAs were both targeted by miR-19a, and the transfection of circORC2 dramatically up-regulated the expression of MLN and NST. On the contrary, the transfection of circORC2 siRNA into SMCs and VSMCs exhibited the opposite effect of circORC2. Collectively, the results of this study established a regulatory relationship among circORC2, miR-19a and neurotensin/motilin, which indicated that the overexpression of circORC2 could up-regulate the levels of neurotensin and motilin, thus exerting a beneficial effect during the treatment of STC.
Topics: Aged; Apoptosis; Biomarkers; Case-Control Studies; Cell Proliferation; Cells, Cultured; Constipation; Female; Gene Expression Regulation; Humans; Male; MicroRNAs; Motilin; Neurotensin; Origin Recognition Complex; Prognosis; RNA, Circular
PubMed: 33629528
DOI: 10.1111/jcmm.16211 -
Journal of Ethnopharmacology Jan 2024Moluodan concentrated pill (MLD) is a traditional herbal formula used in China for the treatment of chronic atrophic gastritis (CAG). However, its pharmacological...
Pharmacodynamics and pharmacological mechanism of Moluodan concentrated pill in the treatment of atrophic gastritis: A network pharmacological study and in vivo experiments.
ETHNOPHARMACOLOGICAL RELEVANCE
Moluodan concentrated pill (MLD) is a traditional herbal formula used in China for the treatment of chronic atrophic gastritis (CAG). However, its pharmacological mechanism of action remains unclear.
AIM OF THE STUDY
The aim of this study was to investigate the therapeutic effect and mechanism of action of MLD in the treatment of CAG using network pharmacology and in vivo experiments.
MATERIALS AND METHODS
The active compounds of MLD were determined using network pharmacology, utilizing various Chinese medicine databases such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Traditional Chinese Medicine Integrated Database, Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine, and a comprehensive database of Traditional Chinese Medicine on Immuno-Oncology. The compounds found in the root of Anemone altaica Fisch. were extracted from the China National Knowledge Infrastructure literature database. Additionally, the Swiss Target Prediction database and Similarity Ensemble Approach were employed to identify the potential targets of these components. CAG-related targets were gathered from the GeneCards and DisGeNET databases. Protein-protein interactions (PPIs) of the genes associated with the drug-disease crossover were examined, and a core PPI network was constructed using the STRING database (version 11.5) and Cytoscape (version 3.7.2). A gene-pathway network was established to identify significant target genes and pathways through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Finally, based on these findings and existing data, the tumor necrosis factor (TNF) signaling pathway was selected for further validation through in vivo experiments.
RESULTS
A total of 724 active molecules in MLD yielded 961 identified target genes, of which 179 were found to be potentially associated with CAG. From the common targets, a PPI network revealed ten core targets. Enrichment analysis suggested that MLD may primarily target TNF and AKT in the treatment of CAG. Essential signaling pathways, such as the PI3K-AKT and TNF pathways, were found to be crucial for the therapeutic effects of MLD on CAG. Furthermore, potential interactions and crosstalk between these pathways were identified. Moreover, we confirmed that MLD effectively improved gastric mucosa atrophy and cellular ultrastructural damage, while increasing pepsinogen secretion and decreasing gastrin, somatostatin, and motilin levels. Subsequent molecular biology studies in rat models of CAG demonstrated that MLD treatment significantly reduced the expression levels of TNF-α, phosphatidylinositol 3'-kinase (PI3K), and phosphorylated Akt (P < 0.05). Notably, the expression of nuclear factor kappa-B (NF-κB) exhibited a contrasting trend (P < 0.05), potentially associated with the crucial tumor suppressor role of NF-κB p105.
CONCLUSION
This study provides evidence that MLD effectively alleviates stomach mucosal atrophy through modulation of the TNF/PI3K/AKT signaling pathway. These findings establish a solid theoretical foundation for the practical management of CAG.
Topics: Animals; Rats; Gastritis, Atrophic; NF-kappa B; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Medicine, Chinese Traditional; Atrophy; Drugs, Chinese Herbal; Molecular Docking Simulation
PubMed: 37480968
DOI: 10.1016/j.jep.2023.116937 -
Evidence-based Complementary and... 2022Many attempts have been made to inhibit the formation of postoperative intraperitoneal adhesions, but the results have been discouraging. Therefore, the identification...
BACKGROUND
Many attempts have been made to inhibit the formation of postoperative intraperitoneal adhesions, but the results have been discouraging. Therefore, the identification of effective preventative measures or treatments is of great importance. In this study, the substantial potential of naringin (NG) to reduce peritoneal adhesions was validated in a rat model.
MATERIALS AND METHODS
A rat peritoneal adhesion model was established by abrasion of the cecum and its opposite intraperitoneal region under aseptic surgical conditions. After the operation, three groups of NG-treated rats were given 2 mL of NG by gavage at different concentrations (40, 60, or 80 mg/kg/d). The sham, control, and hyaluronan (HA) groups were given equal volumes of normal saline daily. On the 8th day, all rats were sacrificed 30 min after the administration of an activated carbon solution (10 mL/kg) by oral gavage. Intraperitoneal adhesion formation was adequately evaluated by necropsy, hematoxylin and eosin (HE) staining, Sirius red staining, immunofluorescence staining, enzyme-linked immunosorbent assays, and reactive oxygen species (ROS) probes. The gastrointestinal dynamics of the rats were assessed on the basis of a small intestinal charcoal powder propulsion test and the detection of motilin and gastrin levels in serum.
RESULTS
Intraperitoneal adhesions were markedly reduced in the group of rats receiving high-dose NG. Compared with the control group, the high-dose NG group showed clear reductions in inflammatory reactions, oxidative stress, collagen deposition, and fibroblast formation in the adhesion tissue and enhanced gastrointestinal dynamics ( < 0.05).
CONCLUSION
NG alleviated the severity of intraperitoneal adhesions in a rat model by reducing inflammation, oxidative stress, collagen deposition, and fibroblast formation, highlighting the potential of NG as a drug candidate to prevent postoperative peritoneal adhesion formation.
PubMed: 35069760
DOI: 10.1155/2022/5331537 -
Journal of Ethnopharmacology Jan 2024In traditional Chinese herbal medicine, rhubarb is said to remove accumulation with purgation, clearing heat, and discharging fire. Modern pharmacology has shown that...
ETHNOPHARMACOLOGICAL RELEVANCE
In traditional Chinese herbal medicine, rhubarb is said to remove accumulation with purgation, clearing heat, and discharging fire. Modern pharmacology has shown that rhubarb extract has a purgative effect when given to experimental animals in an appropriate dose. However, the active components and their mechanism of action are still not clearly defined.
AIM OF THE STUDY
The current research aimed to evaluate the synergistic stool-softening effects and explore the action mechanism of rhubarb free anthraquinones (RhA) and their monomers on constipation in rats.
MATERIALS AND METHODS
A rat model of water deficit-induced constipation was established to induce constipation, and these rats were treated with RhA and its monomers. ELISA, histopathology, immunohistochemistry, qPCR and Western blotting based on network pharmacology and molecular docking were conducted to explore the possible mechanism of action of RhA and its monomers.
RESULTS
RhA, aloe-emodin, rhein, and chrysophanol showed stool-softening activity, and the combination of aloe-emodin and rhein had the strongest softening effect on faecal pellets. Aloe-emodin, rhein, and chrysophanol significantly increased the serum levels of vasoactive intestinal peptide (VIP), motilin (MTL), and substance P (SP), upregulated the expression of VIP, cyclase-associated protein 1 (CAP1), protein kinase A (PKA), cystic fibrosis transmembrane conductance regulator (CFTR), aquaporin 3 (AQP3), aquaporin 4 (AQP4), and aquaporin 8 (AQP8), decreased the expression of epithelial sodium channel (ENaC) and Na/H exchanger 3 (NHE3), and reduced the colonic tissue concentration of Na-K-ATPase in the constipated rats. Osmolality of colonic fluid in model rats treated by RhA, aloe-emodin, rhein, and chrysophanol was increased.
CONCLUSION
Aloe-emodin, rhein, and chrysophanol were the stool-softening components of the RhA extract, and there were certain drug-interactions between the components. RhA upregulated VIP expression, activated the cyclic adenosine monophosphate protein kinase A (cAMP/PKA) pathway, and further stimulated CFTR expression while inhibiting NHE3 and ENaC expression, resulting in a hypertonic state in the colonic lumen. Water transport could then be driven by an osmotic gradient, which in turn led to the upregulation of AQP3, AQP4, and AQP8 expression. In addition, RhA likely improved gastrointestinal motility by increasing serum VIP, SP, and MTL concentrations, thus promoting faecal excretion.
Topics: Animals; Rats; Rheum; Cystic Fibrosis Transmembrane Conductance Regulator; Emodin; Molecular Docking Simulation; Sodium-Hydrogen Exchanger 3; Constipation; Anthraquinones; Aquaporin 3; Cyclic AMP-Dependent Protein Kinases; Plant Extracts
PubMed: 37907143
DOI: 10.1016/j.jep.2023.117336 -
Surgery Sep 2022The impact of early oral feeding after esophagectomy on brain-gut peptide secretion and gut function recovery has not been well investigated. This study aimed to fill... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The impact of early oral feeding after esophagectomy on brain-gut peptide secretion and gut function recovery has not been well investigated. This study aimed to fill this research gap.
METHODS
This study was based on a randomized clinical trial (ClinicalTrials.gov: NCT01998230). The patients in the early oral feeding group started oral food intake on postoperative day 1. In the late oral feeding group, nasogastric/nasoenteral feeding was applied from postoperative day 1 to 7, after which the patients began oral food intake. Serum brain-gut peptides were selected as the primary end points and tested before surgery and on postoperative days 1, 3, and 5. The time to first flatus and first defecation after surgery were evaluated.
RESULTS
A total of 110 participants undergoing minimally invasive McKeown esophagectomy were prospectively included, with 63 patients in the early oral feeding group and 47 patients in the late oral feeding group. The distribution of clinicopathological characteristics was balanced between the 2 groups. Perioperative dynamic surveillance demonstrated higher serum concentrations of excitatory brain-gut peptides (gastrin P = .021, motilin P = .027, and substance-P P = .023) and lower serum concentrations of inhibitory brain-gut peptides (cholecystokinin P = .004 and somatostatin P = .019) in the early oral feeding group. Perioperative serum levels of brain-gut peptides correlated with postoperative early flatus and defecation. The multivariate analysis showed early oral feeding (versus late oral feeding) to be an independent predictive factor for early flatus and defecation (hazard ratio 2.40, P < .001; hazard ratio 2.73, P < .001, respectively).
CONCLUSION
The early oral feeding program may accelerate the recovery of gut function by regulating brain-gut peptide secretion. Brain-gut peptides are possible treatment targets to improve early oral feeding benefits and promote personalized early oral feeding programs.
Topics: Brain; Esophagectomy; Flatulence; Humans; Intubation, Gastrointestinal; Postoperative Complications; Recovery of Function
PubMed: 35794044
DOI: 10.1016/j.surg.2022.04.041 -
Food & Nutrition Research 2023To explore the risk factors of duodenogastric reflux (DGR) in relation to different dietary habits.
OBJECTIVE
To explore the risk factors of duodenogastric reflux (DGR) in relation to different dietary habits.
METHODS
A total of 106 patients with symptoms of DGR who underwent electronic gastroscopy from June 2019 to June 2020 were selected and divided into the DGR group ( = 33) and the non-DGR group ( = 73) according to the diagnosis of bile reflux. Questionnaires were used to collect the basic information and dietary habits of the patients, including age, gender, body mass index, place of residence, comorbidities, dietary composition, salt intake, smoking and drinking consumption. The total bile acid (TBA) and cholesterol (CHO) of the gastric juice were measured using a fully automated biochemical analyser, with an enzyme-linked immunosorbent assay used for the serum cholecystokinin, gastrin and gastrin levels. Univariate analysis and multivariate logistic regression analysis were used to predict the attendant DGR risk factors.
RESULTS
There was no significant difference in age or gender between the DGR and the non-DGR groups ( > 0.05). The proportion of patients living in the Bashang region was significantly higher in the DGR group (78.79%) than in the non-DGR group (38.36%) ( < 0.05). The levels of TBA and CHO in the gastric juice and the cholecystokinin and gastrin levels in the serum of the DGR group were higher than those in the non-DGR group, while the serum motilin levels were significantly lower in the DGR group than in the non-DGR group ( < 0.05). The univariate analysis indicated that the proportion of patients with daily consumption of dairy products and fried foods, a high salt intake and smoking and drinking consumption were significantly higher in the DGR than in the non-DGR group ( < 0.05).
CONCLUSION
The daily consumption of dairy products and a preference for fried food are independent risk factors for the occurrence of DGR (odds ratio ≥ 1, < 0.05).
PubMed: 37920676
DOI: 10.29219/fnr.v67.9385 -
Journal of Neuroinflammation Nov 2020Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease affecting the CNS. Recent studies have indicated that intestinal alterations play key pathogenic...
BACKGROUND
Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease affecting the CNS. Recent studies have indicated that intestinal alterations play key pathogenic roles in the development of autoimmune diseases, including MS. The triterpene oleanolic acid (OA), due to its anti-inflammatory properties, has shown to beneficially influence the severity of the experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS. We herein investigate EAE-associated gut intestinal dysfunction and the effect of OA treatment.
METHODS
Mice with MOG-induced EAE were treated with OA or vehicle from immunization day and were daily analyzed for clinical deficit. We performed molecular and histological analysis in serum and intestinal tissues to measure oxidative and inflammatory responses. We used Caco-2 and HT29-MTX-E12 cells to elucidate OA in vitro effects.
RESULTS
We found that OA protected from EAE-induced changes in intestinal permeability and preserved the mucin-containing goblet cells along the intestinal tract. Serum levels of the markers for intestinal barrier damage iFABP and monocyte activation sCD14 were consistently and significantly reduced in OA-treated EAE mice. Beneficial OA effects also included a decrease of pro-inflammatory mediators both in serum and colonic tissue of treated-EAE mice. Moreover, the levels of some immunoregulatory cytokines, the neurotrophic factor GDNF, and the gastrointestinal hormone motilin were preserved in OA-treated EAE mice. Regarding oxidative stress, OA treatment prevented lipid peroxidation and superoxide anion accumulation in intestinal tissue, while inducing the expression of the ROS scavenger Sestrin-3. Furthermore, short-chain fatty acids (SCFA) quantification in the cecal content showed that OA reduced the high iso-valeric acid concentrations detected in EAE-mice. Lastly, using in vitro cell models which mimic the intestinal epithelium, we verified that OA protected against intestinal barrier dysfunction induced by injurious agents produced in both EAE and MS.
CONCLUSION
These findings reveal that OA ameliorates the gut dysfunction found in EAE mice. OA normalizes the levels of gut mucosal dysfunction markers, as well as the pro- and anti-inflammatory immune bias during EAE, thus reinforcing the idea that OA is a beneficial compound for treating EAE and suggesting that OA may be an interesting candidate to be explored for the treatment of human MS.
Topics: Animals; Caco-2 Cells; Encephalomyelitis, Autoimmune, Experimental; Female; HT29 Cells; Humans; Intestinal Mucosa; Mice; Mice, Inbred C57BL; Multiple Sclerosis; Oleanolic Acid; Oxidative Stress; Permeability
PubMed: 33246492
DOI: 10.1186/s12974-020-02042-6