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World Journal of Psychiatry Sep 2023Gastric ulcer (GU) is a common digestive tract disease, and medical records of GU combined with depression are increasingly common. Currently, the risk factors and...
BACKGROUND
Gastric ulcer (GU) is a common digestive tract disease, and medical records of GU combined with depression are increasingly common. Currently, the risk factors and pathogenesis of GU complicated with depression remain unclear. Low immune function and gastrointestinal hormone levels may also be significant risk factors. Therefore, this study explored the immune function and gastrointestinal hormone levels in patients with GU combined with depression.
AIM
To explore the immune function, gastrointestinal hormone level, and clinical significance of patients with GU combined with depression.
METHODS
A retrospective analysis was conducted on 300 patients with GU combined with depression admitted to Guizhou Provincial People's Hospital from January 2021 to June 2022 as the study subjects. According to the Hamilton Depression Scale (HAMD) score, patients were divided into mild-to-moderate ( = 210) and heavy ( = 90) groups. Basic data, immune function indices [immunoglobulin A (IgA), IgM, IgG, serum CD4 and CD8 percentage, and CD4/CD8 ratio], and gastrointestinal hormone indices [serum gastrin (GAS), cholecystokinin (CCK), and motilin (MTL) levels] were collected. The basic data of the two groups were compared, and the immune function and gastrointestinal hormone indices were analyzed. Multivariate logistic regression was used to analyze the factors influencing the severity of GU complicated with depression. The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to analyze the value of the immune function index, gastrointestinal hormone index, and combined index in predicting the severity of GU complicated with depression.
RESULTS
There were no marked differences in sex, age, body mass index, abdominal distension, abdominal pain, belching, nausea, vomiting, or sleep disorders between the heavy and mild-to-moderate groups ( > 0.05). There was a marked difference in the family history of depression between the heavy and mild-to-moderate groups ( < 0.05). There were significant differences in serum IgA and IgM levels and serum CD4, CD8, and CD4/CD8 ratios between the heavy and mild-to-moderate groups ( < 0.05). Multivariate analysis showed that IgA, IgM, GAS, and CCK serum levels influenced the severity of GU with depression ( < 0.05). The AUC of the ROC curve for serum IgA level predicting GU with depression severity was 0.808 [95% confidence interval (CI): 0.760-0.857], the AUC of the serum IgM level was 0.757 (95%CI: 0.700-0.814), the AUC of the serum GAS level was 0.853 (95%CI: 0.810-0.897), the AUC of the serum CCK level was 0.762 (95%CI: 0.709-0.822), the AUC of immune function (IgA, IgM) and gastrointestinal hormone levels (GAS, CCK) for the prediction of GU with depression severity was 0.958 (95%CI: 0.933-0.976).
CONCLUSION
Important factors influencing GU complicated with depression are serum IgA, IgM, GAS, and CCK indicators. They can be used as indicators to predict the severity of GU complicated with depression.
PubMed: 37771644
DOI: 10.5498/wjp.v13.i9.665 -
World Journal of Gastroenterology Sep 2023Patients with sepsis are at high risk for acute gastrointestinal injury (AGI), but the diagnosis and treatment of AGI due to sepsis are unsatisfactory. Heparanase (HPA)... (Randomized Controlled Trial)
Randomized Controlled Trial Clinical Trial
BACKGROUND
Patients with sepsis are at high risk for acute gastrointestinal injury (AGI), but the diagnosis and treatment of AGI due to sepsis are unsatisfactory. Heparanase (HPA) plays an important role in septic AGI (S-AGI), but its specific mechanism is not completely understood, and few clinical reports are available.
AIM
To explore the effect and mechanism of HPA inhibition in S-AGI patients.
METHODS
In our prospective clinical trial, 48 patients with S-AGI were randomly assigned to a control group to receive conventional treatment, whereas 47 patients were randomly assigned to an intervention group to receive conventional treatment combined with low molecular weight heparin. AGI grade, sequential organ failure assessment score, acute physiology and chronic health evaluation II score, D-dimer, activated partial thromboplastin time (APTT), anti-Xa factor, interleukin-6, tumour necrosis factor-α, HPA, syndecan-1 (SDC-1), LC3B (autophagy marker), intestinal fatty acid binding protein, D-lactate, motilin, gastrin, CD4/CD8, length of intensive care unit (ICU) stay, length of hospital stay and 28-d survival on the 1, 3 and 7 d after treatment were compared. Correlations between HPA and AGI grading as well as LC3B were compared. Receiver operator characteristic (ROC) curves were generated to evaluate the diagnostic value of HPA, intestinal fatty acid binding protein and D-lactate in S-AGI.
RESULTS
Serum HPA and SCD-1 levels were significantly reduced in the intervention group compared with the control group ( < 0.05). In addition, intestinal fatty acid-binding protein, D-lactate, AGI grade, motilin, and gastrin levels and sequential organ failure assessment score were significantly decreased ( < 0.05) in the intervention group. However, LC3B, APTT, anti-Xa factor, and CD4/CD8 were significantly increased ( < 0.05) in the intervention group. No significant differences in interleukin-6, tumour necrosis factor-α, d-dimer, acute physiology and chronic health evaluation II score, length of ICU stay, length of hospital stay, or 28-d survival were noted between the two groups ( > 0.05). Correlation analysis revealed a significant negative correlation between HPA and LC3B and a significant positive correlation between HPA and AGI grade. ROC curve analysis showed that HPA had higher specificity and sensitivity in diagnosis of S-AGI.
CONCLUSION
HPA has great potential as a diagnostic marker for S-AGI. Inhibition of HPA activity reduces SDC-1 shedding and alleviates S-AGI symptoms. The inhibitory effect of HPA in gastrointestinal protection may be achieved by enhanced autophagy.
Topics: Humans; Gastrins; Interleukin-6; Motilin; Tumor Necrosis Factor-alpha; Sepsis; Lactic Acid; Abdominal Injuries; Fatty Acid-Binding Proteins; Heparin, Low-Molecular-Weight
PubMed: 37744293
DOI: 10.3748/wjg.v29.i35.5154 -
General and Comparative Endocrinology Dec 2023Rabbit duodenum has been used for examining the ability of motilin to cause muscle contraction in vitro. A motilin-related peptide, ghrelin, is known to be involved in...
Rabbit duodenum has been used for examining the ability of motilin to cause muscle contraction in vitro. A motilin-related peptide, ghrelin, is known to be involved in the regulation of gastrointestinal (GI) motility in various animals, but its ability to cause rabbit GI contraction have not been well examined. The aim of this study is to clarify the action of rat ghrelin and its interaction with motilin in the rabbit duodenum. The mRNA expression of ghrelin and motilin receptors was also examined using RT-PCR. Rat ghrelin (10-10 M) did not change the contractile activity of the duodenum measured by the mean muscle tonus and area under the curve of contraction waves. In agreement with this result, the distribution of ghrelin receptor mRNA in the rabbit GI tract varied depending on the GI region from which the samples were taken; the expression level in the duodenum was negligible, but that in the esophagus or stomach was significant. On the other hand, motilin (10-10 M) caused a concentration-dependent contraction by means of increased mean muscle tonus, and consistently, motilin receptor mRNA was expressed heterogeneously depending on the GI region (esophagus = stomach = colon = rectum < duodenum = jejunum = ileum < cecum). Expression level of motilin receptor was comparable to that of ghrelin receptor in the esophagus and stomach. Pretreatment with ghrelin (10 M) prior to motilin did not affect the contractile activity of motilin in the duodenum. In conclusion, ghrelin does not affect muscle contractility or motilin-induced contraction in the rabbit duodenum, which is due to the lack of ghrelin receptors. The present in vitro results suggest that ghrelin might not be a regulator of intestinal motility in rabbits.
Topics: Rabbits; Rats; Animals; Ghrelin; Motilin; Receptors, Ghrelin; Duodenum; Gastrointestinal Motility; Muscle Contraction; RNA, Messenger
PubMed: 37722460
DOI: 10.1016/j.ygcen.2023.114384 -
BMJ Open Sep 2023After rectal cancer surgery, a majority of patients suffer from sequelae known as low anterior resection syndrome (LARS). It is a collection of symptoms consisting of...
INTRODUCTION
After rectal cancer surgery, a majority of patients suffer from sequelae known as low anterior resection syndrome (LARS). It is a collection of symptoms consisting of flatus and/or stool incontinence, evacuation frequency, re-evacuation and urgency. The circadian hormone, melatonin, has shown to possess anti-inflammatory properties, and in high doses, it reduces bowel movements. The aim of the study is to investigate if locally administered melatonin has an alleviating effect on LARS. Secondarily, the effect of melatonin on bowel movements, other patient-reported symptoms, quality of life, depression, anxiety, sleep disturbances, motilin levels and rectal mucosa histology will be examined.
METHODS AND ANALYSIS
This is a randomised, placebo-controlled, double-blinded, two-period crossover trial. The participants are randomised to 28 days of 25 mg melatonin administered rectally via an enema daily (or placebo) followed by a 28-day washout and then 28 days of placebo (or melatonin). Three participants will be included in an internal feasibility test. They will receive 25 mg of melatonin daily for 28 days. Data from these participants will be used to assess the feasibility of the rectally administered melatonin and to analyse the course of recruitment and outcome measurements. Afterwards, 18 participants will be included in the crossover trial. The severity of the LARS symptoms will be evaluated using the LARS Score on the first and last day of each treatment period.
ETHICS AND DISSEMINATION
The Regional Ethics Committee, the Danish Medicines Agency and the Data and Development Support in Region Zealand approved this study. The study will be performed according to the Helsinki II declaration. Written informed consent will be obtained from all participants. The results of the study will be submitted to peer-reviewed journals for publication and presented at congresses.
TRIAL REGISTRATION NUMBERS
EudraCT Registry (2020-004442-11) and ClinicalTrial.gov Registry (NCT05042700).
Topics: Humans; Cross-Over Studies; Low Anterior Resection Syndrome; Melatonin; Postoperative Complications; Quality of Life; Randomized Controlled Trials as Topic; Rectal Neoplasms
PubMed: 37696629
DOI: 10.1136/bmjopen-2022-067763 -
Nutrients Aug 2023Slow transit constipation (STC) is a prevalent gastrointestinal condition with slow transit, and some probiotics can effectively relieve constipation, but the exact...
Slow transit constipation (STC) is a prevalent gastrointestinal condition with slow transit, and some probiotics can effectively relieve constipation, but the exact mechanisms have not been fully understood. In this study, we evaluate the impact of GUANKE (GUANKE) on diphenoxylate-induced slow transit constipation and speculate on the underlying mechanisms in a mouse model. Administration of GUANKE alleviated constipation indexes, including defecation time, fecal output and water content, and gastrointestinal transit ratio. In addition, GUANKE restored the protein expression of constipation-related intestinal factors (aquaporins (AQPs) and interstitial Cajal cells (ICCs)) in colon tissues measured using immunofluorescence staining; regulated the neurotransmitters and hormones, such as increased levels of 5-hydroxytryptamine, substance P, and motilin; and decreased levels of vasoactive intestinal peptide and nitric oxide in serum, as measured by an ELISA. 16S rRNA and correlation analysis of feces indicated that GUANKE administration effectively reduced constipation-induced enrichment and suggested a potential contribution of to diphenoxylate-induced STC in mice. GUANKE had no effect on short-chain fatty acids (SCFAs) in cecum content. This study revealed that GUANKE may alleviate constipation in mice through regulating intestinal neurotransmitter and hormone release and altering specific bacterial taxa, rather than by affecting SCFAs and the diversity of microbiota in the gut. Further research is needed to confirm if the findings observed in this study will be consistent in other animal studies or clinical trials.
Topics: Animals; Mice; Gastrointestinal Microbiome; Diphenoxylate; RNA, Ribosomal, 16S; Constipation
PubMed: 37686774
DOI: 10.3390/nu15173741 -
Biochemical and Biophysical Research... Oct 2023The peptide hormone ghrelin (an agonist) and LEAP2 (an antagonist) play important functions in energy metabolism via their receptor GHSR, an A-class G protein-coupled...
The peptide hormone ghrelin (an agonist) and LEAP2 (an antagonist) play important functions in energy metabolism via their receptor GHSR, an A-class G protein-coupled receptor. Ghrelin, LEAP2, and GHSR are widely present from fishes to mammals. However, our recent study suggested that fish GHSRs have different binding properties to ghrelin: a GHSR from the lobe-finned fish Latimeria chalumnae (coelacanth) is efficiently activated by ghrelin, but GHSRs from the ray-finned fish Danio rerio (zebrafish) and Larimichthys crocea (large yellow croaker) have lost binding to ghrelin. Do fish GHSRs use another peptide as their agonist? In the present study we tested to two fish motilins from D. rerio and L. chalumnae because motilin is distantly related to ghrelin. In ligand binding and activation assays, the fish GHSRs from D. rerio and L. crocea displayed no detectable or very low binding to all tested motilins; however, the fish GHSR from L. chalumnae bound to its motilin with high affinity and was efficiently activated by it. Therefore, it seemed that motilin is not a ligand for GHSR in the ray-finned fish D. rerio and L. crocea, but is an efficient agonist for GHSR in the lobe-finned fish L. chalumnae, one of the closest fish relatives of tetrapods. The results of present study suggested that GHSR might have two efficient agonists, ghrelin and motilin, in ancient fishes; however, this feature might be only preserved in some extant fishes with ancient evolutionary origins.
PubMed: 37677979
DOI: 10.1016/j.bbrc.2023.09.002 -
Frontiers in Pharmacology 2023The unique pharmaceutical methods for the processing of botanical drugs according to the theory of traditional Chinese medicine (TCM) affect clinical syndrome...
The unique pharmaceutical methods for the processing of botanical drugs according to the theory of traditional Chinese medicine (TCM) affect clinical syndrome differentiation and treatment. The objective of this study was to comprehensively elucidate the principles and mechanisms of an herbal processing method by investigating the alterations in the metabolites of Rhizoma Atractylodis Macrocephalae (AMR) processed by Aurantii Fructus Immaturus (AFI) decoction and to determine how these changes enhance the efficacy of aqueous extracts in treating functional dyspepsia (FD). A qualitative analysis of AMR before and after processing was conducted using UPLC-Q-TOF-MS/MS, and HPLC was employed for quantitative analysis. A predictive analysis was then conducted using a network analysis strategy to establish a botanical drug-metabolite-target-disease (BMTD) network and a protein-protein interaction (PPI) network, and the predictions were validated using an FD rat model. A total of 127 metabolites were identified in the processed AMR (PAMR), and substantial changes were observed in 8 metabolites of PAMR after processing, as revealed by the quantitative analysis. The enhanced aqueous extracts of processed AMR (PAMR) demonstrate improved efficacy in treating FD, which indicates that this processing method enhances the anti-inflammatory properties and promotes gastric motility by modulating DRD2, SCF, and c-kit. However, this enhancement comes at the cost of attenuating the regulation of motilin (MTL), gastrin (GAS), acetylcholine (Ach), and acetylcholinesterase (AchE). Through this series of investigations, we aimed to unravel the factors influencing the efficacy of this herbal formulation in improving FD in clinical settings.
PubMed: 37601055
DOI: 10.3389/fphar.2023.1236656 -
Frontiers in Nutrition 2023Our aim was to determine the efficacy of four-week probiotic supplementation on gastrointestinal health. The secondary objectives were to assess probiotic effects on...
OBJECTIVE
Our aim was to determine the efficacy of four-week probiotic supplementation on gastrointestinal health. The secondary objectives were to assess probiotic effects on immune reaction, as well as weight control and metabolic health.
METHODS
We conducted two randomized sub-trials, respectively, among subjects who were diagnosed with functional constipation (FC) or functional diarrhea (FDr) according to the Rome IV criteria. In each sub-trial, 70 eligible Chinese adults were randomized to receive a multi-strain probiotic combination or a placebo. Gastrointestinal symptoms, defecation habits, stool characteristics, blood and fecal biochemistry markers, anthropometrics measures, stress-associated responses, and intestinal flora changes were assessed at baseline and after probiotics intervention.
RESULTS
Four weeks of probiotic supplementation reduced overall gastrointestinal symptoms scores in FC participants ( < 0.0001). Their mean weekly stool frequency increased from 3.3 times to 6.2 times; immune response and inflammation markers improved with increases in serum IgA, IFN-γ and fecal sIgA, and decrease in hsCRP; most components of lipid profile were significantly ameliorated, with increases in HDL-C and reductions in TC and TG; body weight, body mass index and basal metabolic rate decreased following probiotics consumption. For FDr participants, probiotics consumption markedly reduced overall gastrointestinal symptom scores ( < 0.0001); decreased stool frequency by 3 times per week; increased IgA, IFN-γ, sIgA concentrations, while lowered hsCRP and IL-4 levels. Both FC and FDr participants had improvement in the scores of defecation habits, anxiety or depression, and perceived stress. Probiotics supplementation promoted the production of all three major short-chain fatty acids. No changes were observed in LDL-C, IgG, IgM, IL-8, IL-10 and motilin.
CONCLUSION
Supplementation with the probiotic formula over a four-week period could help relieving gastrointestinal symptoms, improving satisfaction with defecation habits, emotional state and immune response, and ameliorating dysbacteriosis in participants with FC or FDr. It also had beneficial effects on lipid metabolism and weight control for FC participants.
PubMed: 37497057
DOI: 10.3389/fnut.2023.1196625 -
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 -
The regulatory effects of fucoidan and laminarin on functional dyspepsia mice induced by loperamide.Food & Function Jul 2023Gastrointestinal dysmotility is a common cause of functional dyspepsia. As two kinds of polysaccharides derived from brown algae, fucoidan and laminarin possess many...
Gastrointestinal dysmotility is a common cause of functional dyspepsia. As two kinds of polysaccharides derived from brown algae, fucoidan and laminarin possess many physiological properties; however, their relative abilities in regulating gastrointestinal motility have not been illustrated yet. In this study, we aimed to investigate the regulatory effect of fucoidan and laminarin on functional dyspepsia mice induced by loperamide. Mice with gastrointestinal dysmotility were treated with fucoidan (100 and 200 mg per kg bw) and laminarin (50 and 100 mg per kg bw). As a result, fucoidan and laminarin reversed the dysfunction mainly through regulating gastrointestinal hormones (motilin and ghrelin), the cholinergic pathway, the total bile acid level, c-kit protein expression, and gastric smooth muscle contraction-related gene expression (ANO1 and RYR3). Moreover, fucoidan and laminarin intervention modulated the gut microbiota profile including the altered richness of Muribaculaceae, Lachnospiraceae, and . The results indicated that fucoidan and laminarin may restore the rhythm of the migrating motor complex and regulate gut microecology. In conclusion, we provided evidence to support that fucoidan and laminarin might have potential abilities to regulate gastrointestinal motility.
Topics: Mice; Animals; Dyspepsia; Loperamide; Polysaccharides
PubMed: 37377021
DOI: 10.1039/d3fo00936j