Abnormal expression of autophagy proteins in the duodenum of patients with functional dyspepsia: A preliminary study.

BACKGROUND AND STUDY AIMS: Functional dyspepsia (FD) is a common disease with an unclear pathology. Autophagy is associated with inflammation and has been proposed to play a role in the development of FD. This study aimed to evaluate expression of the autophagy proteins beclin1 and p62/SQSTM1 in patients with FD. PATIENTS AND METHODS: Duodenal mucosal tissues were collected from 10 patients with FD and 10 asymptomatic controls. The extent of autophagy was determined by examining expression levels of beclin1 and p62/SQSTM1 using quantitative polymerase chain reaction and immunohistochemistry techniques. RESULTS: Lower expression levels of beclin1 protein were detected in the duodenal bulb (D1) and the second portion of the duodenum (D2) in patients with FD compared with asymptomatic controls. Higher levels of p62 protein were expressed in D1 in patients with FD than in controls. No differences in mRNA expression of beclin1 and p62 were observed between patients with FD and controls. CONCLUSION: Abnormal autophagy was involved in FD, which may be associated with the pathogenesis of FD.

Chemometric-based analysis and bioassay guided identification of potent compounds with intestinal motility promoting effects from Dalitong Granules.

ETHNOPHARMACOLOGICAL RELEVANCE: Dalitong Granules (DLT), a potent Traditional Chinese Medicine known for its ability to promote gastrointestinal motility, is widely used in clinical practice for the treatment of Functional Dyspepsia (FD). Despite the remarkable clinical efficacy of DLT, the specific components responsible for its effectiveness remains unclear. AIM OF THE STUDY: The study aimed to identify potential active ingredients of DLT for treating FD through spectrum-effect relationship analysis, multivariate statistical analysis and network pharmacology analysis. The efficacy of these identified compounds was subsequently validated using the zebrafish intestinal peristalsis model. MATERIALS AND METHODS: The fingerprints of various solvent-extracted DLT were analyzed using high performance liquid chromatography coupled with tandem high-resolution mass spectrometry. The intestinal motility-promoting activities of DLT extracted by different solvents were evaluated through an intestinal propulsion test in mice. Potential therapeutic substances in DLT for treating FD were screened via chemometric analysis based on spectrum-effect relationship analysis. The correlation between the intensity of common peaks in the total ion chromatogram and the pharmacodynamic indices was assessed using multivariate statistical analysis. Additionally, given the complexity of Traditional Chinese Medicine, which comprises multiple components and targets, a network pharmacology analysis was performed to investigate the potential active ingredients in DLT. Finally, the pharmacological effects of these compounds in DLT were validated using a zebrafish intestinal motility model. RESULTS: Through spectral-effect relationships analysis and network pharmacology analysis, it was determined that ten ingredients in DLT contribute to the promotion of intestinal motility. In a zebrafish intestinal motility model, it was observed that eight chemicals (excluding tetrahydropalmatine) demonstrate favorable activity of promoting gastrointestinal motility. These findings suggest that these ingredients may serve as potential therapeutic agents for improving gastric motility disorders. CONCLUSIONS: This study employed spectral-effect relationship and network pharmacology analysis to identify the active ingredients in DLT. The findings were then validated using a zebrafish intestinal peristalsis model. These results provide a scientific foundation for the clinical application of DLT as a key traditional herbal formula for managing FD.

The Bidirectional Relationship Between Sleep Disturbance and Functional Dyspepsia: A Systematic Review to Understand Mechanisms and Implications on Management.

Functional dyspepsia (FD) is a prevalent chronic digestive disorder that significantly impacts patients' quality of life. Sleep disturbance (SD) is common among FD patients, yet the relationship between SD and FD remains poorly characterized. This systematic review explores the bidirectional relationship between FD and SD, investigating underlying mechanisms and implications for management. A rigorous and comprehensive systematic search was conducted across PubMed, PubMed Central (PMC), Google Scholar, Cochrane Library, and ScienceDirect using select keywords related to SD and FD. Only studies published in English from the past 10 years that met inclusion and exclusion criteria were included. Quality assessment tools specific to study types were employed to minimize bias. After applying inclusion and exclusion criteria and quality assessments, the review encompassed 30 studies. The key findings reveal that FD is frequently associated with SD, with a significant proportion of FD patients reporting poor sleep quality. The mechanisms linking SD and FD are complex, involving the circadian rhythm, visceral hypersensitivity, immune responses, and psychological factors. Nonpharmacological treatments like cognitive behavioral therapy (CBT), acupuncture, and pharmacological neuromodulators have shown promise in managing FD and SD, offering hope for improved patient outcomes. SD and FD share a significant bidirectional relationship, influenced by a complex interplay of physiological, psychological, and lifestyle factors. Addressing SD in FD patients may improve overall symptom management. Further research is crucial, as it should focus on isolating specific SD causes and their direct impacts on FD and other functional gastrointestinal disorders (FGIDs), opening up new avenues for understanding and treatment.

Intestinal permeability in disorders of gut-brain interaction (DGBI): From bench to bedside.

Intestinal barrier function lies at a critical interface of a range of peripheral and central processes that influence disorders of gut brain interactions (DGBI). While rigorously tested, the role of barrier dysfunction in driving clinical phenotype of DGBI remains to be fully elucidated. In vitro, in vivo and ex vivo strategies can test various aspects of the broader permeability and barrier mechanisms in the gut. Luminal mediators of host, bacterial and dietary origin can influence the barrier function and a disrupted barrier can also influence the luminal milieu. Critical to our understanding is how barrier dysfunction is influenced by stress and other comorbidities that associate with DGBI and the crosstalk between barrier and neural, hormonal, and immune responses . Additionally, the microbiome's significant role in the communication between the brain and gut has led to the integrative model of a microbiome gut brain axis with reciprocal interactions between brain networks and networks comprised of multiple cells in the gut, including immune cells, enterochromaffin cells, gut microbiota and the derived luminal mediators. This review highlights the techniques for assessment of barrier function, appraises evidence for barrier dysfunction in DGBI including mechanistic studies in humans as well as provides an overview of therapeutic strategies that can be used to directly or indirectly restore barrier function in DGBI patients.

Efficacy of jing Si herbal tea in functional dyspepsia: A double-blind, randomized, placebo-controlled study.

BACKGROUND: Functional dyspepsia (FD) is prevalent worldwide and is associated with gastrointestinal inflammation, mucosal anomalies, and shifts in microbiota metabolites like short chain fatty acids. This study assesses the efficacy of Jing Si herbal tea (JSHT) in alleviating FD symptoms, psychological distress, and influencing metabolites. METHODS: Adults with FD based on Rome IV criteria were included. Participants underwent physical and psychological evaluations, pre-treatment blood sampling, and were randomly assigned to JSHT or placebo groups for four weeks. Post-treatment, evaluations and Liquid Chromatography-Mass Spectrometry for gut metabolites were done. Successful response was defined by a 50% symptom reduction. Symptom intensity, sleep, depression, anxiety, and stress were measured using questionnaires. RESULTS: 26 patients (median age 55.5 years, range 22-77 years, 60.6% female) were studied. Both JSHT and placebo groups were similar at baseline. JSHT showed a higher response rate (69.2%) than placebo (23.1%, P = 0.018). JSHT recipients experienced notable reduction in upper gastrointestinal symptoms and anxiety (P = 0.005; P = 0.037). Increased serum butyrate was observed in improved patients (P = 0.01), whereas no major changes were detected in the placebo group. CONCLUSION: Four weeks of JSHT treatment ameliorated FD symptoms and anxiety, potentially linked to increased serum butyrate. This study suggests that JSHT has potential therapeutic role in patients with FD.

The efficacy of removal of animal milk from the diet in functional dyspepsia: A cross-sectional study.

BACKGROUND AND STUDY AIMS: We aimed to investigate the effect of removing milk and dairy products from diets on functional dyspepsia (FD) symptoms, as the aetiology remains unclear and new management approaches are needed. PATIENTS AND METHODS: This cross-sectional cohort study included 120 patients, with a mean age of 42.5 ± 12.3, of whom 77 (64.2 %) were female, with FD diagnosed by the Rome IV criteria. Patients were divided equally into two groups: those who eliminated milk and dairy products from their diet under the advice of a dietician without medical treatment and those who did not. The severity of symptoms was assessed using the gastrointestinal symptom rating scale (GSRS) at the beginning and end of a one-month period. RESULTS: The restricted and unrestricted diet groups showed no significant differences in age, body mass index, symptom frequency and duration, weight changes, FD subtype, and gastroscopy results (p > 0.05). The diet group had more female patients (p = 0.01) and higher GSRS scores at the beginning (p = 0.01) but similar scores at the end of the study (p = 0.99). After one month, both groups had improved GSRS scores (p = 0.01), but the diet group had a more significant decrease in total symptom scores (p = 0.01) and in 7 of the 15 subsets (p < 0.05). CONCLUSION: Of the 120 FD patients who followed up for one month, 60 who removed milk products had a more significant reduction in GSRS symptom score and 7 of the 15 symptom subset scores than 60 patients receiving an unrestricted diet.

Acupuncture and moxibustion intervention in functional dyspepsia: Gastric and duodenal regulation.

Functional dyspepsia (FD) is a brain-gut interaction disorder located in the stomach and duodenum, which has complex pathophysiological mechanisms, and there is no effective treatment for FD. Acupuncture and moxibustion have been proven to have definite and significant efficacy on FD. Focusing on the affected area and combined with the potential pathophysiology of FD, here we discuss the possible mechanisms of acupuncture and moxibustion in treating FD to guide future clinical and experimental research. We argue that the pathological causes of FD can be roughly divided into gastrointestinal dysfunction, duodenal low-grade inflammation, visceral hypersensitivity, and duodenal intestinal barrier and microbial imbalance. Correspondingly, the possible mechanisms of acupuncture and moxibustion in treating FD are elucidated from the perspective of how they improve gastric accommodation, regulate gastrointestinal motility, reduce gastric visceral sensitivity, regulate eosinophil-mast cell axis, inhibit low-grade inflammatory responses, and possibly regulate intestinal microbial homeostasis and duodenal barrier function through the microbiota-gut-brain axis. Although some evidence is still lacking, acupuncture remains a promising treatment for FD. In the future, it is necessary to conduct additional clinical and experimental research on acupuncture and moxibustion in treating FD to further explore their effects and mechanisms.

The role of psychotherapeutic approaches in treatment of functional dyspepsia, systematic review, and meta-analysis.

Background: Functional dyspepsia is a common functional gastrointestinal disorder that is often challenging to treat. Psychotherapeutic interventions have been proposed as an alternative or adjunctive approach to conventional treatments, but their efficacy remains unclear. Objective: This systematic review and meta-analysis aimed to evaluate the efficacy of psychotherapeutic interventions in the treatment of functional dyspepsia. Methods: A comprehensive search of electronic databases was conducted, from inception to March 2023, for randomized controlled trials (RCTs) that evaluated the effects of psychotherapeutic interventions on patients with functional dyspepsia. The primary outcome measures were gastrointestinal symptoms, quality of life, depression, and anxiety. Data were extracted and analyzed using Review Manager 5.3 software. The risk of bias of the included studies was assessed using the Cochrane Risk of Bias tool. Results: Sixteen RCTs comprising 1550 patients with functional dyspepsia were included in the meta-analysis. The types of psychotherapeutic interventions used in the included studies were cognitive-behavioral therapy (CBT), hypnotherapy, and mindfulness-based stress reduction (MBSR). The control groups were usual care, placebo, supportive therapy, or no treatment. The meta-analysis showed that psychotherapeutic interventions had a significant effect on reducing gastrointestinal symptoms,depression and anxiety in patients with functional dyspepsia. However, no significant improvement was observed in the quality-of-life scores of patients who received psychotherapeutic interventions compared to those in the control group. Conclusion: Psychotherapeutic interventions, such as CBT, hypnotherapy, and MBSR, could be a useful adjunct to conventional treatments for functional dyspepsia, as they were found to significantly reduce gastrointestinal symptoms and anxiety in patients. However, further studies are needed to assess the long-term effects and generalizability of these interventions.

Causality between major depressive disorder and functional dyspepsia: a two-sample Mendelian randomization study.

Background: To investigate the causal relationship between major depression and functional dyspepsia using two-sample Mendelian randomization. Methods: Data for major depression and functional dyspepsia were obtained from genome-wide association studies. We selected Single Nucleotide Polymorphisms (SNPs) strongly associated with severe depression. Mendelian randomization analysis was conducted using methods such as Inverse-Variance Weighted (IVW), MR-Egger, and Weighted Median Estimator (WME). Sensitivity analysis was performed to assess the robustness of the results. Results: A total of 31 eligible SNPs were identified as instrumental variables for major depression. IVW analysis indicated a positive causal relationship between the two conditions (ß = 0.328; SE = 0.137; p = 0.017), suggesting that severe depression increases the risk of functional dyspepsia (OR = 1.389; 95% CI: 1.062-1.816). Sensitivity tests showed no evidence of heterogeneity or horizontal pleiotropy (p > 0.05). Conclusion: MR analysis had shown that major depressive disorder is associated with an increased risk of functional dyspepsia.

Outcomes of pediatric endoscopic ultrasound-guided celiac plexus block: A single center pilot study.

Celiac plexus blocks (CPB) using endoscopic ultrasound (EUS) guidance provide significant pain relief in adults with chronic pancreatitis. We present on EUS-guided CPB for pediatric patients with abdominal pain from chronic pancreatitis or severe functional dyspepsia necessitating clinically assisted nutrition and hydration. Patients who underwent EUS-CPB were included and followed prospectively at 2-, 4-, and 8-weeks postprocedure about pain, enteral tolerance, and school/activity attendance. Thirteen patients underwent EUS-guided CPB with a total of 21 procedures. In the pancreatitis cohort, mean pain relief was 11.7 weeks for those who responded. In the functional dyspepsia cohort, mean improvement (in either pain or enteral tolerance) was 4.8 weeks. Symptom improvement varied between the two cohorts. Acute recurrent/chronic pancreatitis patients demonstrated more sustained relief than the functional dyspepsia cohort. This study adds to the limited data investigating the utility of EUS-CPB as part of a multimodal treatment plan in pediatrics.

A primer for the gastroenterology provider on psychosocial assessment of patients with disorders of gut-brain interaction.

BACKGROUND: GI-specific psychological factors are important contributors to patients' symptom experience and quality of life across all disorders of gut-brain interaction (DGBI). Clinicians' ability to recognize the role of these psychological factors is essential for formulating a biopsychosocial case conceptualization and informing treatment decisions. PURPOSE: This article will familiarize gastroenterology providers with conceptualizing the role of GI-specific psychological factors in DGBI and provides stepwise, practical guidance for how to assess these during clinical encounters in a time-efficient manner.

Metabolomic comparison of postprandial distress syndrome patients with and without duodenal eosinophilia.

OBJECTIVE: In functional dyspepsia patients, duodenal mucosal eosinophilia has been associated with early satiety but is not present in all patients suggesting varied pathways to symptom generation. The objective of the current study was to explore metabolic differences comparing those with duodenal mucosal eosinophilia to those without eosinophilia. METHODS: This study was conducted utilizing an existing biorepository. Patients had plasma samples obtained at the time of endoscopy. All had undergone endoscopy for dyspepsia and reported early satiety. Two groups were identified including those with peak duodenal mucosal eosinophil densities above 30/high power field (N = 28) and those below 30 (N = 16). The fasting plasma samples were analyzed by liquid chromatography/high-resolution mass spectrometry. Significant differences between groups were determined. RESULTS: The eosinophilia group demonstrated significant elevations in several gamma-glutamyl amino acids. The eosinophilia group had elevations of metabolites associated with oxidative stress including glutathione metabolites (cysteinlyglycine and cys-gly oxidized), and metabolites related to nitric oxide synthesis (arginine, citrulline, ornithine, and dimethylarginine). Eosinophilia was also associated with alterations in lipid metabolism including several long-chain acylcarnitine conjugated fatty acids. Carnitine levels were lower in the eosinophilia group. Lastly, vanillymandelate, a derivative of norepinephrine and epinephrine was elevated in the eosinophilia group. CONCLUSIONS: In patients with dyspepsia and early satiety, duodenal mucosal eosinophilia is associated with metabolites levels which are consistent with increased oxidative stress and alterations in lipid metabolism. Eosinophilia was also associated with lower carnitine levels. These alterations may contribute to pathophysiology and represent therapeutic targets.

Uncovering the material basis and mechanism of Jianwei Xiaoshi tablet against functional dyspepsia using ultra-high-performance liquid chromatography-mass spectrometry and network pharmacology.

Functional dyspepsia (FD) is a common digestive disease. Jianwei Xiaoshi (JWXS) tablet is composed of Radix Pseudostellariae (TZS), Pericarpium Citri Reticulatae (CP), Rhizoma Dioscoreae (SY), fired Hordei Fructus Germinatus (CMY) and Crataegi Fructus (SZ). It is a commonly used drug in the treatment of FD in China and has good therapeutic effects. However, there is very little research about the substance basis and action mechanism of JWXS tablet. In this research, ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS) and network pharmacology were used to explore the substance basis and action mechanism of the JWXS tablet. Finally, 19, 79, 22, 22 and 39 constituents were identified in the extracts of TZS, CP, SY, CMY and SZ, respectively. Based on these findings, a total of 104 ingredients were identified in JWXS tablet and 29 potentially absorbed ingredients were detected in rat plasma. The results of network pharmacology indicated that the inhibition of gastric acid secretion, the regulation of gastrointestinal motility, inflammation and immune response were the key approaches for treating FD with JWXS tablet. The material basis and potential action mechanism of JWXS tablet in treating FD were comprehensively clarified for the first time. This study will improve our understanding of JWXS tablet.

Duodenal microbiota dysbiosis in functional dyspepsia and its potential role of the duodenal microbiota in gut-brain axis interaction: a systematic review.

Background and aims: Functional dyspepsia (FD) is a common gastrointestinal disorder associated with brain-gut interaction disturbances. In recent years, accumulating evidence points to the duodenum as a key integrator in dyspepsia symptom generation. Investigations into the pathological changes in the duodenum of FD patients have begun to focus on the role of duodenal microbiota dysbiosis. This review summarizes duodenal microbiota changes in FD patients and explores their relationship with gut-brain interaction dysregulation. Methods: Ten databases, including PubMed, MEDLINE, and the Cochrane Library, were searched from inception to 10th October 2023 for clinical interventional and observational studies comparing the duodenal microbiota of FD patients with controls. We extracted and qualitatively summarized the alpha diversity, beta diversity, microbiota composition, and dysbiosis-related factors. Results: A total of nine studies, consisting of 391 FD patients and 132 non-FD controls, were included. The findings reveal that the alpha diversity of the duodenal microbiota in FD patients does not exhibit a significant difference compared to non-FD controls, although an upward trend is observed. Furthermore, alterations in the duodenal microbiota of FD patients are associated with the symptom burden, which, in turn, impacts their quality of life. In FD patients, a considerable number of duodenal microbiota demonstrate a marked ascending trend in relative abundance, including taxa such as the phylum Fusobacteria, the genera Alloprevotella, Corynebacterium, Peptostreptococcus, Staphylococcus, Clostridium, and Streptococcus. A more pronounced declining trend is observed in the populations of the genera Actinomyces, Gemella, Haemophilus, Megasphaera, Mogibacterium, and Selenomonas within FD patients. A negative correlation in the relative abundance changes between Streptococcus and Prevotella is identified, which correlates with the severity of symptom burden in FD patients. Moreover, the alterations in specific microbial communities in FD patients and their potential interactions with the gut-brain axis merit significant attention. Conclusion: Microbial dysbiosis in FD patients is linked to the onset and exacerbation of symptoms and is related to the disorder of gut-brain interaction. Larger-scale, higher-quality studies, along with comprehensive meta-omics research, are essential to further elucidate the characteristics of the duodenal microbiota in FD patients and its role in FD pathogenesis.Systematic review registration: CRD42023470279, URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023470279.

Factors Predicting Effectiveness of Eradication Therapy for Helicobacter pylori-Associated Dyspepsia Symptoms.

Functional dyspepsia is distinguishable from Helicobacter pylori-associated dyspepsia. However, distinguishing H. pylori-associated dyspepsia from functional dyspepsia before H. pylori eradication is difficult. Therefore, in the present study, we aimed to investigate whether serum pepsinogen levels before H. pylori eradication are associated with the amelioration of dyspepsia after successful H. pylori eradication. Additionally, we examined the usefulness of serum pepsinogen levels and other factors in predicting dyspepsia outcomes. H. pylori eradication was effective in 14 patients (Responders) and ineffective in 19 patients (Non-responders). The pepsinogen I/II ratio in Responders (3.4 ± 1.2) and Non-responders (2.3 ± 1.0) differed significantly (p = 0.006). The optimal cut-off pepsinogen I/II value was 2.3. Multivariate logistic regression analysis showed that the adjusted odds ratio for Non-responders was 26.1 (95% confidence interval: 2.0-338.0, p = 0.012) for a pepsinogen I/II ratio ≤ 2.3 and 8.10 (95% confidence interval: 1.1-57.6, p = 0.037) for smoking habits. The pepsinogen I/II ratio and smoking habits were associated with the effects of H. pylori eradication on dyspeptic symptoms. Thus, the pepsinogen I/II ratio cut-off value can be used to identify patients likely to respond to H. pylori eradication after the resolution of dyspeptic symptoms.

Efficacy of antidepressants in functional dyspepsia: Systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.

INTRODUCTION: The beneficial effects of using antidepressants in improving functional dyspepsia (FD) symptoms have been reported in previous meta-analyses; however, the results have not been conclusive. The aim was to perform an updated meta-analysis coupled with trial sequential analysis (TSA) to assess the efficacy of the use of any antidepressants in the treatment of FD in adults. METHODS: Electronic databases were searched up to March 2024 for randomized controlled trials (RCTs) recruiting adults with FD. Data of overall symptoms improved between the antidepressants and placebo groups was pooled to obtain risk ratio (RR) employing the random-effects model. The effect of random errors was evaluated with TSA. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence. Analyses were performed using STATA version 16.0. RESULTS: Nine RCTs with 924 patients met the eligible criteria. The RRs of FD symptoms improving with any antidepressants, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors were (n = 9, RR = 1.30 [95% CI, 1.02-1.67]), (n = 5, RR = 1.41 [95% CI, 1.07-1.85]) and (n = 2, RR = 0.97 [95% CI, 0.72-1.29]), respectively. TSA demonstrated conclusive evidence for the beneficial effect of TCAs. The number needed to treat (NNT) with any depressants and TCAs were 11 (95% CI, 7-36) and 6 (95% CI, 4-15), respectively. The certainty of the evidence for an effect of TCAs was that of moderate GRADE quality. The benefit, however, was limited to the western population (n = 3, RR = 1.43 [95% CI, 1.04-1.96]) and did not extend to the Asian population (n = 2, RR = 1.32 [95% CI, 0.75-2.32]). Conversely, antidepressant-using patients experienced adverse events more frequently. However, no statistically significant association was found between TCAs and any adverse events (n = 3; RR = 1.36 [95% CI, 0.91-2.04]). CONCLUSION: Evidence was obtained suggesting TCAs can be an effective alternative in the treatment of FD, but more evidence from high-quality large trials is required to support their use, especially in the Asian population.

Fermented Gold Kiwi for Improved Gastric Health: Evaluation of Efficacy and Safety in a Randomised, Double-Blind, Placebo-Controlled Trial.

This randomised double-blind placebo-controlled trial evaluated the efficacy and safety of fermented gold kiwi (FGK) in improving gastrointestinal health. A total of 100 participants were enrolled and randomly assigned to treatment or placebo groups. Over 8 weeks, the participants consumed an FGK or placebo preparation daily. Primary outcomes included changes in gastrointestinal symptoms assessed using the Gastrointestinal Symptom Rating Scale (GSRS) and the Korean version of the Nepean Dyspepsia Index (NDI-K), as well as quality of life assessed using the Functional Dyspepsia-related Quality of Life questionnaire. The FGK group showed significant improvements in GSRS and NDI-K total and subdomain scores compared with the placebo group. Moreover, the quality of life scores were significantly better in the FGK group than in the placebo group. Safety evaluations revealed no significant adverse events or clinically meaningful changes upon assessing laboratory test results. This study demonstrated that FGK is a safe and effective dietary supplement for improving gastrointestinal health in adults with gastrointestinal symptoms.

Effect of sex on chronic stress induced alterations in hindbrain catecholaminergic system and autonomic dysfunction resulting in gastrointestinal dysmotility.

It has been reported that the clinical symptoms of functional dyspepsia (FD) exacerbate upon stress while the gender-related factors have been incompletely understood. This study aims to investigate the role of sex in chronic heterotypic stress (CHS)-induced autonomic and gastric motor dysfunction. For CHS, the rats were exposed to the combination of different stressors for 7 consecutive days. Subsequently, electrocardiography was recorded in anesthetized rats to evaluate heart rate variability (HRV) for the determination of autonomic outflow and sympathovagal balance. Solid gastric emptying (GE) was measured in control and CHS-loaded male and female rats. The immunoreactivities of catecholaminergic cell marker tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), corticotropin releasing factor (CRF), and estrogen receptor (ER-α/ß) were evaluated in medullary and pontine brainstem sections by immunohistochemistry. Compared with the controls, CHS significantly delayed GE in males but not in females. There was no significant sex-related difference in parasympathetic indicator HF under either control or CHS conditions. Sympathetic indicator LF was significantly higher in control females compared to the males. The higher sympathetic output in females was found to be attenuated upon CHS; in contrast, the elevated sympathetic output was detected in CHS-loaded males. No sex- or stress-related effect was observed on ChAT immunoreactivity in the dorsal motor nucleus of N.vagus (DMV). In males, greater number of TH-ir cells was observed in the caudal locus coeruleus (LC), while they were more densely detected in the rostral LC of females. Regardless of sex, CHS elevated immunoreactivity of TH throughout the LC. Under basal conditions, greater number of TH-ir cells was detected in the rostral ventrolateral medulla (RVLM) of females. In contrast, CHS remarkably increased the number of TH-ir cells in the RVLM of males which was found to be decreased in females. There was no sex-related alteration in TH immunoreactivity in the nucleus tractus solitarius (NTS) of control rats, while CHS affected both sexes in a similar manner. Compared with females, CRF immunoreactivity was prominently observed in control males, while both of which were stimulated by CHS. ER-α/ß was found to be co-expressed with TH in the NTS and LC which exhibit no alteration related to either sex or stress status. These results indicate a sexual dimorphism in the catecholaminergic and the CRF system in brainstem which might be involved in the CHS-induced autonomic and visceral dysfunction occurred in males.

The Efficacy of the Herbal Formula of Bunium persicum and Coriandrum sativum on Clinical Symptoms of Patients with Functional Dyspepsia: A Double-Blind Randomized Controlled Trial.

INTRODUCTION: Functional dyspepsia (FD) is one of the most prevalent chronic disorders affecting up to 30% of the world population with considerable impairment of quality of life. This study evaluated the efficacy of the herbal preparation of Bunium persicum (Boiss.) B.Fedtsch. and Coriandrum sativum L. on symptom severity, symptom frequency, and quality of life of patients with FD. METHODS: This double-blind randomized controlled clinical trial, with parallel groups allocation ratio of 1:1, was conducted in a referral clinic of Afzalipour Hospital affiliated with Kerman University of Medical Sciences in Kerman, southeastern Iran. A total of 90 patients with FD (diagnosed based on the Rome IV criteria) were included in this study. The patients with complications during the intervention, pregnancy or lactation, a history of allergy to herbal drugs, use of other medication that affect the symptoms of FD during the study, and severe organic or psychiatric disorders were excluded. The participants received one capsule containing 500 mg of herbal preparation or placebo twice a day for 4 weeks and were subsequently followed up for 4 more weeks. Clinical outcomes were assessed via the Dyspepsia Severity Questionnaire, the Rome IV Diagnostic Questionnaire, and Nepean Dyspepsia Index Questionnaire. RESULTS: A total 40 participants in each group completed the follow-up period, and their data were analyzed statistically. All clinical outcomes showed significant improvements by herbal preparation compared to the placebo without serious side effects (p < 0.05). CONCLUSIONS: This herbal preparation can significantly improve the quality of life, and symptoms of FD compared to placebo.