Background:Recurrent acute cholecystitis(RAC)can occur after non-surgical treatment for acute cholecystitis(AC),and can be more severe in comparison to the first episode of AC.Low skeletal muscle mass or adiposity hav...Background:Recurrent acute cholecystitis(RAC)can occur after non-surgical treatment for acute cholecystitis(AC),and can be more severe in comparison to the first episode of AC.Low skeletal muscle mass or adiposity have various effects in several diseases.We aimed to clarify the relationship between RAC and body parameters.Methods:Patients with AC who were treated at our hospital between January 2011 and March 2022 were enrolled.The psoas muscle mass and adipose tissue area at the third lumbar level were measured using computed tomography at the first episode of AC.The areas were divided by height to obtain the psoas muscle mass index(PMI)and subcutaneous/visceral adipose tissue index(SATI/VATI).According to median VATI,SATI and PMI values by sex,patients were divided into the high and low PMI groups.We performed propensity score matching to eliminate the baseline differences between the high PMI and low PMI groups and analyzed the cumulative incidence and predictors of RAC.Results:The entire cohort was divided into the high PMI(n=81)and low PMI(n=80)groups.In the propensity score-matched cohort there were 57 patients in each group.In Kaplan-Meier analysis,the low PMI group and the high VATI group had a significantly higher cumulative incidence of RAC than their counterparts(log-rank P=0.001 and 0.015,respectively).In a multivariate Cox regression analysis,the hazard ratios of low PMI and low VATI for RAC were 5.250(95%confidence interval 1.083-25.450,P=0.039)and 0.158(95%confidence interval:0.026-0.937,P=0.042),respectively.Conclusions:Low skeletal muscle mass and high visceral adiposity were independent risk factors for RAC.展开更多
BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diar...BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea(IBS-D)was investigated in the present study.AIM To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D.METHODS Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls.The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores.The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint.Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1(TRPV1)expression were examined following 5-HT2B receptor antagonist adminis-tration.Changes in visceral sensitivity after administration of the TRPV1 antago-INTRODUCTION Irritable bowel syndrome(IBS)is a chronic functional bowel disorder characterized by recurrent abdominal pain with altered bowel habits that affects approximately 15%of the population worldwide[1].IBS significantly impacts the quality of life of patients.Although the pathogenesis of IBS is not completely understood,the role of abnormal visceral sensitivity in IBS has recently emerged[2,3].5-Hydroxytryptamine(5-HT)is known to play a key role in the physiological states of the gastrointestinal tract.Plasma 5-HT levels in IBS with diarrhea(IBS-D)patients were greater than those in healthy controls[4],suggesting a possible role of 5-HT in the pathogenesis of IBS-D.The serotonin receptor 2(5-HT2 receptor)family comprises three subtypes:5-HT2A,5-HT2B,and 5-HT2c.All 5-HT2 receptors exhibit 46%-50%overall sequence identity,and all of these receptors preferentially bind to Gq/11 to increase inositol phosphates and intracellular calcium mobilization[5].5-HT2B receptors are widely expressed throughout the gut,and experimental evidence suggests that the primary function of 5-HT2B receptors is to mediate contractile responses to 5-HT through its action on smooth muscle[6].The 5-HT2B receptor is localized to both neurons of the myenteric nerve plexus and smooth muscle in the human colon.The 5-HT2B receptor mediates 5-HT-evoked contraction of longitudinal smooth muscle[6].These findings suggest that the 5-HT2B receptor could play an important role in modulating colonic motility,which could affect sensory signaling in the gut.Other laboratories have shown that the 5-HT2B receptor participates in the development of mechanical and formalin-induced hyperalgesia[7,8].A 5-HT2B receptor antagonist reduced 2,4,6-trinitrobenzene sulfonic acid(TNBS)and stress-induced visceral hyperalgesia in rats[9,10].However,the role of the 5-HT2B receptor in IBS-D patients and in acetic acid-and wrap restraint-induced IBS-D rat models was not investigated.展开更多
Visceral leishmaniasis(VL)is a neglected tropical disease,and this review has summarized the current treatment scenario and its prospects.It also highlights alternative approaches used by research groups in India and ...Visceral leishmaniasis(VL)is a neglected tropical disease,and this review has summarized the current treatment scenario and its prospects.It also highlights alternative approaches used by research groups in India and around the world to develop cutting-edge and potent anti-leishmanial treatments.Even though numerous medications could be utilized to treat VL,the limitations of current treatments including their toxicity,cost,route of administration,and duration of doses,have contributed to the emergence of resistance.Combination therapy might be a better option due to its shorter duration,easier route of administration,and ability to extend the lifespan of individual drugs.However,there is a risk of not delivering both the drugs to the target site together,which can be overcome by the liposomal entrapment of those drugs and at a time knock an opportunity to reduce the dosage of amphotericin B if the combination drug provides a synergistic effect with it.Therefore,this review presents a novel strategy to fight against VL by introducing dual drug-loaded liposomes.展开更多
BACKGROUND Visceral obesity is increasingly prevalent among adolescents and young adults and is commonly recognized as a risk factor for type 2 diabetes.Estrogen[17β-estradiol(E2)]is known to offer protection against...BACKGROUND Visceral obesity is increasingly prevalent among adolescents and young adults and is commonly recognized as a risk factor for type 2 diabetes.Estrogen[17β-estradiol(E2)]is known to offer protection against obesity via diverse me-chanisms,while its specific effects on visceral adipose tissue(VAT)remain to be fully elucidated.AIM To investigate the impact of E2 on the gene expression profile within VAT of a mouse model of prediabetes.METHODS Metabolic parameters were collected,encompassing body weight,weights of visceral and subcutaneous adipose tissues(VAT and SAT),random blood glucose levels,glucose tolerance,insulin tolerance,and overall body composition.The gene expression profiles of VAT were quantified utilizing the Whole Mouse Genome Oligo Microarray and subsequently analyzed through Agilent Feature Extraction software.Functional and pathway analyses were conducted employing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses,respectively.RESULTS Feeding a high-fat diet(HFD)moderately increased the weights of both VAT and SAT,but this increase was mitigated by the protective effect of endogenous E2.Conversely,ovariectomy(OVX)led to a significant increase in VAT weight and the VAT/SAT weight ratio,and this increase was also reversed with E2 treatment.Notably,OVX diminished the expression of genes involved in lipid metabolism compared to HFD feeding alone,signaling a widespread reduction in lipid metabolic activity,which was completely counteracted by E2 adminis-tration.This study provides a comprehensive insight into E2's local and direct protective effects against visceral adiposity in VAT at the gene level.CONCLUSION In conclusion,the present study demonstrated that the HFD-induced over-nutritional challenge disrupted the gene expression profile of visceral fat,leading to a universally decreased lipid metabolic status in E2 deficient mice.E2 treatment effectively reversed this condition,shedding light on the mechanistic role and therapeutic potential of E2 in combating visceral obesity.展开更多
BACKGROUND The preoperative prediction of peritoneal metastasis(PM)in gastric cancer would prevent unnecessary surgery and promptly indicate an appropriate treatment plan.AIM To explore the predictive value of viscera...BACKGROUND The preoperative prediction of peritoneal metastasis(PM)in gastric cancer would prevent unnecessary surgery and promptly indicate an appropriate treatment plan.AIM To explore the predictive value of visceral fat(VF)parameters obtained from preoperative computed tomography(CT)images for occult PM and to develop an individualized model for predicting occult PM in patients with gastric carcinoma(GC).METHODS A total of 128 confirmed GC cases(84 male and 44 female patients)that underwent CT scans were analyzed and categorized into PM-positive(n=43)and PM-negative(n=85)groups.The clinical characteristics and VF parameters of two regions of interest(ROIs)were collected.Univariate and stratified analyses based on VF volume were performed to screen for predictive characteristics for occult PM.Prediction models with and without VF parameters were established by multivariable logistic regression analysis.RESULTS The mean attenuations of VF_(ROI 1)and VF_(ROI 2)varied significantly between the PM-positive and PMnegative groups(P=0.044 and 0.001,respectively).The areas under the receiver operating characteristic curves(AUCs)of VF_(ROI 1)and VF_(ROI 2)were 0.599 and 0.657,respectively.The mean attenuation of VF_(ROI 2)was included in the final prediction combined model,but not an independent risk factor of PM(P=0.068).No significant difference was observed between the models with and without mean attenuation of VF(AUC:0.749 vs 0.730,P=0.339).CONCLUSION The mean attenuation of VF is a potential auxiliary parameter for predicting occult PM in patients with GC.展开更多
Objective:The present study was conducted to demonstrate the age-dependent changes in skeletal muscle mass and visceral fat area in a population of Chinese adults aged 30-92 years old.Methods:A total of 6669 healthy C...Objective:The present study was conducted to demonstrate the age-dependent changes in skeletal muscle mass and visceral fat area in a population of Chinese adults aged 30-92 years old.Methods:A total of 6669 healthy Chinese men and 4494 healthy Chinese women aged 30-92 years old were assessed for their skeletal muscle mass and visceral fat area.Results:The results showed age-dependent decreases in the total skeletal muscle mass indexes in both men and women aged 40-92 years old as well as age-dependent increases in the visceral fat area in men aged 30-92 years old and in women aged 30-80 years old.Multivariate regression models showed that the total skeletal muscle mass index was positively associated with the body mass index and negatively associated with the age and visceral fat area in both sexes.Conclusion:The loss of skeletal muscle mass becomes obvious at approximately 50 years of age,and the visceral fat area commences to increase at approximately 40 years of age in this Chinese population.展开更多
In recent years, the use of fluorescence-guided surgery(FGS) to treat benign and malignant visceral, hepatobiliary and pancreatic neoplasms has significantly increased. FGS relies on the fluorescence signal emitted by...In recent years, the use of fluorescence-guided surgery(FGS) to treat benign and malignant visceral, hepatobiliary and pancreatic neoplasms has significantly increased. FGS relies on the fluorescence signal emitted by injected substances(fluorophores) after being illuminated by ad hoc laser sources to help guide the surgical procedure and provide the surgeon with real-time visualization of the fluorescent structures of interest that would be otherwise invisible. This review surveys and discusses the most common and emerging clinical applications of indocyanine green(ICG)-based fluorescence in visceral, hepatobiliary and pancreatic surgery. The analysis, findings, and discussion presented here rely on the authors' significant experience with this technique in their medical institutions, an up-to-date review of the most relevant articles published on this topic between 2014 and 2018, and lengthy discussions with key opinion leaders in the field during recent conferences and congresses. For each application, the benefits and limitations of this technique, as well as applicable future directions, are described. The imaging of fluorescence emitted by ICG is a simple, fast,relatively inexpensive, and harmless tool with numerous different applications in surgery for both neoplasms and benign pathologies of the visceral and hepatobiliary systems. The ever-increasing availability of visual systems that can utilize this tool will transform some of these applications into the standard of care in the near future. Further studies are needed to evaluate the strengths and weaknesses of each application of ICG-based fluorescence imaging in abdominal surgery.展开更多
BACKGROUND Visceral hypersensitivity is considered to play a vital role in the pathogenesis of irritable bowel syndrome(IBS). Neurotrophins have drawn much attention in IBS recently. Brain-derived neurotrophic factor(...BACKGROUND Visceral hypersensitivity is considered to play a vital role in the pathogenesis of irritable bowel syndrome(IBS). Neurotrophins have drawn much attention in IBS recently. Brain-derived neurotrophic factor(BDNF) was found to mediate visceral hypersensitivity via facilitating sensory nerve growth in pre-clinical studies. We hypothesized that BDNF might play a role in the pathogenesis of diarrhea-predominant IBS(IBS-D).AIM To investigate BDNF levels in IBS-D patients and its role in IBS-D pathophysiology.METHODS Thirty-one IBS-D patients meeting the Rome IV diagnostic criteria and 20 ageand sex-matched healthy controls were recruited. Clinical and psychological assessments were first conducted using standardized questionnaires. Visceral sensitivity to rectal distension was tested using a high-resolution manometry system. Colonoscopic examination was performed and four mucosal pinch biopsies were taken from the rectosigmoid junction. Mucosal BDNF expression and nerve fiber density were analyzed using immunohistochemistry. Mucosal BDNF mRNA levels were quantified by quantitative real-time polymerase chain reaction. Correlations between these parameters were examined.RESULTS The patients had a higher anxiety score [median(interquartile range), 6.0(2.0-10.0) vs 3.0(1.0-4.0), P = 0.003] and visceral sensitivity index score [54.0(44.0-61.0)vs 21.0(17.3-30.0), P < 0.001] than controls. The defecating sensation threshold[60.0(44.0-80.0) vs 80.0(61.0-100.0), P = 0.009], maximum tolerable threshold[103.0(90.0-128.0) vs 182.0(142.5-209.3), P < 0.001] and rectoanal inhibitory reflex threshold [30.0(20.0-30.0) vs 30.0(30.0-47.5), P = 0.032] were significantly lower in IBS-D patients. Intestinal mucosal BDNF protein [3.46 E-2(3.06 E-2-4.44 E-2) vs3.07 E-2(2.91 E-2-3.48 E-2), P = 0.031] and mRNA [1.57(1.31-2.61) vs 1.09(0.74-1.42), P = 0.001] expression and nerve fiber density [4.12 E-2(3.07 E-2-7.46 E-2) vs1.98 E-2(1.21 E-2-4.25 E-2), P = 0.002] were significantly elevated in the patients.Increased BDNF expression was positively correlated with abdominal pain and disease severity and negatively correlated with visceral sensitivity parameters.CONCLUSION Elevated mucosal BDNF may participate in the pathogenesis of IBS-D via facilitating mucosal nerve growth and increasing visceral sensitivity.展开更多
AIM:To investigate the roles of toll-like receptor 4(TLR4) and nuclear factor(NF)-κB on cystathionine βsynthetase(CBS) expression and visceral hypersensitivity in rats.METHODS:This study used 1-7-wk-old male Sprague...AIM:To investigate the roles of toll-like receptor 4(TLR4) and nuclear factor(NF)-κB on cystathionine βsynthetase(CBS) expression and visceral hypersensitivity in rats.METHODS:This study used 1-7-wk-old male SpragueDawley rats.Western blot analysis was employed to measure the expression of TLR4,NF-kB and the endogenous hydrogen sulfide-producing enzyme CBS in colon dorsal root ganglia(DRG) from control and "irritable bowel syndrome" rats induced by neonatal colonic inflammation(NCI).Colon-specific DRG neurons were labeled with Dil and acutely dissociated to measure excitability with patch-clamp techniques.Immunofluorescence was employed to determine the co-expression of TLR4,NF-kB and CBS in Dil-labeled DRG neurons.RESULTS:NCI significantly upregulated the expression of TLR4 in colon-related DRGs(0.34 ± 0.12 vs 0.72 ±0.02 for the control and NCI groups,respectively,P <0.05).Intrathecal administration of the TLR4-selective inhibitor CLI-095 significantly enhanced the colorectal distention threshold of NCI rats.CLI-095 treatment also markedly reversed the hyperexcitability of colonspecific DRG neurons and reduced the expression of CBS(1.7 ± 0.1 vs 1.1 ± 0.04,p < 0.05) and of the NF-kB subunit p65(0.8 ± 0.1 vs 0.5 ± 0.1,P< 0.05).Furthermore,the NF-KB-selective inhibitor pyrrolidine dithiocarbamate(PDTC) significantly reduced the upregulation of CBS(1.0 ± 0.1 vs 0.6 ± 0.1,P< 0.05)and attenuated visceral hypersensitivity in the NCI rats.In vitro,incubation of cultured DRG neurons with the TLR4 agonist lipopolysaccharide significantly enhanced the expression of p65(control vs 8 h:0.9 ± 0.1 vs1.3 ± 0.1;control vs 12 h:0.9 ± 0.1 vs 1.3 ± 0.1,P< 0.05;control vs 24 h:0.9 ± 0.1 vs 1.6 ± 0.1,P <0.01) and CBS(control vs 12 h:1.0 ± 0.1 vs 2.2 ±0.4;control vs 24 h:1.0 ± 0.1 vs 2.6 ± 0.1,P< 0.05),whereas the inhibition of p65 via pre-incubation with PDTC significantly reversed the upregulation of CBS expression(1.2 ± 0.1 vs 0.6 ± 0.0,P< 0.01).CONCLUSION:Our results suggest that the activation of TLR4 by NCI upregulates CBS expression,which is mediated by the NF-kB signaling pathway,thus contributing to visceral hypersensitivity.展开更多
BACKGROUND Irritable bowel syndrome (IBS) is a common chronic non-organic disease of the digestive system. Berberine (BBR) has been used to treat patients with IBS, but the underlying therapeutic mechanism is little u...BACKGROUND Irritable bowel syndrome (IBS) is a common chronic non-organic disease of the digestive system. Berberine (BBR) has been used to treat patients with IBS, but the underlying therapeutic mechanism is little understood. We believe that BBR achieves its therapeutic effect on IBS by preventing stress intestinal inflammation and visceral hypersensitivity and reducing bowel motility. AIM To test the hypothesis that BBR achieves its therapeutic effect on IBS by preventing subclinical inflammation of the intestinal mucosa and reducing visceral hypersensitivity and intestinal motility. METHODS IBS was induced in rats via water avoidance stress (WAS). qRT-PCR and histological analyses were used to evaluate the levels of cytokines and mucosal inflammation, respectively. Modified ELISA and qRT-PCR were used to evaluate the nuclear factor kappa-B (NF-κB) signal transduction pathway. Colorectal distention test, gastrointestinal transit measurement, Western blot, and qRT-PCR were used to analyze visceral sensitivity, intestinal motility, the expression of Ckit (marker of Cajal mesenchymal cells), and the expression of brain derived neurotrophic factor (BDNF) and its receptor TrkB.RESULTS WAS led to mucosal inflammation, visceral hyperalgesia, and high intestinal motility. Oral administration of BBR inhibited the NF-κB signal transduction pathway, reduced the expression of pro-inflammatory cytokines [interleukin (IL)- 1β, IL-6, interferon-γ, and tumor necrosis factor-α], promoted the expression of anti-inflammatory cytokines (IL-10 and transforming growth factor-β), and improved the terminal ileum tissue inflammation. BBR inhibited the expression of BDNF, TrkB, and C-kit in IBS rats, leading to the reduction of intestinal motility and visceral hypersensitivity. The therapeutic effect of BBR at a high dose (100 mg/kg) was superior to than that of the low-dose (25 mg/kg) group. CONCLUSION BBR reduces intestinal mucosal inflammation by inhibiting the intestinal NF-κB signal pathway in the IBS rats. BBR reduces the expression of BDNF, its receptor TrkB, and C-kit. BBR also reduces intestinal motility and visceral sensitivity to achieve its therapeutic effect on IBS.展开更多
AIM: To assess the protective effect of berberine administration and the role of nitric oxide (NO) in visceral hypersensitivity. METHODS: Fifty male Sprague-Dawley rats were randomly assigned to five groups. An inflam...AIM: To assess the protective effect of berberine administration and the role of nitric oxide (NO) in visceral hypersensitivity. METHODS: Fifty male Sprague-Dawley rats were randomly assigned to five groups. An inflammatory bowel disease model was induced in rats by intracolonic instillation of 1 mL 4% acetic acid at 8 cm proximal to the anus for 30 s and restraint stress. After subsidence of inflammation on day 7 of the experiment, the rats were subjected to rectal distension, performed by a balloon (6-Fr, 2 mm external diameter, disposable silicon balloon-urethral catheter for pediatric use) which was rapidly inflated with increasing volumes of prewarmed (37 ℃) water (0.1, 0.2, 0.3, 0.4, 0.6, 0.8 and 1 mL) for 30 s at four-minute intervals, and then the abdominal withdrawal reflex (AWR) and the level of fecal output were measured, respectively. AWR scores either 0, 1, 2, 3 or 4 were obtained by blinded observers. Rats had been pretreated with berberine or aminoguanidine (NO synthetase inhibitor) or berberine + aminoguanidine before measurement. RESULTS: The rats in the placebo group showed a hypersensitive response to rectal distension (2.69 ± 0.08 vs 1.52 ± 0.08, P = 0.000) and defecated more frequently than those in the control group (5.0 ± 0.16 vs 0.44 ± 0.16, P = 0.000). Comparing the berberine with placebo group, the AWR scores were reduced for all distension volumes and were significant at 0.2-1 mL (1.90 ± 0.08 vs 2.69 ± 0.08, P = 0.000), while the numbers of hard pellets, soft pellets, formless stools, and total fecal output in the placebo group were significantly larger than in the berberine group (5.0 ± 0.16 vs 2.56 ± 0.16, P = 0.000). Administration of aminoguanidine or berberine + aminoguanidine before VH score measurement reversed the antinociceptive effect of berberine (2.52 ± 0.08 vs 1.90 ± 0.08, P = 0.000; 2.50 ± 0.08 vs 1.90 ± 0.08, P = 0.000). The numbers of hard pellets, soft pellets, formless stool, and total of fecal output in aminoguanidine group were significantly larger than the corresponding values in control group, berberine group, and berberine + aminoguanidine group (4.81 ± 0.16 vs 0.44 ± 0.16, P = 0.000; 4.81 ± 0.16 vs 2.56 ± 0.16, P = 0.000; 4.81 ± 0.16 vs 3.75 ± 0.16, P = 0.000). The berberine and berberine + aminoguanidine groups showed reduced defecation, but aminoguanidine alone did not reduce defecation (2.56 ± 0.16 vs 4.81 ± 0.16, P = 0.000; 3.75 ± 0.16 vs 4.81 ± 0.16, P = 0.000). CONCLUSION: Berberine had an antinociceptive effect on visceral hypersensitivity, and NO might play a role in this effect.展开更多
AIM: To explore the role of nesfatin-1 on irritable bowel syndrome (IBS)-like visceral hypersensitivity. METHODS: The animal model of IBS-like visceral hypersensitivity was induced by intracolonic infusion of 0.5% ace...AIM: To explore the role of nesfatin-1 on irritable bowel syndrome (IBS)-like visceral hypersensitivity. METHODS: The animal model of IBS-like visceral hypersensitivity was induced by intracolonic infusion of 0.5% acetic acid (AA) in saline once daily from postnatal days 8-21. Experiments were performed when rats became adults. The visceral sensitivity of rats was evaluated by abdominal withdrawal reflex (AWR) and electromyographic (EMG) activity of the external oblique muscle to graded colorectal distension. The content of nesfatin-1 in serum was determined using enzyme-linked immunosorbent assay. After implantation of an intracerebroventricular (ICV) cannula and two electrodes into the external oblique muscle, model rats were randomly divided into four groups. Animals then received ICV injection of 8 μg of anti-nesfatin-1/ nucleobindin-2 (NUCB2), 50 μg of α-helical cortico-tropin releasing factor (CRF) 9-41 (non-selective CRF receptor antagonist), 50 μg of NBI-27914 (selective CRF1 receptor antagonist) or 5 μL of vehicle. After 1 h of ICV administration, visceral sensitivity of each group was measured again, and comparisons between groups were made. RESULTS: Rats treated with AA showed higher mean AWR scores and EMG activity at all distension pressures compared with controls (P < 0.05). On histopathologic examination, no evidence of inflammation or abnormalities in structure were noted in the colon of either control or AA-treated groups. Myeloperoxidase values were not significantly different between the two groups. The level of nesfatin-1 in serum was significantly higher in the AA-treated group than in the control group (5.34 ± 0.37 ng/mL vs 4.81 ± 0.42 ng/mL, P < 0.01). Compared with rats injected with vehicle, rats which received ICV anti-nesfatin-1/NUCB2, α-helical CRF9-41 or NBI-27914 showed decreased mean AWR scores and EMG activity at all distension pressures (P < 0.05). CONCLUSION: Nesfatin-1 may be associated with IBS-like visceral hypersensitivity, which may be implicated in brain CRF/CRF1 signaling pathways.展开更多
AIM: To investigate the effect of electroacupuncture on corticotropin-releasing hormone(CRH) in the colon, spinal cord, and hypothalamus of rats with chronic visceral hypersensitivity.METHODS: A rat model of chronic v...AIM: To investigate the effect of electroacupuncture on corticotropin-releasing hormone(CRH) in the colon, spinal cord, and hypothalamus of rats with chronic visceral hypersensitivity.METHODS: A rat model of chronic visceral hypersensitivity was generated according to the internationally accepted method of colorectal balloon dilatation. In the 7th week after the procedure, rats were randomly divided into a model group(MG), electroacupuncture group(EA), and sham electroacupuncture group(S-EA). After treatment, the abdominal withdrawal reflex(AWR) score was used to assess the behavioral response of visceral hyperalgesia. Immunohistochemistry(En Vision method), ELISA, and fluorescence quantitative PCR methods were applied to detect the expression of CRH protein and m RNA in the colon, spinal cord, and hypothalamus.RESULTS: The sensitivity of the rats to the colorectal distension stimulus applied at different strengths(20-80 mm Hg) increased with increasing stimulus strength, resulting in increasing AWR scores in each group. Compared with NG, the AWR score of MG was significantly increased(P < 0.01). After conducting EA, the AWR scores of the rats were decreased compared with MG rats. The relative expression of CRH m RNA in the colon, spinal cord, and hypothalamus of MG rats was significantly increased compared with NG rats(P < 0.01). CRH m RNA in the colon and spinal cord of EA and S-EA rats was decreased to varying degrees(P > 0.05) compared with normal rats(NG). However, the decrease in EA compared with MG rats was statistically significant(P < 0.01). The average optical density of CRH expression in the colon of the MG rats was significantly enhanced compared with NG(P < 0.05), while the average optical density of CRH expression in the EA and S-EA rats was significantly decreased compared with MG rats(P < 0.01, P < 0.05, respectively). Compared with MG rats, the CRH concentration in the spinal cord of EA rats was significantly reduced(P < 0.01), but there was no significant change in S-EA rats(P > 0.05).CONCLUSION: Electroacupuncture at the Shangjuxu acupoint was able to significantly reduce the visceral hypersensitivity in rats, and regulated the expression of CRH protein and m RNA in the colon, spinal cord and hypothalamus at different levels, playing a therapeutic role in this model of irritable bowel syndrome.展开更多
BACKGROUND Visceral hypersensitivity and psychological performance are the main pathophysiological mechanisms of irritable bowel syndrome(IBS).Previous studies have found that cholecystokinin(CCK)can enhance colon mov...BACKGROUND Visceral hypersensitivity and psychological performance are the main pathophysiological mechanisms of irritable bowel syndrome(IBS).Previous studies have found that cholecystokinin(CCK)can enhance colon movement and that serotonin transporter(SERT)is a transmembrane transport protein with high affinity for 5-hydroxytryptamine,which can rapidly reuptake 5-hydroxytryptamine and then regulate its action time and intensity.We speculate that SERT and CCK might play a role in the pathogenesis of diarrheapredominant IBS(IBS-D)by affecting visceral sensitivity and the brain-gut axis.AIM To determine SERT and CCK levels in IBS-D patients diagnosed using Rome IV criteria and to analyze their associations with abdominal pain,visceral hypersensitivity and psychological performance.METHODS This study collected data from 40 patients with IBS-D at the China-Japan Friendship Hospital from September 2017 to April 2018 and 18 healthy controls.The severity of abdominal pain,visceral sensitivity and psychological performance were evaluated in IBS-D patients and healthy controls,the levels of SERT and CCK in plasma and colonic mucosa were evaluated,and the correlations between them were analyzed.RESULTS There were significant differences in the initial sensation threshold(31.00±8.41 mL vs 52.22±8.09 mL,P<0.001),defecating sensation threshold(51.75±13.57 mL vs 89.44±8.73 mL,P<0.001)and maximum tolerable threshold(97.25±23.64 mL vs 171.11±20.83 mL,P<0.001)between the two groups.IBS-D patients had more severe anxiety(7.78±2.62 vs 2.89±1.02,P<0.001)and depressive(6.38±2.43 vs 2.06±0.73,P<0.001)symptoms than healthy controls.Significant differences were also found in mucosal CCK(2.29±0.30 vs 1.66±0.17,P<0.001)and SERT(1.90±0.51 vs 3.03±0.23,P<0.001)between the two groups.There was a significant positive correlation between pain scores and mucosal CCK(r=0.96,0.93,0.94,P<0.001).Significant negative correlations between anxiety(r=-0.98;P<0.001),depression(r=-0.99;P<0.001),pain evaluation(r=-0.96,-0.93,-0.95,P<0.001)and mucosal SERT were observed.CONCLUSION IBS-D patients had psychosomatic disorders and visceral hypersensitivity.SERT and CCK might be involved in the pathogenesis of IBS-D by regulating the braingut axis and affecting visceral sensitivity.This provides a new potential method for identifying a more specific and effective therapeutic target.展开更多
AIM To observe whether there are differences in the effects of electro-acupuncture(EA) and moxibustion(Mox) in rats with visceral hypersensitivity. METHODS EA at 1 m A and 3 m A and Mox at 43?℃ and 46?℃ were applied...AIM To observe whether there are differences in the effects of electro-acupuncture(EA) and moxibustion(Mox) in rats with visceral hypersensitivity. METHODS EA at 1 m A and 3 m A and Mox at 43?℃ and 46?℃ were applied to the Shangjuxu(ST37, bilateral) acupoints in model rats with visceral hypersensitivity. Responses of wide dynamic range neurons in dorsal horns of the spinal cord were observed through the extracellular recordings. Mast cells(MC) activity in the colons of rats were assessed, and 5-hydroxytryptamine(5-HT), 5-hydroxytryptamine 3 receptor(5-HT3R) and 5-HT4Rexpressions in the colons were measured.RESULTS Compared with normal control group, responses of wide dynamic range neurons in the dorsal horn of the spinal cord were increased in the EA at 1 m A and 3 m A groups(1 m A: 0.84 ± 0.74 vs 2.73 ± 0.65, P < 0.001; 3 m A: 1.91 ± 1.48 vs 6.44 ± 1.26, P < 0.001) and Mox at 43?℃ and 46?℃ groups(43?℃: 1.76 ± 0.81 vs 4.14 ± 1.83, P = 0.001; 46?℃: 5.19 ± 2.03 vs 7.91 ± 2.27, P = 0.01). MC degranulation rates and the expression of 5-HT, 5-HT3 R and 5-HT4 R in the colon of Mox 46?℃ group were decreased compared with model group(MC degranulation rates: 0.47 ± 0.56 vs 0.28 ± 0.78, P < 0.001; 5-HT: 1.42 ± 0.65 vs 7.38 ± 1.12, P < 0.001; 5-HT3R: 6.62 ± 0.77 vs 2.86 ± 0.88, P < 0.001; 5-HT4R: 4.62 ± 0.65 vs 2.22 ± 0.97, P < 0.001). CONCLUSION The analgesic effects of Mox at 46?℃ are greater than those of Mox at 43?℃, EA 1 m A and EA 3 m A.展开更多
AIM: To investigate the role of epidermal growth factor(EGF) in visceral hypersensitivity and its effect on the serotonin transporter(SERT).METHODS: A rat model for visceral hypersensitivity was established by intra-c...AIM: To investigate the role of epidermal growth factor(EGF) in visceral hypersensitivity and its effect on the serotonin transporter(SERT).METHODS: A rat model for visceral hypersensitivity was established by intra-colonic infusion of 0.5% acetic acid in 10-d-old Sprague-Dawley rats. The visceral sensitivity was assessed by observing the abdominal withdrawal reflex and recording electromyographic activity of the external oblique muscle in response to colorectal distension. An enzyme-linked immunosorbent assay was used to measure the EGF levels in plasma and colonic tissues. SERT mRNA expression was detected by real-time PCR while protein level was determined by Western blot. The correlation between EGF and SERT levels in colon tissues was analyzed by Pearson's corre-lation analysis. SERT function was examined by tritiated serotonin(5-HT) uptake experiments. Rat intestinal epithelial cells(IEC-6) were used to examine the EGF regulatory effect on SERT expression and function via the EGF receptor(EGFR).RESULTS: EGF levels were significantly lower in th rats with visceral hypersensitivity as measured in plas ma(2.639 ± 0.107 ng/mL vs 4.066 ± 0.573 ng/mL, < 0.01) and in colonic tissue(3.244 ± 0.135 ng/10 mg vs 3.582 ± 0.197 ng/100 mg colon tissue, P 0.01) compared with controls. Moreover, the EGF leve were positively correlated with SERT levels(r = 0.820 P < 0.01). EGF displayed dose- and time-dependen increased SERT gene expressions in IEC-6 cells. A EGFR kinase inhibitor inhibited the effect of EGF o SERT gene upregulation. SERT activity was enhance following treatment with EGF(592.908 ± 31.515 fmo min per milligram vs 316.789 ± 85.652 fmol/min pe milligram protein, P < 0.05) and blocked by the EGF kinase inhibitor in IEC-6 cells(590.274 ± 25.954 fmo min per milligram vs 367.834 ± 120.307 fmol/min pe milligram protein, P < 0.05).CONCLUSION: A decrease in EGF levels may contribute to the formation of visceral hypersensitivity through downregulation of SERT-mediated 5-HT uptake into enterocytes.展开更多
AIM:To evaluate the therapeutic effect of Shugan-decoction(SGD)on visceral hyperalgesia and colon gene expressions using a rat model.METHODS:Ninety-six adult male Wistar rats were randomized into six equal groups for ...AIM:To evaluate the therapeutic effect of Shugan-decoction(SGD)on visceral hyperalgesia and colon gene expressions using a rat model.METHODS:Ninety-six adult male Wistar rats were randomized into six equal groups for assessment of SGD effects on psychological stress-induced changes using the classic water avoidance stress(WAS)test.Untreated model rats were exposed to chronic(1 h/d for 10 d consecutive)WAS conditions;experimental treatment model rats were administered with intragastric SGD at1 h before WAS on consecutive days 4-10(low-dose:0.1g/mL;mid-dose:0.2 g/mL;high-dose:0.4 g/mL);control treatment model rats were similarly administered with the irritable bowel syndrome drug,dicetel(0.0042g/mL);untreated normal control rats received no drug and were not subjected to the WAS test.At the end of the 10-d WAS testing period,a semi-quantitative measurement of visceral sensitivity was made by assessing the abdominal withdrawal reflex(AWR)to colorectal balloon-induced distension(at 5 mmHg increments)to determine the pain pressure threshold(PPT,evidenced by pain behavior).Subsequently,the animals were sacrificed and colonic tissues collected for assessment of changes in expressions of proteins related to visceral hypersensitivity(transient receptor potential vanilloid 1,TRPV1)and sustained visceral hyperalgesia(substance P,SP)by immunohistochemistry and real-time polymerase chain reaction.Inter-group differences were assessed by paired t test or repeated measures analysis of variance.RESULTS:The WAS test successfully induced visceral hypersensitivity,as evidenced by a significantly reduced AWR pressure in the untreated model group as compared to the untreated normal control group(190.4±3.48 mmHg vs 224.0±4.99 mmHg,P<0.001).SGD treatments at mid-dose and high-dose and the dicetel treatment significantly increased the WAS-reduced PPT(212.5±2.54,216.5±3.50 and 217.7±2.83 mmHg respectively,all P<0.001);however,the low-dose SGD treatment produced no significant effect on the WAS-reduced PPT(198.3±1.78 mmHg,P>0.05).These trends corresponded to the differential expressions observed for both TRPV1 protein(mid-dose:1.64±0.08 and high-dose:1.69±0.12 vs untreated model:3.65±0.32,P<0.001)and mRNA(0.44±0.16 and0.15±0.03 vs 1.39±0.15,P<0.001)and SP protein(0.99±0.20 and 1.03±0.23 vs 2.03±0.12,P<0.01)and mRNA(1.64±0.19 and 1.32±0.14 vs 2.60±0.33,P<0.05).These differential expressions of TRPV1 and SP related to mid-and high-dose SGD treatments were statistically similar to the changes induced by dicetel treatment.No signs of overt damage to the rat system were observed for any of the SGD dosages.CONCLUSION:Shugan-decoction can reduce chronic stress-induced visceral hypersensitivity in rats,and the regulatory mechanism may involve mediating the expressions of TRPV1 and SP in colon tissues.展开更多
Objective:To investigate the impact of the preinduced intestinal heat shock protein 70(HSP70)on the visceral hypersensitivity and abnormal intestinal motility in a post-infectious irritable bowel syndrome(PI-IBS) mous...Objective:To investigate the impact of the preinduced intestinal heat shock protein 70(HSP70)on the visceral hypersensitivity and abnormal intestinal motility in a post-infectious irritable bowel syndrome(PI-IBS) mouse model.Methods:Eighty-four female C57BL/6 mice were randomly assigned to four groups:control group(n=21) and induction+PI-IBS group(n=21),PI-IBS group(n=21) and induction group(n=21).The mice in PI-IBS group were infected in vivo with trichinella spiralis by oral administration.The visceral hypersensitivity and intestinal motility were evaluated respectively with abdominal withdrawal reflex and colon transportation test.The intestinal HSP70 protein and mRNA level was measured by Western blot and realtime PCR.Meanwhile,the intestinal proinflammatory cytokines IL-10 and TNF-α level was detected by ELISA.Results:Compared with their counterparts in PI-IBS group,the animals in the Induction+PI-IBS group show significantly increased intestinal level of HSP70 and obviously ameliorative clinical tigurcs.including abdominal withdrawal reflex score,intestine transportation time and Bristol scores(P<0.05).Meanwhile,the intestinal post-inflammatory cytokines remarkably changed,including increased IL-10 level and decreased TNF-αlevel(P<0.05).Conclusions:Intestinal IISP70 may play a potential protective role through improving the imbalance between the intestinal post-inflammatory and anti-inflammatory cytokines in PI-IBS.展开更多
BACKGROUND Fecal metabolites are associated with gut visceral sensitivity,mucosal immune function and intestinal barrier function,all of which have critical roles in the pathogenesis of irritable bowel syndrome(IBS).H...BACKGROUND Fecal metabolites are associated with gut visceral sensitivity,mucosal immune function and intestinal barrier function,all of which have critical roles in the pathogenesis of irritable bowel syndrome(IBS).However,the metabolic profile and pathophysiology of IBS are still unclear.We hypothesized that altered profiles of fecal metabolites might be involved in the pathogenesis of IBS with predominant diarrhea(IBS-D).AIM To investigate the fecal metabolite composition and the role of metabolites in IBSD pathophysiology.METHODS Thirty IBS-D patients and 15 age-and sex-matched healthy controls(HCs)underwent clinical and psychological assessments,including the IBS Symptom Severity System(IBS-SSS),an Italian modified version of the Bowel Disease Questionnaire,the Bristol Stool Form Scale(BSFS),the Hospital Anxiety and Depression Scale,and the Visceral Sensitivity Index.Visceral sensitivity to rectal distension was tested using high-resolution manometry system by the same investigator.Fecal metabolites,including amino acids and organic acids,were measured by targeted metabolomics approaches.Correlation analyses between these parameters were performed.RESULTS The patients presented with increased stool water content,more psychological symptoms and increased visceral hypersensitivity compared with the controls.In fecal metabolites,His[IBS-D:0.0642(0.0388,0.1484),HC:0.2636(0.0780,0.3966),P=0.012],Ala[IBS-D:0.5095(0.2826,0.9183),HC:1.0118(0.6135,1.4335),P=0.041],Tyr[IBS-D:0.1024(0.0173,0.4527),HC:0.5665(0.2436,1.3447),P=0.018],Phe[IBS-D:0.1511(0.0775,0.3248),HC:0.3967(0.1388,0.7550),P=0.028],and Trp[IBS-D:0.0323(0.0001,0.0826),HC:0.0834(0.0170,0.1759),P=0.046]were decreased in IBS-D patients,but isohexanoate[IBS-D:0.0127(0.0060,0.0246),HC:0.0070(0.0023,0.0106),P=0.028]was significantly increased.Only Tyr was mildly correlated with BSFS scores in all subjects(r=-0.347,P=0.019).A possible potential biomarker panel was identified to correlate with IBS-SSS score(R2 Adjusted=0.693,P<0.001).In this regression model,the levels of Tyr,Val,hexanoate,fumarate,and pyruvate were significantly associated with the symptom severity of IBS-D.Furthermore,visceral sensation,including abdominal pain and visceral hypersensitivity,was correlated with isovalerate,valerate and isohexanoate.CONCLUSION Altered profiles of fecal metabolites may be one of the origins or exacerbating factors of symptoms in IBS-D via increasing visceral sensitivity.展开更多
Abdominal obesity,rather than total amount of fat,is linked to obesity-related disorders.Visceral adiposity is an important component of obesity-related disorders in Japanese individuals with a mild degree of adiposit...Abdominal obesity,rather than total amount of fat,is linked to obesity-related disorders.Visceral adiposity is an important component of obesity-related disorders in Japanese individuals with a mild degree of adiposity compared with Western subjects.In 1983,our group reported techniques for body fat analysis using computed tomography(CT)and established the concept of visceral fat obesity in which intra-abdominal fat accumulation is an important factor in the development of obesity-related complications,such as diabetes,lipid disorders,hypertension and atherosclerosis.Our group also established ideal imaging conditions for determining abdominal fat area at the umbilical level CT scan.Visceral fat area(VFA)measured in a single slice at L4level correlated significantly with the total abdominal visceral fat volume measured on multislice CT scan.In a large-scale study of a Japanese population,the mean number of obesity-related cardiovascular risk factors(hypertension,low high-density lipoprotein cholesterolemia and/or hypertriglyceridemia,and hyperglycemia)was greater than 1.0 at 100 cm2 of VFA,irrespective of gender,age and body mass index.Our group also demonstrated that reduction of visceral fat accumulation subsequent to voluntary lifestyle modification,"Hokenshido",correlated with a decrease in the number of obesity-related cardiovascular risk factors.It is important to select the most appropriate subjects from the general population(e.g.,non-obese subjects with a cluster of risk factors for the metabolic syndrome)that are most suitable for body weight reduction,with the goal of preventing atherosclerotic cardiovascular diseases.展开更多
基金This study was approved by the Ethics Committee of Kyushu Rosai Hospital Moji Medical Center(No:04-01,date of approval:June 2,2022).This study was conducted in compliance with the principles of the Declaration of Helsinki.
文摘Background:Recurrent acute cholecystitis(RAC)can occur after non-surgical treatment for acute cholecystitis(AC),and can be more severe in comparison to the first episode of AC.Low skeletal muscle mass or adiposity have various effects in several diseases.We aimed to clarify the relationship between RAC and body parameters.Methods:Patients with AC who were treated at our hospital between January 2011 and March 2022 were enrolled.The psoas muscle mass and adipose tissue area at the third lumbar level were measured using computed tomography at the first episode of AC.The areas were divided by height to obtain the psoas muscle mass index(PMI)and subcutaneous/visceral adipose tissue index(SATI/VATI).According to median VATI,SATI and PMI values by sex,patients were divided into the high and low PMI groups.We performed propensity score matching to eliminate the baseline differences between the high PMI and low PMI groups and analyzed the cumulative incidence and predictors of RAC.Results:The entire cohort was divided into the high PMI(n=81)and low PMI(n=80)groups.In the propensity score-matched cohort there were 57 patients in each group.In Kaplan-Meier analysis,the low PMI group and the high VATI group had a significantly higher cumulative incidence of RAC than their counterparts(log-rank P=0.001 and 0.015,respectively).In a multivariate Cox regression analysis,the hazard ratios of low PMI and low VATI for RAC were 5.250(95%confidence interval 1.083-25.450,P=0.039)and 0.158(95%confidence interval:0.026-0.937,P=0.042),respectively.Conclusions:Low skeletal muscle mass and high visceral adiposity were independent risk factors for RAC.
基金The Health Commission of Jinshan District,Shanghai,China,No.JSKJ-KTMS-2019-01The Youth Research Foundation of Jinshan Hospital of Fudan University,No.JYQN-JC-202101 and No.JYQN-JC-202216The Reserve Discipline Construction of Jinshan Hospital of Fudan University,No.HBXK-2021-2.
文摘BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea(IBS-D)was investigated in the present study.AIM To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D.METHODS Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls.The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores.The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint.Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1(TRPV1)expression were examined following 5-HT2B receptor antagonist adminis-tration.Changes in visceral sensitivity after administration of the TRPV1 antago-INTRODUCTION Irritable bowel syndrome(IBS)is a chronic functional bowel disorder characterized by recurrent abdominal pain with altered bowel habits that affects approximately 15%of the population worldwide[1].IBS significantly impacts the quality of life of patients.Although the pathogenesis of IBS is not completely understood,the role of abnormal visceral sensitivity in IBS has recently emerged[2,3].5-Hydroxytryptamine(5-HT)is known to play a key role in the physiological states of the gastrointestinal tract.Plasma 5-HT levels in IBS with diarrhea(IBS-D)patients were greater than those in healthy controls[4],suggesting a possible role of 5-HT in the pathogenesis of IBS-D.The serotonin receptor 2(5-HT2 receptor)family comprises three subtypes:5-HT2A,5-HT2B,and 5-HT2c.All 5-HT2 receptors exhibit 46%-50%overall sequence identity,and all of these receptors preferentially bind to Gq/11 to increase inositol phosphates and intracellular calcium mobilization[5].5-HT2B receptors are widely expressed throughout the gut,and experimental evidence suggests that the primary function of 5-HT2B receptors is to mediate contractile responses to 5-HT through its action on smooth muscle[6].The 5-HT2B receptor is localized to both neurons of the myenteric nerve plexus and smooth muscle in the human colon.The 5-HT2B receptor mediates 5-HT-evoked contraction of longitudinal smooth muscle[6].These findings suggest that the 5-HT2B receptor could play an important role in modulating colonic motility,which could affect sensory signaling in the gut.Other laboratories have shown that the 5-HT2B receptor participates in the development of mechanical and formalin-induced hyperalgesia[7,8].A 5-HT2B receptor antagonist reduced 2,4,6-trinitrobenzene sulfonic acid(TNBS)and stress-induced visceral hyperalgesia in rats[9,10].However,the role of the 5-HT2B receptor in IBS-D patients and in acetic acid-and wrap restraint-induced IBS-D rat models was not investigated.
基金SKM gratefully acknowledges the support of Indian Council of Medical Research(ICMR),New Delhi,India(File No:6/9-7(308)/2023-ECD-II)RH acknowledges the SVMCM fellowship,West Bengal.
文摘Visceral leishmaniasis(VL)is a neglected tropical disease,and this review has summarized the current treatment scenario and its prospects.It also highlights alternative approaches used by research groups in India and around the world to develop cutting-edge and potent anti-leishmanial treatments.Even though numerous medications could be utilized to treat VL,the limitations of current treatments including their toxicity,cost,route of administration,and duration of doses,have contributed to the emergence of resistance.Combination therapy might be a better option due to its shorter duration,easier route of administration,and ability to extend the lifespan of individual drugs.However,there is a risk of not delivering both the drugs to the target site together,which can be overcome by the liposomal entrapment of those drugs and at a time knock an opportunity to reduce the dosage of amphotericin B if the combination drug provides a synergistic effect with it.Therefore,this review presents a novel strategy to fight against VL by introducing dual drug-loaded liposomes.
基金Supported by National Natural Science Foundation of China,No.81270901 and No.81970672.
文摘BACKGROUND Visceral obesity is increasingly prevalent among adolescents and young adults and is commonly recognized as a risk factor for type 2 diabetes.Estrogen[17β-estradiol(E2)]is known to offer protection against obesity via diverse me-chanisms,while its specific effects on visceral adipose tissue(VAT)remain to be fully elucidated.AIM To investigate the impact of E2 on the gene expression profile within VAT of a mouse model of prediabetes.METHODS Metabolic parameters were collected,encompassing body weight,weights of visceral and subcutaneous adipose tissues(VAT and SAT),random blood glucose levels,glucose tolerance,insulin tolerance,and overall body composition.The gene expression profiles of VAT were quantified utilizing the Whole Mouse Genome Oligo Microarray and subsequently analyzed through Agilent Feature Extraction software.Functional and pathway analyses were conducted employing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses,respectively.RESULTS Feeding a high-fat diet(HFD)moderately increased the weights of both VAT and SAT,but this increase was mitigated by the protective effect of endogenous E2.Conversely,ovariectomy(OVX)led to a significant increase in VAT weight and the VAT/SAT weight ratio,and this increase was also reversed with E2 treatment.Notably,OVX diminished the expression of genes involved in lipid metabolism compared to HFD feeding alone,signaling a widespread reduction in lipid metabolic activity,which was completely counteracted by E2 adminis-tration.This study provides a comprehensive insight into E2's local and direct protective effects against visceral adiposity in VAT at the gene level.CONCLUSION In conclusion,the present study demonstrated that the HFD-induced over-nutritional challenge disrupted the gene expression profile of visceral fat,leading to a universally decreased lipid metabolic status in E2 deficient mice.E2 treatment effectively reversed this condition,shedding light on the mechanistic role and therapeutic potential of E2 in combating visceral obesity.
基金Supported by Henan Province 2023 Scientific Research Projects Focused on Higher Education Project,China,No.23A320059.
文摘BACKGROUND The preoperative prediction of peritoneal metastasis(PM)in gastric cancer would prevent unnecessary surgery and promptly indicate an appropriate treatment plan.AIM To explore the predictive value of visceral fat(VF)parameters obtained from preoperative computed tomography(CT)images for occult PM and to develop an individualized model for predicting occult PM in patients with gastric carcinoma(GC).METHODS A total of 128 confirmed GC cases(84 male and 44 female patients)that underwent CT scans were analyzed and categorized into PM-positive(n=43)and PM-negative(n=85)groups.The clinical characteristics and VF parameters of two regions of interest(ROIs)were collected.Univariate and stratified analyses based on VF volume were performed to screen for predictive characteristics for occult PM.Prediction models with and without VF parameters were established by multivariable logistic regression analysis.RESULTS The mean attenuations of VF_(ROI 1)and VF_(ROI 2)varied significantly between the PM-positive and PMnegative groups(P=0.044 and 0.001,respectively).The areas under the receiver operating characteristic curves(AUCs)of VF_(ROI 1)and VF_(ROI 2)were 0.599 and 0.657,respectively.The mean attenuation of VF_(ROI 2)was included in the final prediction combined model,but not an independent risk factor of PM(P=0.068).No significant difference was observed between the models with and without mean attenuation of VF(AUC:0.749 vs 0.730,P=0.339).CONCLUSION The mean attenuation of VF is a potential auxiliary parameter for predicting occult PM in patients with GC.
基金supported by the Basic Public Welfare Research Program of Zhejiang Province(No.LGF20H020009)a Taizhou Science and Technology Plan Project(No.22ywb105)。
文摘Objective:The present study was conducted to demonstrate the age-dependent changes in skeletal muscle mass and visceral fat area in a population of Chinese adults aged 30-92 years old.Methods:A total of 6669 healthy Chinese men and 4494 healthy Chinese women aged 30-92 years old were assessed for their skeletal muscle mass and visceral fat area.Results:The results showed age-dependent decreases in the total skeletal muscle mass indexes in both men and women aged 40-92 years old as well as age-dependent increases in the visceral fat area in men aged 30-92 years old and in women aged 30-80 years old.Multivariate regression models showed that the total skeletal muscle mass index was positively associated with the body mass index and negatively associated with the age and visceral fat area in both sexes.Conclusion:The loss of skeletal muscle mass becomes obvious at approximately 50 years of age,and the visceral fat area commences to increase at approximately 40 years of age in this Chinese population.
文摘In recent years, the use of fluorescence-guided surgery(FGS) to treat benign and malignant visceral, hepatobiliary and pancreatic neoplasms has significantly increased. FGS relies on the fluorescence signal emitted by injected substances(fluorophores) after being illuminated by ad hoc laser sources to help guide the surgical procedure and provide the surgeon with real-time visualization of the fluorescent structures of interest that would be otherwise invisible. This review surveys and discusses the most common and emerging clinical applications of indocyanine green(ICG)-based fluorescence in visceral, hepatobiliary and pancreatic surgery. The analysis, findings, and discussion presented here rely on the authors' significant experience with this technique in their medical institutions, an up-to-date review of the most relevant articles published on this topic between 2014 and 2018, and lengthy discussions with key opinion leaders in the field during recent conferences and congresses. For each application, the benefits and limitations of this technique, as well as applicable future directions, are described. The imaging of fluorescence emitted by ICG is a simple, fast,relatively inexpensive, and harmless tool with numerous different applications in surgery for both neoplasms and benign pathologies of the visceral and hepatobiliary systems. The ever-increasing availability of visual systems that can utilize this tool will transform some of these applications into the standard of care in the near future. Further studies are needed to evaluate the strengths and weaknesses of each application of ICG-based fluorescence imaging in abdominal surgery.
基金Supported by the National Key Technology Support Program during "12th Five-Year Plan"Period of China,No.2014BAI08B00the Leapforward Development Program for Beijing Biopharmaceutical Industry(G20),No.Z171100001717008
文摘BACKGROUND Visceral hypersensitivity is considered to play a vital role in the pathogenesis of irritable bowel syndrome(IBS). Neurotrophins have drawn much attention in IBS recently. Brain-derived neurotrophic factor(BDNF) was found to mediate visceral hypersensitivity via facilitating sensory nerve growth in pre-clinical studies. We hypothesized that BDNF might play a role in the pathogenesis of diarrhea-predominant IBS(IBS-D).AIM To investigate BDNF levels in IBS-D patients and its role in IBS-D pathophysiology.METHODS Thirty-one IBS-D patients meeting the Rome IV diagnostic criteria and 20 ageand sex-matched healthy controls were recruited. Clinical and psychological assessments were first conducted using standardized questionnaires. Visceral sensitivity to rectal distension was tested using a high-resolution manometry system. Colonoscopic examination was performed and four mucosal pinch biopsies were taken from the rectosigmoid junction. Mucosal BDNF expression and nerve fiber density were analyzed using immunohistochemistry. Mucosal BDNF mRNA levels were quantified by quantitative real-time polymerase chain reaction. Correlations between these parameters were examined.RESULTS The patients had a higher anxiety score [median(interquartile range), 6.0(2.0-10.0) vs 3.0(1.0-4.0), P = 0.003] and visceral sensitivity index score [54.0(44.0-61.0)vs 21.0(17.3-30.0), P < 0.001] than controls. The defecating sensation threshold[60.0(44.0-80.0) vs 80.0(61.0-100.0), P = 0.009], maximum tolerable threshold[103.0(90.0-128.0) vs 182.0(142.5-209.3), P < 0.001] and rectoanal inhibitory reflex threshold [30.0(20.0-30.0) vs 30.0(30.0-47.5), P = 0.032] were significantly lower in IBS-D patients. Intestinal mucosal BDNF protein [3.46 E-2(3.06 E-2-4.44 E-2) vs3.07 E-2(2.91 E-2-3.48 E-2), P = 0.031] and mRNA [1.57(1.31-2.61) vs 1.09(0.74-1.42), P = 0.001] expression and nerve fiber density [4.12 E-2(3.07 E-2-7.46 E-2) vs1.98 E-2(1.21 E-2-4.25 E-2), P = 0.002] were significantly elevated in the patients.Increased BDNF expression was positively correlated with abdominal pain and disease severity and negatively correlated with visceral sensitivity parameters.CONCLUSION Elevated mucosal BDNF may participate in the pathogenesis of IBS-D via facilitating mucosal nerve growth and increasing visceral sensitivity.
基金Supported by National Natural Science Foundation of China,No.81230024,No.81471137(to GYX)and No.31400947(to HHZ)Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘AIM:To investigate the roles of toll-like receptor 4(TLR4) and nuclear factor(NF)-κB on cystathionine βsynthetase(CBS) expression and visceral hypersensitivity in rats.METHODS:This study used 1-7-wk-old male SpragueDawley rats.Western blot analysis was employed to measure the expression of TLR4,NF-kB and the endogenous hydrogen sulfide-producing enzyme CBS in colon dorsal root ganglia(DRG) from control and "irritable bowel syndrome" rats induced by neonatal colonic inflammation(NCI).Colon-specific DRG neurons were labeled with Dil and acutely dissociated to measure excitability with patch-clamp techniques.Immunofluorescence was employed to determine the co-expression of TLR4,NF-kB and CBS in Dil-labeled DRG neurons.RESULTS:NCI significantly upregulated the expression of TLR4 in colon-related DRGs(0.34 ± 0.12 vs 0.72 ±0.02 for the control and NCI groups,respectively,P <0.05).Intrathecal administration of the TLR4-selective inhibitor CLI-095 significantly enhanced the colorectal distention threshold of NCI rats.CLI-095 treatment also markedly reversed the hyperexcitability of colonspecific DRG neurons and reduced the expression of CBS(1.7 ± 0.1 vs 1.1 ± 0.04,p < 0.05) and of the NF-kB subunit p65(0.8 ± 0.1 vs 0.5 ± 0.1,P< 0.05).Furthermore,the NF-KB-selective inhibitor pyrrolidine dithiocarbamate(PDTC) significantly reduced the upregulation of CBS(1.0 ± 0.1 vs 0.6 ± 0.1,P< 0.05)and attenuated visceral hypersensitivity in the NCI rats.In vitro,incubation of cultured DRG neurons with the TLR4 agonist lipopolysaccharide significantly enhanced the expression of p65(control vs 8 h:0.9 ± 0.1 vs1.3 ± 0.1;control vs 12 h:0.9 ± 0.1 vs 1.3 ± 0.1,P< 0.05;control vs 24 h:0.9 ± 0.1 vs 1.6 ± 0.1,P <0.01) and CBS(control vs 12 h:1.0 ± 0.1 vs 2.2 ±0.4;control vs 24 h:1.0 ± 0.1 vs 2.6 ± 0.1,P< 0.05),whereas the inhibition of p65 via pre-incubation with PDTC significantly reversed the upregulation of CBS expression(1.2 ± 0.1 vs 0.6 ± 0.0,P< 0.01).CONCLUSION:Our results suggest that the activation of TLR4 by NCI upregulates CBS expression,which is mediated by the NF-kB signaling pathway,thus contributing to visceral hypersensitivity.
基金the National Natural Science Foundation of China,No.81800489Shenzhen Health and Family Planning System Research Project,No.SZXJ2017030Technical Research and Development Project of Shenzhen,Nos.JCYJ20170307100538697 and JCYJ20170307100911479
文摘BACKGROUND Irritable bowel syndrome (IBS) is a common chronic non-organic disease of the digestive system. Berberine (BBR) has been used to treat patients with IBS, but the underlying therapeutic mechanism is little understood. We believe that BBR achieves its therapeutic effect on IBS by preventing stress intestinal inflammation and visceral hypersensitivity and reducing bowel motility. AIM To test the hypothesis that BBR achieves its therapeutic effect on IBS by preventing subclinical inflammation of the intestinal mucosa and reducing visceral hypersensitivity and intestinal motility. METHODS IBS was induced in rats via water avoidance stress (WAS). qRT-PCR and histological analyses were used to evaluate the levels of cytokines and mucosal inflammation, respectively. Modified ELISA and qRT-PCR were used to evaluate the nuclear factor kappa-B (NF-κB) signal transduction pathway. Colorectal distention test, gastrointestinal transit measurement, Western blot, and qRT-PCR were used to analyze visceral sensitivity, intestinal motility, the expression of Ckit (marker of Cajal mesenchymal cells), and the expression of brain derived neurotrophic factor (BDNF) and its receptor TrkB.RESULTS WAS led to mucosal inflammation, visceral hyperalgesia, and high intestinal motility. Oral administration of BBR inhibited the NF-κB signal transduction pathway, reduced the expression of pro-inflammatory cytokines [interleukin (IL)- 1β, IL-6, interferon-γ, and tumor necrosis factor-α], promoted the expression of anti-inflammatory cytokines (IL-10 and transforming growth factor-β), and improved the terminal ileum tissue inflammation. BBR inhibited the expression of BDNF, TrkB, and C-kit in IBS rats, leading to the reduction of intestinal motility and visceral hypersensitivity. The therapeutic effect of BBR at a high dose (100 mg/kg) was superior to than that of the low-dose (25 mg/kg) group. CONCLUSION BBR reduces intestinal mucosal inflammation by inhibiting the intestinal NF-κB signal pathway in the IBS rats. BBR reduces the expression of BDNF, its receptor TrkB, and C-kit. BBR also reduces intestinal motility and visceral sensitivity to achieve its therapeutic effect on IBS.
文摘AIM: To assess the protective effect of berberine administration and the role of nitric oxide (NO) in visceral hypersensitivity. METHODS: Fifty male Sprague-Dawley rats were randomly assigned to five groups. An inflammatory bowel disease model was induced in rats by intracolonic instillation of 1 mL 4% acetic acid at 8 cm proximal to the anus for 30 s and restraint stress. After subsidence of inflammation on day 7 of the experiment, the rats were subjected to rectal distension, performed by a balloon (6-Fr, 2 mm external diameter, disposable silicon balloon-urethral catheter for pediatric use) which was rapidly inflated with increasing volumes of prewarmed (37 ℃) water (0.1, 0.2, 0.3, 0.4, 0.6, 0.8 and 1 mL) for 30 s at four-minute intervals, and then the abdominal withdrawal reflex (AWR) and the level of fecal output were measured, respectively. AWR scores either 0, 1, 2, 3 or 4 were obtained by blinded observers. Rats had been pretreated with berberine or aminoguanidine (NO synthetase inhibitor) or berberine + aminoguanidine before measurement. RESULTS: The rats in the placebo group showed a hypersensitive response to rectal distension (2.69 ± 0.08 vs 1.52 ± 0.08, P = 0.000) and defecated more frequently than those in the control group (5.0 ± 0.16 vs 0.44 ± 0.16, P = 0.000). Comparing the berberine with placebo group, the AWR scores were reduced for all distension volumes and were significant at 0.2-1 mL (1.90 ± 0.08 vs 2.69 ± 0.08, P = 0.000), while the numbers of hard pellets, soft pellets, formless stools, and total fecal output in the placebo group were significantly larger than in the berberine group (5.0 ± 0.16 vs 2.56 ± 0.16, P = 0.000). Administration of aminoguanidine or berberine + aminoguanidine before VH score measurement reversed the antinociceptive effect of berberine (2.52 ± 0.08 vs 1.90 ± 0.08, P = 0.000; 2.50 ± 0.08 vs 1.90 ± 0.08, P = 0.000). The numbers of hard pellets, soft pellets, formless stool, and total of fecal output in aminoguanidine group were significantly larger than the corresponding values in control group, berberine group, and berberine + aminoguanidine group (4.81 ± 0.16 vs 0.44 ± 0.16, P = 0.000; 4.81 ± 0.16 vs 2.56 ± 0.16, P = 0.000; 4.81 ± 0.16 vs 3.75 ± 0.16, P = 0.000). The berberine and berberine + aminoguanidine groups showed reduced defecation, but aminoguanidine alone did not reduce defecation (2.56 ± 0.16 vs 4.81 ± 0.16, P = 0.000; 3.75 ± 0.16 vs 4.81 ± 0.16, P = 0.000). CONCLUSION: Berberine had an antinociceptive effect on visceral hypersensitivity, and NO might play a role in this effect.
基金Supported by Natural Science Foundation of China,No.81070308/H0308
文摘AIM: To explore the role of nesfatin-1 on irritable bowel syndrome (IBS)-like visceral hypersensitivity. METHODS: The animal model of IBS-like visceral hypersensitivity was induced by intracolonic infusion of 0.5% acetic acid (AA) in saline once daily from postnatal days 8-21. Experiments were performed when rats became adults. The visceral sensitivity of rats was evaluated by abdominal withdrawal reflex (AWR) and electromyographic (EMG) activity of the external oblique muscle to graded colorectal distension. The content of nesfatin-1 in serum was determined using enzyme-linked immunosorbent assay. After implantation of an intracerebroventricular (ICV) cannula and two electrodes into the external oblique muscle, model rats were randomly divided into four groups. Animals then received ICV injection of 8 μg of anti-nesfatin-1/ nucleobindin-2 (NUCB2), 50 μg of α-helical cortico-tropin releasing factor (CRF) 9-41 (non-selective CRF receptor antagonist), 50 μg of NBI-27914 (selective CRF1 receptor antagonist) or 5 μL of vehicle. After 1 h of ICV administration, visceral sensitivity of each group was measured again, and comparisons between groups were made. RESULTS: Rats treated with AA showed higher mean AWR scores and EMG activity at all distension pressures compared with controls (P < 0.05). On histopathologic examination, no evidence of inflammation or abnormalities in structure were noted in the colon of either control or AA-treated groups. Myeloperoxidase values were not significantly different between the two groups. The level of nesfatin-1 in serum was significantly higher in the AA-treated group than in the control group (5.34 ± 0.37 ng/mL vs 4.81 ± 0.42 ng/mL, P < 0.01). Compared with rats injected with vehicle, rats which received ICV anti-nesfatin-1/NUCB2, α-helical CRF9-41 or NBI-27914 showed decreased mean AWR scores and EMG activity at all distension pressures (P < 0.05). CONCLUSION: Nesfatin-1 may be associated with IBS-like visceral hypersensitivity, which may be implicated in brain CRF/CRF1 signaling pathways.
基金Supported by China Postdoctoral Science Foundation funded project,No.200801260,No.20080430117the National Basic Research Program of China 973 program,No.2009CB522900the Specialized Research Fund for the Doctoral Program of Higher Education No.20123107110008
文摘AIM: To investigate the effect of electroacupuncture on corticotropin-releasing hormone(CRH) in the colon, spinal cord, and hypothalamus of rats with chronic visceral hypersensitivity.METHODS: A rat model of chronic visceral hypersensitivity was generated according to the internationally accepted method of colorectal balloon dilatation. In the 7th week after the procedure, rats were randomly divided into a model group(MG), electroacupuncture group(EA), and sham electroacupuncture group(S-EA). After treatment, the abdominal withdrawal reflex(AWR) score was used to assess the behavioral response of visceral hyperalgesia. Immunohistochemistry(En Vision method), ELISA, and fluorescence quantitative PCR methods were applied to detect the expression of CRH protein and m RNA in the colon, spinal cord, and hypothalamus.RESULTS: The sensitivity of the rats to the colorectal distension stimulus applied at different strengths(20-80 mm Hg) increased with increasing stimulus strength, resulting in increasing AWR scores in each group. Compared with NG, the AWR score of MG was significantly increased(P < 0.01). After conducting EA, the AWR scores of the rats were decreased compared with MG rats. The relative expression of CRH m RNA in the colon, spinal cord, and hypothalamus of MG rats was significantly increased compared with NG rats(P < 0.01). CRH m RNA in the colon and spinal cord of EA and S-EA rats was decreased to varying degrees(P > 0.05) compared with normal rats(NG). However, the decrease in EA compared with MG rats was statistically significant(P < 0.01). The average optical density of CRH expression in the colon of the MG rats was significantly enhanced compared with NG(P < 0.05), while the average optical density of CRH expression in the EA and S-EA rats was significantly decreased compared with MG rats(P < 0.01, P < 0.05, respectively). Compared with MG rats, the CRH concentration in the spinal cord of EA rats was significantly reduced(P < 0.01), but there was no significant change in S-EA rats(P > 0.05).CONCLUSION: Electroacupuncture at the Shangjuxu acupoint was able to significantly reduce the visceral hypersensitivity in rats, and regulated the expression of CRH protein and m RNA in the colon, spinal cord and hypothalamus at different levels, playing a therapeutic role in this model of irritable bowel syndrome.
基金Supported by the National Key Technology Support Program during “12th Five-Year Plan”period of China,No.2014BAI08B00the Leapforward Development Program for Beijing Biopharmaceutical Industry(G20),No. Z171100001717008.
文摘BACKGROUND Visceral hypersensitivity and psychological performance are the main pathophysiological mechanisms of irritable bowel syndrome(IBS).Previous studies have found that cholecystokinin(CCK)can enhance colon movement and that serotonin transporter(SERT)is a transmembrane transport protein with high affinity for 5-hydroxytryptamine,which can rapidly reuptake 5-hydroxytryptamine and then regulate its action time and intensity.We speculate that SERT and CCK might play a role in the pathogenesis of diarrheapredominant IBS(IBS-D)by affecting visceral sensitivity and the brain-gut axis.AIM To determine SERT and CCK levels in IBS-D patients diagnosed using Rome IV criteria and to analyze their associations with abdominal pain,visceral hypersensitivity and psychological performance.METHODS This study collected data from 40 patients with IBS-D at the China-Japan Friendship Hospital from September 2017 to April 2018 and 18 healthy controls.The severity of abdominal pain,visceral sensitivity and psychological performance were evaluated in IBS-D patients and healthy controls,the levels of SERT and CCK in plasma and colonic mucosa were evaluated,and the correlations between them were analyzed.RESULTS There were significant differences in the initial sensation threshold(31.00±8.41 mL vs 52.22±8.09 mL,P<0.001),defecating sensation threshold(51.75±13.57 mL vs 89.44±8.73 mL,P<0.001)and maximum tolerable threshold(97.25±23.64 mL vs 171.11±20.83 mL,P<0.001)between the two groups.IBS-D patients had more severe anxiety(7.78±2.62 vs 2.89±1.02,P<0.001)and depressive(6.38±2.43 vs 2.06±0.73,P<0.001)symptoms than healthy controls.Significant differences were also found in mucosal CCK(2.29±0.30 vs 1.66±0.17,P<0.001)and SERT(1.90±0.51 vs 3.03±0.23,P<0.001)between the two groups.There was a significant positive correlation between pain scores and mucosal CCK(r=0.96,0.93,0.94,P<0.001).Significant negative correlations between anxiety(r=-0.98;P<0.001),depression(r=-0.99;P<0.001),pain evaluation(r=-0.96,-0.93,-0.95,P<0.001)and mucosal SERT were observed.CONCLUSION IBS-D patients had psychosomatic disorders and visceral hypersensitivity.SERT and CCK might be involved in the pathogenesis of IBS-D by regulating the braingut axis and affecting visceral sensitivity.This provides a new potential method for identifying a more specific and effective therapeutic target.
基金Supported by National Basic Research Program of China(973 Program)No.2009CB522900 and No.2015CB554501National Natural Science Foundation of China,No.30973784
文摘AIM To observe whether there are differences in the effects of electro-acupuncture(EA) and moxibustion(Mox) in rats with visceral hypersensitivity. METHODS EA at 1 m A and 3 m A and Mox at 43?℃ and 46?℃ were applied to the Shangjuxu(ST37, bilateral) acupoints in model rats with visceral hypersensitivity. Responses of wide dynamic range neurons in dorsal horns of the spinal cord were observed through the extracellular recordings. Mast cells(MC) activity in the colons of rats were assessed, and 5-hydroxytryptamine(5-HT), 5-hydroxytryptamine 3 receptor(5-HT3R) and 5-HT4Rexpressions in the colons were measured.RESULTS Compared with normal control group, responses of wide dynamic range neurons in the dorsal horn of the spinal cord were increased in the EA at 1 m A and 3 m A groups(1 m A: 0.84 ± 0.74 vs 2.73 ± 0.65, P < 0.001; 3 m A: 1.91 ± 1.48 vs 6.44 ± 1.26, P < 0.001) and Mox at 43?℃ and 46?℃ groups(43?℃: 1.76 ± 0.81 vs 4.14 ± 1.83, P = 0.001; 46?℃: 5.19 ± 2.03 vs 7.91 ± 2.27, P = 0.01). MC degranulation rates and the expression of 5-HT, 5-HT3 R and 5-HT4 R in the colon of Mox 46?℃ group were decreased compared with model group(MC degranulation rates: 0.47 ± 0.56 vs 0.28 ± 0.78, P < 0.001; 5-HT: 1.42 ± 0.65 vs 7.38 ± 1.12, P < 0.001; 5-HT3R: 6.62 ± 0.77 vs 2.86 ± 0.88, P < 0.001; 5-HT4R: 4.62 ± 0.65 vs 2.22 ± 0.97, P < 0.001). CONCLUSION The analgesic effects of Mox at 46?℃ are greater than those of Mox at 43?℃, EA 1 m A and EA 3 m A.
基金Supported by National Natural Science Foundation of China,No.81270469Key Medical Personnel of Jiangsu Province,No.RC2011063m
文摘AIM: To investigate the role of epidermal growth factor(EGF) in visceral hypersensitivity and its effect on the serotonin transporter(SERT).METHODS: A rat model for visceral hypersensitivity was established by intra-colonic infusion of 0.5% acetic acid in 10-d-old Sprague-Dawley rats. The visceral sensitivity was assessed by observing the abdominal withdrawal reflex and recording electromyographic activity of the external oblique muscle in response to colorectal distension. An enzyme-linked immunosorbent assay was used to measure the EGF levels in plasma and colonic tissues. SERT mRNA expression was detected by real-time PCR while protein level was determined by Western blot. The correlation between EGF and SERT levels in colon tissues was analyzed by Pearson's corre-lation analysis. SERT function was examined by tritiated serotonin(5-HT) uptake experiments. Rat intestinal epithelial cells(IEC-6) were used to examine the EGF regulatory effect on SERT expression and function via the EGF receptor(EGFR).RESULTS: EGF levels were significantly lower in th rats with visceral hypersensitivity as measured in plas ma(2.639 ± 0.107 ng/mL vs 4.066 ± 0.573 ng/mL, < 0.01) and in colonic tissue(3.244 ± 0.135 ng/10 mg vs 3.582 ± 0.197 ng/100 mg colon tissue, P 0.01) compared with controls. Moreover, the EGF leve were positively correlated with SERT levels(r = 0.820 P < 0.01). EGF displayed dose- and time-dependen increased SERT gene expressions in IEC-6 cells. A EGFR kinase inhibitor inhibited the effect of EGF o SERT gene upregulation. SERT activity was enhance following treatment with EGF(592.908 ± 31.515 fmo min per milligram vs 316.789 ± 85.652 fmol/min pe milligram protein, P < 0.05) and blocked by the EGF kinase inhibitor in IEC-6 cells(590.274 ± 25.954 fmo min per milligram vs 367.834 ± 120.307 fmol/min pe milligram protein, P < 0.05).CONCLUSION: A decrease in EGF levels may contribute to the formation of visceral hypersensitivity through downregulation of SERT-mediated 5-HT uptake into enterocytes.
基金Supported by National Natural Science Foundation of China,No.81072786the Innovation Program of the Shanghai Municipal Education Commission,No.12YZ065the Longhua Medical Project,No.D-09
文摘AIM:To evaluate the therapeutic effect of Shugan-decoction(SGD)on visceral hyperalgesia and colon gene expressions using a rat model.METHODS:Ninety-six adult male Wistar rats were randomized into six equal groups for assessment of SGD effects on psychological stress-induced changes using the classic water avoidance stress(WAS)test.Untreated model rats were exposed to chronic(1 h/d for 10 d consecutive)WAS conditions;experimental treatment model rats were administered with intragastric SGD at1 h before WAS on consecutive days 4-10(low-dose:0.1g/mL;mid-dose:0.2 g/mL;high-dose:0.4 g/mL);control treatment model rats were similarly administered with the irritable bowel syndrome drug,dicetel(0.0042g/mL);untreated normal control rats received no drug and were not subjected to the WAS test.At the end of the 10-d WAS testing period,a semi-quantitative measurement of visceral sensitivity was made by assessing the abdominal withdrawal reflex(AWR)to colorectal balloon-induced distension(at 5 mmHg increments)to determine the pain pressure threshold(PPT,evidenced by pain behavior).Subsequently,the animals were sacrificed and colonic tissues collected for assessment of changes in expressions of proteins related to visceral hypersensitivity(transient receptor potential vanilloid 1,TRPV1)and sustained visceral hyperalgesia(substance P,SP)by immunohistochemistry and real-time polymerase chain reaction.Inter-group differences were assessed by paired t test or repeated measures analysis of variance.RESULTS:The WAS test successfully induced visceral hypersensitivity,as evidenced by a significantly reduced AWR pressure in the untreated model group as compared to the untreated normal control group(190.4±3.48 mmHg vs 224.0±4.99 mmHg,P<0.001).SGD treatments at mid-dose and high-dose and the dicetel treatment significantly increased the WAS-reduced PPT(212.5±2.54,216.5±3.50 and 217.7±2.83 mmHg respectively,all P<0.001);however,the low-dose SGD treatment produced no significant effect on the WAS-reduced PPT(198.3±1.78 mmHg,P>0.05).These trends corresponded to the differential expressions observed for both TRPV1 protein(mid-dose:1.64±0.08 and high-dose:1.69±0.12 vs untreated model:3.65±0.32,P<0.001)and mRNA(0.44±0.16 and0.15±0.03 vs 1.39±0.15,P<0.001)and SP protein(0.99±0.20 and 1.03±0.23 vs 2.03±0.12,P<0.01)and mRNA(1.64±0.19 and 1.32±0.14 vs 2.60±0.33,P<0.05).These differential expressions of TRPV1 and SP related to mid-and high-dose SGD treatments were statistically similar to the changes induced by dicetel treatment.No signs of overt damage to the rat system were observed for any of the SGD dosages.CONCLUSION:Shugan-decoction can reduce chronic stress-induced visceral hypersensitivity in rats,and the regulatory mechanism may involve mediating the expressions of TRPV1 and SP in colon tissues.
基金supported by Natural Science Foundation of China Grant(No.81160057):International Science and Technique Corporation Foundation of Hainan Province Grant(No.KJHZ2013-14)
文摘Objective:To investigate the impact of the preinduced intestinal heat shock protein 70(HSP70)on the visceral hypersensitivity and abnormal intestinal motility in a post-infectious irritable bowel syndrome(PI-IBS) mouse model.Methods:Eighty-four female C57BL/6 mice were randomly assigned to four groups:control group(n=21) and induction+PI-IBS group(n=21),PI-IBS group(n=21) and induction group(n=21).The mice in PI-IBS group were infected in vivo with trichinella spiralis by oral administration.The visceral hypersensitivity and intestinal motility were evaluated respectively with abdominal withdrawal reflex and colon transportation test.The intestinal HSP70 protein and mRNA level was measured by Western blot and realtime PCR.Meanwhile,the intestinal proinflammatory cytokines IL-10 and TNF-α level was detected by ELISA.Results:Compared with their counterparts in PI-IBS group,the animals in the Induction+PI-IBS group show significantly increased intestinal level of HSP70 and obviously ameliorative clinical tigurcs.including abdominal withdrawal reflex score,intestine transportation time and Bristol scores(P<0.05).Meanwhile,the intestinal post-inflammatory cytokines remarkably changed,including increased IL-10 level and decreased TNF-αlevel(P<0.05).Conclusions:Intestinal IISP70 may play a potential protective role through improving the imbalance between the intestinal post-inflammatory and anti-inflammatory cytokines in PI-IBS.
基金the National Key Technology Support Program for the “12th Five-Year Plan” of China,No.2014BAI08B00the Research Projects on Biomedical Transformation of China-Japan Friendship Hospital,No.PYBZ1815
文摘BACKGROUND Fecal metabolites are associated with gut visceral sensitivity,mucosal immune function and intestinal barrier function,all of which have critical roles in the pathogenesis of irritable bowel syndrome(IBS).However,the metabolic profile and pathophysiology of IBS are still unclear.We hypothesized that altered profiles of fecal metabolites might be involved in the pathogenesis of IBS with predominant diarrhea(IBS-D).AIM To investigate the fecal metabolite composition and the role of metabolites in IBSD pathophysiology.METHODS Thirty IBS-D patients and 15 age-and sex-matched healthy controls(HCs)underwent clinical and psychological assessments,including the IBS Symptom Severity System(IBS-SSS),an Italian modified version of the Bowel Disease Questionnaire,the Bristol Stool Form Scale(BSFS),the Hospital Anxiety and Depression Scale,and the Visceral Sensitivity Index.Visceral sensitivity to rectal distension was tested using high-resolution manometry system by the same investigator.Fecal metabolites,including amino acids and organic acids,were measured by targeted metabolomics approaches.Correlation analyses between these parameters were performed.RESULTS The patients presented with increased stool water content,more psychological symptoms and increased visceral hypersensitivity compared with the controls.In fecal metabolites,His[IBS-D:0.0642(0.0388,0.1484),HC:0.2636(0.0780,0.3966),P=0.012],Ala[IBS-D:0.5095(0.2826,0.9183),HC:1.0118(0.6135,1.4335),P=0.041],Tyr[IBS-D:0.1024(0.0173,0.4527),HC:0.5665(0.2436,1.3447),P=0.018],Phe[IBS-D:0.1511(0.0775,0.3248),HC:0.3967(0.1388,0.7550),P=0.028],and Trp[IBS-D:0.0323(0.0001,0.0826),HC:0.0834(0.0170,0.1759),P=0.046]were decreased in IBS-D patients,but isohexanoate[IBS-D:0.0127(0.0060,0.0246),HC:0.0070(0.0023,0.0106),P=0.028]was significantly increased.Only Tyr was mildly correlated with BSFS scores in all subjects(r=-0.347,P=0.019).A possible potential biomarker panel was identified to correlate with IBS-SSS score(R2 Adjusted=0.693,P<0.001).In this regression model,the levels of Tyr,Val,hexanoate,fumarate,and pyruvate were significantly associated with the symptom severity of IBS-D.Furthermore,visceral sensation,including abdominal pain and visceral hypersensitivity,was correlated with isovalerate,valerate and isohexanoate.CONCLUSION Altered profiles of fecal metabolites may be one of the origins or exacerbating factors of symptoms in IBS-D via increasing visceral sensitivity.
文摘Abdominal obesity,rather than total amount of fat,is linked to obesity-related disorders.Visceral adiposity is an important component of obesity-related disorders in Japanese individuals with a mild degree of adiposity compared with Western subjects.In 1983,our group reported techniques for body fat analysis using computed tomography(CT)and established the concept of visceral fat obesity in which intra-abdominal fat accumulation is an important factor in the development of obesity-related complications,such as diabetes,lipid disorders,hypertension and atherosclerosis.Our group also established ideal imaging conditions for determining abdominal fat area at the umbilical level CT scan.Visceral fat area(VFA)measured in a single slice at L4level correlated significantly with the total abdominal visceral fat volume measured on multislice CT scan.In a large-scale study of a Japanese population,the mean number of obesity-related cardiovascular risk factors(hypertension,low high-density lipoprotein cholesterolemia and/or hypertriglyceridemia,and hyperglycemia)was greater than 1.0 at 100 cm2 of VFA,irrespective of gender,age and body mass index.Our group also demonstrated that reduction of visceral fat accumulation subsequent to voluntary lifestyle modification,"Hokenshido",correlated with a decrease in the number of obesity-related cardiovascular risk factors.It is important to select the most appropriate subjects from the general population(e.g.,non-obese subjects with a cluster of risk factors for the metabolic syndrome)that are most suitable for body weight reduction,with the goal of preventing atherosclerotic cardiovascular diseases.
