Cytotoxicity,in Vivo Skin Irritation and Acute Systemic Toxicity of the Mesoporous Magnesium Carbonate Upsalite^(█)

Upsalite®is a mesoporous magnesium carbonate synthesized without using surfactants and therefore highly attractive from environmental and production economy points of view. The material has recently been suggested as drug delivery vehicle and as topical bacteriostatic agent. In order to continue exploring these and other bio-related applications of the material, primary biocompatibility studies are needed. Herein we present the first in vivo acute systemic toxicity and skin irritation analyses as well as in vitro cytotoxicity evaluations of Upsalite®. The material was found to be non-toxic for human dermal fibroblasts cells up to a concentration of 1000 μg/ml and 48 h exposure in contrast to the mesoporous silica material SBA-15, used as reference, which significantly affected cell viability at particle concentration of 500 and 1000 μg/ml after the same exposure time. Topical application of Upsalite®resulted in negligible cutaneous reactions in a rabbit skin irritation model and no evidence of significant systemic toxicity was found when saline extracts of Upsalite®were injected in mice. Injection of sesame oil extract, however, resulted in transient weight loss, most likely due to injection of particles, and not toxic leachables. The presented results form the basis for future development of Upsalite®and similar mesoporous materials in biomedical applications and further toxicity as well as biocompatibility studies should be directed towards specific areas of use.

Evaluation of Dermal Irritation and Skin Sensitization by Curaderm

Purpose: To establish whether Curaderm, a topical pharmacotherapy for skin cancer, irritates or sensitizes normal skin. Methods: The dermal irritation and skin sensitization toxicity of Curaderm were investigated in rabbits and guinea pigs in compliance with the Organization for Economic Cooperation and Development guideline. To assess dermal irritation, rabbits were dermally exposed to Curaderm for varying periods of time. To assess hypersensitivity, the guinea-pig maximisation test was applied. Results: Curaderm was only negligibly irritating using the criteria of erythema and oedema. Curaderm did not produce any sensitization toxicity of the skin. Conclusion: These studies confirm the non-toxic observations on normal skin experienced in the clinical setting when treating skin cancer and reinforce the specificity of Curaderm towards cancer cells.

Evaluation of the Skin Irritation and Sensitization Potential of the Cussons Baby Sensicare Skin Range of Products in Healthy Volunteers

Introduction: The Cussons Baby Sensicare Range is a newly developed set of products specially formulated for newborn, sensitive and eczema prone skin. As such, these products need to be tested to evaluate their skin irritation and sensitization potential before use. The products were evaluated with two separate tests. The first test was conducted in a single-center, within-subject comparison using assessor-blind, randomised human skin irritation patch test (48 hour/96 hour exposure) and conducted on healthy adults with sensitive, atopic skin. The second test was conducted in a single-center, controlled (sterile water), within subject using human repeat-insult patch tests (HRIPTs) and conducted on healthy female Indonesian and Asian adult female subjects, with sensitive skin. The sensitization potential of each product was determined from International Contact Dermatitis Research Group (ICDRG) scores at 30 minutes, 24 hours, 48 hours and 72 hours after patch removal. Skin irritation tests show that all products were significantly lower than the positive control sodium lauryl sulphate (SLS) (p < 0.05) but not significantly different to the negative control (sterile water) in terms of irritation scores at the respective time points. HRIPTs results show that Cussons Baby Sensicare Range was non-sensitizing. As such, it can be concluded that the Cussons Baby Sensicare Range tested is well tolerated on skin and has low skin irritation and sensitization potential. Thus, they can be considered hypoallergenic on sensitive skin and suitable for eczema prone skin.

In Vitro Assessment of Irritation Potential of an Anti-Melanogenic Agent,PF3758309,in a Reconstructed Human Epidermis Model

Purpose:This study was designed to determine whether a novel anti-melanogenic agent,PF3758309,has the potential to cause acute cutaneous irritation using a human skin equivalent model (HSEM).Methods:Human skin equivalent was constructed through incubation of normal human derived epidermal keratinocytes (HEKs)on collagen matrix insert with proliferation media.Using constructed human skin equivalent,the irritation potential of PF3758309 were investigated whether the viability of this agent-treated HESM is under 50%(irritant)or not (non-irritant)using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)assay after applying the agent to the epidermal surface of the HSEM.Also,the PF3758309-mediated anti-pigmentation effects were analyzed using Fontana-Masson staining in the HSEM.Results:The integrity of the constructed HSEM was confirmed using immunohistochemical staining with differentiation markers of epidermis,and observed that Keratin 5,Keratin I and Involucrin were stained in basal,supra-basal and granular layers,respectively.In vitro irritation assay showed that the mean viabilities of the PF3758309 was 83.6%,78.8%and 77.8%at the treatment doses of 0.2,0.5 and I mg,respectively;however,the mean viability of the positive control (5%sodium dodecyl sulfate)-treated HESM was 2.8%.Also,in vitro corrosion assay showed that the mean viabilities of the PF3758309 was 95.3%,95.0%and 94.2% at the treatment doses of 0.2,0.5 and 1 mg,respectively.Furthermore,using a Fontana-Masson staining assay,the melanin levels in the PF3758309-treated HSEM was significantly decreased compared with the levels in control HSEM.Conclusion: The anti-melanogenic agent,PF3758309,has no skin irritation potential under the conditions used in this study.

Differential effects of glutamate receptor antagonists on dorsal horn neurons responding to colorectal distension in a neonatal colon irritation rat model

AIM: To investigate and compare the effects of spinal D-(-)-2-amino-7-phosphonoheptanoic acid (AP-7) and 6-cyano-7-nitroquinoxaline-2,3-dione disodium (CNQX),two glutamate receptor antagonists, on the responses of dorsal horn neurons to colorectal distension (CRD) in adult rats exposed to neonatal colon irritation (CI).METHODS: Hypersensitive SD rats were generated by CI during postnatal days 8, 10 and 12. Experiments on adult rats were performed using extracellular single-unit recording. The effects of spinal application of AP-7 (0.001,0.01, 0.1, 1 mmoL) were tested on the CRD-evoked neuronal responses in 16 controls and 17 CI rats. The effects of CNQX (0.2, 2, 5, 10 μmoL) were also tested on the CRD-evoked responses of 17 controls and 18 CI neurons.RESULTS: (1) The average responses of lumbosacral neurons to all intensities of CRD in CI rats were significantly higher than those in control rats; (2) In control rats, AP-7 (0.01 mmoL) had no significant effect on the neuronal response to all intensities of CRD (20,40, 60, 80 mmHg); while AP-7 (0.1 mmoL) inhibited the neuronal response to 80-mmHg CRD. By contrast, in CI rats, AP-7 (0.01-1 mmoL) attenuated the CRD-evoked neuronal responses to all distention pressures in a dosedependent manner; (3) In control rats, CNQX (2 μmoL)had no significantly effect on the neuronal response to all intensities of CRD; however, CNQX (5 μmoL) significantly attenuated the responses to CRD in the 40-80 mmHg range. By contrast, CNQX (2-10 μmoL)significantly decreased the neuronal responses in CI rats to non-noxious and noxious CRD in a dose-dependent manner.CONCLUSION: Our results suggest that spinal N-methyl-D-aspartate (NMDA) and non-NMDA receptors may contribute to the processing of central sensitivity in a neonatal CI rat model, but they may play different roles in it.

Research on strategies for reducing the irritability of potassium cocoyl glycinate in cleansing

Background:Potassium cocoyl glycinate,a kind of amino acid surfactant,is widely used as major component for facial cleansing.However,the interaction between surfactants and compounds in the stratum corneum has been suggested as a contributing factor to their potential skin irritancy.Objective:This study aimed to the effects of adding surfactants,polymers,lipids and active substances on diminishing skin irritation caused by potassium cocoyl glycinate.Materials and methods:Zein test and Hemolysis test enabled the identification of irritation to proteins and cells in the studied binary systems.The critical micelle concentration(CMC)was evaluated by the surface tension method.The power of the analyzed polymers to diminish irritation of potassium cocoyl glycinate was represented by the reduction rate.Results:(1)Amphoteric surfactants and nonionic surfactants are effective at reducing the irritation of potassium cocoyl glycinate in some cases by reducing CMC;(2)Addition of polymers to the potassium cocoyl glycinate solutions improves its safety of use.Hydroxypropyl methylcellulose could reduce the irritation by 88.63%;(3)Combining most lipids can assist in declining the irritation,Lppg-28-Buteth-35 could inhibit the irritation of red blood cells by 16.52%;(4)The effects of active substances varied,hydrolyzed sodium hyaluronate results in a significant reduction in irritation to cells.Conclusion:In facial cleansers based on potassium cocoyl glycinate,supplying co-surfactant,polymers,lipids and active substances can reduce the irritation to some extent,however,the effects are various.

Chitin-glucan improves important pathophysiological features of irritable bowel syndrome

BACKGROUND Irritable bowel syndrome(IBS)is one of the most frequent and debilitating conditions leading to gastroenterological referrals.However,recommended treatments remain limited,yielding only limited therapeutic gains.Chitin-glucan(CG)is a novel dietary prebiotic classically used in humans at a dosage of 1.5-3.0 g/d and is considered a safe food ingredient by the European Food Safety Authority.To provide an alternative approach to managing patients with IBS,we performed preclinical molecular,cellular,and animal studies to evaluate the role of chitin-glucan in the main pathophysiological mechanisms involved in IBS.AIM To evaluate the roles of CG in visceral analgesia,intestinal inflammation,barrier function,and to develop computational molecular models.METHODS Visceral pain was recorded through colorectal distension(CRD)in a model of long-lasting colon hypersensitivity induced by an intra-rectal administration of TNBS[15 milligrams(mg)/kilogram(kg)]in 33 Sprague-Dawley rats.Intracolonic pressure was regularly assessed during the 9 wk-experiment(weeks 0,3,5,and 7)in animals receiving CG(n=14)at a human equivalent dose(HED)of 1.5 g/d or 3.0 g/d and compared to negative control(tap water,n=11)and positive control(phloroglucinol at 1.5 g/d HED,n=8)groups.The anti-inflammatory effect of CG was evaluated using clinical and histological scores in 30 C57bl6 male mice with colitis induced by dextran sodium sulfate(DSS)administered in their drinking water during 14 d.HT-29 cells under basal conditions and after stimulation with lipopolysaccharide(LPS)were treated with CG to evaluate changes in pathways related to analgesia μ-opioid receptor(MOR),cannabinoid receptor 2(CB2),peroxisome proliferator-activated receptor alpha,inflammation[interleukin(IL)-10,IL-1b,and IL-8]and barrier function[mucin 2-5AC,claudin-2,zonula occludens(ZO)-1,ZO-2]using the real-time PCR method.Molecular modelling of CG,LPS,lipoteichoic acid(LTA),and phospholipomannan(PLM)was developed,and the ability of CG to chelate microbial pathogenic lipids was evaluated by docking and molecular dynamics simulations.Data were expressed as the mean±SEM.RESULTS Daily CG orally-administered to rats or mice was well tolerated without including diarrhea,visceral hypersensitivity,or inflammation,as evaluated at histological and molecular levels.In a model of CRD,CG at a dosage of 3 g/d HED significantly decreased visceral pain perception by 14%after 2 wk of administration(P<0.01)and reduced inflammation intensity by 50%,resulting in complete regeneration of the colonic mucosa in mice with DSS-induced colitis.To better reproduce the characteristics of visceral pain in patients with IBS,we then measured the therapeutic impact of CG in rats with TNBS-induced inflammation to long-lasting visceral hypersensitivity.CG at a dosage of 1.5 g/d HED decreased visceral pain perception by 20%five weeks after colitis induction(P<0.01).When the CG dosage was increased to 3.0 g/d HED,this analgesic effect surpassed that of the spasmolytic agent phloroglucinol,manifesting more rapidly within 3 wk and leading to a 50%inhibition of pain perception(P<0.0001).The underlying molecular mechanisms contributing to these analgesic and anti-inflammatory effects of CG involved,at least in part,a significant induction of MOR,CB2 receptor,and IL-10,as well as a significant decrease in pro-inflammatory cytokines IL-1b and IL-8.CG also significantly upregulated barrier-related genes including muc5AC,claudin-2,and ZO-2.Molecular modelling of CG revealed a new property of the molecule as a chelator of microbial pathogenic lipids,sequestering gram-negative LPS and gram-positive LTA bacterial toxins,as well as PLM in fungi at the lowesr energy conformations.CONCLUSION CG decreased visceral perception and intestinal inflammation through master gene regulation and direct binding of microbial products,suggesting that CG may constitute a new therapeutic strategy for patients with IBS or IBSlike symptoms.

Immune cell signatures and causal association with irritable bowel syndrome:A mendelian randomization study

BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(IBS).Prior studies linking immune inflammation with IBS have been inconsistent.To further elucidate this relationship,we conducted a Mendelian randomization(MR)analysis of 731 immune cell markers to dissect the influence of various immune phenotypes on IBS.Our goal was to deepen our understanding of the disrupted brain-gut axis in IBS and to identify novel therapeutic targets.AIM To leverage publicly available data to perform MR analysis on 731 immune cell markers and explore their impact on IBS.We aimed to uncover immunophenotypic associations with IBS that could inform future drug development and therapeutic strategies.METHODS We performed a comprehensive two-sample MR analysis to evaluate the causal relationship between immune cell markers and IBS.By utilizing genetic data from public databases,we examined the causal associations between 731 immune cell markers,encompassing median fluorescence intensity,relative cell abundance,absolute cell count,and morphological parameters,with IBS susceptibility.Sensitivity analyses were conducted to validate our findings and address potential heterogeneity and pleiotropy.RESULTS Bidirectional false discovery rate correction indicated no significant influence of IBS on immunophenotypes.However,our analysis revealed a causal impact of IBS on 30 out of 731 immune phenotypes(P<0.05).Nine immune phenotypes demonstrated a protective effect against IBS[inverse variance weighting(IVW)<0.05,odd ratio(OR)<1],while 21 others were associated with an increased risk of IBS onset(IVW≥0.05,OR≥1).CONCLUSION Our findings underscore a substantial genetic correlation between immune cell phenotypes and IBS,providing valuable insights into the pathophysiology of the condition.These results pave the way for the development of more precise biomarkers and targeted therapies for IBS.Furthermore,this research enriches our comprehension of immune cell roles in IBS pathogenesis,offering a foundation for more effective,personalized treatment approaches.These advancements hold promise for improving IBS patient quality of life and reducing the disease burden on individuals and their families.

Physicochemical Properties and Gastric Mucosa Irritation of Cantharidin-hydroxypropyl-β-cyclodextrin Inclusion Complex

Objective To increase the solubility and relieve the mucous irritation of cantharidin (CA) by preparing cantharidin-hydroxypropyl-β-cyclodextrin (CA/HP-β-CD) inclusion complex. Methods The inclusion complex was prepared by co-evaporation method and characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and nuclear magnetic resonance (NMR). Results The disappearance of CA as well as the shift of exothermic peaks shown in DSC results indicated the complexation phenomenon. XRD results showed that the crystalline CA pattern had disappeared, and in NMR results, H-5 shifted from δ 3.731 to 3.695 after complexation and H-2 shifted from δ 3.626 to 3.598, which suggested that part of the drug had entered the HP-β-CD cavity to form an inclusion complex. The solubility increased 10.3 times after complexation and the mucous irritation of CA was relieved remarkably. Conclusion Through complexation with HP-β-CD, the solubility and dissolution rate of CA are improved significantly, and the irritation of musous is relieved.

A target lipidomics approach to investigate the acute inflammatory irritation induced by indolealkylamines from Chansu water fraction in rats

Chansu has demonstrated adverse reactions in clinical settings,which is associated with its toxicity and limits its clinical applications.But there are methodological limitations for drug safety evaluation.In the current study,ultra-high performance liquid chromatography,lipidomic profiling,and molecular docking were used to systemically assess Chansu-induced acute inflammatory irritation and further identify the underlying drug targets.Compared with the EtOAc extract,Chansu water fraction containing indolealkylamines caused acute inflammatory irritation in rats,including acute pain(spontaneous raising foot reaction),and inflammation(paw edema).At the molecular level,lipids analysis revealed significantly higher levels of pro-inflammatory mediators of the COX and LOX pathways.However,anti-inflammatory mediators from the CYP 450,ALA,and DHA pathways markedly decreased after exposure to Chansu water fraction.Moreover,four indolealkylamines from Chansu showed a high theoretical affinity to a known irritation target,5-HT_(2A)R.These results suggest that Chansu-induced inflammatory irritation is related to the distinct dysregulation of inflammatory lipids,and peripheral 5-HT_(2A)R is a potential target for irritation therapy.The strategy used in this study can be a crucial approach in the safety evaluation of natural medicinal substances.

Needle-free injection of insulin powder: delivery efficiency and skin irritation assessment

Insulin is widely used in treating diabetes, but still needs to be administered by needle injection. This study investigated a new needle-free approach for insulin delivery. A portable powder needleless injection（PNI） device with an automatic mechanical unit was designed. Its efficiency in delivering insulin was evaluated in alloxan-induced diabetic rabbits. The skin irritation caused by the device was investigated and the results were analyzed in relation to aerodynamic parameters. Inorganic salt-carried insulin powders had hypoglycemic effects, while raw insulin powders were not effective when delivered by PNI, indicating that salt carriers play an important role in the delivery of insulin via PNI. The relative delivery efficiency of phosphate-carried insulin powder using the PNI device was 72.25%. A safety assessment test showed that three key factors（gas pressure, cylinder volume, and nozzle distance） were related to the amount of skin irritation caused by the PNI device. Optimized injection conditions caused minimal skin lesions and are safe to use in practice. The results suggest that PNI has promising prospects as a novel technology for delivering insulin and other biological drugs.

Associations of daily sedentary behavior,physical activity,and sleep with irritable bowel syndrome:A prospective analysis of 362,193 participants

Background:Irritable bowel syndrome(IBS)substantially affects quality of life and requires early prevention.This study aimed to elucidate the relationships between IBS and daily behaviors,including sedentary behavior(SB),physical activity(PA),and sleep.In particular,it seeks to identify healthy behaviors to reduce IBS risk,which previous studies have rarely addressed.Methods:Daily behaviors were retrieved from self-reported data of 362,193 eligible UK Biobank participants.Incident cases were determined by self-report or health care data according to RomeⅣcriteria.Results:A total of 345,388 participants were IBS-free at baseline,during a median follow-up of 8.45 years,19,885 incident IBS cases were recorded.When examined individually,SB and shorter(≤7 h/day)or longer(>7 h/day)sleep duration were each positively associated with increased IBS risk,and PA was associated with lower IBS risk.The isotemporal substitution model suggested that replacing SB with other activities could provide further protective effects against IBS risk.Among people sleeping≤7 h/day,replacing 1 h of SB with equivalent light PA,vigorous PA,or sleep was associated with 8.1%(95%confidence interval(95%CI):0.901-0.937),5.8%(95%CI:0.896-0.991),and 9.2%(95%CI:0.885-0.932)reduced IBS risk,respectively.For people sleeping>7 h/day,light and vigorous PA were associated with a 4.8%(95%CI:0.926-0.978)and a 12.0%(95%CI:0.815-0.949)lower IBS risk,respectively.These benefits were mostly independent of genetic risk for IBS.Conclusion:SB and unhealthy sleep duration are risk factors for IBS.A promising way to mitigate IBS risk for individuals sleeping≤7 h/day and for those sleeping>7 h/day appears to be by replacing SB with adequate sleep or vigorous PA,respectively,regardless of the genetic predisposition of IBS.

Lactobacillus plantarum AR495 improves stress-induced irritable bowel syndrome in rats by targeting gut microbiota and Mast cell-PAR2-TRPV1 signaling pathway

Probiotics have great potential in regulating intestinal pain.In this study,the effects of Lactobacillus plantarum AR495 on the visceral sensitivity and gut microbiota of irritable bowel syndrome(IBS)rats were studied.The results showed that tryptase released after mast cell activation and degranulation plays a key role in visceral pain,and L.plantarum AR495 reduced the stimulation of colonic mast cells and the expression of protease-activated receptor 2(PAR2)and TRPV1 in dorsal root ganglia.Research further showed that supplementation with L.plantarum AR495 increased the level of short-chain fatty acids(SCFAs)and enhanced the barrier function of the colon.In addition,the microbiota analysis of the colon indicated that L.plantarum AR495 promoted the proliferation of Bifidobacterium and inhibited the proliferation of Lachnospiraceae,which alleviated the imbalance of the intestinal microbiota caused by IBS to a certain extent.In total,L.plantarum AR495 might reduce visceral sensitivity through the Mast cell-PAR2-TRPV1 signaling pathway by maintaining the homeostasis of the intestinal barrier.

Correlation between the neuroendocrine axis,microbial species,inflammatory response,and gastrointestinal symptoms in irritable bowel syndrome

BACKGROUND This study examines the complex relationships among the neuroendocrine axis,gut microbiome,inflammatory responses,and gastrointestinal symptoms in patients with irritable bowel syndrome(IBS).The findings provide new insights into the pathophysiology of IBS and suggest potential therapeutic targets for improving patient outcomes.AIM To investigate the interactions between the neuroendocrine axis,gut microbiome,inflammation,and gastrointestinal symptoms in patients with IBS.METHODS Patients diagnosed with IBS between January 2022 and January 2023 were selected for the study.Healthy individuals undergoing routine check-ups during the same period served as the control group.Data were collected on neuroendocrine hormone levels,gut microbiome profiles,inflammatory biomarkers,and gastrointestinal symptomatology to analyze their interrelations and their potential roles in IBS pathogenesis.RESULTS IBS patients exhibited significant dysregulation of the neuroendocrine axis,with altered levels of cortisol,serotonin,and neuropeptides compared to healthy controls.The gut microbiome of IBS patients showed reduced diversity and specific alterations in bacterial genera,including Bifidobacterium,Lactobacillus,and Faecalibacterium,which were associated with neuroendocrine disturbances.Additionally,elevated levels of inflammatory markers,such as C-reactive protein,interleukin-6,and tumor necrosis factor-α,were observed and correlated with the severity of gastrointestinal symptoms like abdominal pain,bloating,and altered bowel habits.CONCLUSION The findings suggest that targeting the neuroendocrine axis,gut microbiome,and inflammatory pathways may offer novel therapeutic strategies to alleviate symptoms and improve the quality of life in IBS patients.

Fecal microbiota transplantation for irritable bowel syndrome:Current evidence and perspectives

In this editorial we comment on the article published in the recent issue of the World journal of Gastroenterology.We focus specifically on the mechanisms underlying the effects of fecal microbiota transplantation(FMT)for irritable bowel syndrome(IBS),the factors which affect the outcomes of FMT in IBS patients,and challenges.FMT has emerged as a efficacious intervention for clostridium difficile infection and holds promise as a therapeutic modality for IBS.The utilization of FMT in the treatment of IBS has undergone scrutiny in numerous randomized controlled trials,yielding divergent outcomes.The current frontier in this field seeks to elucidate these variations,underscore the existing knowledge gaps that necessitate exploration,and provide a guideline for successful FMT implementation in IBS patients.At the same time,the application of FMT as a treatment for IBS confronts several challenges.

Diagnostic Accuracy of Computerized Bowel Sound Analysis with Non-Invasive Devices for Irritable Bowel Syndrome:A Systematic Review and Meta-Analysis

Objective To assess the diagnostic accuracy of bowel sound analysis for irritable bowel syndrome(IBS)with a systematic review and meta-analysis.Methods We searched MEDLINE,Embase,the Cochrane Library,Web of Science,and IEEE Xplore databases until September 2023.Cross-sectional and case-control studies on diagnostic accuracy of bowel sound analysis for IBS were identified.We estimated the pooled sensitivity,specificity,positive likelihood ratio,negative likeli-hood ratio,and diagnostic odds ratio with a 95% confidence interval(CI),and plotted a summary receiver operat-ing characteristic curve and evaluated the area under the curve.Results Four studies were included.The pooled diagnostic sensitivity,specificity,positive likelihood ratio,nega-tive likelihood ratio,and diagnostic odds ratio were 0.94(95%CI,0.87‒0.97),0.89(95%CI,0.81‒0.94),8.43(95%CI,4.81‒14.78),0.07(95%CI,0.03‒0.15),and 118.86(95%CI,44.18‒319.75),respectively,with an area under the curve of 0.97(95%CI,0.95‒0.98).Conclusions Computerized bowel sound analysis is a promising tool for IBS.However,limited high-quality data make the results'validity and applicability questionable.There is a need for more diagnostic test accuracy studies and better wearable devices for monitoring and analysis of IBS.

Unveiling the intricacies of irritable bowel syndrome

Irritable bowel syndrome(IBS)remains a challenging condition both for patients and clinicians,characterized by its chronic nature and the elusive complexity of its underlying mechanisms.The multifaceted relationship between the neuroendocrine axis,gut microbiota,and inflammatory response has emerged as a focal point in recent research,offering new insights into the pathophysiology of IBS.The neuroendocrine axis plays a crucial role in maintaining the delicate balance between the brain and the gut,often referred to as the“gut-brain axis”.This bidirectional communication is essential for regulating gastrointestinal function,stress responses,and overall homeostasis.Dysregulation of this axis,as highlighted by elevated cortisol and serotonin levels in IBS patients,suggests that neuroendocrine imbalances may significantly contribute to the severity of gastrointestinal symptoms.These findings underscore the need for a broader understanding of how stress and emotional factors influence IBS,potentially guiding more effective,personalized treatment approaches.Equally important is the role of the gut microbiota,a diverse and dynamic ecosystem that directly impacts gut health.This dysbiosis disrupts gut function and appears to exacerbate the neuroendocrine and inflammatory responses.These findings align with the growing recognition that gut microbiota is a critical player in IBS,influencing both the disease's onset and progression.

Alleviative effects of Bacillus coagulans strains on irritable bowel syndrome-unraveling strain specificity through physiological and genomic analysis

The high intraspecies heterogeneity of Baciillus coagulans leads to significant phenotypic differences among different strains.Thus,6 B.coagulans strains were tested in the present study using an irritable bowel syndrome(IBS)animal model to determine whether the IBS-alleviating effects of B.coagulans strains are strain-specific.The results of this study showed that the ingestion of B.coagulans GBI-30,6086,and B.coagulans CCFM1041 significantly alleviated IBS symptoms in mice.In contrast,other B.coagulans strains showed no or limited alleviating effects on IBS symptoms.According to our experimental results,the two main common features of these strains were as follows:1)The resistance of vegetative cells to bile salts,and 2)ability to synthesize specific lipids and secondary metabolites.Screening strains based on these two indicators may greatly reduce costs and provide a basis for mining new functional B.coagulans strains.Our results also suggest that administration of B.coagulans could significantly regulate microbiota dysbiosis in animal models.Moreover,the close relationships between the gut microbiota,gut microbiota metabolites,and IBS were further confirmed in this study.

Serotonin receptor 2B induces visceral hyperalgesia in rat model and patients with diarrhea-predominant irritable bowel syndrome

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.

Based on network pharmacology,molecular docking and experimental validation to reveal the potential molecular mechanism of quercetin for the treatment of diarrheal irritable bowel syndrome

Objective:To explore the potential mechanism of action of quercetin in the treatment of diarrhea irritable bowel syndrome(IBS-D).Methods:The potential targets of quercetin were obtained from the TCMSP,SwissTar-getPrediction,and BATMAN-TCM databases.The targets of IBS-D were obtained by searching the GeneCards database with"diarrhea irritable bowel syndrome"as the keyword,and the targets of quercetin and IBS-D were intersected.The PPI network was constructed by Cytoscape 3.7.1 software.The intersected targets were imported into the DAVID database for GO functional analysis and KEGG pathway enrichment analysis.The binding ability of quercetin to the core targets was observed using molecular docking.Based on this,we established an IBS-D rat model,administered quercetin for intervention,and experimentally validated the network pharmacology prediction results by HE staining and ELISA assay.Results:Network pharmacology analysis showed that TP53,TNF-α,AKT1,VEGF-A,IL-6 factors and MAPK,PI3K-Akt signaling pathway as the core targets and pathways of quercetin for the treatment of IBS-D.The results of animal experiments revealed that quercetin could inhibit the secretion of TP53,TNF-α,AKT1,VEGF-A,IL-1βand IL-6,reduce the inflammatory response and improve IBS-D.Conclusion:Quercetin could protect colon tissue by regulating the expression of TP53,TNF-α,AKT1,VEGF-A,IL-1βand IL-6,thereby treating IBS-D.