Gastric precancerous lesions (GPLs) are critical stages in gastric carcinogenesis, where early and precise identification and intervention are pivotal for improving patient prognosis. Recent advancements in artificial intelligence (AI) and organoid technology have revolutionized GPL research, with their synergistic applications progressively overcoming limitations of traditional methodologies. This review systematically summarizes the latest progress in AI and organoid technology for GPLs, focusing on mechanistic exploration, diagnostic optimization, and therapeutic innovation. We highlight how AI enhances diagnostic accuracy in endoscopy and pathology, while organoids provide unparalleled models for studying disease progression and drug screening. Critically, we discuss the pioneering integration of both technologies, wherein AI analyzes dynamic organoid phenotypes and fuses multimodal data for risk prediction. Current challenges hindering clinical translation, such as data standardization and model interpretability, are critically examined. We conclude that the future of GPL management lies in harnessing this synergy through interdisciplinary collaboration, which is poised to bridge the bench-to-bedside gap and usher in a new paradigm of mechanism-based precision prevention for gastric cancer.
ETHNOPHARMACOLOGICAL RELEVANCE:Functional dyspepsia (FD) is a common functional gastrointestinal disease. Chaihu-Shugan-San (CSS), a classical traditional Chinese medicine (TCM) formula from the Ming Dynasty "Jingyue Quanshu". Clinical evidence suggests that CSS is a highly effective therapeutic approach for the treatment of FD, however, its therapeutic mechanism for FD has not been fully clarified. AIM OF THE STUDY:The present study aimed to explore the potential mechanism of CSS in treating FD from the perspective of disorders of gut-brain interaction (DGBI). MATERIALS AND METHODS:The FD rat model was established via modified tail-clamp stimulation combined with gavage, followed by 4 weeks of CSS decoction intervention. An open-field test (OFT) was used to assess anxiety-like behaviors, gastric emptying rate was measured to evaluate gastrointestinal motility function, and spinal cord c-fos expression was detected to reflect visceral hypersensitivity. Hematoxylin and eosin (HE) staining was employed to clarify gastric tissue pathological changes, while transmission electron microscopy was performed to examine the microstructural integrity of nerve cells, synaptic clefts, and synaptic vesicles. Quantitative targeted metabolomics was used to screen potential metabolites involved in gut-brain interaction. C-fos was evaluated through immunohistochemistry. Ionized calcium-binding adapter molecule 1 (Iba1) and NADPH oxidase 2 (NOX2), Excitatory amino acid transporters (EAAT2) and Vesicular Glutamate Transporter 1 (VGLUT1) in the amygdala were evaluated through multiple immunofluorescences, quantitative real-time polymerase chain reaction (qPCR), and Western blot were applied to analyze the expression levels of proteins and mRNA in the NMDAR/CaMKII pathway in the gastric antrum and spinal cords. RESULTS:We identified 607 bioactive components, with 129 detected in serum and 134 in the cerebral cortex, confirming systemic exposure and cerebral penetration of key constituents. FD rats exhibited lower gastric motility, and immunohistochemistry showed strong activation of c-fos, a marker of hypersensitivity. CSS improved the gastric emptying rate and alleviated central sensitization. Fecal metabolomics revealed that CSS treats FD by regulating Linoleic acid metabolism, Cyanoamino acid metabolism, and Glycine, serine, and threonine metabolism. Serum Metabolomics revealed that CSS treats FD by regulating alanine, aspartate, and glutamate metabolism. After CSS treatement, Iba1 and NOX2 in the amygdala decreased compared to the FD rats, indicating the inhibition of central sensitization. CSS increased the levels of postsynaptic density protein 95 (PSD95), EAAT2 and VGLUT1 in the amygdala and spinal cord, and reducing the protein levels of Calcium-calmodulin-dependent protein kinase II (CaMKII), N-methyl-d-aspartate receptors (NMDAR), and Interleukin-1β (IL-1β) in the spinal cord. Correlation analysis also showed that CSS treatment significantly modulated the glutamate metabolic pathway in FD rats. CONCLUSION:These findings demonstrate that CSS ameliorates FD by inhibiting central sensitization - related activity and modulating glutamate metabolism, potentially mediated by the NMDAR/CaMKII signaling pathway.
Liu et al recently published research suggesting that multistrain probiotics significantly relieved bismuth quadruple therapy (BQT)-associated gastrointestinal symptoms without affecting eradication success. They conducted a rigorous randomized, double-blind, placebo-controlled trial, demonstrating that a 4-week regimen of a multistrain probiotic supplement significantly reduced symptoms such as reflux, dyspepsia, and diarrhea. The reduction in side effects and enhanced patient comfort highlight the clinical utility of probiotics as a safe and well-tolerated adjunct to BQT. Our contribution was about to involve the traditional Chinese medicine treating Helicobacter pylori -related chronic gastritis. They can have similar functions in regulating gut microbiota. Future research should build on this foundation to refine probiotic formulations, explore their long-term effects, and clarify their role in achieving higher eradication rates.
Objective: This multi-center, randomized, double-blind, placebo-controlled study aimed to evaluate the clinical efficacy and safety of Elian Granule in treating chronic atrophic gastritis (CAG). Methods: Over a 24-week period, 240 CAG patients were randomized to receive either Elian Granule or placebo. Primary outcomes included histological improvement of gastric mucosa via biopsy, while secondary outcomes assessed dyspepsia symptom scores and quality of life (QOL) scores. Safety was monitored through physical examinations, laboratory tests (blood and urine tests, liver function, and renal function), and electrocardiograms (ECGs). Results: The Elian Granule group exhibited significantly higher improvement rates in gastric mucosal atrophy (76.29% vs. 48.96%, P < 0.001) and intestinal metaplasia (62.89% vs. 34.38%, P < 0.001) compared to the placebo group. Total dyspepsia scores improved at 4, 12, and 24 weeks (P < 0.001), the individual symptom scores showed significant improvement in epigastric pain, epigastric distension, epigastric discomfort, early satiety, heartburn, belching and acid reflux at both the 4-week and 12-week timepoints (P < 0.05, P < 0.01, P < 0.001), of these, epigastric pain, epigastric distension, early satiety, belching and acid reflux maintained their statistically significant improvement through the 24-week evaluation period (P < 0.05, P < 0.01, P < 0.001). The total effective rate for symptom relief was 85.57% in the Elian group versus 47.92% in the placebo group (P < 0.001). QOL scores for physical health (GH, PF, BP, and PCS total score) and mental health (VT, SF, MH, and MCS total score) also improved significantly (P < 0.05, P < 0.01). No adverse impact was observed. Conclusion: Elian Granule significantly improves gastric mucosal atrophy and intestinalization, alleviates dyspeptic symptoms, and enhances QOL in CAG patients, demonstrating a favorable safety profile. Clinical Trial Registration:: http://itmctr.ccebtcm.org.cn/zh-CN/Home/ProjectView?pid=7a00ecee-da6a-4939-bae1-e6a58cd97cdb, identifier ChiMCTR2000003929, 2020-9-13.
Precancerous lesions of gastric cancer (PLGC) are crucial for the progression to gastric cancer, and early intervention in PLGC is pivotal in preventing its development into gastric cancer. In order to illustrate the molecular mechanisms underlying PLGC and the roles of associated genes within these lesions, genetically engineered mouse models (GEMMs) have been developed. We systematically summarize the current GEMMs, and highlight the principal pathological mechanisms involved, including gastrin/gastric acid balance, inflammatory factors, the interplay between cancer-promoting and cancer-suppressing genes, and apoptotic pathways. We further discuss the mechanisms involved in the existing GEMMs of PLGC.
IntroductionFunctional dyspepsia (FD) is a prevalent functional gastrointestinal disorder associated with oxidative stress (OS) and dysbiosis. Chaihushugan powder (CHSGP) demonstrates efficacy in treating FD; however, the underlying therapeutic mechanism is not yet elucidated. This study aims to investigate the effects of CHSGP on OS and gut microbiota (GM) in FD rats, with a particular emphasis on the role of GM as a potential target for the antioxidant properties of CHSGP.MethodsThe FD rat model was established with a modified tail-clamp stimulation and the administration of the CHSGP decoction at a dosage of 9.6 g/kg via gavage for a duration of 4 weeks. The GM was depleted by the administration of a cocktail of metronidazole (200 mg/kg), ampicillin (200 mg/kg), neomycin sulfate (200 mg/kg), and vancomycin (100 mg/kg). Fecal microbiota transplantation (FMT) was performed with CHSGP-treated fecal supernatant at a dosage of 10 mL/kg. The gastrointestinal motility was measured using the rates of gastric emptying and small intestine propulsion. Hematoxylin and eosin staining was employed to elucidate the pathological changes, while the transmission electron microscope was used to examine the microstructures of the interstitial cells of Cajal (ICC). Chemiluminescence, colorimetric assay, immunofluorescence co-staining, and western blot assay were employed to identify the OS-related markers (ROS, SOD, NOX4, PRDX1, and TRX2). Sequencing of fecal microbiota was performed utilizing 16S rDNA.ResultsThe CHSGP decoction promoted gastrointestinal motility, protected the microstructure of ICC, and reduced OS in FD rats. The GM composition was also regulated by CHSGP. However, these effects disappeared after microbiota depletion. Fortunately, the FMT therapy reinstated them.ConclusionChaihushugan powder decoction might regulate the GM to alleviate mitochondrial OS in the gastric tissues of FD rats.
BACKGROUND:Runchangningshen paste (RCNSP) is a paste made of four medicinal and edible homologous Chinese medicine mixed with honey. It is known for its ability to nourish yin and blood as well as to loosen the bowel to relieve constipation. The pathophysiology of functional constipation (FC) is associated with a reduction in mucin-2 (MUC2) secretion and microbial dysbiosis. AIM:To investigate the underlying mechanism of RCNSP against FC through MUC2 and the gut mucosal microbiota. METHODS:Ultra-performance liquid chromatography tandem mass spectrometry characterized RCNSP composition to elucidate the material basis of action. FC model was induced via loperamide gavage (16 mg/kg) twice daily for 7 days. Applying defecation function and gastrointestinal motility to assess constipation severity. Hematoxylin and eosin and Alcian blue-periodic acid-schiff staining analyzed colonic mucosal morphology. Transmission electron microscope was used to observe the ultrastructure of goblet cells (GCs). Immunofluorescence colocalization, quantitative PCR, and western blot assessed the impact of RCNSP on gene and protein expression within the NLRP6/autophagy pathway. 16S rDNA was employed to sequence the gut mucosal microbiota. RESULTS:RCNSP contained 12 components with potential laxative effects. It enhanced defecation function, accelerated gastrointestinal motility, and maintained colonic mucosal integrity. RCNSP treatment significantly increased GC abundance and MUC2 production while preserving GC ultrastructure. At the molecular level, RCNSP enhanced the colocalized expression of key regulatory proteins and modulated mRNA and protein expressions in the NLRP6/autophagy pathway. Through 16S rDNA sequencing analysis, RCNSP significantly altered the mucosal microbiota composition. Specifically, it increased beneficial bacterial strains while reducing harmful ones. Simultaneously, RCNSP reduced butyrate-producing bacteria like Proteobacteria, Enterobacteriaceae, Blautia, and Eubacterium and decreased hydrogen sulfide-producing species, such as Prevotellaceae. It also reduced bile acid-inhibiting species, such as g_Eubacter_coprostanoligenes_group and Erysipelotrichaceae while increasing bile acid-producing species, such as Colidextribacter. CONCLUSION:Our findings suggested that RCNSP ameliorated constipation through a dual mechanism: It stimulated colonic MUC2 secretion by activating NLRP6 inflammasome-mediated autophagy and modulated the composition of the mucosal microbiota.
Current experimental models struggle to simulate the complex process of the transformation from atrophic gastritis to gastric cancer, while gastric organoid technology, especially region-specific modeling, provides a more precise in vitro platform for studying this carcinogenic mechanism. Helicobacter pylori activates carcinogenic signaling pathways through virulence factors, inducing DNA damage, epigenetic dysregulation, and immune microenvironment imbalance, driving inflammation-cancer conversion. Intestinal metaplasia and spasmolytic polypeptide-expressing metaplasia serve as critical precursor lesions, gradually developing into dysplasia and adenocarcinoma under the influence of chronic inflammation and genetic instability through intestinal cell transformation and high trefoil factor 2-expressing cell expansion. The immune suppression, metabolic reprogramming, and matrix remodeling within the tumor microenvironment collaboratively create a pro-cancer ecosystem that accelerates inflammation-carcinogenesis transformation. The gastric organoid model successfully simulates the spatiotemporal dynamics of the carcinogenesis process in atrophic gastritis, and its future integration with single-cell omics, real-time imaging technologies, and artificial intelligence technologies could provide a more precise platform for elucidating molecular mechanisms and screening intervention strategies. These advances position gastric organoids as pivotal tools for clinical translation, enabling personalized risk stratification, early intervention targeting precancerous transitions, and ex vivo prediction of patient-specific therapeutic responses to guide precision management of gastric cancer.
BACKGROUND:Three-dimensional organoid culture systems have been established as a robust tool for elucidating mechanisms and performing drug efficacy testing. The use of gastric organoid models holds significant promise for advancing personalized medicine research. However, a comprehensive bibliometric review of this bur-geoning field has not yet been published.AIM:To analyze and understand the development, impact, and direction of gastric organoid research using bibliometric methods using data from the Web of Science Core Collection (WoSCC) database.METHODS:This analysis encompassed literature pertaining to gastric organoids published between 2010 and 2023, as indexed in the WoSCC. CiteSpace and VOSviewer were used to depict network maps illustrating collaborations among authors, institutions and keywords related to gastric organoid. Citation, co-citation, and burst analysis methodologies were applied to assess the impact and progress of research.RESULTS:A total of 656 relevant studies were evaluated. The majority of research was published in gastroenterology-focused journals. Globally, Yana Zavros, Hans Clevers, James M Wells, Sina Bartfeld, and Chen Zheng were the 5 most productive authors, while Hans Clevers, Huch Meritxell, Johan H van Es, Marc Van de Wetering, and Sato Toshiro were the foremost influential scientists in this area. Institutions from the University Medical Center Utrecht, Netherlands Institute for Developmental Biology (Utrecht), and University of Cincinnati (Cincinnati, OH, United States) made the most significant contributions. Currently, gastric organoids are used mainly in studies investigating gastric cancer (GC), Helicobacter pylori-infective gastritis, with a focus on the mechanisms of GC, and drug screening tests.CONCLUSION:Key focus areas of research using gastric organoids include unraveling disease mechanisms and enhancing drug screening techniques. Major contributions from renowned academic institutions highlight this field's dynamic growth.
Ethnopharmacological relevance: Chaihu-Shugan-San (CSS) is a classic traditional Chinese medicine (TCM) formula from the Ming Dynasty "Jingyue's Complete Works". In China, it is prevalent for the treatment of a wide range of ailments, with a particular emphasis on functional gastrointestinal disorders (FGIDs). Clinical evidence suggests that CSS has been found to be a highly effective therapeutic approach for the treatment of Functional Dyspepsia (FD), however, there is a limited amount of high-quality clinical evidence, particularly randomized, double-blind, placebo-controlled trials to support this claim. Aim of the study: To evaluate the therapeutic efficacy of Chaihu-Shugan-San (CSS) for treating functional dyspepsia (FD) by comparing it to placebos, as well as to investigate the impact of CSS on the gut microbiota in individuals diagnosed with FD. Materials and methods: This was a randomized double-blind, placebo-controlled clinical trial implemented at Shuguang Hospital in Shanghai. Between May 2021 and December 2022, 94 participants satisfying the Rome IV diagnostic criteria for FD were enrolled. They were assigned randomly to either the CSS group or the placebo group, with an equal allocation ratio of 1:1. Patients in both groups received the intervention for four weeks. The primary outcome was the dyspepsia symptom scores evaluated by using single dyspepsia symptom scale (SDS) after four weeks of treatment. The secondary outcomes were the solid gastric empties rate measured by a barium strip method, Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD), and Functional dyspepsia Quality of life scale (FDDQL). In addition, after unblinding, 30 patients in the CSS group were randomly selected and divided into before and after treatment of the FD groups (FD1, FD2), and 30 healthy participants were selected as healthy control group (HC), and the gut microbiota was analyzed by 16S rRNA sequencing. Results: After four weeks of treatment, the SDS score exhibited a significant improvement in the CSS group compared to the placebo group (t = 4.882; P < 0.001). The difference in barium strip gastric emptying rate in the CSS group showed a significant ascent compared to the control group (P < 0.01). The HAMA, HAMD, and FDDQL scores in the CSS group showed a statistically significant increase compared to the control group (all P < 0.01). The results of 16S rRNA sequencing revealed that FD patients had less diverse and abundant microbiota than the healthy people. Additionally, the application of CSS resulted in the modulation of certain bacterial populations, leading to both up-regulation and down-regulation of their quantities. Conclusions: These findings suggested that CSS is more effective compared to a placebo in treating FD, relieves anxiety and depression, increases gastric emptying rate in FD patients, and that CSS also affects the bacterial community structure in FD patients.
BACKGROUND Human-derived gastric cancer organoids (GCOs) are widely used in gastric cancer research; however, the culture success rate is generally low. AIM To explore the potential influencing factors, and the literature on successful culture rates of GCOs was reviewed using meta-analysis. METHODS PubMed, Web of Science, and EMBASE were searched for studies. Two trained researchers selected the studies and extracted data. STATA 17.0 software was used for meta-analysis of the incidence of each outcome event. The adjusted Methodological Index for Non-Randomized Studies scale was used to assess the quality of the included studies. Funnel plots and Egger’s test were used to detect publication bias. Subgroup analyses were conducted for sex, tissue source, histological classification, and the pathological tumor-node-metastasis (pTNM) cancer staging system. RESULTS Eight studies with a pooled success rate of 66.6% were included. GCOs derived from women and men had success rates of 67% and 46.7%, respectively. GCOs from surgery or biopsy/endoscopic submucosal dissection showed success rates of 70.9% and 53.7%, respectively. GCOs of poorly-differentiated, moderately-differentiated and signet-ring cell cancer showed success rates of 64.6%, 31%, and 32.7%, respectively. GCOs with pTNM stages I-II and III-IV showed success rates of 38.3% and 65.2%, respectively. Y-27632 and non-Y-27632 use showed success rates of 58.2% and 70%, respectively. GCOs generated with collagenase were more successful than those constructed with Liberase TH and TrypLE (72.1% vs 71%, respectively). EDTA digestion showed a 50% lower success rate than other methods (P = 0.04). CONCLUSION GCO establishment rate is low and varies by sex, tissue source, histological type, and pTNM stage. Omitting Y-27632, and using Liberase TH, TrypLE, or collagenase yields greater success than EDTA.
功能性消化不良是以消化不良为主要症状但并无器质性病变的临床常见疾患,是中医治疗的优势病种.本文通过对近年来中医药治疗功能性消化不良的实验及临床研究文献进行整理,分别从促进胃肠动力、调节脑肠肽、降低内脏高敏感、调节肠道菌群等机制及临床应用方面进行综述,为后续深入研究及临床应用提供参考.
慢性胰腺炎是发生胰腺癌的独立危险因素,高度重视慢性胰腺炎"炎-癌转化"并进行干预具有重要意义.基于李东垣的阴火理论,认为阴火主要是指脾胃气虚所致的气郁郁火及湿热之邪,是慢性胰腺炎"炎-癌转化"的关键.从阴火理论出发探讨中医药干预慢性胰腺炎"炎-癌转化",需把握其动态变化,紧扣阴火这一核心环节,健脾益气、因势利导、攻伐有道,才能取得临床效益的最大化.
Background:Chronic atrophic gastritis (CAG), premalignant lesions of gastric cancer (GC), greatly increases the risk of GC. Gastroscopy with tissue biopsy is the most commonly used technology for CAG diagnosis. However, due to the invasive nature, both ordinary gastroscope and painless gastroscope result in a certain degree of injury to the esophagus as well as inducing psychological pressure on patients. In addition, patients need fast for at least half a day and take laxatives. Methods:In this study, fecal metabolites and microbiota profiles were detected by metabolomics and 16S rRNA V4-V5 region sequencing. Results:Alteration of fecal metabolites and microbiota profiles was found in CAG patients, compared with healthy volunteers. To identify the most relevant features, 7 fecal metabolites and 4 microbiota were selected by random forest (RF), from A and B sample sets, respectively. Furthermore, we constructed support vector machines (SVM) classifification model using 7 fecal metabolites or 4 gut microbes, or 7 fecal metabolites with 4 gut microbes, respectively, on C sample set. The accuracy of classifification model was 0.714, 0.857, 0.857, respectively, and the AUC was 0.71, 0.88, 0.9, respectively. In C sample set, Spearman's rank correlation analysis demonstrated heptadecanoic acid and pentadecanoic acid were signifificantly negatively correlated to Erysipelotrichaceae_UCG-003 and Haemophilus, respectively. We constructed SVM classifification model using 2 correlated fecal metabolites and 2 correlated gut microbes on C sample set. The accuracy of classification model was 0.857, and the AUC was 0.88. Conclusion:Therefore, heptadecanoic acid and pentadecanoic acid, crosstalk with fecal-derived gut microbiota namely Erysipelotrichaceae_UCG-003 and Haemophilus, are potential non-invasive biomarkers for CAG diagnosis.
功能性胃肠病是临床常见的一组证候群疾病,症状重叠、病程迁延,严重影响患者的生活质量.其发病机制较为复杂,治疗效果欠佳,常规治疗超过12周效果不理想者,可称为难治性功能性胃肠病.乌梅丸是《伤寒论》中厥阴病的主方,能养肝阴、疏肝用,清上热、温下寒,燮理阴阳,具有安蛔制蛔、调肝理脾等功效,临床应用广泛.凌江红教授认为,乌梅丸与难治性功能性胃肠病病机相参、方证相应,在临证中常用乌梅丸加减治疗功能性胃肠病,效果颇佳.兹分享其临证思路和验案如下,以期为中医药治疗难治性功能性胃肠病提供临床新思路.
目的 基于氧化应激及腺苷一磷酸(AMP)活化蛋白激酶(AMPK)/沉默信息调节因子3(SIRT3)信号通路探讨柴胡疏肝散干预功能性消化不良(FD)大鼠的作用机制.方法 将32只SD大鼠随机分为正常组、模型组、柴胡疏肝散组、多潘立酮组,每组8只.模型组、柴胡疏肝散组、多潘立酮组均用改良夹尾刺激法造模,造模的同时正常组和模型组予质量分数为0.9%的氯化钠溶液灌胃,柴胡疏肝散组和多潘立酮组分别予柴胡疏肝散水煎液(4.8 g/kg)、多潘立酮混悬液(4.5 mg/kg)灌胃,连续干预4周.干预结束后,检测大鼠胃排空率,苏木精-伊红(HE)染色法观察胃组织病理变化,透射电镜观察胃Cajal间质细胞(ICCs)线粒体超微结构,酶联免疫吸附试验(ELISA)法检测大鼠血清活性氧(ROS)、丙二醛(MDA)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平,实时荧光定量逆转录聚合酶链式反应(RT-qPCR)法检测大鼠胃组织AMPK、SIRT3、锰超氧化物歧化酶(MnSOD)mRNA表达水平,Western blot法检测大鼠胃组织磷酸化AMPK(p-AMPK)、AMPK、SIRT3、MnSOD、微管相关蛋白轻链3(LC3)、P62蛋白表达.结果 ①与正常组比较,模型组大鼠胃排空率降低(P<0.05),ICCs线粒体肿胀、形态欠规则,分支较多,呈空泡化改变,见自噬小体;与模型组比较,柴胡疏肝散组、多潘立酮组大鼠胃排空率升高(P<0.05),ICCs线粒体结构损伤减轻.②与正常组比较,模型组大鼠血清ROS、MDA水平升高(P<0.05),SOD、CAT、GSH-Px水平降低(P<0.05);与模型组比较,柴胡疏肝散组、多潘立酮组大鼠血清ROS、MDA水平降低(P<0.05),SOD、CAT、GSH-Px水平升高(P<0.05).③与正常组比较,模型组大鼠胃组织AMPK、SIRT3、MnSOD mRNA表达水平降低(P<0.05);与模型组比较,柴胡疏肝散组、多潘立酮组大鼠胃组织AMPK、SIRT3、MnSOD mRNA表达水平升高(P<0.05).④与正常组比较,模型组大鼠胃组织LC3Ⅱ蛋白表达水平升高(P<0.05),SIRT3、MnSOD、P62蛋白表达水平及p-AMPK/AMPK值降低(P<0.05);与模型组比较,柴胡疏肝散组、多潘立酮组大鼠胃组织LC3Ⅱ蛋白表达水平降低(P<0.05),SIRT3、MnSOD、P62蛋白表达水平及p-AMPK/AMPK值升高(P<0.05).结论 柴胡疏肝散可有效促进FD大鼠胃动力,其作用与激活AMPK/SIRT3通路、减轻线粒体氧化应激、抑制ICCs自噬有关.
Ethnopharmacological relevance: Chaihu Shugan Powder (CHSGP) has significant clinical efficacy in the treatment of functional dyspepsia (FD), but the specific mechanism requires further study. Aim of study: The aim of this study was to investigate the therapeutic effect of CHSGP on FD rats and the underlying mechanism of the effect on interstitial cells of cajal (ICC) mitophagy. Materials and methods: The tail-clamping stimulation method was utilized to establish an FD rat model in vivo. Gastric emptying rate and small intestinal propulsion rate test, H&E staining, and Immunohistochemistry were conducted to evaluate the therapeutic effects of CHSGP on FD rats. In vitro, the regulatory effect of CHSGP on CCCP-mediated ICC mitophagy was further investigated by CCK8, Transmission electron microscope, immunofluorescence co-staining, Quantitative polymerase chain reaction and Western blot to reveal the potential mechanisms of CHSGP inhibited ICC mitophagy. Results: Animal experiments provided evidence that CHSGP promoted gastric motility, increased ICC numbers, reduced Parkin expression, and elevated USP30 expression in FD rats. In vitro, further mechanism research demonstrated that CHSGP decreased LC3II/LC3I,PINK1,Parkin,PHB2 protein expression and increased USP30 protein expression. Furthermore, CHSGP increased Mfn2 protein expression by suppressing activation of the PINK1/Parkin pathway when USP30 is knocked down, consequently reducing CCCP-induced ICC mitophagy. Conclusions: These results suggest that CHSGP may treat FD against CCCP-induced ICC mitophagy by the upregulation of via PINK1/Parkin pathway.
OBJECTIVE: To objectively reveal the relationship between tongue coating microbes and bitter taste, sticky and greasy taste in chronic atrophic gastritis(CAG) patients. METHODS: 16S rRNA high-throughput sequencing was used to detect bacterial diversity and community composition of tongue coating microbes from samples of CAG patients. LEfSe algorithm was used for discovering the different tongue coating microbes in CAG patients with or without bitter taste, also that in CAG patients with or without sticky and greasy taste. RESULTS: We respectively compared the features of tongue coating microbes in bitter taste, sticky and greasy taste of CAG patients. At the genus level, 25 tongue coating microbes were significantly different in CAG patients with bitter taste or without bitter taste; 17 tongue coating microbes were significantly different in CAG patients with sticky and greasy taste or without sticky and greasy taste. Campylobacter and Rothia were closely related to CAG patients with bitter taste. Enterococcus, Serratia, Leptotrichia and Selenomonas were closely related to CAG patients with stick and greasy taste. CONCLUSION: Campylobacter and Rothia possibly contribute to bitter taste of CAG patients, and Enterococcus, Serratia, Leptotrichia and Selenomonas contribute to stick and greasy taste of CAG patients, which is potential for the diagnosis and treatment of CAG.
目的:探讨马齿苋多糖对反流性食管炎大鼠的作用及相关机制.方法:选取40只SD大鼠,随机分为对照组、模型组、马齿苋多糖低剂量组、马齿苋多糖中剂量组和马齿苋多糖高剂量组,每组8只.除对照组外,其他组采用刺激法+导尿管球囊扩张法建立反流性食管炎大鼠模型.马齿苋多糖低、中、高剂量组分别给予7.5、15、30 g/kg马齿苋多糖灌胃,对照组和模型组给予等剂量0.9%氯化钠溶液灌胃,连续10 d.采用酶联免疫吸附试验(ELISA)法检测相关炎症因子[肿瘤坏因子(TNF)-α、白细胞介素(IL)-1β和IL-8]及胃肠激素[血管活性肠肽(VIP)、胃肠饥饿激素(Ghrelin)、胃泌素(GAS)]表达水平.采用Western blot检测核因子(NF)-κB和IL-6蛋白表达水平.采用实时荧光定量PCR(qRT-PCR)检测原癌基因c-myb、增殖细胞核抗原(PCNA)和Ki-67 mRNA相对表达水平.结果:与对照组比较,模型组和马齿苋多糖不同剂量组TNF-α、IL-8、IL-1β表达水平明显更高,且马齿苋多糖高剂量组显著低于模型组、马齿苋多糖低剂量组和中剂量组(均P<0.05).与对照组比较,模型组和马齿苋多糖不同剂量组NF-κB、IL-6蛋白表达水平明显更高,且马齿苋多糖高剂量组低于模型组、马齿苋多糖低剂量组和中剂量组(均P<0.05).与对照组比较,模型组和马齿苋多糖不同剂量组Ghrelin、GAS表达水平明显更低,VIP明显更高;马齿苋多糖高剂量组Ghrelin、GAS表达水平显著高于模型组、马齿苋多糖低剂量组和中剂量组,VIP显著低于模型组、马齿苋多糖低剂量组和中剂量组(均P<0.05).与对照组比较,模型组和马齿苋多糖不同剂量组c-myb、PCNA、Ki-67 mRNA表达水平明显更高,且马齿苋多糖高剂量组显著低于模型组、马齿苋多糖低剂量组和中剂量组(均P<0.05).结论:反流性食管炎大鼠采用马齿苋多糖进行干预可有效抑制食管组织炎症,其机制与抑制NF-κB/IL-6信号通路有关.此外,马齿苋多糖可调节胃肠激素表达以促进胃排空,同时还可抑制促增殖基因表达而降低食管恶性病变的发生风险.