Journal of Advanced Research最新文献

{"title":"The potential of circular RNAs as biomarkers and therapeutic targets for gastric cancer: A comprehensive review","authors":"Junlin Pu, Xiuli Yan, Hui Zhang","doi":"10.1016/j.jare.2024.11.032","DOIUrl":"https://doi.org/10.1016/j.jare.2024.11.032","url":null,"abstract":"<h3>Background</h3>Gastric cancer (GC) is a global health concern, contributing significantly to cancer-related mortality rates. Early detection is vital for improving patient outcomes. Recently, circular RNAs (circRNAs) have emerged as crucial players in the development and progression of various cancers, including GC.<h3>Aim</h3><em>of Review</em>: This comprehensive review underscores the promising potential of circRNAs as innovative biomarkers for the early diagnosis of GC, as well as their possible utility as therapeutic targets for this life-threatening disease. Specifically, the review focuses on recent findings, mechanistic insights, and clinical applications of circRNAs in GC.<em>Key Scientific Concepts of Review</em>: Dysregulation of circRNAs has been consistently observed in GC tissues, offering potential diagnostic value due to their stability in bodily fluids such as blood and urine. For instance, circPTPN22 and hsa_circ_000200. Furthermore, the expression levels of circRNAs such as circCUL2, hsa_circ_0000705 and circSHKBP1 have shown strong associations with critical clinical features of GC, including diagnosis, prognosis, tumor size, lymph node metastasis, tumor-node-metastasis (TNM) stage, and treatment response. Additionally, circRNAs such as circBGN, circLMO7, and circMAP7D1 have shown interactions with specific microRNAs (miRNAs), proteins, and other molecules that play key roles in development and progression of GC. This further highlighting their potential as therapeutic targets. Despite their potential, several challenges need to be addressed to effectively apply circRNAs as GC biomarkers. These include standardizing detection methods, establishing cutoff values for diagnostic accuracy, and validating findings in larger patient cohorts. Moreover, the functional mechanisms by which circRNAs contribute to GC pathogenesis and therapeutic resistance warrant further investigation. Advances in circRNAs research could provide valuable insights into the early detection and targeted treatment of GC, ultimately improving patient outcomes.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"5 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142742449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Full dimensional dynamic 3D convolution and point cloud in pulmonary nodule detection","authors":"Yun Tie, Ying Wang, Dalong Zhang, Zepeng Zhang, Fenghui Liu, Lin Qi","doi":"10.1016/j.jare.2024.11.033","DOIUrl":"https://doi.org/10.1016/j.jare.2024.11.033","url":null,"abstract":"Lung cancer is a leading cause of death worldwide, making early and accurate diagnosis essential for improving patient outcomes. Recently, deep learning (DL) has proven to be a powerful tool, significantly enhancing the accuracy of computer-aided pulmonary nodule detection (PND). In this study, we introduce a novel approach called the Omni-dimension Dynamic Residual 3D Net (ODR3DNet) for PND, which utilizes full-dimensional dynamic 3D convolution, along with a specialized machine learning algorithm for detecting lung nodules in 3D point clouds. The primary goal of ODR3DNet is to overcome the limitations of conventional 3D Convolutional Neural Networks (CNNs), which often struggle with adaptability and have limited feature extraction capabilities. Our ODR3DNet algorithm achieves a high CPM (Competition Performance Metric) score of 0.885, outperforming existing mainstream PND algorithms and demonstrating its effectiveness. Through detailed ablation experiments, we confirm that the OD3D module plays a crucial role in this performance boost and identify the optimal configuration for the algorithm. Moreover, we developed a dedicated machine learning detection algorithm tailored for lung 3D point cloud data. We outline the key steps for reconstructing the lungs in 3D and establish a comprehensive process for building a lung point cloud dataset, including data preprocessing, 3D point cloud conversion, and 3D volumetric box annotation. Experimental results validate the feasibility and effectiveness of our proposed approach.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"62 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142742450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise-regulated lipolysis: Its role and mechanism in health and diseases","authors":"Jie-Ying Zhu, Liang Guo","doi":"10.1016/j.jare.2024.11.031","DOIUrl":"https://doi.org/10.1016/j.jare.2024.11.031","url":null,"abstract":"Exercise has received considerable attention because of its importance not just in regulating physiological function, but also in ameliorating multiple pathological processes. Among these processes, lipolysis may play an important role in exercise-induced benefits. It is generally accepted that active lipolysis contributes to breakdown of fats, leading to the release of free fatty acids (FFAs) that serve as an energy source for muscles and other tissues during exercise. However, the significance of lipolysis in the context of exercise has not been fully understood. This review comprehensively outlines the potential regulatory mechanisms by which exercise stimulates lipolysis. The potential roles of exercise-mediated lipolysis in various physiological and pathological processes are also summarized. Additionally, we also discussed the potential non-classical effects of key lipolytic effectors induced by exercise. This will enhance our understanding of how exercise improves lipolytic function to bring about beneficial effects, offering new insights into potential therapeutic avenues for promoting health and alleviating diseases.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"81 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fungus-derived opine enhances plant photosynthesis","authors":"Dekun Kong, Li Cui, Xiaozheng Wang, Jing Wo, Fangjie Xiong","doi":"10.1016/j.jare.2024.11.029","DOIUrl":"https://doi.org/10.1016/j.jare.2024.11.029","url":null,"abstract":"<h3>Introduction</h3>Plant-fungal interactions stimulate endophytic fungi to produce a plethora of metabolites that enhance plant growth and improve stress resistance. Opines, naturally occurring compounds formed through the condensation of amino acids with <em>α</em>-keto acids or sugars, have diverse biological functions and are mainly present in bacteria. Interestingly, investigations have revealed the presence of opine synthases (OSases) in fungal species as well, and their functions are yet to be studied.<h3>Objectives</h3>The objective of this study is to investigate the occurrence of OSases in fungal species, identify their products, and characterize the potential biological activity of the metabolites.<h3>Methods</h3>We identified a putative class of OSases in fungi through sequence similarity network (SSN) analysis. The function of these enzymes was elucidated using methods including protein heterologous expression, <em>in vitro</em> biochemical characterization, <em>in vivo</em> gene knock-out, as well as product isolation and identification. Additionally, we conducted plant activity testing on the secondary metabolites through foliar spraying and performed transcriptomic analysis to uncover their functions.<h3>Results</h3>A quarter of the PF18631 family members, which contain the C-terminal helical bundle domain of cucumopine synthase, are derived from endophytic fungi. Some of these enzymes catalyze the synthesis of tryptopine A (1-acetyl-3-carboxy-<em>β</em>-carboline) by condensing L-tryptophan and methylglyoxal. The tryptopine A can act as a growth regulator, promoting plant growth and transcriptionally reprogramming photosynthesis-related pathways, while enhancing the rate of plant photosynthesis by 25 %.<h3>Conclusion</h3>The findings of this study suggest that tryptopine A plays a crucial role as a signaling molecule in the establishment and maintenance of mutualistic associations between endophytic fungi and host plants, thereby enhancing our comprehension of fungal-plant symbiosis.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"264 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends, clinicopathological features, surgical treatment patterns and prognoses of early-onset versus late-onset gastric cancer: A retrospective cohort study","authors":"Yingxue Liu, Xiaoyan Zhang, Lu Gan, Zhikai Chen, Xin Wang, Jiayu Zhang, Jie Chen, Cong Tan, Weiqi Sheng, Midie Xu","doi":"10.1016/j.jare.2024.11.028","DOIUrl":"https://doi.org/10.1016/j.jare.2024.11.028","url":null,"abstract":"<h3>Introduction</h3>This study investigates the differences between early-onset gastric carcinoma (EOGC) and late-onset gastric carcinoma (LOGC) by examining trends, demographics, clinical and molecular features, treatments, and outcomes at a leading cancer center in China.<h3>Objectives</h3>To delineate the distinctions between EOGC and LOGC in terms of patient characteristics, disease progression, and treatment outcomes, and to suggest appropriate screening strategies.<h3>Methods</h3>We analyzed 18,877 gastric carcinoma cases treated at Fudan University Shanghai Cancer Center (FUSCC) from 2000 to 2022. Descriptive statistics were performed using IBM SPSS. Survival rates were assessed via the Kaplan-Meier method and log-rank test, while COX regression analysis identified factors affecting disease-free survival (DFS) and overall survival (OS).<h3>Results</h3>The average age of gastric cancer diagnosis has increased slightly since 2000, with a steady rise in both EOGC and LOGC cases, though EOGC’s proportion has slightly decreased. EOGC had a higher proportion of female patients and was more common in the gastric body and antrum pylorus. EOGC cases showed lower levels of cancer biomarkers, HER2 expression, vascular and lymphatic invasion, and lower differentiation and invasion depth. They also exhibited more advanced N and TNM staging, Borrmann IV type, and low adhesive carcinoma. EOGC underwent more extensive D2 lymphadenectomy and neoadjuvant chemotherapy. There were no significant differences in Claudin18.2 and MMR protein status between EOGC and LOGC. EOGC had higher rates of ovarian and peritoneal metastases, with a better early prognosis but faster late-stage progression.<h3>Conclusion</h3>EOGC and LOGC cases have increased over the past two decades. EOGC presents unique clinical and pathological features, requiring thorough surgical treatment and has a better early prognosis but more rapid late-stage progression. Enhanced screening for younger adults is recommended to address the rising EOGC trend.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"103 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Manipulation of artificial light environment improves plant biomass and fruit nutritional quality in tomato","authors":"Ying Zhang, Kangyou Zhu, Xiujie Wang, Jiarong Yan, Haiyan Zhu, Nan Zhang, Yiting Wang, Qi Zhao, Yanan Liu, Xin Bu, Chenghao Jiang, Xin Sun, Golam Jalal Ahammed, Shuyu Cai, Sida Meng, Zhouping Sun, Mingfang Qi, Tianlai Li, Feng Wang","doi":"10.1016/j.jare.2024.11.030","DOIUrl":"https://doi.org/10.1016/j.jare.2024.11.030","url":null,"abstract":"<h3>Introduction</h3>The yield and quality of tomato (<em>Solanum lycopersicum.</em> L) are often decreased when plants suffer from low light intensity and short-photoperiod in winter. Manipulation of the artificial light environment is a feasible technology to promote off-seasonal production and improve fruit nutritional quality in the greenhouse.<h3>Objectives</h3>Here we aim to investigate the appropriate balance between red (R) and blue (B) light to improve tomato yield and quality traits.<h3>Methods</h3>Biochemical, molecular and genetic analysis were used to study the photosynthetic traits, pigments, sugar and volatile accumulation pathway genes.<h3>Results</h3>Tomato plants subjected to R1B0.8, a ratio between monochromatic red (R) and blue (B) light, for 16 h photoperiod showed significantly increased chlorophyll and biomass accumulation compared to white (W) light treatment. R1B0.8 light treatment enhanced electron transfer efficiency and photosynthetic capacity by improving the light energy utilization rate and inducing photosystem core subunit genes (<em>SlPsaC, SlPsaB, SlPsaA</em>) and light-harvesting complex genes (<em>SlLHCB/A</em>). Compared to W light, R1B0.8 light also induced carotenoid accumulation and accelerated fruit ripening, which was associated with the upregulation of carotenoid biosynthesis genes (<em>SlPSY1, SlPDS</em>) and ethylene biosynthesis genes (<em>SlACS2, SlACO2</em>) in tomato fruits. Moreover, fruits exposed to R1B0.8 light treatments significantly improved fructose and glucose accumulation and the expression of the volatile-related gene (<em>SlAADC1a)</em> and flavor-related gene (<em>SlGORKY</em>).<h3>Conclusion</h3>Our results showed that R1B0.8 light with a 16 h photoperiod could prominently promote photosynthetic traits, pigments, sugar and volatile accumulation in tomato. Our findings on the manipulation of artificial light environments in protected horticulture offer possibilities for enhancing crop yield and quality to meet the increasing global demand for food.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"24 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-3606-3p alleviates skin fibrosis by integratively suppressing the integrin/FAK, p-AKT/p-ERK, and TGF-β signaling cascades","authors":"Yahui Chen, Yiyi Gong, Mengkun Shi, Haoxing Zhu, Yulong Tang, Delin Huang, Wei Wang, Chenyi Shi, Xueyi Xia, Ying Zhang, Jianlan Liu, Jia Huang, Mengguo Liu, Huyan Chen, Yanyun Ma, Ziyu Wang, Lei Wang, Wenzhen Tu, Yinhuan Zhao, Jinran Lin, Xiangguang Shi","doi":"10.1016/j.jare.2024.11.027","DOIUrl":"https://doi.org/10.1016/j.jare.2024.11.027","url":null,"abstract":"<h3>Introduction</h3>Fibroblast abnormalities are crucial causes of skin fibrosis, including systemic sclerosis (SSc) and keloids. However, their mechanisms, including underlying microRNA regulatory mechanisms, remain elusive.<h3>Objectives</h3>This study aimed to evaluate the roles, mechanisms, and therapeutic potential of miR-3606-3p in regulating multiple fibroblast abnormalities.<h3>Methods</h3>The miR-3606-3p levels were evaluated in skin tissues and primary fibroblasts. RNA-seq and luciferase assays were employed to identify miR-3606-3p targets. Collagen contraction, western blotting, <em>in vivo</em> imaging, and real-time cellular analysis were used to assess fibroblast abnormalities. The therapeutic potential of miR-3606-3p was evaluated in mice.<h3>Results</h3>MiR-3606-3p decreased in skin tissues (SSc: Fold Change (FC) = − 2.95, P = 0.0101; keloid: FC = − 3.42, P &lt; 0.0001) and primary fibroblasts (SSc: FC = − 12.74, P = 0.0278; keloid: FC = − 2.08, P = 0.0021) from skin fibrosis patients, and negatively correlated with disease severity. Mechanistically, miR-3606-3p targeted the 3′-untranslated regions (3′-UTRs) of Integrin αV (<em>ITGAV</em>), GRB2-associated binding protein 1 (<em>GAB1</em>), and transforming growth factor beta receptor 2 (<em>TGFBR2</em>), all of these three targets increased in skin fibrosis. Simultaneously, miR-3606-3p inhibited fibroblast’s fibrogenesis, migration, inflammation, and proliferation by inhibiting ITGAV/integrin/FAK, GAB1/p-AKT/p-ERK, and TGFBR2/p-SMAD2/3 signaling. ITGAV-mediated integrin/FAK signaling unidirectionally activated the p-AKT/p-ERK and p-SMAD2/3 pathways. Knockdown of <em>GAB1</em> and <em>TGFRB2</em> reduced ITGAV-induced p-AKT/p-ERK and p-SMAD2/3 activities. MiR-3606-3p, <em>si-ITGAV</em>, <em>si-GAB1</em>, and <em>si-TGFBR2</em> exhibited significant inhibition of fibrogenesis and migration. Inflammation was primarily inhibited by si-ITGAV and si-GAB1, while proliferation was primarily inhibited by <em>si-TGFBR2</em>. Moreover<em>,</em> miR-3606-3p significantly attenuates skin fibrosis in keloid-bearing mice.<h3>Conclusions</h3>MiR-3606-3p is downregulated in skin fibrosis. Moreover, it negatively correlates with disease severity. Functionally, miR-3606-3p inhibits fibrogenesis, migration, inflammation, and proliferation of fibroblasts. Mechanistically, miR-3606-3p inhibits <em>ITGAV</em>, <em>GAB1</em>, and <em>TGFBR2</em> by targeting their 3′-UTRs. ITGAV-, GAB1-, and TGFBR2-activated integrin/AKT/ERK/SMAD2/3 signaling induced fibroblast abnormalities. In vivo, miR-3606-3p inhibits skin fibrosis in mice. Therefore, the multi-targeting, multi-phenotypic regulatory properties of miR-3606-3p suggest its potential utility in clinical treatment.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"223 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An accurate prediction for respiratory diseases using deep learning on bronchoscopy diagnosis images","authors":"Weiling Sun, Pengfei Yan, Minglei Li, Xiang Li, Yuchen Jiang, Hao Luo, Yanbin Zhao","doi":"10.1016/j.jare.2024.11.023","DOIUrl":"https://doi.org/10.1016/j.jare.2024.11.023","url":null,"abstract":"<h3>Introduction</h3>Bronchoscopy is of great significance in diagnosing and treating respiratory illness. Using deep learning, a diagnostic system for bronchoscopy images can improve the accuracy of tracheal, bronchial, and pulmonary disease diagnoses for physicians and ensure timely pathological or etiological examinations for patients. Improving the diagnostic accuracy of the algorithms remains the key to this technology.<h3>Objectives</h3>To deal with the problem, we proposed a multiscale attention residual network (MARN) for diagnosing lung conditions through bronchoscopic images. The multiscale convolutional block attention module (MCBAM) was designed to enable accurate focus on lesion regions by enhancing spatial and channel features. Gradient-weighted Class Activation Map (Grad-CAM) was provided to increase the interpretability of diagnostic results.<h3>Methods</h3>We collected 615 cases from Harbin Medical University Cancer Hospital, including 2900 images. The dataset was partitioned randomly into training sets, validation sets and test sets to update model parameters, evaluate the model’s training performance, select network architecture and parameters, and estimate the final model. In addition, we compared MARN with other algorithms. Furthermore, three physicians with different qualifications were invited to diagnose the same test images, and the results were compared to those of the model.<h3>Results</h3>In the dataset of normal and lesion images, our model displayed an accuracy of 97.76% and an AUC of 99.79%. The model recorded 92.26% accuracy and 96.82% AUC for datasets of benign and malignant lesion images, while it achieved 93.10% accuracy and 99.02% AUC for normal, benign, and malignant lesion images.<h3>Conclusion</h3><!-- -->These results demonstrated that our network outperforms other methods in diagnostic performance. The accuracy of our model is roughly the same as that of experienced physicians and the efficiency is much higher than doctors. MARN has great potential for assisting physicians with assessing the bronchoscopic images precisely.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"197 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacteroides uniformis ameliorates pro-inflammatory diet-exacerbated colitis by targeting endoplasmic reticulum stress-mediated ferroptosis","authors":"Caiguang Liu, Linxin Liu, Zhenyi Tian, Shukai Zhan, Yun Qiu, Manying Li, Tong Li, Ren Mao, Shenghong Zhang, Minhu Chen, Zhirong Zeng, Xiaojun Zhuang","doi":"10.1016/j.jare.2024.11.025","DOIUrl":"https://doi.org/10.1016/j.jare.2024.11.025","url":null,"abstract":"<h3>Introduction</h3>A pro-inflammatory diet is positively associated with the risk and progression of inflammatory bowel diseases (IBD). Recently, ferroptosis has been observed in patients with different dietary patterns-associated intestinal inflammation, while the mechanisms underlying the effects of a pro-inflammatory diet and whether it mediates ferroptosis are unknown.<h3>Objectives</h3>This study aims to elucidate the mechanisms underlying pro-inflammatory diet-mediated colitis and explore potential intervention strategies.<h3>Methods</h3>Mice were fed a dietary inflammatory index-based pro-inflammatory diet for 12 weeks. Subsequently, colitis was chemically induced using 2.5 % dextran sulfate sodium. The body weight, pathological score, immune response and mucosal barrier function were evaluated to assess intestinal inflammation. Intestine tissue transcriptomics, fecal microbiome analysis and serum metabolomics were applied to identify diet–microbe–host interactions. Additionally, the dietary inflammatory index (DII) scores and intestinal specimens of 32 patients with Crohn’s disease were evaluated. The biological functions of <em>Bacteroides uniformis</em> were observed <em>in vitro</em> and <em>in vivo</em>.<h3>Results</h3>Pro-inflammatory diet induces low-grade intestinal inflammation in mice and exacerbates colitis by activating glutathione peroxidase 4-associated ferroptosis in the endoplasmic reticulum stress-mediated pathway. These effects are reversed by ferrostatin-1 treatment. Additionally, the pro-inflammatory diet triggers colitis by modulating the gut microbiota and metabolites. Notably, supplementation with <em>B. uniformis</em> improves the pro-inflammatory diet-aggravated colitis by inhibiting endoplasmic reticulum stress-mediated ferroptosis. Moreover, <em>B. uniformis</em> is non-enterotoxigenic and non-enteroinvasive in co-cultures with intestinal epithelial cells.<h3>Conclusions</h3>Pro-inflammatory diet drives colitis by targeting endoplasmic reticulum stress-mediated ferroptosis, possibly in a gut microbiota-dependent manner. Pro-inflammatory diet restriction and microbial-based therapies may be effective strategies for preventing and treating IBD.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"11 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142670842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-10 deficiency suppresses colorectal cancer metastasis by enriching gut Parabacteroides distasonis","authors":"Jing Yu, Lili Feng, Zhanhao Luo, Jingyi Yang, Qiang Zhang, Chen Liu, Dayi Liang, Yanchun Xie, Hongmin Li, Junli Gong, Zhen He, Ping Lan","doi":"10.1016/j.jare.2024.11.024","DOIUrl":"https://doi.org/10.1016/j.jare.2024.11.024","url":null,"abstract":"<h3>Introduction</h3>The intricate interplay of interleukin-10 (IL-10) and gut microbiota influences tumor development and progression, yet the impacts on colorectal cancer (CRC) metastasis remain incompletely understood.<h3>Methods</h3>The impact of <em>Il10</em> deficiency on CRC metastasis was first evaluated in CRC metastasis tumor samples and mouse model. Antibiotic sterilization and fecal microbiota transplantation (FMT) experiment were used to assess the role of gut microbiota in IL-10 mediated CRC metastasis, and full-length 16S rDNA sequencing analysis further identified the potential target bacteria influencing CRC metastasis. The inhibitory effect of <em>Parabacteroides distasonis</em> (<em>P. distasonis</em>) on CRC metastasis was evaluated by oral administration in mice. Key metabolites involved in <em>P. distasonis</em> inhibition of CRC metastasis was identified by widely-targeted metabolome analysis and validated both <em>in vivo</em> and <em>in vitro</em>. The underlying mechanisms of P-hydroxyphenyl acetic acid (4-HPAA) inhibiting CRC metastasis was investigated via RNA-sequencing and validated in cellular experiments.<h3>Results</h3>We revealed that serum IL-10 levels were markedly elevated in metastatic CRC patients compared to non-metastatic cases. In parallel, <em>Il10</em>-deficiency (<em>Il10^−/</em>) in mice resulted in decreased CRC metastasis in a gut microbiota-dependent manner. Mechanistically, <em>Il10^−/−</em> mice reshaped gut microbiota composition, notably enriching <em>P. distasonis</em>. The enriched <em>P. distasonis</em> produced 4-HPAA, which activated the aryl hydrocarbon receptor (AHR) and subsequently inhibited the expression of <em>VEGFA</em>, a typical oncogene, thereby sequentially suppressing CRC metastasis. Importantly, engineered bacteria capable of producing 4-HPAA effectively hindered CRC metastasis. Furthermore, AHR depletion significantly disrupted the 4-HPAA-induced reduction in CRC cell migration and the inhibition of metastasis in both <em>in vitro</em> and <em>in vivo</em> lung metastasis mouse models.<h3>Conclusions</h3>These findings demonstrate the significance of IL-10 deficiency in suppressing CRC metastasis through the 4-HPPA-AHR-<em>VEGFA</em> axis mediated by gut <em>P. distasonis</em>, suggesting that <em>P. distasonis</em> or 4-HPAA supplementation could offer a promising therapeutic strategy for CRC metastasis prevention.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"9 5 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}