Journal of Advanced Research最新文献

{"title":"From inflammation to remodelling: A novel BASP1+ monocyte subset as a catalyst for acute aortic dissection","authors":"Wenhui He, Sanjiu Yu, Jun Li, Siyu Li, Zongtao Chen, Jingyu Zhang, Yangwuyue Liu, Mi Zhou, Teng Yang, Wei Cheng, Shuang-Shuang Dai","doi":"10.1016/j.jare.2025.03.003","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.003","url":null,"abstract":"<h3>Introduction</h3>Monocytes comprise heterogeneous cell populations. However, beyond traditionally considered as precursors of tissue macrophages, heterogeneity and detailed effects of monocytes in acute aortic dissection (AAD) are largely unknown.<h3>Objectives</h3>To investigate the role of brain soluble acid protein 1 positive (BASP1⁺) monocyte subset in promoting AAD development as well as the underlying mechanism.<h3>Methods</h3>Monocyte/macrophage heterogeneity in both human peripheral blood and aortic tissues were assayed by scRNA-seq. Monocyte trafficking and lineage tracing were detected by immunofluorescence and using BASP1-CreER/Lyz2-DreER-tdT reporter mice with AAD. The effects and underlying mechanism were investigated by laser speckle image, ultrasound imaging, Co-IP, ChIP-sequencing. Conditional knockout of BASP1 on monocyte and BASP1 siRNA were used to observe BASP1⁺ monocyte subset-targeted AAD intervention.<h3>Results</h3>“PIP2-SP1-ACTN1/VAV3” and “ITGB1-Rac1-GSN” signalling mediated BASP1⁺ monocyte subset as the first line immune cells infiltrating aortic tissues in AAD induction and partial of them transformed to BASP1⁺ macrophages to amplify the inflammation. Meanwhile, BASP1⁺ monocyte subset induced an inflammatory phenotype vascular smooth muscle cell (VSMC) subset and a ROS-enriched endothelial cell (EC) subset accompanied with promoting the apoptosis of normal VSMC and EC, contributing to vascular remodelling and dampening the myo-endothelial gap junction. Selective deletion of BASP1⁺ monocyte subset and interference with BASP1 expression in monocytes both inhibited the development of AAD in mice.<h3>Conclusion</h3>Interpretation BASP1⁺ monocyte subset and its regulatory network provides deep insight into AAD pathogenesis and a novel potential target for early intervention in AAD formation","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"7 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143561290","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":"The LRP1-SHP2 pathway regulates TRPV1 sensitivity in the peripheral nervous system: Insights from amyloid beta 1–42 modulation","authors":"Sung-Min Hwang, Jueun Roh, Eun Jin Go, Jing-Ying Pan, Jaeik Park, Mahbubur Rahman, YunJae Jung, Sun-Ho Lee, Inbo Han, Gehoon Chung, Sang Hoon Lee, Temugin Berta, Chul-Kyu Park, Yong Ho Kim","doi":"10.1016/j.jare.2025.03.005","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.005","url":null,"abstract":"<h3>Introduction</h3>Mature adults often exhibit higher pain thresholds than younger individuals. However, this phenomenon is poorly understood, especially with regards to peripheral nervous system signaling.<h3>Objectives</h3>We investigated the involvement of amyloid beta (Aβ) in regulating heat pain sensitivity within the dorsal root ganglion (DRG) during adult maturation.<h3>Methods</h3>We employed various in vivo and in vitro techniques to investigate the modulatory effect of Aβ_1–42. Heat pain sensitivity alteration was examined in spared nerve injury (SNI) models of young and mature adult Aβ_1–42-treated mice. Phosphorylation and receptor inhibition assays were performed to elucidate the molecular mechanisms involved in pathway interactions in vitro.<h3>Results</h3>Mature adult mice had higher thermal pain thresholds and elevated levels of Aβ_1–42 compared to younger mice<em>.</em> In vitro analyses indicated that Aβ_1–42-induced activation of low-density lipoprotein receptor-related protein 1 (LRP1) led to phosphorylation of the src-homology domain-2–containing protein tyrosine phosphatase 2 (SHP2), which in turn inhibited transient receptor potential vanilloid 1 (TRPV1) function in primary DRG neurons. Similar mechanisms were observed in Aβ_1–42-treated human DRG neurons. Additionally, α₂-macroglobulin (α₂M), a potent LRP1 agonist, also inhibited TRPV1 activity and reduced heat pain sensitivity through the LRP1-SHP2 pathway. In vivo studies with the mouse SNI model demonstrated that intraplantar injection of Aβ_1–42 and α₂M enhanced the paw withdrawal latency; these effects were reversed by low-density lipoprotein receptor-related protein-associated protein 1.<h3>Conclusion</h3>The findings suggest a crucial role of Aβ in modulating heat pain sensitivity during maturation through TRPV1 inhibition. The study offers new insights into the regulation of pain sensitivity during the maturation process by revealing a novel intrinsic mechanism involving Aβ_1–42 in heat pain sensitivity and its regulation through the LRP1/SHP2 pathway in mature adults. This pathway could be a potential therapeutic target for age-related chronic pain management.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"50 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546959","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":"Endophyte Acrocalymma vagum establishes the holobiont with rice to attract beneficial microorganisms and promote disease resistance","authors":"Yulan Zeng, Xuanjun Lu, Mengrong Wang, Rui Chen, Qianxi Li, Jianan Zhu, Zhenzhu Su, Fucheng Lin","doi":"10.1016/j.jare.2025.03.008","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.008","url":null,"abstract":"<h3>Introduction</h3>Endophytic fungi are essential microorganisms in promoting plant health. However, the mechanism of endophytic fungi regulating root microbiota to enhance crop production and resistance remains unclear.<h3>Objectives</h3>We aimed i) to explore the microbial alteration driven by endophytic <em>Acrocalymma vagum</em> in developing crop yield and rice resistance; ii) to reveal the mechanism of root-released compound stimulated by <em>A. vagum</em> in recruiting benefit microbes.<h3>Methods</h3>The microbiome was applied in a culture-dependent and culture-independent method to study the microbial communities of the <em>A. vagum</em>-rice holobiont using 16S rRNA and ITS gene metabarcoding. Non-target metabolome identified distinct metabolites responsible for community variations. Label-free proteomic analyses investigated the association between primary genes related to the holobiont formation. CRISPR/Cas9 technique and homologous recombination replacement were used to characterize the functions of putative genes.<h3>Results</h3><em>A. vagum</em> enhanced cultivated rice yield by 5.73 ± 1.76 % and induced 83.24 ± 9.86 % control efficiency against rice blast. We discovered that <em>A. vagum</em> simplified rice microbial structure based on co-occurrence networks, by lowering the proportion of potentially pathogenic predominant <em>Burkholderia</em> and driving rice to recruit beneficial <em>Lactobacillus</em>, <em>Sarocladium</em> and <em>Nigrospora</em> to promote rice growth with the increases of 44.41 ± 5.10 % shoot height and 70.21 ± 9.57 % shoot biomass. Moreover, the holobiont released coumaric and <em>trans</em>-ferulic acids to attract beneficial microbes. 206 rice proteins were notably up-regulated in the holobiont, particularly the OsPrxs. CRISPR/Cas9-edited mutants of <em>OsPRX70</em> and <em>OsPRX95</em> reduced the promotion effect of <em>A. vagum</em> on rice growth. Furthermore, the pathways of 39 overexpressed proteins in <em>A. vagum</em> were enriched in invading the host and inducing resistance. The knockouts of <em>AvGH3</em>, <em>AvGH7</em>, <em>AvMFS1</em>, and <em>AvCBA</em> transformed <em>A. vagum</em> role from endophyte to pathogen.<h3>Conclusions</h3>The <em>A. vagum</em>-rice holobiont releases recruitment signals and improves the rice community structure. We provide ecological and molecular evidence to confirm the mutualism of endophyte-plant-promoting growth and disease resistance.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"36 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546883","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":"Saccharide mapping apparatus for real-time PAGE detection of polysaccharides","authors":"Baojie Zhu, Jing Zhao, Shaoping Li","doi":"10.1016/j.jare.2025.03.006","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.006","url":null,"abstract":"<h3>Introduction</h3>As a key technique in saccharide mapping, polysaccharides analysis using carbohydrate gel electrophoresis (PACE) analysis platform has always been self-assembled and built in various laboratories independently, but there is no unified commercial analysis instrument platform so far.<h3>Objective</h3>This research aimed to establish an integrated commercially viable PACE analysis platform to standardize the application of PACE in the field of saccharides analysis and the quality control of polysaccharides.<h3>Methods</h3>We established an online detection platform of saccharide-mapping apparatus (SMA) and took advantage of it to characterize the oligosaccharides for quality control of polysaccharides in herbal medicine. The polysaccharides from <em>Gastrodia elata</em> Bl. were finally selected to verify the potential of SMA including precision, repeatability, stability, and sensitivity.<h3>Results</h3>The online detection platform of SMA was more integrated and commercially viable, which can investigate oligosaccharides from polysaccharides after hydrolysis more quickly and accurately for quality control. Consequently, it could enable real-time monitoring of oligosaccharide migration, facilitate the determination of the optimal endpoint of polyacrylamide gel electrophoresis (PAGE), and improve the sensitivity of PACE. In addition, the refrigeration device configured in SMA can solve the problem of temperature fluctuation caused by joule heat during gel electrophoresis, which greatly enhances the separation resolution. Finally, the proposed platform was applied to real samples of polysaccharides from <em>Gastrodia elata</em> Bl., and the results successfully distinguished the polysaccharides from <em>Gastrodia elata</em> Bl. with different cultivars.<h3>Conclusion</h3>The developed online detection platform of SMA offers a rapid and convenient approach for quality control of polysaccharides in Chinese medicines and can be applied for future advancements toward commercialization.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"2020 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538416","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":"Nutrient supplementation mitigates retinal dysfunction in Acox1 knockout mice with impaired peroxisomal fatty acid oxidation","authors":"Myriam Boeck, Hitomi Yagi, Chuck T. Chen, Yan Zeng, Deokho Lee, Shen Nian, Taku Kasai, Jeff Lee, Victoria Hirst, Chaomei Wang, Katherine Neilsen, Tori C. Rodrick, Andrew McCutcheon, Mathew Yu, Irfan J. Lodhi, Sasha A. Singh, Masanori Aikawa, Richard P. Bazinet, Zhongjie Fu","doi":"10.1016/j.jare.2025.03.004","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.004","url":null,"abstract":"<h3>Introduction</h3>Dyslipidemia contributes to many retinal diseases, but underlying lipid processing pathways are not fully understood. Peroxisomes oxidize very long-chain fatty acids and generate docosahexaenoic acid (DHA). Mutations in peroxisomal genes can result in severe neural retinal dysfunction. However, therapeutic approaches for peroxisomal diseases remain scarce, and dietary strategies yield inconsistent results.<h3>Objectives</h3>This study sought to elucidate retinal metabolic adaptations resulting from impaired peroxisomal fatty acid oxidation and to evaluate the therapeutic potential of nutrient supplementation in peroxisomal retinal disease.<h3>Methods</h3>In mice with global knockout (KO) of acyl-coenzyme A oxidase 1 (<em>Acox1</em>), encoding the first and rate-limiting enzyme in peroxisomal fatty acid oxidation, the retina was characterized at postnatal day (P) 30 during development. Retinal thickness, photoreceptor structure, and function were examined. Proteome analysis was utilized for molecular mechanistic investigation. Metabolomics and fatty acid profiling were conducted to study metabolic alterations in the retina. Nutrient intervention was performed to test if providing deficient nutrients could attenuate the observed retinal dysfunction.<h3>Results</h3>In P30 <em>Acox1</em> KO mice, we observed impaired neural retinal signaling, accompanied by reduced expression of genes involved in phototransduction. Proteomics suggested diminished glucose and mitochondrial metabolism, supported by decreased mitochondrial number and mitochondrial DNA copy number. Metabolomics showed reduced abundance of retinal pyruvate, and pyruvate supplementation from P30-P60 attenuated neural retinal dysfunction in <em>Acox1</em> KO mice at P60. Furthermore, <em>Acox1</em> KO mice at P30 exhibited a significant decrease in omega–3 (n-3) fatty acids and a compensatory increase in n-6 fatty acids. Dietary supplementation with DHA (n-3) or DHA plus arachidonic acid (n-6) from P30-P60 mitigated the progression of retinal dysfunction in <em>Acox1</em> KO mice.<h3>Conclusion</h3>Retinal dysfunction, decreased mitochondrial number, and metabolic imbalance were observed in mice with impaired peroxisomal fatty acid oxidation. Nutrient intervention may offer a promising therapeutic approach for peroxisomal diseases.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"2 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538417","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":"The Power of Exercise: Unlocking the biological Mysteries of Peripheral-Central crosstalk in Parkinson’s disease","authors":"Jingwen Li, Tingting Liu, Meiyan Xian, Ke Zhou, Jianshe Wei","doi":"10.1016/j.jare.2025.03.001","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.001","url":null,"abstract":"<h3>Background</h3>Exercise is a widely recognized non-pharmacological treatment for Parkinson’s Disease (PD). The bidirectional regulation between the brain and peripheral organs has emerged as a promising area of research, with the mechanisms by which exercise impacts PD closely linked to the interplay between peripheral signals and the central nervous system.<h3>Aim of Review</h3>This review aims to summarize the mechanisms by which exercise influences peripheral-central crosstalk to improve PD, discuss the molecular processes mediating these interactions, elucidate the pathways through which exercise may modulate PD pathophysiology, and identify directions for future research.<h3>Key Scientific Concepts of Review</h3>This review examines how exercise-induced cytokine release promotes neuroprotection in PD. It discusses how exercise can stimulate cytokine secretion through various pathways, including the gut-brain, muscle-brain, liver-brain, adipose-brain, and bone-brain axes, thereby alleviating PD symptoms. Additionally, the potential contributions of the heart-brain, lung-brain, and spleen-brain axes, as well as multi-axis crosstalk—such as the brain-gut-muscle and brain-gut-bone axes—are explored in the context of exercise therapy. The study highlights the need for further research into peripheral-central crosstalk and outlines future directions to address challenges in clinical PD therapy.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"145 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538515","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":"Cracking melanoma’s armor: Supramolecular dual-strike on XPO1 and β-catenin to overcome resistance","authors":"Yinliang Lu, Ruishan Guo, Wenfei Song, Jing Wang, Hanmin Tang, Minghui Wei, Jing Zhao, Jinlu Ma, Tianya Liu, Wangxiao He, Suxia Han","doi":"10.1016/j.jare.2025.02.042","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.042","url":null,"abstract":"<h3>Introduction</h3>XPO1 plays a crucial role in the nuclear export machinery, making it an attractive target for inhibiting nuclear-cytoplasmic transport in melanoma, where its overexpression is linked to unfavorable prognosis. However, XPO1 monotherapy has not demonstrated sufficient efficacy to be considered a first-line treatment option for melanoma.<h3>Objectives</h3>This research aimed to delve into the resistance mechanism of XPO1-targeting therapy in melanoma and fabricate a proteinoid microsphere which could target XPO1 and β-catenin to maximize the effect of XPO1 inhibitors.<h3>Methods</h3>Transcriptome sequencing was used to analyze the effects of XPO1 interference on the signaling pathways of melanoma. Nuclear-cytoplasmic protein separation, co-immunoprecipitation, and confocal microscopic analyses were conducted to clarify the resistance mechanism of XPO1 targeting therapy. A proteinoid microsphere named XPinβ was developed by co-assembling a specially designed XPO1 antagonistic peptide (XPin) and a β-catenin antagonist (Carnosic acid/CA). Cell model, mouse allograft and patient-derived xenograft (PDX) models were used to evaluate the antitumor effect of XPinβ.<h3>Results</h3>In our study, inhibition of XPO1 led to the nuclear accumulation of β-catenin, altered the nuclear-cytoplasmic localization of APC, and activated the Wnt/β-catenin signaling pathway. XPinβ was efficiently internalized into melanoma cells via macropinocytosis, achieving simultaneous inhibition of both XPO1 and β-catenin. As expected, XPinβ demonstrated robust anti-tumor efficacy in an <u>allograft</u> melanoma mouse model, with significantly superior therapeutic effects compared to monotherapy targeting XPO1 or CA treatment alone. Moreover, XPinβ effectively inhibited growth of patient-derived xenograft (PDX) tumors overexpressing XPO1, outperforming both CA and the commercially available XPO1 inhibitor KPT-330. Most importantly, XPinβ significantly suppressed pulmonary metastasis of melanoma while maintaining excellent biosafety.<h3>Conclusions</h3>This study demonstrates the enhanced efficacy of XPO1-targeted therapy through the inhibition of the Wnt/β-catenin signaling pathway and introduces XPinβ, a proteinoid microsphere with promising clinical translational potential for dual targeting therapy against melanoma involving both XPO1 and β-catenin.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"29 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532684","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":"Activation of Sirt6 by icariside Ⅱ alleviates depressive behaviors in mice with poststroke depression by modulating microbiota-gut-brain axis","authors":"Jianmei Gao, Yifan He, Fuguo Shi, Fangqin Hou, Xiaoyu Wu, Yang Yi, Yuandong Zhang, Qihai Gong","doi":"10.1016/j.jare.2025.03.002","DOIUrl":"https://doi.org/10.1016/j.jare.2025.03.002","url":null,"abstract":"<h3>Background</h3>Sirt6-mediated gut microbiota plays a vital role in poststroke depression (PSD). Icariside Ⅱ (ICS Ⅱ) is a naturally-occurring neuroprotectant with Sirt6 induction potency. However, it is unknown whether ICS Ⅱ protects against PSD through modulation of gut microbiota.<h3>Objective</h3>This study aimed to reveal the effect and potential mechanisms of ICS Ⅱ on PSD, and the role of the microbiota-gut-brain axis was investigated.<h3>Methods</h3>Using middle cerebral artery occlusion (MCAO) and chronic unpredictable mild stress (CUMS) to establish post-stroke depression (PSD) mice, we assessed anti-depressant effects of ICS Ⅱ <em>via</em> behavioral tests, immunohistochemistry, and western blot. Transcriptome profiling, molecular docking, and surface plasmon resonance were used to identify key targets. 16S rDNA genomic-derived taxonomic profiling and fecal microbiota transplantation (FMT) were conducted to figure out the mechanistic role of the gut microbiota and short-chain fatty acids (SCFAs).<h3>Results</h3>ICS Ⅱ ameliorated depressive-like behaviors in PSD mice as evidenced by sucrose preference test, forced swimming test and tail suspension test. ICS Ⅱ restored mitochondrial function, reduced oxidative damage and pro-inflammatory cytokines both in brain and intestine through regulation of Sirt6/NF-κB pathway. ICS Ⅱ significantly increased the abundance of gut microbiota (such as<!-- --> <!-- -->Akkermansia and Ligilactobacillus), enhanced SCFAs concentrations, repaired intestinal barrier integrity and upreglated the tight junction protein expression. FMT from ICS II-treated mice replicated these benefits, confirming gut microbiota’s role. Mechanistically, ICS Ⅱ directly bound to Sirt6 and enhanced its activity. However, ICS Ⅱ-mediated neuroprotection was neutralized in PSD mice or hydrogen peroxide-induced enteric glial cells when Sirt6 was absent.<h3>Conclusion</h3>Our findings expand the pharmacological properties of ICS II by demonstrating its ability to ameliorate PSD through modulation of the microbiota-gut-brain axis. ICS Ⅱ, as a novel Sirt6 activator, could be translated into an alternative microbiota-targeted avenue for coping with PSD.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"39 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532827","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":"The causal links between long-term exposure to major chemical components of PM2.5 and overall outpatient visits in mainland China: A nationwide study in the difference-in-differences framework","authors":"Shuaiqi Zhang, Zhibing Chen, Zhicheng Du, Shenghao Wang, Dan Chen, Xingling Ruan, Ziqiang Lin, Zihan Zheng, Kunying Li, Xudan Chen, Zhishen Wu, Qing Qin, Man Zhang, Shuming Zhu, Shaomin Wu, Fangfang Zeng, Ying Wang, Wangjian Zhang","doi":"10.1016/j.jare.2025.02.041","DOIUrl":"https://doi.org/10.1016/j.jare.2025.02.041","url":null,"abstract":"<h3>Introduction</h3>Although the adverse health effects of PM_2.5 exposure has been well documented, evidence of its adverse effect on overall outpatient visits was still limited. Besides, the adverse health effects of PM_2.5 exposure get complicated due to various components within the particles. So far, little is known about the relationship between PM_2.5 components and overall outpatient visits.<h3>Objectives</h3>This study aims to evaluate the causal relationships between long-term exposure to primary chemical components of PM_2.5 and outpatient visits, while estimating the mixture effect and relative contribution of the components.<h3>Methods</h3>Based on nationwide provincial-level surveillance data of outpatient visits in China and well-validated simulations of PM_2.5 components concentration, we employed the Difference-In-Differences (DID) approach to evaluate the causal relationships between long-term exposure to primary chemical components of PM_2.5 and outpatient visits, and used a Bayesian Weighted Quantile Sum (BWQS) regression to assess the mixture effect of the components.<h3>Results</h3>We found a 20.44% increase in the risk (<em>IR%</em>) of outpatient visits following each InterQuartile Range (<em>IQR</em>) increment in PM_2.5 concentration. Our estimation further suggested a 17.07%, 15.91%, and 14.04% increase in the risk of outpatient visits for organic matter, sulfate, and nitrate, but non-significant increases for other components. However, when considering the inter-components correlation, sulfate and black carbon contributed most (42.3% and 28.1%, respectively) to the overall mixture effect of PM_2.5 which was indicated by a 4.84% increase (95%<em>CI</em>: 1.92%, 7.83%) in the risk of outpatient visits following every unit increase in the overall BWQS index. Additionally, stratified analyses showed a stronger association among aged provinces and provinces with lower education rates.<h3>Conclusion</h3>Our findings would improve understanding of the individual and mixture impact of major chemical components of PM_2.5 and may contribute to more targeted and optimized environmental programs for pollution control.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"38 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532872","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":"Sedanolide alleviates DSS-induced colitis by modulating the intestinal FXR-SMPD3 pathway in mice","authors":"Shengjie Li ,&nbsp;Aoxiang Zhuge ,&nbsp;Hui Chen ,&nbsp;Shengyi Han ,&nbsp;Jian Shen ,&nbsp;Kaicen Wang ,&nbsp;Jiafeng Xia ,&nbsp;He Xia ,&nbsp;Shiman Jiang ,&nbsp;Youhe Wu ,&nbsp;Lanjuan Li","doi":"10.1016/j.jare.2024.03.026","DOIUrl":"10.1016/j.jare.2024.03.026","url":null,"abstract":"<div><h3>Introduction</h3><div>Inflammatory bowel disease (IBD) is a global disease with limited therapy. It is reported that sedanolide exerts anti-oxidative and anti-inflammatory effects as a natural phthalide, but its effects on IBD remain unclear.</div></div><div><h3>Objectives</h3><div>In this study, we investigated the impacts of sedanolide on dextran sodium sulfate (DSS)-induced colitis in mice.</div></div><div><h3>Methods</h3><div>The mice were administered sedanolide or vehicle followed by DSS administration, after which colitis symptoms, inflammation levels, and intestinal barrier function were evaluated. Transcriptome analysis, 16S rRNA sequencing, and targeted metabolomics analysis of bile acids and lipids were performed.</div></div><div><h3>Results</h3><div>Sedanolide protected mice from DSS-induced colitis, suppressed the inflammation, restored the weakened epithelial barrier, and modified the gut microbiota by decreasing bile salt hydrolase (BSH)-expressing bacteria. The downregulation of BSH activity by sedanolide increased the ratio of conjugated/unconjugated bile acids (BAs), thereby inhibiting the intestinal farnesoid X receptor (FXR) pathway. The roles of the FXR pathway and gut microbiota were verified using an intestinal FXR-specific agonist (fexaramine) and germ-free mice, respectively. Furthermore, we identified the key effector ceramide, which is regulated by sphingomyelin phosphodiesterase 3 (SMPD3). The protective effects of ceramide (d18:1/16:0) against inflammation and the gut barrier were demonstrated in vitro using the human cell line Caco-2.</div></div><div><h3>Conclusion</h3><div>Sedanolide could reshape the intestinal flora and influence BA composition, thus inhibiting the FXR-SMPD3 pathway to stimulate the synthesis of ceramide, which ultimately alleviated DSS-induced colitis in mice. Overall, our research revealed the protective effects of sedanolide against DSS-induced colitis in mice, which indicated that sedanolide may be a clinical treatment for colitis. Additionally, the key lipid ceramide (d18:1/16:0) was shown to mediate the protective effects of sedanolide, providing new insight into the associations between colitis and lipid metabolites.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 413-426"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140604261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}