Muhammad Noman , Temoor Ahmed , Muhammad Shahid , Muhammad Mudassir Nazir , Azizullah , Dayong Li , Fengming Song
{"title":"Salicylic acid-doped iron nano-biostimulants potentiate defense responses and suppress Fusarium wilt in watermelon","authors":"Muhammad Noman , Temoor Ahmed , Muhammad Shahid , Muhammad Mudassir Nazir , Azizullah , Dayong Li , Fengming Song","doi":"10.1016/j.jare.2023.06.011","DOIUrl":"10.1016/j.jare.2023.06.011","url":null,"abstract":"<div><h3>Introduction</h3><p>Chemo- and bio-genic metallic nanoparticles (NPs), as a novel nano-enabled strategy, have demonstrated a great potential in crop health management.</p></div><div><h3>Objective</h3><p>The current study aimed to explore the efficacy of advanced nanocomposites (NCs), integrating biogenic (bio) metallic NPs and plant immunity-regulating hormones, in crop disease control.</p></div><div><h3>Methods</h3><p>Iron (Fe) NPs were biosynthesized using cell-free supernatant of a Fe-resistant strains, <em>Bacillus marisflavi</em> ZJ-4. Further, salicylic acid-coated bio-FeNPs (SI) NCs were prepared <em>via</em> co-precipitation method under alkaline conditions. Both bio-FeNPs and SINCs were characterized using basic analytical techniques, including Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction analysis, and scanning/transmission electron microscopy.</p></div><div><h3>Results</h3><p>Bio-FeNPs and SINCs had variable shapes with average sizes of 72.35 nm and 65.87 nm, respectively. Under greenhouse conditions, bio-FeNPs and SINCs improved the agronomic traits of the watermelon plants, and SINCs outperformed bio-FeNPs, providing the maximum growth promotion of 32.5%. Soil-drenching with bio-FeNPs and SINCs suppressed <em>Fusarium oxysporum</em> f. sp. <em>niveum</em>-caused Fusarium wilt in watermelon, and SINCs provided better protection than bio-FeNPs, through inhibiting the fungal invasive growth within host plants. SINCs improved the antioxidative capacity and primed a systemic acquired resistance (SAR) response <em>via</em> activating the salicylic acid signaling pathway genes. These findings indicate that SINCs can reduce the severity of Fusarium wilt in watermelon by modulating antioxidative capacity and potentiating SAR to restrict <em>in planta</em> fungal invasive growth.</p></div><div><h3>Conclusion</h3><p>This study provides new insights into the potential of bio-FeNPs and SINCs as biostimulants and bioprotectants for growth promotion and Fusarium wilt suppression, ensuring sustainable watermelon production.</p></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"59 ","pages":"Pages 19-33"},"PeriodicalIF":10.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2090123223001741/pdfft?md5=52842304c97456e4c1e61f9de1227693&pid=1-s2.0-S2090123223001741-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9763875","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}
Yaqi Zhao , Junyan Shi , Bihong Feng , Shuzhi Yuan , Xiaozhen Yue , Wenlin Shi , Zhicheng Yan , Dongying Xu , Jinhua Zuo , Qing Wang
{"title":"Multi-omic analysis of the extension of broccoli quality during storage by folic acid","authors":"Yaqi Zhao , Junyan Shi , Bihong Feng , Shuzhi Yuan , Xiaozhen Yue , Wenlin Shi , Zhicheng Yan , Dongying Xu , Jinhua Zuo , Qing Wang","doi":"10.1016/j.jare.2023.07.001","DOIUrl":"10.1016/j.jare.2023.07.001","url":null,"abstract":"<div><h3>Introduction</h3><p>Folic acid (FA) is a critical metabolite in all living organisms and an important nutritional component of broccoli. Few studies have been conducted on the impact of an exogenous application of FA on the postharvest physiology of fruits and vegetables during storage. In this regard, the mechanism by which an exogenous application of FA extends the postharvest quality of broccoli is unclear.</p></div><div><h3>Objective</h3><p>This study utilized a multicomponent analysis to investigate how an exogenous application of FA effects the postharvest quality of broccoli.</p></div><div><h3>Methods</h3><p>Broccoli was soaked in 5 mg/L FA for 10 min and the effect of the treatment on the appearance and nutritional quality of broccoli was evaluated. These data were combined with transcriptomic, metabolomic, and DNA methylation data to provide insight into the potential mechanism by which FA delays senescence.</p></div><div><h3>Results</h3><p>The FA treatment inhibited the yellowing of broccoli during storage. CHH methylation was identified as the main type of methylation that occurs in broccoli and the FA treatment was found to inhibit DNA methylation, promote the accumulation of endogenous FA and chlorophyl, and inhibit ethylene biosynthesis in stored broccoli. The FA treatment also prevented the formation of off-odors by inhibiting the degradation of glucosinolate.</p></div><div><h3>Conclusions</h3><p>FA treatment inhibited the loss of nutrients during the storage of broccoli, delayed its yellowing, and inhibited the generation of off-odors. Our study provides deeper insight into the mechanism by which the postharvest application of FA delays postharvest senescence in broccoli and provides the foundation for further studies of postharvest metabolism in broccoli.</p></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"59 ","pages":"Pages 65-78"},"PeriodicalIF":10.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2090123223001807/pdfft?md5=ff296707feab4011450c4afac68cf785&pid=1-s2.0-S2090123223001807-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9843487","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}
Nathalie Rohmann , Paula Stürmer , Corinna Geisler , Kristina Schlicht , Carina Knappe , Katharina Hartmann , Kathrin Türk , Tim Hollstein , Alexia Beckmann , Anna K. Seoudy , Ulla Becker , Perdita Wietzke-Braun , Ute Settgast , Florian Tran , Philip Rosenstiel , Jan H. Beckmann , Witigo von Schönfels , Stephan Seifert , Jan Heyckendorf , Andre Franke , Matthias Laudes
{"title":"Effects of lifestyle and associated diseases on serum CC16 suggest complex interactions among metabolism, heart and lungs","authors":"Nathalie Rohmann , Paula Stürmer , Corinna Geisler , Kristina Schlicht , Carina Knappe , Katharina Hartmann , Kathrin Türk , Tim Hollstein , Alexia Beckmann , Anna K. Seoudy , Ulla Becker , Perdita Wietzke-Braun , Ute Settgast , Florian Tran , Philip Rosenstiel , Jan H. Beckmann , Witigo von Schönfels , Stephan Seifert , Jan Heyckendorf , Andre Franke , Matthias Laudes","doi":"10.1016/j.jare.2023.06.005","DOIUrl":"10.1016/j.jare.2023.06.005","url":null,"abstract":"<div><h3>Introduction</h3><p>Clara cell 16-kDa protein (CC16) is an anti-inflammatory, immunomodulatory secreted pulmonary protein with reduced serum concentrations in obesity according to recent data.</p></div><div><h3>Objective</h3><p>Studies focused solely on bodyweight, which does not properly reflect obesity-associated implications of the metabolic and reno-cardio-vascular system. The purpose of this study was therefore to examine CC16 in a broad physiological context considering cardio-metabolic comorbidities of primary pulmonary diseases.</p></div><div><h3>Methods</h3><p>CC16 was quantified in serum samples in a subset of the FoCus (N = 497) and two weight loss intervention cohorts (N = 99) using ELISA. Correlation and general linear regression analyses were applied to assess CC16 effects of lifestyle, gut microbiota, disease occurrence and treatment strategies. Importance and intercorrelation of determinants were validated using random forest algorithms.</p></div><div><h3>Results</h3><p>CC16 A38G gene mutation, smoking and low microbial diversity significantly decreased CC16. Pre-menopausal female displayed lower CC16 compared to post-menopausal female and male participants. Biological age and uricosuric medications increased CC16 (all <em>p</em> < 0.01). Adjusted linear regression revealed CC16 lowering effects of high waist-to-hip ratio (est. −11.19 [−19.4; −2.97], <em>p</em> = 7.99 × 10<sup>−3</sup>), severe obesity (est. −2.58 [−4.33; −0.82], <em>p</em> = 4.14 × 10<sup>−3</sup>) and hypertension (est. −4.31 [−7.5; −1.12], <em>p</em> = 8.48 × 10<sup>−3</sup>). ACEi/ARB medication (<em>p</em> = 2.5 × 10<sup>−2</sup>) and chronic heart failure (est. 4.69 [1.37; 8.02], <em>p</em> = 5.91 × 10<sup>−3</sup>) presented increasing effects on CC16. Mild associations of CC16 were observed with blood pressure, HOMA-IR and NT-proBNP, but not manifest hyperlipidemia, type 2 diabetes, diet quality and dietary weight loss intervention.</p></div><div><h3>Conclusion</h3><p>A role of metabolic and cardiovascular abnormalities in the regulation of CC16 and its modifiability by behavioral and pharmacological interventions is indicated. Alterations by ACEi/ARB and uricosurics could point towards regulatory axes comprising the renin-angiotensin-aldosterone system and purine metabolism. Findings altogether strengthen the importance of interactions among metabolism, heart and lungs.</p></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"59 ","pages":"Pages 161-171"},"PeriodicalIF":10.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2090123223001686/pdfft?md5=63492328022031a161b8be41b7c6e912&pid=1-s2.0-S2090123223001686-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9672247","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}
Wenli Guo , Shuai Liu , Muhammad Z. Khan , Jingjun Wang , Tianyu Chen , Gibson M. Alugongo , Shengli Li , Zhijun Cao
{"title":"Bovine milk microbiota: Key players, origins, and potential contributions to early-life gut development","authors":"Wenli Guo , Shuai Liu , Muhammad Z. Khan , Jingjun Wang , Tianyu Chen , Gibson M. Alugongo , Shengli Li , Zhijun Cao","doi":"10.1016/j.jare.2023.06.016","DOIUrl":"10.1016/j.jare.2023.06.016","url":null,"abstract":"<div><h3>Background</h3><p>Bovine milk is a significant substitute for human breast milk and holds great importance in infant nutrition and health. Apart from essential nutrients, bovine milk also contains bioactive compounds, including a microbiota derived from milk itself rather than external sources of contamination.</p></div><div><h3>Aim of review</h3><p>Recognizing the profound impact of bovine milk microorganisms on future generations, our review focuses on exploring their composition, origins, functions, and applications.</p></div><div><h3>Key scientific concepts of review</h3><p>Some of the primary microorganisms found in bovine milk are also present in human milk. These microorganisms are likely transferred to the mammary gland through two pathways: the entero-mammary pathway and the rumen-mammary pathway. We also elucidated potential mechanisms by which milk microbiota contribute to infant intestinal development. The mechanisms include the enhancing of the intestinal microecological niche, promoting the maturation of immune system, strengthening the intestinal epithelial barrier function, and interacting with milk components (e.g., oligosaccharides) via cross-feeding effect. However, given the limited understanding of bovine milk microbiota, further studies are necessary to validate hypotheses regarding their origins and to explore their functions and potential applications in early intestinal development.</p></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"59 ","pages":"Pages 49-64"},"PeriodicalIF":10.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2090123223001790/pdfft?md5=c12eecb261558106822b263ac2edb249&pid=1-s2.0-S2090123223001790-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10219895","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}
Ke Xu , Mingyang Wang , Haiyang Wang , Shuang Zhao , Dianji Tu , Xue Gong , Wenxia Li , Xiaolei Liu , Lianmei Zhong , Jianjun Chen , Peng Xie
{"title":"HMGB1/STAT3/p65 axis drives microglial activation and autophagy exert a crucial role in chronic Stress-Induced major depressive disorder","authors":"Ke Xu , Mingyang Wang , Haiyang Wang , Shuang Zhao , Dianji Tu , Xue Gong , Wenxia Li , Xiaolei Liu , Lianmei Zhong , Jianjun Chen , Peng Xie","doi":"10.1016/j.jare.2023.06.003","DOIUrl":"10.1016/j.jare.2023.06.003","url":null,"abstract":"<div><h3>Introduction</h3><p>Neuroinflammation and autophagy are implicated in stress-related major depressive disorder (MDD), but the underlying molecular mechanisms remain largely unknown.</p></div><div><h3>Objectives</h3><p>Here, we identified that MDD regulated by HMGB1/STAT3/p65 axis mediated microglial activation and autophagy for the first time. Further investigations were performed to uncover the effects of this axis on MDD <em>in vivo</em> and <em>in vitro</em>.</p></div><div><h3>Methods</h3><p>Bioinformatics analyses were used to re-analysis the transcriptome data from the dorsolateral prefrontal cortex (dlPFC) of post-mortem male MDD patients. The expression level of HMGB1 and its correlation with depression symptoms were explored in MDD clinical patients and chronic social defeat stress (CSDS)-induced depression model mice. Specific adeno-associated virus and recombinant (r)HMGB1 injection into the medial PFC (mPFC) of mice, and pharmacological inhibitors with rHMGB1 in two microglial cell lines exposed to lipopolysaccharide were used to analyze the effects of HMGB1/STAT3/p65 axis on MDD.</p></div><div><h3>Results</h3><p>The differential expression of genes from MDD patients implicated in microglial activation and autophagy regulated by HMGB1/STAT3/p65 axis. Serum HMGB1 level was elevated in MDD patients and positively correlated with symptom severity. CSDS not only induced depression-like states in mice, but also enhanced microglial reactivity, autophagy as well as activation of the HMGB1/STAT3/p65 axis in mPFC. The expression level of HMGB1 was mainly increased in the microglial cells of CSDS-susceptible mice, which also correlated with depressive-like behaviors. Specific HMGB1 knockdown produced a depression-resilient phenotype and suppressed the associated microglial activation and autophagy effects of CSDS-induced. The effects induced by CSDS were mimicked by exogenous administration of rHMGB1 or specific overexpression of HMGB1, while blocked by STAT3 inhibitor or p65 knockdown. <em>In vitro</em>, inhibition of HMGB1/STAT3/p65 axis prevented lipopolysaccharide-induced microglial activation and autophagy, while rHMGB1 reversed these changes.</p></div><div><h3>Conclusion</h3><p>Our study established the role of microglial HMGB1/STAT3/p65 axis in mPFC in mediating microglial activation and autophagy in MDD.</p></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"59 ","pages":"Pages 79-96"},"PeriodicalIF":10.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2090123223001522/pdfft?md5=a1d5512bd9b434886a92e62d84392e0d&pid=1-s2.0-S2090123223001522-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10035331","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}
Bing Wu , Ye Li , Baoguo Shi , Xiyu Zhang , Yongqiang Lai , Fuqiang Cui , Xiaodan Bai , Wenjing Xiang , Guihong Geng , Bei Liu , Mingli Jiao , Qunhong Wu , Huiying Yang , Chenxi Zhang , Xinwei Liu , Yulu Tian , Hongyu Li
{"title":"Temporal trends of breast cancer burden in the Western Pacific Region from 1990 to 2044: Implications from the Global Burden of Disease Study 2019","authors":"Bing Wu , Ye Li , Baoguo Shi , Xiyu Zhang , Yongqiang Lai , Fuqiang Cui , Xiaodan Bai , Wenjing Xiang , Guihong Geng , Bei Liu , Mingli Jiao , Qunhong Wu , Huiying Yang , Chenxi Zhang , Xinwei Liu , Yulu Tian , Hongyu Li","doi":"10.1016/j.jare.2023.07.003","DOIUrl":"10.1016/j.jare.2023.07.003","url":null,"abstract":"<div><h3>Introduction</h3><p>Breast cancer (BC) is a malignant disease that occurs worldwide and poses serious health burden.</p></div><div><h3>Objectives</h3><p>To assess the prevalence of BC burden in the Western Pacific region (WPR) from 1990 to 2019, and to predict trends from 2020 to 2044. To analyze the driving factors and put forward the region-oriented improvement.</p></div><div><h3>Methods</h3><p>Based on the Global Burden of Disease Study 2019, BC cases, deaths, disability-adjusted life years (DALYs) cases, age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and age-standardized DALYs rate in WPR from 1990 to 2019 was obtained and analysed. Age-period-cohort (APC) model was used to analyze age, period, and cohort effects in BC, and Bayesian APC (BAPC) was used to predict trends over the next 25 years.</p></div><div><h3>Results</h3><p>In conclusion, BC incidence and deaths in the WPR have increased rapidly over the past 30 years and are expected to continue to increase between 2020 and 2044. Among behavioral and metabolic factors, high body-mass index was the main risk factor for BC mortality in middle-income countries, whereas alcohol use was the main risk factor in Japan. Age is a key factor in the development of BC, with 40 years being the critical point. Incidence trends coincide with the course of economic development.</p></div><div><h3>Conclusions</h3><p>The BC burden remains an essential public health issue in the WPR and will increase substantially in the future. More efforts should be made in middle-income countries to prompt the health behavior and minimize the burden of BC because these nations accounts for the majority of BC burden in the WPR.</p></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"59 ","pages":"Pages 189-199"},"PeriodicalIF":10.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2090123223001820/pdfft?md5=9d5caf49aecd9449108bed677b956192&pid=1-s2.0-S2090123223001820-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9777672","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}
Guangliang Zhang , Junhong Bai , Yujia Zhai , Jia Jia , Qingqing Zhao , Wei Wang , Xingyun Hu
{"title":"Microbial diversity and functions in saline soils: A review from a biogeochemical perspective","authors":"Guangliang Zhang , Junhong Bai , Yujia Zhai , Jia Jia , Qingqing Zhao , Wei Wang , Xingyun Hu","doi":"10.1016/j.jare.2023.06.015","DOIUrl":"10.1016/j.jare.2023.06.015","url":null,"abstract":"<div><h3>Background</h3><p>Soil salinization threatens food security and ecosystem health, and is one of the important drivers to the degradation of many ecosystems around the world. Soil microorganisms have extremely high diversity and participate in a variety of key ecological processes. They are important guarantees for soil health and sustainable ecosystem development. However, our understanding of the diversity and function of soil microorganisms under the change of increased soil salinization is fragmented.</p></div><div><h3>Aim of Review</h3><p>Here, we summarize the changes in soil microbial diversity and function under the influence of soil salinization in diverse natural ecosystems. We particularly focus on the diversity of soil bacteria and fungi under salt stress and the changes in their emerging functions (such as their mediated biogeochemical processes). This study also discusses how to use the soil microbiome in saline soils to deal with soil salinization for supporting sustainable ecosystems, and puts forward the knowledge gaps and the research directions that need to be strengthened in the future.</p></div><div><h3>Key Scientific Concepts of Review</h3><p>Due to the rapid development of molecular-based biotechnology (especially high-throughput sequencing technology), the diversity and community composition and functional genes of soil microorganisms have been extensively characterized in different habitats. Clarifying the responding pattern of microbial-mediated nutrient cycling under salt stress and developing and utilizing microorganisms to weaken the adverse effects of salt stress on plants and soil, which are of guiding significance for agricultural production and ecosystem management in saline lands.</p></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"59 ","pages":"Pages 129-140"},"PeriodicalIF":10.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2090123223001789/pdfft?md5=eec56813be8f603e9805badae1b9a561&pid=1-s2.0-S2090123223001789-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9799825","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}
Xingzhao Ji, Mingqiang Liu, Tianyi Zhang, Weiying Zhang, Fuyuan Xue, Qiang Wan, Yi Liu
{"title":"KRAS/PI3K axis driven GTF3C6 expression and promotes LUAD via FAK pathway","authors":"Xingzhao Ji, Mingqiang Liu, Tianyi Zhang, Weiying Zhang, Fuyuan Xue, Qiang Wan, Yi Liu","doi":"10.1016/j.jare.2024.04.028","DOIUrl":"https://doi.org/10.1016/j.jare.2024.04.028","url":null,"abstract":"Effective targeting drugs for KRAS mutation-mediated Lung Adenocarcinoma (LUAD) are currently are limited. Investigating and intervening in the downstream key target genes of KRAS is crucial for clinically managing KRAS mutant-driven LUAD. GTF3C6, a newly identified member of the general transcription factor III (GTF3) family, plays a role in the transcription of RNA polymerase III (pol III)-dependent genes. However, its involvement in cancer remains unexplored. This study examined the expression, roles, and potential molecular mechanisms of GTF3C6 in LUAD tissues, LSL-Kras;LSL-p53 LUAD mouse models, and LUAD patients-derived organoid using Western blot, qRT-PCR, immunofluorescence, immunohistochemistry, and gene manipulation assays. We present the first evidence that GTF3C6 is highly expressed in LUAD tissues, LSL-Kras;LSL-p53 LUAD mouse models, and LUAD organoids, correlating with poor clinical prognosis. Furthermore, GTF3C6 was found to promote anchorage-independent proliferation, migration, and invasion of LUAD cells. Mechanistically, KRAS mutation drives GTF3C6 expression through the PI3K pathway, and GTF3C6 knockdown reverses the malignant phenotype of KRAS mutation-driven LUAD cells. Additionally, the FAK pathway emerged as a crucial downstream signaling pathway through which GTF3C6 mediates the malignant phenotype of LUAD. Finally, GTF3C6 knockdown suppresses LUAD organoid formation and inhibits tumor growth in vivo. Our findings demonstrate that GTF3C6, driven by KRAS mutation, promotes LUAD development by regulating FAK phosphorylation, suggesting its potential as a biomarker and therapeutic target in KRAS mutant-driven LUAD.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"6 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140818090","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":"Tolerogenic dendritic cell-mediated regulatory T cell differentiation by Chinese herbal formulation attenuates colitis progression","authors":"Chunhua Huang, Cheng Lyu, Heung-Lam Mok, Yiqi Xu, Ka-Wing Cheng, Cheng Zhang, Die Hu, Lin Zhu, Chengyuan Lin, Xin Chen, Hor-Yue Tan, Zhaoxiang Bian","doi":"10.1016/j.jare.2024.04.023","DOIUrl":"https://doi.org/10.1016/j.jare.2024.04.023","url":null,"abstract":"Ulcerative colitis (UC) is a chronic inflammatory disease characterized by loss of immune tolerance to luminal antigens and progressive intestinal tissue injury. Thus, the re-establishment of immune tolerance is crucial for suppressing aberrant immune responses and UC progression. This study aimed to investigate the mechanisms underlying the action of CDD-2103 and its bioactive compounds in mediating immune regulation in mouse models of colitis. Two experimental colitis models, chronic 2,4,6-trinitrobenzene sulfonic acid (TNBS)- and T-cell transfer-induced mice, were used to determine the effects of CDD-2103 on colitis progression. Single-cell transcriptome analysis was used to profile the immune landscape and its interactions after CDD-2103 treatment. Liquid chromatography-mass spectrometry (LC-MS) was used to analyze the major components interacting with lymphoid cells. A primary cell co-culture system was used to confirm the effects of bioactive component. CDD-2103 dose-dependently suppresses the progression of colitis induced by chemicals or T cell transplantation in mice. The effect of CDD-2103 is primarily attributable to an increase in the generation of regulatory T cells (Tregs) in the lamina propria (LP). Single-cell transcriptomic analysis revealed that CDD-2103 treatment increased the number of tolerogenic dendritic cells (DCs). Mechanistically, CDD-2103 promoted tolerogenic DCs accumulation and function by upregulating several genes in the electron transport chain related to oxidative phosphorylation, leading to increased differentiation of Tregs. Further LC-MS analysis identified several compounds in CDD-2103, particularly those distributed within the mesenteric lymph nodes of mice. Subsequent studies revealed that palmatine and berberine promoted tolerogenic bone marrow-derived dendritic cells (BMDC)-mediated Treg differentiation. Overall, our study demonstrated that the clinically beneficial effect of CDD-2103 in the treatment of UC is based on the induction of immune tolerance. In addition, this study supports berberine and palmatine as potential chemical entities in CDD-2103 that modulate immune tolerance.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"33 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140818099","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}