MedComm最新文献

{"title":"Tumor cells utilize acetate for tumor growth and immune evasion","authors":"Peng Sun, Juanjuan Liu, Deliang Guo","doi":"10.1002/mco2.717","DOIUrl":"https://doi.org/10.1002/mco2.717","url":null,"abstract":"<p>A recent study from Zhimin Lu's group published in <i>Nature Metabolism</i><span><sup>1</sup></span> demonstrates that acetate reprogrammed cancer cell metabolism and promoted tumor immune evasion. Notably, nutrients, such as glucose and short-chain fatty acids (SCFAs), in the tumor microenvironment impact tumor growth.<span><sup>1</sup></span> It is well known that tumor cells, regardless of oxygen supply, utilize glucose to produce ATP and building blocks for macromolecule synthesis<span><sup>2, 3</sup></span>; however, recent research has shown that glucose uptake by these cells not only supports the Warburg effect but also triggers non-metabolic functions.<span><sup>4</sup></span> Similar to glucose as a nutrient derived from the diet, acetate, as a main SCFA, is also enriched in the tumor microenvironment. Acetate plays a critical role in mitochondrial oxidation, lipogenesis, and histone acetylation to support tumor cell growth.<span><sup>5</sup></span> However, it remains unclear whether acetate contributes to tumor cell proliferation and immune evasion by directly influencing oncogenic proteins.</p><p>Through metabolomic analysis of human non-small cell lung cancer (NSCLC) specimens, Lu's team revealed that acetate was the most abundant short-chain fatty acid (SCFA). They found that the carbon-13 (<sup>13</sup>C)- or deuterium (<sup>3</sup>D)-labeled acetate was more enriched in lung tumor tissues and tumor cells than in normal lung tissues and tumor interstitial fluid in mice, with a corresponding increase in <sup>13</sup>C-acetyl-CoA in tumor tissues.<span><sup>1</sup></span> Depletion studies of monocarboxylate transporters (MCT)1-4 and sodium-coupled MCT (SMCT)1-2 showed that only the depletion of MCT1, which is highly expressed in NSCLC tissues, led to reduced levels of acetate, acetyl-CoA, and synthesized fatty acids in tumor cells or mouse lung tumors. These results indicate that highly expressed MCT1 transports acetate into tumor cells. Notably, acetate supported tumor cell proliferation and mouse tumor growth only under conditions of low glucose or depletion of glucose transporters GLUT1 and GLUT3,<span><sup>1</sup></span> suggesting that glucose is a primary resource for tumor growth and that acetate counteracts energy stress to sustain tumor cell proliferation.</p><p>In addition to supporting anabolic synthesis, acetate-derived acetyl-CoA, produced by the enzyme acetyl-CoA synthetase 2 (ACSS2), is utilized for protein acetylation. Mass spectrometry analysis of cellular immunoprecipitates with an anti-acetylated lysine antibody showed that acetate increased both the acetylation and expression of c-Myc. In addition, acetate increased the interaction between c-Myc and dihydrolipoamide S-acetyltransferase (DLAT), a component of pyruvate dehydrogenase complex (PDC).<span><sup>1</sup></span> Remarkably, purified DLAT was able to acetylate purified c-Myc at the K148 site in vitro. In NSCLC cells, depletion of DLAT reduced the acetyl","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.717","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statins, but not proprotein convertase subtilisin-kexin type 9 inhibitors, lower chemerin in hypercholesterolemia via low-density lipoprotein receptor upregulation","authors":"Lunbo Tan,&nbsp;Na Wang,&nbsp;Annet M. H. Galema-Boers,&nbsp;Leonie van Vark-van der Zee,&nbsp;Jeanine Roeters van Lennep,&nbsp;Monique T. Mulder,&nbsp;Xifeng Lu,&nbsp;A. H. Jan Danser,&nbsp;Koen Verdonk","doi":"10.1002/mco2.681","DOIUrl":"https://doi.org/10.1002/mco2.681","url":null,"abstract":"<p>Hypercholesterolemia is characterized by elevated low-density lipoprotein (LDL)-cholesterol levels and an increased risk of cardiovascular disease. The adipokine chemerin is an additional risk factor. Here we investigated whether cholesterol-lowering with statins or proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i) affects chemerin. Both statins and PCKS9i lowered plasma LDL-cholesterol, triglycerides and total cholesterol in hypercholesterolemic patients, and increased high-density lipoprotein (HDL)-cholesterol. Yet, only statins additionally reduced chemerin and high-sensitivity C-reactive protein (hsCRP). Applying PCSK9i on top of statins did not further reduce chemerin. Around 20% of chemerin occurred in the HDL₂/HDL₃ fractions, while &gt;75% was free. Statins lowered both HDL-bound and free chemerin. Pull-down assays revealed that chemerin binds to the HDL-component Apolipoprotein A-I (ApoA-I). The statins, but not PCSK9i, diminished chemerin secretion from HepG2 cells by upregulating LDL receptor mRNA. Furthermore, chemerin inhibited HDL-mediated cholesterol efflux via its chemerin chemokine-like receptor 1 in differentiated macrophages. In conclusion, statins, but not PCSK9i, lower circulating chemerin by directly affecting its release from hepatocytes. Chemerin binds to ApoA-I and inhibits HDL-mediated cholesterol efflux. Statins prevent this by lowering HDL-bound chemerin. Combined with their anti-inflammatory effect evidenced by hsCRP suppression, this represents a novel cardiovascular protective function of statins that distinguishes them from PCSK9i.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.681","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitor of differentiation 3 confers the robust anti-tumor activity of Kupffer cells","authors":"Jiang Ren,&nbsp;Sijia Liu,&nbsp;Long Zhang","doi":"10.1002/mco2.708","DOIUrl":"https://doi.org/10.1002/mco2.708","url":null,"abstract":"&lt;p&gt;A recent landmark study published in &lt;i&gt;Nature&lt;/i&gt; by Deng et al. reveals that inhibitor of differentiation 3 (ID3) empowers Kupffer cells (KCs) to efficiently engulf live tumor cells and activate the lymphoid anti-tumor immune response, orchestrating a potent anti-tumor niche and restricting liver tumor growth (Figure 1).&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The intricate interplay between macrophages and cancer has been the subject of intense research in recent decades. This study represents a milestone in the field of cell therapy, providing novel insights into tumor dynamics in an organ-specific context and offering promising prospects for the future application of engineered ID3-expressing macrophages in cancer immunotherapy.&lt;/p&gt;&lt;p&gt;The macrophage population comprises cells derived from diverse lineages that undergo differentiation during embryonic development, with KCs predominantly representing hepatic resident macrophages.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; The authors initially employed the CSF1R inhibitor PLX5622 or the genetic tool &lt;i&gt;Clec4f&lt;/i&gt;&lt;sup&gt;cre&lt;/sup&gt;&lt;i&gt;Csf1r&lt;/i&gt;&lt;sup&gt;f/f&lt;/sup&gt;/&lt;i&gt;Spi1&lt;/i&gt;&lt;sup&gt;f/f&lt;/sup&gt; to deplete KCs in tumor-bearing mice, and the results demonstrated a significant increase in liver metastatic tumor cells in KC-deficient mice. The spatial distributions of macrophages within the tumor microenvironment (TME) of liver metastases exhibit substantial heterogeneity. Tumor-associated macrophages (F4/80&lt;sup&gt;+&lt;/sup&gt;TIM4&lt;sup&gt;−&lt;/sup&gt;) are clustered within the tumor nodules, while KCs (TIM4&lt;sup&gt;+&lt;/sup&gt;CLEC4F&lt;sup&gt;+&lt;/sup&gt;) form a peritumoral niche consistently surrounding the tumor nodules.&lt;/p&gt;&lt;p&gt;The subsequent RNA-seq analysis of sorted KCs isolated from tumor-bearing livers revealed an upregulated expression of various receptors associated with the activation of macrophages and effector lymphoid cells, including activating receptors such as dectins, chemotactic factors like CCL2/3/4/5/6/7, and interleukins like IL-12/15/18. The authors observed a high abundance of KCs in tumor-derived material in both short- and long-term orthotopic models, as well as in endogenous KPC tumor models with spontaneous metastasis. The direct engulfment and killing of live tumor cells by KCs were demonstrated through in vitro and in vivo live-cell time-lapse imaging. Immunofluorescence staining experiments conducted on tumor-bearing livers have substantiated the production of CCR5 ligands (CCL3/4/5) and cytokines (IL-12/15/18) by KCs at the periphery of tumors. Additionally, the authors observed preferential enrichment of activated natural killer (NK) cells and CD8&lt;sup&gt;+&lt;/sup&gt; T cells at the tumor margin in the metastatic liver. This was accompanied by KCs expressing CCL3, CCL4, CCL5, IL-12, IL-15, and IL-18, which may contribute to enhanced phagocytosis of tumor cells.&lt;/p&gt;&lt;p&gt;KCs serve as resident immune sentinels and are regarded as a robust immune barrier against tumor progression owing to their high phagocytic capacity, however, the underlying mechanism remains","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.708","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-derived ovarian cancer organoid carries immune microenvironment and blood vessel keeping high response to cisplatin","authors":"Yuqing Zhao,&nbsp;Chen Wang,&nbsp;Wei Deng,&nbsp;Lanyang Li,&nbsp;Jiping Liu,&nbsp;Yanghua Shi,&nbsp;Xiang Tao,&nbsp;Jian Zhang,&nbsp;Qi Cao,&nbsp;Chunhui Cai,&nbsp;Xinxin Han","doi":"10.1002/mco2.697","DOIUrl":"https://doi.org/10.1002/mco2.697","url":null,"abstract":"<p>Ovarian cancer is high recurrence and mortality malignant tumor. The most common ovarian cancer was High-Grade Serous Ovarian Cancer. However, High-Grade Serous Ovarian Cancer organoid is rare, which organoid with patient immune microenvironment and blood vessels even absence. Here, we report a novel High-Grade Serous Ovarian Cancer organoid system derived from patient ovarian cancer samples. These organoids recapitulate High-Grade Serous Ovarian Cancer organoids' histological and molecular heterogeneity while preserving the critical immune microenvironment and blood vessels, as evidenced by the presence of <i>CD34</i>⁺ endothelial cells. Whole exome sequencing identifies key mutations (<i>CSMD3</i>, <i>TP53</i>, <i>GABRA6</i>). Organoids show promise in testing cisplatin sensitivity for patients resistant to carboplatin and paclitaxel, with notable responses in cancer proteoglycans and <i>p53</i> (<i>TP53</i>) signaling, like <i>ACTG</i>/<i>ACTB1</i>/<i>AKT2</i> genes and <i>BBC3</i>/<i>MDM2</i>/<i>PERP</i>. Integration of immune microenvironment and blood vessels enhances potential for novel therapies like immunotherapies and angiogenesis inhibitors. Our work may provide a new detection system and theoretical basis for ovarian cancer research and individual therapy.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.697","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142089861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Manganese boosts natural killer cell function via cGAS–STING mediated UTX expression","authors":"Qianyi Ming,&nbsp;Jiejie Liu,&nbsp;Zijian Lv,&nbsp;Tiance Wang,&nbsp;Runjia Fan,&nbsp;Yan Zhang,&nbsp;Meixia Chen,&nbsp;Yingli Sun,&nbsp;Weidong Han,&nbsp;Qian Mei","doi":"10.1002/mco2.683","DOIUrl":"https://doi.org/10.1002/mco2.683","url":null,"abstract":"<p>Natural killer (NK) cells play a crucial role in both innate immunity and the activation of adaptive immunity. The activating effect of Mn²⁺ on cyclic GMP-AMP(cGAS)–stimulator of interferon genes (STING signaling has been well known, but its effect on NK cells remains elusive. In this study, we identified the vital role of manganese (Mn²⁺) in NK cell activation. Mn²⁺ directly boosts cytotoxicity of NK cells and promotes the cytokine secretion by NK cells, thereby activating CD8+ T cells and enhancing their antitumor activity. Furthermore, Mn²⁺ can simultaneously activate NK-cell intrinsic cGAS and STING and consequently augment the expression of ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX to promote the responsiveness of NK cells. Our results contribute to a broader comprehension of how cGAS–STING regulates NK cells. As a potent agonist of cGAS–STING, Mn²⁺ provides a promising option for NK cell-based immunotherapy of cancers.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.683","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142089862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An inflammatory liquid fingerprint predicting tumor recurrence after liver transplantation for hepatocellular carcinoma","authors":"Modan Yang,&nbsp;Zuyuan Lin,&nbsp;Li Zhuang,&nbsp;Linhui Pan,&nbsp;Rui Wang,&nbsp;Hao Chen,&nbsp;Zhihang Hu,&nbsp;Wei Shen,&nbsp;Jianyong Zhuo,&nbsp;Xinyu Yang,&nbsp;Huigang Li,&nbsp;Chiyu He,&nbsp;Zhe Yang,&nbsp;Qinfen Xie,&nbsp;Siyi Dong,&nbsp;Junli Chen,&nbsp;Renyi Su,&nbsp;Xuyong Wei,&nbsp;Junjie Yin,&nbsp;Shusen Zheng,&nbsp;Di Lu,&nbsp;Xiao Xu","doi":"10.1002/mco2.678","DOIUrl":"10.1002/mco2.678","url":null,"abstract":"<p>Tumor recurrence is a life-threatening complication after liver transplantation (LT) for hepatocellular carcinoma (HCC). Precise recurrence risk stratification before transplantation is essential for the management of recipients. Here, we aimed to establish an inflammation-related prediction model for posttransplant HCC recurrence based on pretransplant peripheral cytokine profiling. Two hundred and ninety-three patients who underwent LT in two independent medical centers were enrolled, and their pretransplant plasma samples were sent for cytokine profiling. We identified four independent risk factors, including alpha-fetoprotein, systemic immune-inflammation index, interleukin 6, and osteocalcin in the training cohort (<i>n</i> = 190) by COX regression analysis. A prediction model named inflammatory fingerprint (IFP) was established based on the above factors. The IFP effectively predicted posttransplant recurrence (area under the receiver operating characteristic curve [AUROC]: 0.792, C-index: 0.736). The high IFP group recipients had significantly worse 3-year recurrence-free survival rates (37.9 vs. 86.9%, <i>p</i> &lt; 0.001). Simultaneous T-cell profiling revealed that recipients with high IFP were characterized by impaired T cell function. The IFP also performed well in the validation cohort (<i>n</i> = 103, AUROC: 0.807, C-index: 0.681). In conclusion, the IFP efficiently predicted posttransplant HCC recurrence and helped to refine pretransplant risk stratification. Impaired T cell function might be the intrinsic mechanism for the high recurrence risk of recipients in the high IFP group.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11345533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoplasmic reticulum stress in diseases","authors":"Yingying Liu,&nbsp;Chunling Xu,&nbsp;Renjun Gu,&nbsp;Ruiqin Han,&nbsp;Ziyu Li,&nbsp;Xianrong Xu","doi":"10.1002/mco2.701","DOIUrl":"10.1002/mco2.701","url":null,"abstract":"<p>The endoplasmic reticulum (ER) is a key organelle in eukaryotic cells, responsible for a wide range of vital functions, including the modification, folding, and trafficking of proteins, as well as the biosynthesis of lipids and the maintenance of intracellular calcium homeostasis. A variety of factors can disrupt the function of the ER, leading to the aggregation of unfolded and misfolded proteins within its confines and the induction of ER stress. A conserved cascade of signaling events known as the unfolded protein response (UPR) has evolved to relieve the burden within the ER and restore ER homeostasis. However, these processes can culminate in cell death while ER stress is sustained over an extended period and at elevated levels. This review summarizes the potential role of ER stress and the UPR in determining cell fate and function in various diseases, including cardiovascular diseases, neurodegenerative diseases, metabolic diseases, autoimmune diseases, fibrotic diseases, viral infections, and cancer. It also puts forward that the manipulation of this intricate signaling pathway may represent a novel target for drug discovery and innovative therapeutic strategies in the context of human diseases.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11345536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of resistance to tyrosine kinase inhibitor-targeted therapy and overcoming strategies","authors":"Xuejin Ou,&nbsp;Ge Gao,&nbsp;Inbar A. Habaz,&nbsp;Yongsheng Wang","doi":"10.1002/mco2.694","DOIUrl":"https://doi.org/10.1002/mco2.694","url":null,"abstract":"<p>Tyrosine kinase inhibitor (TKI)-targeted therapy has revolutionized cancer treatment by selectively blocking specific signaling pathways crucial for tumor growth, offering improved outcomes with fewer side effects compared with conventional chemotherapy. However, despite their initial effectiveness, resistance to TKIs remains a significant challenge in clinical practice. Understanding the mechanisms underlying TKI resistance is paramount for improving patient outcomes and developing more effective treatment strategies. In this review, we explored various mechanisms contributing to TKI resistance, including on-target mechanisms and off-target mechanisms, as well as changes in the tumor histology and tumor microenvironment (intrinsic mechanisms). Additionally, we summarized current therapeutic approaches aiming at circumventing TKI resistance, including the development of next-generation TKIs and combination therapies. We also discussed emerging strategies such as the use of dual-targeted antibodies and PROteolysis Targeting Chimeras. Furthermore, we explored future directions in TKI-targeted therapy, including the methods for detecting and monitoring drug resistance during treatment, identification of novel targets, exploration of dual-acting kinase inhibitors, application of nanotechnologies in targeted therapy, and so on. Overall, this review provides a comprehensive overview of the challenges and opportunities in TKI-targeted therapy, aiming to advance our understanding of resistance mechanisms and guide the development of more effective therapeutic approaches in cancer treatment.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.694","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142045283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic reprogramming in gastrointestinal cancer: biology and translational perspectives","authors":"Yingjie Wang,&nbsp;Hongyu Liu,&nbsp;Mengsha Zhang,&nbsp;Jing Xu,&nbsp;Liuxian Zheng,&nbsp;Pengpeng Liu,&nbsp;Jingyao Chen,&nbsp;Hongyu Liu,&nbsp;Chong Chen","doi":"10.1002/mco2.670","DOIUrl":"https://doi.org/10.1002/mco2.670","url":null,"abstract":"<p>Gastrointestinal tumors, the second leading cause of human mortality, are characterized by their association with inflammation. Currently, progress in the early diagnosis and effective treatment of gastrointestinal tumors is limited. Recent whole-genome analyses have underscored their profound heterogeneity and extensive genetic and epigenetic reprogramming. Epigenetic reprogramming pertains to dynamic and hereditable alterations in epigenetic patterns, devoid of concurrent modifications in the underlying DNA sequence. Common epigenetic modifications encompass DNA methylation, histone modifications, noncoding RNA, RNA modifications, and chromatin remodeling. These modifications possess the potential to invoke or suppress a multitude of genes associated with cancer, thereby governing the establishment of chromatin configurations characterized by diverse levels of accessibility. This intricate interplay assumes a pivotal and indispensable role in governing the commencement and advancement of gastrointestinal cancer. This article focuses on the impact of epigenetic reprogramming in the initiation and progression of gastric cancer, esophageal cancer, and colorectal cancer, as well as other uncommon gastrointestinal tumors. We elucidate the epigenetic landscape of gastrointestinal tumors, encompassing DNA methylation, histone modifications, chromatin remodeling, and their interrelationships. Besides, this review summarizes the potential diagnostic, therapeutic, and prognostic targets in epigenetic reprogramming, with the aim of assisting clinical treatment strategies.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.670","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142045282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing the effectiveness of anti-respiratory virus vaccines by bolstering mucosal immunity and cellular defenses","authors":"Rubing Xue,&nbsp;Sijia Liu,&nbsp;Fangfang Zhou","doi":"10.1002/mco2.616","DOIUrl":"10.1002/mco2.616","url":null,"abstract":"<p>A schematic diagram of intratracheal (IT) boosting, which leads to enhanced mucosal immunity and protective efficacy. IT boosting leads to significant expansion of mucosal neutralizing antibodies, along with robust CD8⁺ and CD4⁺ T-cell responses. Notably, IT boosting results in substantial and sustained activation of cytokine, natural killer, T, and B-cell pathways in the lung, contributing to enhanced mucosal immunity and overall protective efficacy.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}