MedComm最新文献

{"title":"The SUMOylated RREB1 interacts with KDM1A to induce 5-fluorouracil resistance via upregulating thymidylate synthase and activating DNA damage response pathway in colorectal cancer","authors":"Ya-Nan Deng,&nbsp;Lan Huang,&nbsp;Shan Gao,&nbsp;Zenghua Sheng,&nbsp;Yinheng Luo,&nbsp;Nan Zhang,&nbsp;Samina Ejaz Syed,&nbsp;Ruiwu Dai,&nbsp;Qiu Li,&nbsp;Xianghui Fu,&nbsp;Shufang Liang","doi":"10.1002/mco2.70105","DOIUrl":"https://doi.org/10.1002/mco2.70105","url":null,"abstract":"<p>Chemoresistance is one main cause of failure in colorectal cancer (CRC) treatment. The role of transcription factor Ras-responsive element binding protein 1 (RREB1) remains unclarified in CRC chemoresistance. Herein, we reveal that RREB1 functions as an oncogene to promote cell proliferation and 5-fluorouracil (5-FU) chemoresistance in CRC, and SUMOylation is required for RREB1 to exert its oncogenic role in CRC. RREB1 induced cell cycle arrest at the S-phase and a decreased apoptosis rate under 5-FU exposure. Mechanistically, the interaction of RREB1 with lysine demethylase 1A (KDM1A) elevated expression of 5-FU targeting proteins thymidylate synthase (TS) and thymidine kinase (TK1) to maintain the nucleotide pool balance under 5-FU treatment, and enhanced activation of Chk1-mediated DNA damage response (DDR) pathway. The deSUMOylation of RREB1 resulted in a reduced interaction of RREB1 with KDM1A, contributing to a downregulation of TS expression and a less activation of DDR pathway. Moreover, KDM1A knockdown improved the DNA damage and reduced RREB1-mediated resistance to 5-FU. These findings provide new insights into RREB1-mediated chemotherapy responses in CRC and indicate RREB1 is a potential target for overcoming 5-FU resistance.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 3","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456071","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 modifications in early stage lung cancer: pathogenesis, biomarkers, and early diagnosis","authors":"Lingfeng Bi,&nbsp;Xin Wang,&nbsp;Jiayi Li,&nbsp;Weimin Li,&nbsp;Zhoufeng Wang","doi":"10.1002/mco2.70080","DOIUrl":"https://doi.org/10.1002/mco2.70080","url":null,"abstract":"<p>The integration of liquid biopsy with epigenetic markers offers significant potential for early lung cancer detection and personalized treatment. Epigenetic alterations, including DNA methylation, histone modifications, and noncoding RNA changes, often precede genetic mutations and are critical in cancer progression. In this study, we explore how liquid biopsy, combined with epigenetic markers, can provide early detection of lung cancer, potentially predicting onset up to 4 years before clinical diagnosis. We discuss the challenges of targeting epigenetic regulators, which could disrupt cellular balance if overexploited, and the need for maintaining key gene expressions in therapeutic applications. This review highlights the promise and challenges of using liquid biopsy and epigenetic markers for early-stage lung cancer diagnosis, with a focus on optimizing treatment strategies for personalized and precision medicine.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 3","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456069","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":"Avelumab mediates antibody-dependent cellular cytotoxicity against monocyte-derived dendritic cells through natural killer cells","authors":"Tatjana Sauerer,&nbsp;Franziska Bremm,&nbsp;Amke C. Beenen,&nbsp;Lukas Heger,&nbsp;Diana Dudziak,&nbsp;Naomi C. Bosch,&nbsp;Michael Erdmann,&nbsp;Carola Berking,&nbsp;Niels Schaft,&nbsp;Jan Dörrie","doi":"10.1002/mco2.70111","DOIUrl":"https://doi.org/10.1002/mco2.70111","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;In recent years, treatment with immune checkpoint inhibitors (ICI) has revolutionized cancer therapy. Monoclonal antibodies that block immune checkpoint receptors such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) or its ligand PD-L1 prevent the tumor from suppressing adaptive immune responses.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Especially PD-L1 is expressed on tumor cells, but also on various healthy cell types.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; When we evaluated a combination therapy of active immunization via dendritic cells (DCs) and ICIs in the context of Merkel cell carcinoma (MCC) in order to improve the efficacy of the treatment, we observed an unexpected inhibitory effect of the anti-PD-L1 ICI Avelumab. In cell culture experiments with the most commonly used type of DCs in clinical trials on therapeutic cancer vaccination,&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; the priming capacity of the tumor antigen-loaded human monocyte-derived DCs was reduced in the presence of Avelumab but not Pembrolizumab (anti-PD-1; Figure S1A). Experiments with GFP-expressing DCs showed a disappearance of the DCs in co-cultures with autologous lymphocytes and Avelumab over time (data not shown). However, no direct toxic effect of the antibody against pure DCs was observed (Figure S1B). Moreover, the DCs’ ability to stimulate T cell receptor-transfected pure CD8&lt;sup&gt;+&lt;/sup&gt; T cells was not influenced by the ICI antibodies (Figure S1C).&lt;/p&gt;&lt;p&gt;From these unanticipated findings, we concluded that Avelumab, in the presence of autologous lymphocytes, had a detrimental effect on the DCs. In contrast to other approved anti-PD-L1 antibodies like Atezolizumab and Durvalumab, Avelumab contains a constant region (Fc-part) of the IgG1 isotype that is capable of inducing antibody-dependent cellular cytotoxicity (ADCC) against PD-L1 expressing tumor cells, which has been shown to be beneficial in preclinical studies.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; However, healthy cells including DCs also express PD-L1. Therefore, Avelumab could induce an unwanted ADCC reaction against the DCs, as any antibody with a suitable Fc-part that binds efficiently to these cells would do.&lt;/p&gt;&lt;p&gt;Flow cytometry experiments showed that monocyte-derived DCs expressed high levels of PD-L1 and that Avelumab, Atezolizumab, and Durvalumab but not Pembrolizumab efficiently bound to the DCs (see Figure 1A). Also, the human primary DC subpopulations cDC1, DC2, and DC3, which are responsible for antigen presentation,&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; expressed PD-L1 upon Toll-like receptor 7/8 stimulation with R848 (see Figure 1A). Primarily, two types of cells exert ADCC: macrophages and natural killer (NK) cells. Since the latter are present in substantial numbers in the lymphocyte fractions we used, we examined whether this was the specific cell type that carried out an Avelumab-dependent ADCC against DCs. In a classical chromium-release cytotoxicity assay, we were able to show that","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 3","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439093","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":"TDP-43/ALKBH5-mediated m6A modification of CDC25A mRNA promotes glioblastoma growth by facilitating G1/S cell cycle transition","authors":"Yunxiao Zhang,&nbsp;Sidi Xie,&nbsp;Weizhao Li,&nbsp;Junwei Gu,&nbsp;Xi-an Zhang,&nbsp;Bowen Ni,&nbsp;Ziyu Wang,&nbsp;Runwei Yang,&nbsp;Haimin Song,&nbsp;Yaxuan Zhong,&nbsp;Peiting Huang,&nbsp;Jinyao Zhou,&nbsp;Yongfu Cao,&nbsp;Jing Guo,&nbsp;Yawei Liu,&nbsp;Songtao Qi,&nbsp;Hai Wang","doi":"10.1002/mco2.70108","DOIUrl":"https://doi.org/10.1002/mco2.70108","url":null,"abstract":"<p>Glioblastoma (GBM) exhibits significant intratumor heterogeneity (ITH), indicating the presence of tumor cells with diverse growth rates. Here, we aimed to identify fast-growing cells in GBM and elucidate the underlying mechanisms. Precisely targeting these cells could offer an improved treatment option. Our results found that targeting ALKBH5 expression impaired GBM proliferation and tumor stemness. Nuclear but not overall expression of ALKBH5 differs between monoclonal cells derived from the same patient with different proliferation rates. Mechanistically, ALKBH5 interacted with TAR DNA-binding protein 43 (TDP-43) in fast-growing cells. Furthermore, TDP-43 facilitated the nuclear localization of ALKBH5 and its binding to cell division cycle 25A (CDC25A) pre-mRNA. The TDP-43/ALKBH5 complex regulates CDC25A mRNA splicing via N6-methyladenosine (m⁶A) demethylation to maintain the expression of its oncogenic isoform (CDC25A-1), ultimately promoting the G1/S phase transition and growth of GBM cells. TRAD01 selectively targeted the interaction between TDP-43 and ALKBH5, leading to significant antitumor effects both in vitro and in vivo. Our study identified a novel epigenetic mechanism by which TDP-43/ALKBH5 contributes to GBM growth via m⁶A modification and alternative splicing. Therefore, targeting the TDP-43/ALKBH5 axis might be a promising therapeutic strategy for GBM patients.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 3","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439191","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":"Differential expression of the MYC-Notch axis drives divergent responses to the front-line therapy in central and peripheral extensive-stage small-cell lung cancer","authors":"Libo Luo,&nbsp;Rui Xia,&nbsp;Shiqi Mao,&nbsp;Qian Liu,&nbsp;He Du,&nbsp;Tao Jiang,&nbsp;Shuo Yang,&nbsp;Yan Wang,&nbsp;Wei Li,&nbsp;Fei Zhou,&nbsp;Jia Yu,&nbsp;Guanghui Gao,&nbsp;Xuefei Li,&nbsp;Chao Zhao,&nbsp;Lei Cheng,&nbsp;Jingyun Shi,&nbsp;Xiaoxia Chen,&nbsp;Caicun Zhou,&nbsp;Luonan Chen,&nbsp;Shengxiang Ren,&nbsp;Fengying Wu","doi":"10.1002/mco2.70112","DOIUrl":"https://doi.org/10.1002/mco2.70112","url":null,"abstract":"<p>Central and peripheral extensive-stage small-cell lung cancer (ES-SCLC) are reported to be two distinct tumor entities, but their responses to the front-line therapies and underlying biological mechanisms remain elusive. In this study, we first compared the outcomes of central and peripheral ES-SCLC receiving front-line chemotherapy or chemo-immunotherapy with a cohort of 265 patients. Then we performed single-cell RNA sequencing (scRNA-seq) on nine treatment-naïve ES-SCLC samples to investigate potential mechanisms underlying the response differences. Under chemotherapy, the peripheral type had a lower objective response rate (44.8% vs. 71.2%, <i>p </i>= 0.008) and shorter progression-free survival (median 3.4 vs. 5.1 months, <i>p </i>= 0.001) than the central type. When comparing chemo-immunotherapy with chemotherapy, the peripheral type showed a greater potential to reduce progression (HR, 0.18 and 0.52, respectively) and death (HR, 0.44 and 0.91 respectively) risks than the central type. Concerning the scRNA-seq data, the peripheral type was associated with chemo-resistant and immune-responsive tumoral and microenvironmental features, including a higher expression level of MYC-Notch-non-neuroendocrine (MYC-Notch-non-NE) axis and a more potent antigen presentation and immune activation status. Our results revealed that central and peripheral ES-SCLC had distinct responses to front-line treatments, potentially due to differential activation statuses of the MYC-Notch-non-NE axis.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 3","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439106","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":"Noncanonical feedback loop between “RIP3–MLKL” and “4EBP1–eIF4E” promotes neuronal necroptosis","authors":"Shuchao Wang,&nbsp;Yun Zhang,&nbsp;Meijuan Wang,&nbsp;Zhihao Zhai,&nbsp;Yating Tan,&nbsp;Weiye Xu,&nbsp;Xiaozhen Ren,&nbsp;Ximin Hu,&nbsp;Jinyou Mo,&nbsp;Jia Liu,&nbsp;Yunfeng Yang,&nbsp;Dan Chen,&nbsp;Bing Jiang,&nbsp;Hualin Huang,&nbsp;Jufang Huang,&nbsp;Kun Xiong","doi":"10.1002/mco2.70107","DOIUrl":"https://doi.org/10.1002/mco2.70107","url":null,"abstract":"<p>Stroke is a leading risk factor for disability and death. Necroptosis is involved in stroke pathogenesis. However, the molecular mechanisms underlying necroptosis in stroke remain unclear. The mammalian target of rapamycin complex 1 (mTORC1) modulates necroptosis in the gut epithelium. Eukaryotic translation initiation factor 4E (eIF4E)-binding protein-1 (4EPB1) is one of the main downstream molecules of mTORC1. This study addresses the role of the 4EBP1–eIF4E pathway in necroptosis. The 4EBP1–eIF4E pathway was found to be activated in both necroptotic HT-22 and mouse middle cerebral artery occlusion (MCAO) models. Functionally, 4EBP1 overexpression, eIF4E knockdown, and eIF4E inhibition suppressed necroptosis, respectively. Furthermore, a positive feedback circuit was observed between the 4EBP1–eIF4E and receptor-interacting protein-3 (RIP3)–mixed lineage kinase domain-like protein (MLKL) pathways, in which RIP3–MLKL activates the 4EBP1–eIF4E pathway by degrading 4EBP1 and activating eIF4E. This in turn enhanced RIP3–MLKL pathway activation. The eIF4E activation derived from this loop may stimulate cytokine production, which is a key factor associated with necroptosis. Finally, using a mouse MCAO model, the application of eIF4E, RIP3, and MLKL inhibitors was found to have a regulatory mechanism similar to that in the in vitro study, reducing the infarct volume and improving neurological function in MCAO mice.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 3","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439192","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":"Changes in L-phenylalanine concentration reflect and predict response to anti-PD-1 treatment combined with chemotherapy in patients with non-small cell lung cancer","authors":"Yaqing Liu,&nbsp;Yu Ping,&nbsp;Liubo Zhang,&nbsp;Qitai Zhao,&nbsp;Yachang Huo,&nbsp;Congcong Li,&nbsp;Jiqi Shan,&nbsp;Yanwen Qi,&nbsp;Liping Wang,&nbsp;Yi Zhang","doi":"10.1002/mco2.70100","DOIUrl":"https://doi.org/10.1002/mco2.70100","url":null,"abstract":"<p>Chemotherapy combined with checkpoint blockade antibodies targeting programmed cell death protein (PD-1) has achieved remarkable success in non-small cell lung cancer. However, few patients benefit from long-term treatment. Therefore, biomarkers capable of guiding the optimal therapeutic selection and reducing unnecessary toxicity are of pressing importance. In our research, we gathered serial blood samples from two groups of non-small cell lung cancer patients: 49 patients received a combination of therapies, and 34 patients went under chemotherapy alone. Utilizing non-targeted metabolomic analysis, we examined different metabolites’ disparity. Among the lot, L-phenylalanine emerged as a significant prognostic marker in the combination treatment of non-small cell lung cancer patients, interestingly absent in patients under sole chemotherapy. The reduced ratio of L-phenylalanine concentration (two-cycle treatment vs. pre-treatment) was associated with improved progression-free survival (hazard ratio = 1.8000, 95% confidence interval: 0.8566‒3.7820, <i>p</i> &lt; 0.0001) and overall survival (hazard ratio = 1.583, 95% confidence interval: 0.7416‒3.3800, <i>p</i> &lt; 0.005). We further recruited two validation cohorts (cohort 1: 40 patients and cohort 2: 30 patients) to validate the sensitivity and specificity of L-phenylalanine prediction. Our results demonstrate that a model based on L-phenylalanine variations could serve as an early risk-assessment tool for non-small cell lung cancer patients undergoing treatment, potentially facilitating strategic clinical decision-making.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 3","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431710","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":"Histidine triad nucleotide-binding protein 2 attenuates doxorubicin-induced cardiotoxicity through restoring lysosomal function and promoting autophagy in mice","authors":"Hao Jiang,&nbsp;Jinyan Zhang,&nbsp;Daile Jia,&nbsp;Liwei Liu,&nbsp;Jinfeng Gao,&nbsp;Beijian Zhang,&nbsp;Zhen Dong,&nbsp;Xiaolei Sun,&nbsp;Wenlong Yang,&nbsp;Tiantong Ou,&nbsp;Suling Ding,&nbsp;Luna He,&nbsp;Yiqin Shi,&nbsp;Kai Hu,&nbsp;Aijun Sun,&nbsp;Junbo Ge","doi":"10.1002/mco2.70075","DOIUrl":"https://doi.org/10.1002/mco2.70075","url":null,"abstract":"<p>Doxorubicin (DOX) is an effective chemotherapy drug widely used against various cancers but is limited by severe cardiotoxicity. Mitochondria–lysosome interactions are crucial for cellular homeostasis. This study investigates the role of histidine triad nucleotide-binding protein 2 (HINT2) in DOX-induced cardiotoxicity (DIC). We found that HINT2 expression was significantly upregulated in the hearts of DOX-treated mice. Cardiac-specific <i>Hint2</i> knockout mice exhibited significantly worse cardiac dysfunction, impaired autophagic flux, and lysosomal dysfunction after DOX treatment. Mechanistically, HINT2 deficiency reduced oxidative phosphorylation complex I activity and disrupted the nicotinamide adenine dinucleotide NAD⁺/NADH ratio, impairing lysosomal function. Further, HINT2 deficiency suppressed sterol regulatory element binding protein 2 activity, downregulating transcription factor A mitochondrial, a critical regulator of complex I. Nicotinamide mononucleotide (NMN) supplementation restored lysosomal function in vitro, while cardiac-specific <i>Hint2</i> overexpression using adeno-associated virus 9 or adenovirus alleviated DIC both in vivo and in vitro. These findings highlight HINT2 as a key cardioprotective factor that mitigates DIC by restoring the NAD⁺/NADH ratio, lysosomal function, and autophagy. Therapeutic strategies enhancing HINT2 expression or supplementing NMN may reduce cardiac damage and heart failure caused by DOX.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 3","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423623","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":"Low versus high peripheral oxygen saturation directed oxygen therapy in critically ill patients: a multicenter randomized controlled trial","authors":"Xiaobo Yang,&nbsp;Xuehui Gao,&nbsp;Xiang Zheng,&nbsp;Xu Zhao,&nbsp;Yanli Liu,&nbsp;Lu Zhang,&nbsp;Junli Sun,&nbsp;Peng Wang,&nbsp;Zhengqin Xu,&nbsp;Ronghua Hu,&nbsp;Hongbin Li,&nbsp;Hong Qi,&nbsp;Yin Yuan,&nbsp;Wei Chen,&nbsp;Jie Liu,&nbsp;Guangqing Huang,&nbsp;Li Yu,&nbsp;Fengsheng Cao,&nbsp;Keke Xin,&nbsp;Min Yu,&nbsp;Xiaoyun Liu,&nbsp;Li Zhang,&nbsp;Siyuan Chang,&nbsp;Xiaojing Zou,&nbsp;Hong Liu,&nbsp;Zhaohui Fu,&nbsp;Huaqing Shu,&nbsp;Yuan Yu,&nbsp;Jiqian Xu,&nbsp;Shiying Yuan,&nbsp;You Shang","doi":"10.1002/mco2.70098","DOIUrl":"https://doi.org/10.1002/mco2.70098","url":null,"abstract":"<p>Whether low peripheral oxygen saturation (SpO₂) directed oxygen therapy is associated with lower mortality in critically ill patients needs further exploration. Adult critically ill patients from 11 intensive care units in China were screened. Participants were randomly assigned to the low SpO₂ (90%–95%) group or the high SpO₂ (≥96%) -group. The primary outcome was 28-day all-cause mortality. The secondary outcomes were hours free from ventilators and from renal replacement therapy (RRT) within 14 days. Note that 857 patients in the low SpO₂ group and 849 in the high SpO₂ group were included. In the low SpO₂ group versus the high SpO₂ group, the time-weighted average of the fraction of inspired oxygen (FiO₂) was significantly lower (33.5 ± 9.7% vs. 39.6 ± 9.3%, <i>p</i> &lt; 0.001), and so was the time-weighted average of SpO₂ (95.9 ± 1.8% vs. 98.0 ± 1.9%, <i>p</i> &lt; 0.001). Within 28 days after randomization, 172 (20.1%) in the low SpO₂ group and 193 (22.7%) in the high SpO₂ group died (<i>p</i> = 0.180). Ventilator-free time and RRT-free time were not significantly different within 14 days. In critically ill patients, low SpO₂directed oxygen therapy did not decrease 28-day mortality, 14-day ventilator-free time, or 14-day RRT-free time.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 3","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423624","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":"Exosomes: a double-edged sword in cancer immunotherapy","authors":"Jiayi Chen,&nbsp;Siyuan Hu,&nbsp;Jiayi Liu,&nbsp;Hao Jiang,&nbsp;Simiao Wang,&nbsp;Zhaogang Yang","doi":"10.1002/mco2.70095","DOIUrl":"https://doi.org/10.1002/mco2.70095","url":null,"abstract":"<p>Over the past few decades, immunotherapy has emerged as a powerful strategy to overcome the limitations of conventional cancer treatments. The use of extracellular vesicles, particularly exosomes, which carry cargoes capable of modulating the immune response, has been extensively explored as a potential therapeutic approach in cancer immunotherapy. Exosomes can deliver their cargo to target cells, thereby influencing their phenotype and immunomodulatory functions. They exhibit either immunosuppressive or immune-activating characteristics, depending on their internal contents. These exosomes originate from diverse cell sources, and their internal contents can vary, suggesting that there may be a delicate balance between immune suppression and stimulation when utilizing them for immunotherapy. Therefore, a thorough understanding of the molecular mechanisms underlying the role of exosomes in cancer progression is essential. This review focuses on the molecular mechanisms driving exosome function and their impact on the tumor microenvironment (TME), highlighting the intricate balance between immune suppression and activation that must be navigated in exosome-based therapies. Additionally, it underscores the challenges and ongoing efforts to optimize exosome-based immunotherapies, thereby making a significant contribution to the advancement of cancer immunotherapy research.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 3","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423619","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}