MedComm最新文献

{"title":"High serum magnesium level is associated with increased mortality in patients with sepsis: an international, multicenter retrospective study","authors":"Le Li,&nbsp;Li Li,&nbsp;Qiuyue Zhao,&nbsp;Xiao Liu,&nbsp;Yaohui Liu,&nbsp;Kailin Guo,&nbsp;Dongsu Zhang,&nbsp;Chang Hu,&nbsp;Bo Hu","doi":"10.1002/mco2.713","DOIUrl":"https://doi.org/10.1002/mco2.713","url":null,"abstract":"<p>Magnesium imbalances commonly exist in septic patients. However, the association of serum magnesium levels with mortality in septic patients remains uncertain. Herein, we elucidated the association between serum magnesium and all-cause mortality in septic patients from American and Chinese cohorts by analyzing data from 9099 patients in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and 1727 patients from a university-affiliated hospital’ intensive care unit in China. Patients in both cohorts were categorized into five groups based on serum magnesium quintiles from the MIMIC-IV dataset. Patients with higher serum magnesium levels exhibited an increased risk of 28-day mortality in both cohorts. The restricted cubic spline (RCS) curves revealed a progressively elevated risk of 28-day mortality with increasing serum magnesium in MIMIC-IV cohort, while a J-shaped correlation was observed in institutional cohort. Our findings have validated the association between high serum magnesium and high mortality in sepsis across different races and medical conditions. Serum magnesium levels might be useful in identifying septic patients at higher mortality risk.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.713","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244544","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":"Liver cirrhosis: molecular mechanisms and therapeutic interventions","authors":"Zihe Dong,&nbsp;Yeying Wang,&nbsp;Weilin Jin","doi":"10.1002/mco2.721","DOIUrl":"https://doi.org/10.1002/mco2.721","url":null,"abstract":"<p>Liver cirrhosis is the end-stage of chronic liver disease, characterized by inflammation, necrosis, advanced fibrosis, and regenerative nodule formation. Long-term inflammation can cause continuous damage to liver tissues and hepatocytes, along with increased vascular tone and portal hypertension. Among them, fibrosis is the necessary stage and essential feature of liver cirrhosis, and effective antifibrosis strategies are commonly considered the key to treating liver cirrhosis. Although different therapeutic strategies aimed at reversing or preventing fibrosis have been developed, the effects have not be more satisfactory. In this review, we discussed abnormal changes in the liver microenvironment that contribute to the progression of liver cirrhosis and highlighted the importance of recent therapeutic strategies, including lifestyle improvement, small molecular agents, traditional Chinese medicine, stem cells, extracellular vesicles, and gut remediation, that regulate liver fibrosis and liver cirrhosis. Meanwhile, therapeutic strategies for nanoparticles are discussed, as are their possible underlying broad application and prospects for ameliorating liver cirrhosis. Finally, we also reviewed the major challenges and opportunities of nanomedicine‒biological environment interactions. We hope this review will provide insights into the pathogenesis and molecular mechanisms of liver cirrhosis, thus facilitating new methods, drug discovery, and better treatment of liver cirrhosis.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.721","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244543","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":"N1-methylpseudouridine modification level correlates with protein expression, immunogenicity, and stability of mRNA","authors":"Shaoyi Chen,&nbsp;Zheng Liu,&nbsp;Jingsheng Cai,&nbsp;Haoran Li,&nbsp;Mantang Qiu","doi":"10.1002/mco2.691","DOIUrl":"https://doi.org/10.1002/mco2.691","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;Messenger RNA (mRNA) has undergone significant evolution, emerging as a robust platform for diverse therapeutic applications such as vaccines, protein replacement, and adoptive cell therapy across infectious, cancer, and immunological diseases. In vitro transcribed mRNA offers distinct advantages, including cytoplasmic transient expression, devoid of the risk of genomic integration. Nucleotide modifications, such as pseudouridine (Ψ), N1-methylpseudouridine (m1Ψ), and 5-methylcytidine (m5C), play pivotal roles in mRNA immunogenicity, stability, and translational efficiency. Notably, standing out as a state-of-the-art modification, global m1Ψ modification has been performed in the two approved mRNA vaccines against severe acute respiratory syndrome coronavirus 2, mRNA-1273, and BNT162b2. The in vivo stability and translational duration of synthesized mRNA are partially restricted by its immunogenicity. Recognition of foreign RNA by toll-like receptor 3 (TLR3), TLR7, TLR8, and retinoic acid-inducible gene I (RIG-I)-like receptors triggers innate immunity, leading to RNA degradation.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; The therapeutic application of mRNA necessitates a delicate balance between immune activation and protein expression. For infectious disease vaccines, chemical modifications can minimize inflammatory responses while ensuring effective mRNA translation. Conversely, cancer vaccines require adequate innate immune stimulation for anti-tumor immunity. Thus far, most studies have investigated alternative m1Ψ modification individually or combined with others. However, it is unknown whether m1Ψ modification ratio in mRNA has an impact on the delicate balance between immunogenicity, stability, and translational efficiency.&lt;/p&gt;&lt;p&gt;Therefore, we synthesized mRNA encoding enhanced green fluorescent protein (mEGFP) with different m1Ψ modification ratios (5%, 10%, 20%, 50%, 75%, and 100%) through in vitro transcription. HEK-293T cells were transfected with unmodified mEGFP or m1Ψ-modified m1ΨEGFP (m1ΨEGFP-5%, m1ΨEGFP-10%, m1ΨEGFP-20%, m1ΨEGFP-50%, m1ΨEGFP-75%, and m1ΨEGFP-100%). The expression and duration of EGFP were assessed using flow cytometry over a 6-day period. As depicted in Figure 1A (upper part), m1ΨEGFP-5%, m1ΨEGFP-10%, and m1ΨEGFP-20% group exhibited a higher percentage of EGFP-positive cells (EGFP&lt;sup&gt;+&lt;/sup&gt;cells %) and mean fluorescence intensity (MFI) compared to mEGFP group. Conversely, m1ΨEGFP-50%, m1ΨEGFP-75%, and m1ΨEGFP-100% group had lower EGFP&lt;sup&gt;+&lt;/sup&gt;cells % and MFI. Notably, the EGFP&lt;sup&gt;+&lt;/sup&gt;cells % and MFI of cells transfected with m1ΨEGFP-50%, m1ΨEGFP-75%, and m1ΨEGFP-100% were barely undetectable on day 6. EGFP expression detected by Western Blot on days 3, 4, and 5 was consistent with the flow cytometry (Figure 1A, bottom part, and Figure S1A). In summary, our finding indicates that the m1Ψ modification ratio might impact both mRNA translational ability and duration in HEK-293T cells.&lt;/p&gt;&lt;p&gt;To valida","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.691","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245013","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":"Copper homeostasis and cuproptosis in health and disease","authors":"Yunuo Yang,&nbsp;Jiaxuan Wu,&nbsp;Lisheng Wang,&nbsp;Guang Ji,&nbsp;Yanqi Dang","doi":"10.1002/mco2.724","DOIUrl":"https://doi.org/10.1002/mco2.724","url":null,"abstract":"<p>Copper is a vital trace element in human physiology, essential for the synthesis of numerous crucial metabolic enzymes and facilitation of various biological processes. Regulation of copper levels within a narrow range is imperative for maintaining metabolic homeostasis. Numerous studies have demonstrated the significant roles of copper homeostasis and cuproptosis in health and disease pathogenesis. However, a comprehensive and up-to-date systematic review in this domain remains absent. This review aims to consolidate recent advancements in understanding the roles of cuproptosis and copper homeostasis in health and disease, focusing on the underlying mechanisms and potential therapeutic interventions. Dysregulation of copper homeostasis, manifesting as either copper excess or deficiency, is implicated in the etiology of various diseases. Cuproptosis, a recently identified form of cell death, is characterized by intracellular copper overload. This phenomenon mediates a diverse array of evolutionary processes in organisms, spanning from health to disease, and is implicated in genetic disorders, liver diseases, neurodegenerative disorders, and various cancers. This review provides a comprehensive summary of the pathogenic mechanisms underlying cuproptosis and copper homeostasis, along with associated targeted therapeutic agents. Furthermore, it explores future research directions with the potential to yield significant advancements in disease treatment, health management, and disease prevention.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.724","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244542","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-reported outcome and survival in premenopausal hormone receptor-positive breast cancer patients at moderate to high risk: comparing toremifene with aromatase inhibitor in a real-world study","authors":"Yaping Yang,&nbsp;Fengxia Gan,&nbsp;Ting Luo,&nbsp;Qun Lin,&nbsp;Wenqian Yang,&nbsp;Lili Chen,&nbsp;Wei Zhang,&nbsp;Qiang Liu,&nbsp;Chang Gong","doi":"10.1002/mco2.698","DOIUrl":"https://doi.org/10.1002/mco2.698","url":null,"abstract":"<p>Toremifene, a selective estrogen receptor modulator, is commonly used in China for premenopausal breast cancer patients. This real-world study aimed to compare patient-reported outcome (PRO) and survival between toremifene and aromatase inhibitor (AI) plus ovarian function suppression (OFS) in patients with moderate-/high-risk premenopausal hormone receptor (HR)-positive breast cancer. The primary endpoint was PROs, assessed using SF-36 and EQ-5D-5L questionnaires between January and March 2023. A total of 392 patients were included, with 171 receiving toremifene and 221 receiving AI. The toremifene group showed significantly higher scores in the role physical (<i>p</i> = 0.034) and mental health (<i>p </i>= 0.009) dimensions of SF-36 and lower anxiety/depression (AD) scores (<i>p </i>= 0.038) in EQ-5D-5L compared to AI group. The estimated 5- and 8-year disease-free survival (DFS) rates were similar in toremifene and AI groups: 96.5% versus 91.9%, and 87.4% versus 87.8% (<i>p </i>= 0.39), respectively. Adverse event rates were similar in two groups, except for a greater risk of endometrial thickening (<i>p </i>&lt; 0.001) and a lower occurrence of morning stiffness (<i>p </i>&lt; 0.001) in the toremifene compared to the AI group. Premenopausal HR-positive breast cancer patients receiving toremifene plus OFS had better role physical and mental health outcomes and lower AD dimensions than those receiving AI plus OFS. Both treatments had comparable DFS and favorable tolerability profiles.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.698","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233998","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":"A novel small molecule ZYZ384 targeting SMYD3 for hepatocellular carcinoma via reducing H3K4 trimethylation of the Rac1 promoter","authors":"Qian Ding,&nbsp;Jianghong Cai,&nbsp;Li Jin,&nbsp;Wei Hu,&nbsp;Wu Song,&nbsp;Peter Rose,&nbsp;Zhiyuan Tang,&nbsp;Yangyang Zhan,&nbsp;Leilei Bao,&nbsp;Wei Lei,&nbsp;Yi Zhun Zhu","doi":"10.1002/mco2.711","DOIUrl":"https://doi.org/10.1002/mco2.711","url":null,"abstract":"<p>SMYD3 (SET and MYND domain-containing 3) is a histone lysine methyltransferase highly expressed in different types of cancer(s) and is a promising epigenetic target for developing novel antitumor therapeutics. No selective inhibitors for this protein have been developed for cancer treatment. Therefore, the current study describes developing and characterizing a novel small molecule ZYZ384 screened and synthesized based on SMYD3 structure. Virtual screening was initially used to identify a lead compound and followed up by modification to get the novel molecules. Several technologies were used to facilitate compound screening about these novel molecules' binding affinities and inhibition activities with SMYD3 protein; the antitumor activity has been assessed in vitro using various cancer cell lines. In addition, a tumor-bearing nude mice model was established, and the activity of the selected molecule was determined in vivo. Both RNA-seq and chip-seq were performed to explore the antitumor mechanism. This work identified a novel small molecule ZYZ384 targeting SMYD3 with antitumor activity and impaired hepatocellular carcinoma tumor growth by reducing H3K4 trimethylation of the Rac1 promoter triggering the tumor cell cycle arrest through the AKT pathway.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.711","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233999","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":"Unlocking fresh perspectives: molecular breakthroughs in pediatric acute myeloid leukemia classification and prognosis","authors":"Yu Tao,&nbsp;Li Wei,&nbsp;Hua You","doi":"10.1002/mco2.750","DOIUrl":"https://doi.org/10.1002/mco2.750","url":null,"abstract":"&lt;p&gt;Recently, a novel transcriptome and genome profiling study published in the &lt;i&gt;Journal of Nature Genetics&lt;/i&gt;, expanded the prognosis-related molecular classification coverage of pediatric acute myeloid leukemia (pAML) from 68.5% (as defined by the WHO 5th edition) to 91.4%.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; This framework was strongly associated with clinical outcomes, potentially shaping future classifications and treatment of pediatric AML.&lt;/p&gt;&lt;p&gt;Differences in molecular profiles between pediatric and adult AML restrict the use of risk stratification tools designed for adults when applied to pediatric patients. For instance, while the TP53 mutation, present in about 8% of adult AML cases and linked to poor outcomes, is emphasized in the European LeukemiaNet (ELN) 2022 guidelines,&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; it is infrequently observed in pediatric AML. Furthermore, numerous driver alterations that are specific to pediatric cases are not adequately represented in the existing classification schemas, and risk stratification for pediatric AML is still evolving. This prompted Umeda and colleagues to comprehensively explore the increasingly intricate genomic landscape within the framework of the latest hematological malignancy classification systems and to create a categorization system uniquely designed for pediatric AML.&lt;/p&gt;&lt;p&gt;In their study, RNA sequencing (RNA-seq) data of 887 pAML patients were assessed, complemented by DNA sequencing data, allowing for a comprehensive examination of genetic features, including internal or partial tandem duplications (ITD/PTD), copy-number variations, single nucleotide mutations, fusions, and insertions and deletions (indels). It was revealed that while WHO 5th identified 68.5% of pAML cases with specified genetic alterations, the new pAML classification system, which incorporates 12 additional molecular categories, captures 91.4% of cases. The discovery of these new major entities such as UBTF tandem duplications, GLIS family rearrangements, and BCL11B structural variants and outlier expression will lead to greater attention and analysis of these patients’ biological and clinical features.&lt;/p&gt;&lt;p&gt;Further clinicopathological association analysis revealed that pAML morphological features are defined by the identified driver alterations and developmental stages. Given that numerous category-defining alterations are either cytogenetically obscure or involve somatic mutations, this underscores the necessity for sequencing techniques to achieve precise molecular diagnosis of pAML. As for gene expression, molecular categories with favorable prognosis (such as CBFB::MYH11, CEBPA, RUNX1::RUNX1T1) typically exhibited high granulocyte–monocyte progenitor scores. Conversely, KMT2Ar, associated with poor prognosis, had low stemness-related scores and variable differentiation-related scores. The differences in the aforementioned prognosis or drug–response-related patterns reflect that molecular categories are associated with unique ","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.750","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233996","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":"Androgen-type 2 innate lymphoid cells-dendritic cell axis modulates sex-associated differences in skin immune responses","authors":"Shi-Jun He,&nbsp;Jian-Ping Zuo,&nbsp;Ze-Min Lin","doi":"10.1002/mco2.732","DOIUrl":"https://doi.org/10.1002/mco2.732","url":null,"abstract":"&lt;p&gt;A recent study by Chi and colleagues in &lt;i&gt;Science&lt;/i&gt; identified skin type 2 innate lymphoid cells (ILC2s) as crucial for maintaining skin dendritic cell (DC) network homeostasis through cytokine production.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Their findings reveal that the interplay between sex hormones and the microbiota shapes tissue immune set points and DC network strength, with hormones influencing local immunity and the microbiota modulating its intensity.&lt;/p&gt;&lt;p&gt;Differences in the immune systems of females and males contribute to observed sexual dimorphisms in susceptibility to a range of diseases, including cancers, autoimmune diseases, allergies, and infectious diseases, including coronavirus disease 2019, particularly in barrier tissues which are primary sites for infections and are regulated by a complex microbial community. Laffont et al. first identified the role of androgen signaling in regulating ILC2 responses, showing that females have more ILC2s than males.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; This disparity arises not from estrogen enhancement in females but from androgen inhibition of ILC2 maintenance and local expansion in males.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Building on this observation, Chi et al. examined the impact of androgen-mediated regulation of ILC2s on the skin DC network and its subsequent effects on adaptive immune responses.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Acting as nuclear regulators, sex hormone receptors play a pivotal role in fine-tuning immune responses at the transcriptional level, which in turn influences disease outcomes. In the domain of cancer immunology, these receptors oversee specific pathways in both the innate and adaptive immune systems, providing potential avenues for therapeutic interventions in reproductive cancers. Specifically, androgen receptor (AR) signaling has been linked to the suppression of CD8&lt;sup&gt;+&lt;/sup&gt; T cell function within the tumor microenvironment.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Meanwhile, testosterone, the primary male hormone governing sex differentiation and the development of male sex characteristics, interacts with cytosolic or membrane-bound ARs to modulate gene transcription either directly or indirectly. ARs are expressed across a variety of cells, including many in developmental stages and some mature immune cells. Further studies across infectious diseases, autoimmunity, and cancer highlight testosterone's direct influence on immune cell development and function, typically leading to immunosuppressive effects.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Additionally, gender disparities in the immune system render males more susceptible to microbial infections and less effective in viral clearance, albeit affording greater protection against autoimmune diseases.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Barrier tissues serve as primary sites for infections and injury and are perpetually inhabited by a diverse microbial community that modulates host defense mechanisms. Despite this, the immune differences specific to each sex in these ","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.732","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234000","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":"The interaction of innate immune and adaptive immune system","authors":"Ruyuan Wang,&nbsp;Caini Lan,&nbsp;Kamel Benlagha,&nbsp;Niels Olsen Saraiva Camara,&nbsp;Heather Miller,&nbsp;Masato Kubo,&nbsp;Steffen Heegaard,&nbsp;Pamela Lee,&nbsp;Lu Yang,&nbsp;Huamei Forsman,&nbsp;Xingrui Li,&nbsp;Zhimin Zhai,&nbsp;Chaohong Liu","doi":"10.1002/mco2.714","DOIUrl":"https://doi.org/10.1002/mco2.714","url":null,"abstract":"<p>The innate immune system serves as the body's first line of defense, utilizing pattern recognition receptors like Toll-like receptors to detect pathogens and initiate rapid response mechanisms. Following this initial response, adaptive immunity provides highly specific and sustained killing of pathogens via B cells, T cells, and antibodies. Traditionally, it has been assumed that innate immunity activates adaptive immunity; however, recent studies have revealed more complex interactions. This review provides a detailed dissection of the composition and function of the innate and adaptive immune systems, emphasizing their synergistic roles in physiological and pathological contexts, providing new insights into the link between these two forms of immunity. Precise regulation of both immune systems at the same time is more beneficial in the fight against immune-related diseases, for example, the cGAS–STING pathway has been found to play an important role in infections and cancers. In addition, this paper summarizes the challenges and future directions in the field of immunity, including the latest single-cell sequencing technologies, CAR-T cell therapy, and immune checkpoint inhibitors. By summarizing these developments, this review aims to enhance our understanding of the complexity interactions between innate and adaptive immunity and provides new perspectives in understanding the immune system.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.714","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233994","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":"Anoikis in cell fate, physiopathology, and therapeutic interventions","authors":"Jie Mei,&nbsp;Xue-Yao Jiang,&nbsp;Hui-Xiang Tian,&nbsp;Ding-Chao Rong,&nbsp;Jia-Nan Song,&nbsp;Luozixian Wang,&nbsp;Yuan-Shen Chen,&nbsp;Raymond C. B. Wong,&nbsp;Cheng-Xian Guo,&nbsp;Lian-Sheng Wang,&nbsp;Lei-Yun Wang,&nbsp;Peng-Yuan Wang,&nbsp;Ji-Ye Yin","doi":"10.1002/mco2.718","DOIUrl":"https://doi.org/10.1002/mco2.718","url":null,"abstract":"<p>The extracellular matrix (ECM) governs a wide spectrum of cellular fate processes, with a particular emphasis on anoikis, an integrin-dependent form of cell death. Currently, anoikis is defined as an intrinsic apoptosis. In contrast to traditional apoptosis and necroptosis, integrin correlates ECM signaling with intracellular signaling cascades, describing the full process of anoikis. However, anoikis is frequently overlooked in physiological and pathological processes as well as traditional in vitro research models. In this review, we summarized the role of anoikis in physiological and pathological processes, spanning embryonic development, organ development, tissue repair, inflammatory responses, cardiovascular diseases, tumor metastasis, and so on. Similarly, in the realm of stem cell research focused on the functional evolution of cells, anoikis offers a potential solution to various challenges, including in vitro cell culture models, stem cell therapy, cell transplantation, and engineering applications, which are largely based on the regulation of cell fate by anoikis. More importantly, the regulatory mechanisms of anoikis based on molecular processes and ECM signaling will provide new strategies for therapeutic interventions (drug therapy and cell-based therapy) in disease. In summary, this review provides a systematic elaboration of anoikis, thus shedding light on its future research.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.718","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233995","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}