MedComm最新文献

{"title":"PRMT5 Promotes Pancreatic Cancer Tumorigenesis via Positive PRMT5/C-Myc Feedback Loop","authors":"Fan Yang,&nbsp;Ping Song,&nbsp;Zhaofeng Xiao,&nbsp;Renyi Su,&nbsp;Xin Fang,&nbsp;Yichao Wu,&nbsp;Xiao Xu,&nbsp;Kai Wang","doi":"10.1002/mco2.70150","DOIUrl":"https://doi.org/10.1002/mco2.70150","url":null,"abstract":"<p>The oncogenic role and underlying mechanism of PRMT5 in pancreatic ductal adenocarcinoma (PAAD) remained to be elucidated. In this study, we aimed to investigate the oncogenic role, underlying molecular mechanisms, and potential therapeutic value of PRMT5 in PAAD. PRMT5 was significantly upregulated in pancreatic cancer than adjacent nontumor pancreas, which was positively correlated with poor prognosis. Genetic and pharmacological inhibition of PRMT5 suppressed PAAD proliferation in vitro and in vivo, exhibiting promising therapeutic effect in vivo. Mechanistically, PRMT5 directly bound to the promoter region of c-Myc and activated its transcription. Transcriptionally activated c-Myc in turn inhibited proteasome-mediated degradation of PRMT5 and enhanced its protein stability, resulting in increased PRMT5 expression. The maintained PRMT5 further enhanced the transcription of c-Myc. In conclusion, PRMT5 forms a positive feedback loop with c-Myc to promote the proliferation of pancreatic cancer. Targeting this oncogenic communication may represent a novel and potential therapeutic approach for pancreatic cancer.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 6","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949983","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":"Minimal Residual Disease Detection: Implications for Clinical Diagnosis and Cancer Patient Treatment","authors":"Meiling Song,&nbsp;Wenjing Pan,&nbsp;Xinjie Yu,&nbsp;Jie Ren,&nbsp;Congli Tang,&nbsp;Zhu Chen,&nbsp;Zhe Wang,&nbsp;Yan Deng,&nbsp;Nongyue He,&nbsp;Hongna Liu,&nbsp;Song Li","doi":"10.1002/mco2.70193","DOIUrl":"https://doi.org/10.1002/mco2.70193","url":null,"abstract":"<p>Minimal residual disease (MRD) serves as a pivotal biomarker for the clinical diagnosis and subsequent treatment of cancer patients. In hematological malignancies, MRD pose an increasingly serious threat to the health of Chinese people. Accurate MRD detection is essential for assessing relapse risk and optimizing therapeutic strategies, yet current methods such as flow cytometry, polymerase chain reaction (PCR), and next-generation sequencing (NGS) each have distinct limitations, and significant gaps remain in achieving optimal sensitivity and specificity of these technologies. This review provides a comprehensive analysis of MRD detection methods, high-lighting their clinical implications, including their roles in treatment decision-making, risk stratification, and patient outcomes. It discusses the strengths and weaknesses of existing techniques and explores emerging technologies that promise enhanced diagnostic precision. Key advancements such as integrating NGS with other methodologies and novel approaches like liquid biopsy and PCR are examined. The review underscores the academic and practical value of early and accurate MRD detection, emphasizing its impact on improving patient management and treatment outcomes. By addressing the limitations of current technologies and exploring future directions, this review aims to advance the field and support personalized medicine approaches to cancer treatment.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 6","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70193","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949984","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":"Targeting the Enhanced Sensitivity of Radiotherapy in Cancer: Mechanisms, Applications, and Challenges","authors":"Yuanyuan Zhao,&nbsp;Fangqin Tan,&nbsp;Jiajia Zhao,&nbsp;Shuchang Zhou,&nbsp;Yao Luo,&nbsp;Chen Gong","doi":"10.1002/mco2.70202","DOIUrl":"https://doi.org/10.1002/mco2.70202","url":null,"abstract":"<p>Cancer is a major public health, societal, and economic challenge worldwide. According to <i>Global Cancer Statistics 2022</i>, it is estimated that by 2050, there will be 35 million new cancer cases globally. Although patient survival rates have improved through various therapeutic approaches, including surgery, chemotherapy, and radiotherapy, treatment efficacy remains limited once tumor metastasis occurs. Among various cancer treatment strategies, radiotherapy plays a crucial role. Along with surgery and chemotherapy, radiotherapy is a cost-effective single-modality treatment, accounting for approximately 5% of total cancer care costs. The use of radiosensitizing agents such as histone deacetylase inhibitors, 2-deoxy-<span>d</span>-glucose, enterolactone, and squalene epoxidase can enhance radiotherapy effectiveness. Recent radiosensitization methods involve physical stimuli and chemical radiosensitizers. However, improving their efficacy, durability, and overcoming radioresistance remain significant challenges. This review first introduces current applications of radiotherapy in cancer treatment, the molecular mechanisms underlying its anticancer effects, and its side effects. Second, it discusses the main types of radiosensitizers, their latest applications, and recent challenges in cancer treatment. Finally, it emphasizes on clinical trials of radiosensitizing agents and explores potential biomarkers for radiotherapy response in cancer. Multifunctional nanoparticles have shown greater clinical applicability than single-functional nanoparticles. Future research will focus on enhancing the drug-carrying capacity of nanomaterials to further improve radiotherapy outcomes.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 6","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70202","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949985","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":"Biallelic DNAH11 Variations Cause Male Infertility with Multiple Morphological Abnormalities of the Sperm Flagellum in Humans","authors":"Xue Yang,&nbsp;Dingming Li,&nbsp;Yihong Yang,&nbsp;Guicheng Zhao,&nbsp;Ying Shen","doi":"10.1002/mco2.70210","DOIUrl":"https://doi.org/10.1002/mco2.70210","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;Asthenoteratozoospermia, defined as reduced sperm motility and abnormal sperm morphology, accounts for approximately 19% of all male infertility. Multiple morphological abnormalities of the sperm flagellum (MMAF) is a severe type of asthenoteratozoospermia, characterized by a variety of sperm tail defects, including short, absent, curl, angle, or irregular sperm flagellum. MMAF is considered as a genetic disorder, with approximately 40 related genes identified so far, yet these genes account for only about 60% of human MMAF cases [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Motile cilia and sperm flagella share highly conserved axoneme with a “9 + 2” microtubule architecture. The inner dynein arms (IDAs) and outer dynein arms (ODAs) are two molecular motors to provide the original energy for ciliary beating and sperm motility in humans. &lt;i&gt;DNAH&lt;/i&gt; family is involved in the formation of axoneme in motile cilia and sperm flagella [&lt;span&gt;1&lt;/span&gt;]. &lt;i&gt;DNAH11&lt;/i&gt; encodes an ODA protein, and mutations in &lt;i&gt;DNAH11&lt;/i&gt; are known to cause primary ciliary dyskinesia (PCD) [&lt;span&gt;2&lt;/span&gt;]. However, the role of &lt;i&gt;DNAH11&lt;/i&gt; in sperm motility and morphology has rarely been investigated.&lt;/p&gt;&lt;p&gt;In this study, we performed whole‑exome sequencing (WES) to investigate the potential genetic causes in two unrelated infertile patients with MMAF phenotype after ruling out conventional risk factors. Remarkably, two biallelic &lt;i&gt;DNAH11&lt;/i&gt; variations (NM_001277115.2) were identified, including a compound heterozygous mutation of c.6233G&gt;A (p.Gly2078Glu) and c.9335A&gt;G (p.Gln3112Arg) in patient A and another compound heterozygous mutation of c.6143C&gt;G (p.Thr2048Arg) and c.10379C&gt;A (p.Thr3460Lys) in patient B (Figure 1A). In addition, these variants were completely absent or presented at an exceedingly low frequency in the ExAC Browser (0, 0.0000352, 0.0003, 0.0003, respectively), GnomAD (0, 0, 0.0002, 0.0002, respectively), and 1000 Genomes Project databases (0, 0, 0.000399361, 0.000199681, respectively), predicted to be deleterious by bioinformatic tools, including SIFT, PolyPhen-2, and M-CAP. Moreover, the affected sites of theses variants are quite conserved across different species (Figure 1A).&lt;/p&gt;&lt;p&gt;Papanicolaou staining and scanning electron microscopy (SEM) analysis were carried out to evaluate the aberrant sperm morphology of the patients. Notably, the two patients presented a typical MMAF phenotype characterized by a combination of short, bent, coiled, absent, and/or irregular sperm flagellum (Figure 1B, i–iii). Moreover, the spermatozoa ultrastructure was analyzed by transmission electron microscopy (TEM). Compared with a normal sperm flagellum composed of a “9 + 2” axonemal arrangement from the control, the sperm flagella from the patients frequently exhibited the absence of central pairs (CPs), as well as disordered or missing peripheral microtubule doublet (MTDs) and outer dense fibers (ODFs) (Figure 1B, iv). The defects in mitochondrial she","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 5","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70210","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930216","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":"Separate Kingdoms, Same Conspiracies: Conserved Viral Strategies for Immune Evasion in Animal and Bacterial Hosts","authors":"Junyi Wang,&nbsp;Xiang He,&nbsp;Guoping Li","doi":"10.1002/mco2.70215","DOIUrl":"https://doi.org/10.1002/mco2.70215","url":null,"abstract":"&lt;p&gt;In a recent study published in &lt;i&gt;Cell&lt;/i&gt;, Hobbs et al. uncovered a strikingly conserved immune evasion strategy shared by animal poxviruses and bacteriophages, involving the degradation of host cyclic nucleotide signals through cyclic GMP–AMP (cGAMP) phosphodiesterases (PDEs) [&lt;span&gt;1&lt;/span&gt;]. This discovery highlights the evolutionary convergence across kingdoms, providing new insights into viral pathogenesis and opening avenues for developing broad-spectrum antiviral therapeutics that target these conserved pathways.&lt;/p&gt;&lt;p&gt;Animal and bacterial cells have evolved complex antiviral defense systems to sense viral invaders and initiate immune responses. A key component of these defense systems is the cyclic GMP–AMP synthase (cGAS)—stimulator of interferon genes (STING) pathway in animals, which is responsible for detecting viral DNA and generating second messengers like 2′3′-cGAMP, leading to the production of interferons and other antiviral molecules [&lt;span&gt;2&lt;/span&gt;]. In bacteria, a similar pathway exists, known as cyclic oligonucleotide-based anti-phage signaling systems (CBASS), which use cyclic nucleotides, such as 3′3′-cGAMP, to initiate antiviral responses, including cell death to prevent phage propagation [&lt;span&gt;3&lt;/span&gt;]. However, recent studies have further demonstrated that diverse strategies employed by phages to inhibit or evade CBASS-mediated immunity, underscoring the ongoing evolutionary arms race between hosts and viruses [&lt;span&gt;4&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Hobbs et al. focused on two classes of viral proteins: cGAMP PDEs from animal poxviruses and the Anti-CBASS1 (Acb1) proteins from bacteriophages [&lt;span&gt;1&lt;/span&gt;]. Acb1 is a phage immune evasion protein that specifically degrades bacterial cyclic nucleotide immune signals, thereby inhibiting host CBASS systems [&lt;span&gt;5&lt;/span&gt;]. Interestingly, poxvirus cGAMP PDE and phage Acb1 share a striking structural and functional resemblance [&lt;span&gt;1&lt;/span&gt;]. The viral proteins share a highly conserved phosphoesterase fold and aligned active-site residues, reflecting architectural and catalytic homology between them. In addition, both poxvirus cGAMP PDE and phage Acb1 proteins use a conserved set of water molecules to coordinate the cyclic nucleotide substrates, enabling efficient cleavage of the phosphodiester bond. Moreover, both viral proteins feature a lid domain—located at the N-terminus in poxvirus PDEs and the C-terminus in bacteriophage Acb1—that stabilizes the substrate within the active site to enhance catalytic efficiency [&lt;span&gt;1&lt;/span&gt;]. Strikingly, recombinant bacteriophages engineered by Hobbs et al., carrying the poxvirus PDE gene instead of their native &lt;i&gt;acb1&lt;/i&gt; gene, successfully evaded bacterial CBASS defenses [&lt;span&gt;1&lt;/span&gt;]. The fact that a eukaryotic viral protein can function in a prokaryotic system suggests that these immune evasion mechanisms are not limited by the host species. Instead, they exploit conserved biochemical pathways that are fundamental to antiviral defens","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 5","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70215","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930218","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":"Death-Associated Protein 3 Triggers Intrinsic Apoptosis via Miro1 Upon Inducing Intracellular Calcium Changes","authors":"Dongxue Hu,&nbsp;Qiaoyun Yang,&nbsp;Hongxu Xian,&nbsp;Minghao Wang,&nbsp;Hong Zheng,&nbsp;Karthik Babu Mallilankaraman,&nbsp;Victor C. Yu,&nbsp;Yih-Cherng Liou","doi":"10.1002/mco2.70214","DOIUrl":"https://doi.org/10.1002/mco2.70214","url":null,"abstract":"<p>Mitochondrial homeostasis is essential for cell survival and function, necessitating quality control mechanisms to ensure a healthy mitochondrial network. Death-associated protein 3 (DAP3) serves as a subunit of the mitochondrial ribosome, playing a pivotal role in the translation of mitochondrial-encoded proteins. Apart from its involvement in protein synthesis, DAP3 has been implicated in the process of cell death and mitochondrial dynamics. In this study, we demonstrate that DAP3 mediates cell death via intrinsic apoptosis by triggering excessive mitochondrial fragmentation, loss of mitochondrial membrane potential (Δ<i>Ψ</i>m), ATP decline, and oxidative stress. Notably, DAP3 induces mitochondrial fragmentation through the Mitochondrial Rho GTPase 1 (Miro1), independently of the canonical fusion/fission machinery. Mechanistically, DAP3 promotes mitochondrial calcium accumulation through the MCU complex, leading to decreased cytosolic Ca²⁺ levels. This reduction in cytosolic Ca²⁺ is sensed by Miro1, which subsequently drives mitochondrial fragmentation. Depletion of Miro1 or MCU alleviates mitochondrial fragmentation, oxidative stress, and cell death. Collectively, our findings reveal a novel function of the mitoribosomal protein DAP3 in regulating calcium signalling and maintaining mitochondrial homeostasis.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 5","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70214","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930217","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":"Effects of Intensive Systolic Blood Pressure Control on Glycometabolic and Cardiovascular Outcomes in Normoglycemic Patients: A Secondary Analysis of a Randomized Trial","authors":"Cheng Yang,&nbsp;Wei-Hua Chen,&nbsp;Jie Qian,&nbsp;Rong-Chong Huang,&nbsp;Jian-Jun Li","doi":"10.1002/mco2.70197","DOIUrl":"https://doi.org/10.1002/mco2.70197","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;The increasing prevalence of diabetes mellitus is a challenge to the global healthcare landscape, imposing a substantial burden of complications and contributing to premature mortality [&lt;span&gt;1&lt;/span&gt;]. Prediabetes, an intermediate stage between normoglycemia and diabetes, is a well-established risk factor for progression to overt diabetes. Prediabetes and diabetes (collectively termed dysglycemia) are direct and independent risk factors for cardiovascular disease (CVD) [&lt;span&gt;2&lt;/span&gt;]. Hypertension and diabetes commonly overlap in the population, exacerbating increased cardiovascular morbidity and mortality [&lt;span&gt;3&lt;/span&gt;]. The relationship between blood pressure (BP) control and dysglycemia is not yet fully elucidated. Posthoc analyses of two major randomized controlled trials, the Systolic Blood Pressure Intervention Trial (SPRINT) and the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP), have yielded contradictory conclusions regarding the impact of BP intervention on glucose metabolism [&lt;span&gt;4, 5&lt;/span&gt;]. The risk of impaired glucose tolerance associated with intensive systolic BP lowering raises concerns about its benefits. Indeed, abnormal glucose metabolism increases additional cardiovascular risk compared with hypertensive patients exhibiting normal blood glucose levels. There is still a lack of detailed studies on the complex relationship between intensive BP control and the development of abnormal glucose metabolism. Furthermore, the cardiovascular risk in individuals who develop abnormal glucose metabolism as a result of intensive BP lowering remains insufficiently examined. Comprehensively understanding the risks and benefits associated with aggressive BP management is essential for informed decision-making by both patients and healthcare providers. We aimed to provide novel insights into the association between intensive BP control and glycometabolic outcomes within the SPRINT population, as well as to evaluate the subsequent cardiovascular outcomes.&lt;/p&gt;&lt;p&gt;Among the 9361 SPRINT participants, those with missing baseline blood glucose data (&lt;i&gt;N&lt;/i&gt; = 618), baseline blood glucose levels ≥100 mg/dL (5.6 mmol/L) (&lt;i&gt;N&lt;/i&gt; = 3657), or a history of diabetes or use of antidiabetic medications at baseline (&lt;i&gt;N&lt;/i&gt; = 179) were excluded. Finally, 5027 participants with normoglycemia at baseline were included in the current analysis (2522 from the intensive BP lowering and 2505 from the standard BP lowering; Figure 1A). Over a median follow-up of 3.76 years, a total of 823 (37.7%) subjects developed dysglycemia, 242 (9.6%) developed a composite of CVD event or all-cause death, 162 (6.4%) developed CVD event, and 121 (4.9%) deaths occurred in the intensive treatment group. In the standard group, a total of 701 (32.3%) subjects developed dysglycemia, 300 (12.0%) developed a composite of CVD event or all-cause death, 209 (8.3%) developed CVD event, and 152 (6.1%) deaths occurred. These ","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 5","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70197","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914567","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":"Novel Mutation at Cys225 in GNAO1-Associated Developmental and Epileptic Encephalopathies: Clinical, Molecular, and Pharmacological Profiling of Case Studies","authors":"Yonika A. Larasati,&nbsp;Gonzalo P. Solis,&nbsp;Alexey Koval,&nbsp;Marie-Céline François-Heude,&nbsp;Julie Piarroux,&nbsp;Agathe Roubertie,&nbsp;Ruihan Yang,&nbsp;Ying Zhang,&nbsp;Dezhi Cao,&nbsp;Christian M. Korff,&nbsp;Vladimir L. Katanaev","doi":"10.1002/mco2.70196","DOIUrl":"https://doi.org/10.1002/mco2.70196","url":null,"abstract":"<p><i>GNAO1</i>-associated disorders have a large spectrum of neurological symptoms, from early-onset developmental and epileptic encephalopathies (DEE) to late-onset movement disorders. First reported in 2013 and now identified in around 400 cases worldwide, this disease is caused by dominant, mostly de novo missense mutations in <i>GNAO1</i>, the gene encoding the major neuronal G protein Gαo. Being the immediate transducer of a number of neuronal G protein-coupled receptors, Gαo plays crucial functions in brain development and physiology. Here, we discover a novel mutation site in <i>GNAO1</i>, Cys225 mutated to Tyr or Arg in pediatric individuals from France and China (p.(Cys225Tyr) and p.(Cys225Arg), respectively), leading to severe early-onset DEE. Molecular investigations characterize the novel pathogenic variants as deficient in the interactions with guanine nucleotides and physiological cellular partners of Gαo, with reduced stability and plasma membrane localization and a strong neomorphic interaction with the chaperone Ric8A. Salts of zinc, emerging as a promising targeted therapy for <i>GNAO1</i>-associated disorders, impose a previously unseen effect on the mutant Gαo, accelerating the loss of its ability to interact with guanine nucleotides. Our study, combining clinical, cellular, molecular, and modeling approaches, describes deep insights into molecular etiology and treatment perspectives of the novel form of <i>GNAO1</i>-associated disorders.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 5","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70196","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914566","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":"Microbiome: A New Perspective on Immunotherapy for Metastatic Tumors","authors":"Hongquan Liu,&nbsp;Tianqi Wang,&nbsp;Jitao Wu","doi":"10.1002/mco2.70185","DOIUrl":"https://doi.org/10.1002/mco2.70185","url":null,"abstract":"&lt;p&gt;A recent study in &lt;i&gt;Cell&lt;/i&gt; by researchers from the Netherlands Cancer Institute used multi-omics methods to explore the microbiome of metastatic tumors [&lt;span&gt;1&lt;/span&gt;]. Analyzing over 4000 biopsy samples, they found correlations between microbial composition and tumor immunity and responses to immunotherapy. This comprehensive resource highlights the connection between tumor immunity and microbial dynamics, contributing to the development of immunotherapy strategies.&lt;/p&gt;&lt;p&gt;With the advancement of sequencing technology, there is a growing recognition of the vast array of symbiotic microorganisms that reside within various organisms. These symbiotic microbes exhibit intricate dynamic interactions with the host's immune system and are involved in various physiological processes. Recent research on symbiotic microbes has shifted our focus to the species and functions of tumor-associated microbes [&lt;span&gt;2&lt;/span&gt;]. The intratumoral microbiome has been demonstrated to not only directly act on tumor cells, promoting or inhibiting their growth, but also indirectly regulate the immune escape mechanisms of tumors by influencing immune cells within the tumor microenvironment. Studies have revealed that gut microbiota can modulate the response to immune checkpoint blockade (ICB) therapy and traditional chemotherapy, as well as reshape the tumor microenvironment through microbes residing in primary tumors [&lt;span&gt;3&lt;/span&gt;]. By offering a detailed fingerprint of an individual's immune status and responsiveness, the microbiome presents a transformative opportunity for personalized medicine. Based on unique microbial signatures, clinicians can customize immunotherapy to individual patients, enhancing outcomes, minimizing adverse effects, and improving quality of life and survival rates for metastatic tumor patients. However, numerous scientific questions remain to be addressed. For instance, the characteristics of the microbiome in metastatic tumors are still undetermined. Do the microbiomes of primary and metastatic tumors exhibit differences? Is the colonization of microbial species determined by tumor type or organ type? Additionally, the evolution of microbial populations during therapeutic interventions is also uncertain.&lt;/p&gt;&lt;p&gt;In Battaglia's work, researchers conducted a thorough analysis of 4160 metastatic tumor biopsy samples from 26 different tissues, using Kraken2, PathSeq, and an assembly-based approach along with corresponding genomics and transcriptomics data to precisely identify and quantify microbial communities within the metastatic tumors. This study revealed that bacterial DNA could be detected in metastatic tumors, and its diversity displayed a close correlation with tumor immune characteristics at the cellular and molecular levels. Among the findings, metastatic colorectal tumors exhibited the greatest species diversity, while head and neck metastatic tumors harbored a greater abundance of dominant bacteria.&lt;/p&gt;&lt;p&gt;Notably, what factors ","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 5","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143896864","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":"Organoid-Guided Precision Medicine: From Bench to Bedside","authors":"Boqaing Tao,&nbsp;Xiaolan Li,&nbsp;Ming Hao,&nbsp;Tian Tian,&nbsp;Yuyang Li,&nbsp;Xiang Li,&nbsp;Chun Yang,&nbsp;Qirong Li,&nbsp;Qiang Feng,&nbsp;Hengzong Zhou,&nbsp;Yicheng Zhao,&nbsp;Dongxu Wang,&nbsp;Weiwei Liu","doi":"10.1002/mco2.70195","DOIUrl":"https://doi.org/10.1002/mco2.70195","url":null,"abstract":"<p>Organoid technology, as an emerging field within biotechnology, has demonstrated transformative potential in advancing precision medicine. This review systematically outlines the translational trajectory of organoids from bench to bedside, emphasizing their construction methodologies, key regulatory factors, and multifaceted applications in personalized healthcare. By recapitulating physiological architectures and disease phenotypes through three-dimensional culture systems, organoids leverage natural and synthetic scaffolds, stem cell sources, and spatiotemporal cytokine regulation to model tissue-specific microenvironments. Diverse organoid types—including skin, intestinal, lung, and tumor organoids—have facilitated breakthroughs in modeling tissue development, drug efficacy and toxicity screening, disease pathogenesis studies, and patient-tailored diagnostics. For instance, patient-derived tumor organoids preserve tumor heterogeneity and genomic profiles, serving as predictive platforms for individualized chemotherapy responses. In precision medicine, organoid-guided multiomics analyses identify actionable biomarkers and resistance mechanisms, while clustered regularly interspaced short palindromic repeats-based functional screens optimize therapeutic targeting. Despite preclinical successes, challenges persist in standardization, vascularization, and ethical considerations. Future integration of artificial intelligence, microfluidics, and spatial transcriptomics will enhance organoid scalability, reproducibility, and clinical relevance. By bridging molecular insights with patient-specific therapies, organoids are poised to revolutionize precision medicine, offering dynamic platforms for drug development, regenerative strategies, and individualized treatment paradigms.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 5","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70195","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897109","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}