MedComm - Future medicine最新文献

{"title":"ROC-325 Attenuates Hypoxia-Induced Pulmonary Hypertension Through Dual Inhibition of Autophagy and Hypoxia-Inducible Factor 2α Signaling","authors":"Changlei Bao,&nbsp;Shuxin Liang,&nbsp;Dingyuan Liu,&nbsp;Xingting Wang,&nbsp;Dan Bai,&nbsp;Chuangjia Huang,&nbsp;Hanliang Sun,&nbsp;Zi Yang,&nbsp;Bitao Wu,&nbsp;Zixuan Chen,&nbsp;Jieyi Feng,&nbsp;Zinan Luo,&nbsp;Jintao Long,&nbsp;Jinsheng Zhu,&nbsp;June Bai,&nbsp;Li Zhang,&nbsp;Aiai Chu,&nbsp;Caojin Zhang,&nbsp;Haiyang Tang","doi":"10.1002/mef2.70045","DOIUrl":"10.1002/mef2.70045","url":null,"abstract":"<p>The activation of autophagy in endothelial cells is a key mechanism underlying vascular remodeling, leading to the development and progression of pulmonary hypertension (PH). In our previous studies, we developed ROC-325, a novel lysosomal autophagy inhibitor, and demonstrated its potent therapeutic effects in severe pulmonary arterial hypertension (PAH). However, its role in chronic hypoxia-induced PH (HPH) remains unknown. Here, we observed increased LC3B-II/I and decreased p62/SQSTM1 in lung tissues of hypoxic mice, indicative of autophagy activation. ROC-325 treatment suppressed this activation by inhibiting LC3B-II accumulation and restoring p62 levels. ROC-325 significantly reduced right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH), and pulmonary artery medial thickening and muscularization, indicating a significantly protective effect against HPH. Endothelial hypoxia-inducible factor 2α (HIF-2α) upregulation, resulting from prolyl hydroxylase domain protein 2 (PHD2) deficiency, was implicated in autophagy activation. Endothelial conditional PHD2 knockout mice, a spontaneous PH model, exhibited elevated LC3B-II/I and HIF-2α levels, both of which were reduced by ROC-325, leading to significant PH attenuation. In vitro, ROC-325 inhibited the proliferation of pulmonary microvascular endothelial cells derived from PHD2-deficient mice and enhanced HIF-2α degradation in human pulmonary artery endothelial cells. These findings, in summary, identify ROC-325 as a promising therapeutic agent for hypoxia-induced PH by modulating both autophagy and endothelial HIF-2α signaling.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.70045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146135958","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":"ROC-325 Attenuates Hypoxia-Induced Pulmonary Hypertension Through Dual Inhibition of Autophagy and Hypoxia-Inducible Factor 2α Signaling","authors":"Changlei Bao,&nbsp;Shuxin Liang,&nbsp;Dingyuan Liu,&nbsp;Xingting Wang,&nbsp;Dan Bai,&nbsp;Chuangjia Huang,&nbsp;Hanliang Sun,&nbsp;Zi Yang,&nbsp;Bitao Wu,&nbsp;Zixuan Chen,&nbsp;Jieyi Feng,&nbsp;Zinan Luo,&nbsp;Jintao Long,&nbsp;Jinsheng Zhu,&nbsp;June Bai,&nbsp;Li Zhang,&nbsp;Aiai Chu,&nbsp;Caojin Zhang,&nbsp;Haiyang Tang","doi":"10.1002/mef2.70045","DOIUrl":"https://doi.org/10.1002/mef2.70045","url":null,"abstract":"<p>The activation of autophagy in endothelial cells is a key mechanism underlying vascular remodeling, leading to the development and progression of pulmonary hypertension (PH). In our previous studies, we developed ROC-325, a novel lysosomal autophagy inhibitor, and demonstrated its potent therapeutic effects in severe pulmonary arterial hypertension (PAH). However, its role in chronic hypoxia-induced PH (HPH) remains unknown. Here, we observed increased LC3B-II/I and decreased p62/SQSTM1 in lung tissues of hypoxic mice, indicative of autophagy activation. ROC-325 treatment suppressed this activation by inhibiting LC3B-II accumulation and restoring p62 levels. ROC-325 significantly reduced right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH), and pulmonary artery medial thickening and muscularization, indicating a significantly protective effect against HPH. Endothelial hypoxia-inducible factor 2α (HIF-2α) upregulation, resulting from prolyl hydroxylase domain protein 2 (PHD2) deficiency, was implicated in autophagy activation. Endothelial conditional PHD2 knockout mice, a spontaneous PH model, exhibited elevated LC3B-II/I and HIF-2α levels, both of which were reduced by ROC-325, leading to significant PH attenuation. In vitro, ROC-325 inhibited the proliferation of pulmonary microvascular endothelial cells derived from PHD2-deficient mice and enhanced HIF-2α degradation in human pulmonary artery endothelial cells. These findings, in summary, identify ROC-325 as a promising therapeutic agent for hypoxia-induced PH by modulating both autophagy and endothelial HIF-2α signaling.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.70045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146135959","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":"Cardiotropic Gene Therapy for Heart Failure: Translational Lessons From AB-1002","authors":"Nghia Phu Nguyen,&nbsp;Phillip Tran","doi":"10.1002/mef2.70046","DOIUrl":"10.1002/mef2.70046","url":null,"abstract":"&lt;p&gt;In a recent study published in &lt;i&gt;Nature Medicine&lt;/i&gt;, Henry et al. [&lt;span&gt;1&lt;/span&gt;] reported the first-in-human trial of AB-1002, a cardiotropic adeno-associated viral (AAV) vector encoding constitutively active inhibitor-1 (I-1c) for the treatment of advanced non-ischemic heart failure. The study demonstrates that a single intracoronary administration of AB-1002 is feasible, well tolerated and provides early evidence that targeted gene therapy may offer a practical translational strategy for restoring cardiac function in patients with limited treatment options.&lt;/p&gt;&lt;p&gt;Heart failure remains a pervasive global challenge, with current therapies largely slowing progression rather than restoring lost myocardial contractile function. The failing heart is characterized by impaired calcium handling, downregulated sarcoplasmic–endoplasmic reticulum calcium ions (Ca&lt;sup&gt;2+&lt;/sup&gt;) ATPase (SERCA2a) pump activity, and maladaptive remodeling that perpetuates systolic dysfunction [&lt;span&gt;2, 3&lt;/span&gt;]. Earlier gene therapy trials, including the CUPID trial targeting SERCA2a, were hindered by limited vector tropism and immune barriers [&lt;span&gt;2, 4&lt;/span&gt;]. Yet advances in capsid engineering and cardiac-specific delivery have reignited the field [&lt;span&gt;3&lt;/span&gt;], culminating in the current clinical translation.&lt;/p&gt;&lt;p&gt;I-1c, the central effector gene in AB-1002, encodes a truncated and constitutively active form of the endogenous protein phosphatase 1 (PP1) inhibitor [&lt;span&gt;3&lt;/span&gt;]. In normal cardiomyocytes, β-adrenergic stimulation phosphorylates phospholamban (PLN) and activates the SERCA2a, enabling calcium reuptake during relaxation [&lt;span&gt;5&lt;/span&gt;]. In heart failure, overactive PP1 dephosphorylates PLN, suppressing SERCA2a and causing cytosolic calcium overload and contractile weakness [&lt;span&gt;5&lt;/span&gt;]. By maintaining PLN phosphorylation, I-1c restores SERCA2a activity, re-establishes Ca&lt;sup&gt;2+&lt;/sup&gt; homeostasis, and improves relaxation and contractility [&lt;span&gt;3, 5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Preclinical work demonstrated that cardiac overexpression of I-1c using a re-engineered AAV2/8 vector improved ejection fraction and reduced left-ventricular dilation in a swine model of ischemic heart failure [&lt;span&gt;3&lt;/span&gt;]. These studies laid the foundation for the cardiotropic AAV2i8 vector used in AB-1002—a hybrid of AAV2 and AAV8 sequences designed to enhance myocardial transduction while minimizing hepatic exposure [&lt;span&gt;3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;In the first-in-human, open-label phase 1 trial [&lt;span&gt;1&lt;/span&gt;], 11 patients with non-ischemic cardiomyopathy, New York Heart Association (NYHA) class III symptoms, and a baseline left ventricular ejection fraction (LVEF) of 15%–35% received a single intracoronary infusion of AB-1002, a chimeric cardiotropic AAV2i8 vector encoding constitutively active inhibitor-1. Two escalating doses were evaluated—3.25 × 10&lt;sup&gt;13&lt;/sup&gt; vg (cohort 1) and 1.08 × 10&lt;sup&gt;14&lt;/sup&gt; vg (cohort 2)—across three study centers in the United States. Participants","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146136673","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":"Advancing Surgical Practice With Mixed Reality: Current Innovations and Future Prospects","authors":"Yifan Ke,&nbsp;Kunpeng Hu","doi":"10.1002/mef2.70043","DOIUrl":"https://doi.org/10.1002/mef2.70043","url":null,"abstract":"<p>Mixed reality is an immersive visualization technology based on simultaneous localization and mapping systems and standalone head-mounted displays. It enables seamless integration and dynamic interaction among users, virtual elements, and the physical environment. Although numerous clinical studies and in vitro experiments have confirmed the value of mixed reality in surgical practice, the hierarchy of evidence remains limited. This review draws on published English-language literature to summarize its technical foundations, clinical applications, current innovations, and existing challenges. Specifically, the primary procedures of mixed reality-assisted surgery consist of three-dimensional reconstruction, holographic visualization, and spatial registration. Its clinical applications span preoperative planning, intraoperative navigation, surgical training, and postoperative rehabilitation. However, current limitations include insufficient computational and display capabilities of head-mounted displays, inadequate accuracy in spatial registration, high costs, workflow complexity, and unresolved ethical concerns. Therefore, we recommend increased resource allocation for technological innovations, multicenter randomized controlled clinical trials, and detailed risk-benefit assessments, aiming to establish and validate standardized clinical workflows. As the first comprehensive narrative review to compare the clinical applicability of mixed reality across all surgical specialties, this article outlines future research directions by analyzing representative clinical studies and offers a reliable report on current progress.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145887289","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":"Air Pollution-Induced Epigenetic Regulation in Respiratory Diseases: Mechanisms, Dysregulation, and Therapeutic Opportunities","authors":"Ruitong Zeng,&nbsp;Jiliu Liu,&nbsp;Guoping Li,&nbsp;Junyi Wang,&nbsp;Anying Xiong,&nbsp;Ying Xiong,&nbsp;Xiang He","doi":"10.1002/mef2.70044","DOIUrl":"https://doi.org/10.1002/mef2.70044","url":null,"abstract":"<p>Air pollution poses a significant threat to respiratory health globally, contributing to the development and worsening of diseases, such as asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, and lung cancer. A key mechanism behind this involves epigenetic reprogramming, where environmental exposures alter gene activity without changing the underlying DNA sequence itself. This review deciphers the multilayered epigenetic mechanisms linking pollutants (e.g., PM_2.5, cigarette smoke, and ozone) to respiratory pathology, emphasizing reversible modifications that bridge environmental exposure and disease phenotypes. Air pollution-induced epigenetic reprogramming regulates critical biological processes, such as immune imbalance, chronic inflammation, oxidative stress, cellular dysfunction (senescence, apoptosis, and ferroptosis), tissue remodeling (epithelial–mesenchymal transition and fibrosis), and genomic instability. Specifically, aberrant DNA methylation, dysregulated RNA methylation, perturbed noncoding RNA networks, and histone modification abnormalities collectively drive disease pathogenesis. Furthermore, emerging epigenetic therapies targeting these modifications, such as DNA methyltransferase inhibitors (5-AZADC), histone deacetylase inhibitors, and RNA methylation regulators (methyltransferase-like 3 inhibitor STM2457), show promising therapeutic potential. This review highlights the reversibility of epigenetic changes as a strategic basis for intervention, emphasizing the need for future research on mixed exposures, tissue-specific mechanisms, and clinical translation to mitigate the global burden of pollution-related respiratory diseases.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.70044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145824856","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":"Artificial Intelligence in Traditional Chinese Medicine: Bridging Ancient Practice and Future Innovation","authors":"Zhehan Jiang,&nbsp;Quanming Peng,&nbsp;Li Li,&nbsp;Shate Xiang","doi":"10.1002/mef2.70042","DOIUrl":"https://doi.org/10.1002/mef2.70042","url":null,"abstract":"<p>Traditional Chinese Medicine (TCM), with its fragmented knowledge system, subjective diagnostics, and limited standardization, faces ongoing challenges in modernization. The rapid development of Large Language Models (LLMs) offers an unprecedented opportunity for the digitalization and standardization of TCM knowledge. By leveraging deep semantic understanding, contextual reasoning, and knowledge-graph–based inference, LLMs can systematize knowledge, integrate multimodal data, and support both standardized and personalized decision-making. Several TCM–LLMs, such as Qibo and MedChatZH, have been developed. Although previous reviews compared individual TCM–LLMs, a comprehensive analysis of common characteristics is lacking. This review addresses this gap by examining the “construction–application–challenges–prospects” paradigm of TCM–LLMs. Construction generally involves collecting authoritative data from diverse sources, standardizing textual content, training and fine-tuning on foundational LLMs, and subsequent evaluation. Key applications include auxiliary diagnosis and treatment, health management, medical education, and drug discovery. Five major challenges are data quality, reasoning performance, multimodal integration, ethical and regulatory compliance, and cultural adaptability. On the basis of this analysis, we propose a classification scheme that categorizes applications into four types and adopt the identified challenges as evaluation dimensions for future TCM–LLMs. This framework aims to clarify conceptual structures, guide methodology, and provide a foundation for innovation and cross-cultural integration in TCM research.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145750836","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":"Optogenetic Regulation of Integrated Stress Responses: Developing Novel Broad-Spectrum Antiviral Strategies","authors":"Shizhan Cui,&nbsp;Zehan Pang,&nbsp;Bixia Hong","doi":"10.1002/mef2.70040","DOIUrl":"https://doi.org/10.1002/mef2.70040","url":null,"abstract":"&lt;p&gt;In a recent publication in &lt;i&gt;Cell&lt;/i&gt;, Wong et al. presented an optogenetic system for screening compounds that specifically modulate the integrated stress response (ISR) [&lt;span&gt;1&lt;/span&gt;]. The authors identified eight non-cytotoxic ISR enhancers as broad-spectrum antiviral agents and revealed their key mechanism: the selective targeting of general control nonderepressible 2 (GCN2) to upregulate activating transcription factor 4 (ATF4) expression, thereby sensitizing cells to stress and apoptosis [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Optogenetics enables precise spatiotemporal control of cellular activity by conferring light sensitivity via heterologous expression of photosensitive proteins. This approach is increasingly being integrated with synthetic biology to facilitate novel paradigms in phenotypic drug discovery [&lt;span&gt;2&lt;/span&gt;]. Meanwhile, the ISR pathway represents a conserved signaling pathway activated by four stress sensor kinases—heme-regulated inhibitor (HRI), protein kinase R (PKR), protein kinase R-like ER kinase (PERK), and GCN2—which respond to diverse stressors such as viral double-stranded RNA [&lt;span&gt;3&lt;/span&gt;]. Upon activation, these kinases phosphorylate the eukaryotic translation initiation factor 2 subunit alpha (eIF2α), leading to the selective translation of ISR-related proteins, such as ATF4, C/EBP homologous protein (CHOP), and growth arrest and DNA damage-inducible protein 34 (GADD34), thereby modulating cell survival and function. Given this regulatory capacity, ISR-enhancing compounds represent a novel strategy for the development of broad-spectrum antiviral therapeutics [&lt;span&gt;3&lt;/span&gt;]. The combination of optogenetics-driven precise manipulation and deeper exploration of the ISR network—particularly its crosstalk with other signaling pathways—may open breakthrough directions for future broad-spectrum antiviral research.&lt;/p&gt;&lt;p&gt;To achieve precise control of the ISR pathway, Taivan et al. developed an optogenetic platform that dynamically stimulates the ISR signaling using a light-activated optogenetic PKR (opto-PKR) [&lt;span&gt;4&lt;/span&gt;]. The dsRBM1 and dsRBM2 regions of PKR were replaced with an optimized mutant of the &lt;i&gt;Arabidopsis&lt;/i&gt; blue light receptor Cry, namely Cry2Olig (E490G). Upon transduction of opto-PKR into cells, exposure to blue light prompted Cry2 aggregation, inducing in PKR oligomerization, kinase activation, and subsequent initiation of ISR. This light-controlled system simulates PKR-mediated ISR activation as observed during viral infection, while avoiding off-target cytotoxicity [&lt;span&gt;4&lt;/span&gt;]. The platform's efficacy was validated through both pharmacological activators and inhibitors of the ISR pathway (Figure 1a) [&lt;span&gt;1&lt;/span&gt;]. Crucially, unlike traditional small-molecule stressors that often cause cross-pathway interference, this approach minimizes such off-target effects and offers immediate deactivation in darkness, enabling transient response unattainable with conventional small-molecule activators.","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695083","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":"Global Burden and Future Projections of Urological Cancers: A Comprehensive Analysis From the Global Burden of Disease Study 2021","authors":"Mengyi Zhu,&nbsp;Haoxuan Wang,&nbsp;Haishan Lin,&nbsp;Guibin Hong,&nbsp;Yun Wang,&nbsp;Fan Jiang,&nbsp;Ye Xie,&nbsp;Runnan Shen,&nbsp;Hongkun Yang,&nbsp;Shaoxu Wu","doi":"10.1002/mef2.70041","DOIUrl":"https://doi.org/10.1002/mef2.70041","url":null,"abstract":"<p>Urological cancers represent a significant and growing global health challenge. This study aims to provide a comprehensive assessment of the global burden, trends, and inequalities of prostate, bladder, and kidney cancers from 1990 to 2021, and to project their future burden to 2050. Utilizing data from the Global Burden of Disease Study 2021, we analyzed incidence, prevalence, mortality, and disability-adjusted life years (DALYs). We employed joinpoint regression to analyze temporal trends, frontier analysis to evaluate healthcare efficiency, and Bayesian age-period-cohort models to project future burden. Risk factor attributions were also quantified. In 2021, prostate cancer demonstrated the highest age-standardized rates across all metrics. From 1990 to 2021, age-standardized mortality and DALY rates declined for all three cancers. The burden was disproportionately higher among males and older populations, with smoking, high fasting plasma glucose, and high body-mass index identified as leading risk factors. Projections to 2050 indicate a continued decline in all age-standardized rates globally. Despite favorable trends in standardized rates, persistent sex disparities, growing absolute case numbers due to population aging, and the influence of modifiable risk factors necessitate targeted public health interventions and strategic healthcare planning.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.70041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145619225","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":"Charting the Shared Genetic Architecture Between Breast Cancer and Major Depressive Disorder","authors":"Yilong Lin,&nbsp;Yuning Wang,&nbsp;Ruidan Zhao,&nbsp;Liyi Zhang,&nbsp;Qingmo Yang","doi":"10.1002/mef2.70039","DOIUrl":"https://doi.org/10.1002/mef2.70039","url":null,"abstract":"&lt;p&gt;Individuals suffering from major depressive disorder (MDD) have been reported to be more susceptible to cancer. A recent meta-analysis revealed that individuals with MDD or anxiety had a moderately elevated likelihood of developing cancer (RR = 1.13, 95% CI = 1.06–1.19) and a higher probability of cancer-related death (RR = 1.21, 95% CI = 1.16–1.26) [&lt;span&gt;1&lt;/span&gt;]. The increased susceptibility to cancer among individuals with MDD may arise from multiple mechanisms. On one hand, patients suffering from this disorder are often less likely to participate in early cancer detection and screening programs. On the other hand, dysregulation of neuroendocrine pathways in MDD may further contribute to tumor progression by altering immune function, promoting chronic inflammation, and affecting tumor biology [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Specially, individuals with MDD also had a higher risk of breast cancer compared to those without MDD [&lt;span&gt;3&lt;/span&gt;], and those patients with both diseases tended to have poorer BC outcomes [&lt;span&gt;2&lt;/span&gt;]. In addition, up to 60% of women experience depression before and throughout their BC diagnosis, affecting women of all races and ages [&lt;span&gt;2&lt;/span&gt;]. However, these observational studies may have been affected by confounding factors and biases.&lt;/p&gt;&lt;p&gt;In this study, we employed a genome-wide cross-trait analysis to chart the shared genetic architecture between BC and MDD, further exploring the genetic and phenotypic relationships. The overview of this study was shown in Figure S1. The genome-wide association studies (GWAS) data of BC and MDD were obtained from The Breast Cancer Association Consortium and Discovery, Biology and Risk of Inherited Variants in Breast Cancer Consortium, and Psychiatric Genomics Consortium. First, we conducted a genetic correlation analysis using linkage disequilibrium score regression (LDSC). Then, we employed two cross-trait meta-analysis methods (the multi-trait analysis of GWAS [MTAG] and the Cross-Phenotype Association analysis [CPASSOC]) to identify common risk SNPs associated with BC and MDD. In addition, pleiotropic analysis under composite null hypothesis (PLACO) was used to identify pleiotropic loci associated with BC and MDD. Based on PLACO analysis, we identified potential pleiotropic loci and genes through Functional Mapping and Annotation of Genetic Associations (FUMA) tool and multimarker analysis of GenoMic annotation (MAGMA) analysis. Finally, we conducted Generalized summary-data-based Mendelian randomization (GSMR) and two-sample Mendelian Randomization (TSMR) to identify the causal associations. MR analysis relies on three core assumptions: (1) the genetic variants used as instrumental variables (IVs) are strongly associated with the exposure; (2) these IVs are independent of confounding factors; and (3) they affect the outcome only through the exposure. The SNPs were selected based on commonly accepted criteria in MR studies: (i) genome-wide significance with a &lt;i&gt;p&lt;/i&gt; ","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145625976","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":"Evaluating the Survival Impact of Neoadjuvant Therapy and Development of Personalized Machine Learning Survival Predictive Model for Breast Cancer Patients Eligible for Breast-Conserving Surgery","authors":"Zhicheng Du,&nbsp;Yongqu Zhang,&nbsp;Weibin Li,&nbsp;Xue Zhao,&nbsp;Xueqi Fan,&nbsp;Jingwen Bai,&nbsp;Guojun Zhang","doi":"10.1002/mef2.70036","DOIUrl":"https://doi.org/10.1002/mef2.70036","url":null,"abstract":"<p>The long-term survival benefit of neoadjuvant therapy (NAT) in breast cancer patients eligible for breast-conserving surgery (BCS) remains uncertain. This retrospective cohort study analyzed 94,677 BCS-eligible patients from the SEER database (2010–2020), including 8565 who received NAT. After propensity score matching (<i>n</i> = 5734 each), NAT significantly improved overall survival (OS) only in patients with triple-negative (HR = 0.79), ER-negative (HR = 0.80), and stage IIA (HR = 0.81) disease. No OS benefit was observed in HER2-positive patients despite high response rates. To guide treatment decisions, two machine learning models using Random Survival Forest were developed to predict 5-year OS, showing good discrimination (C-index: 0.743 for BCS, 0.690 for NAT-BCS). SHAP analysis identified age, stage, and breast subtype as key prognostic factors. Cross-stratification based on predicted OS revealed that 8.9% of BCS patients could benefit from NAT, while 90.8% of NAT-BCS patients might safely omit it. Patients whose treatment matched model recommendations had significantly better survival. These findings suggest that NAT provides limited survival benefit in BCS-eligible patients, with the advantage concentrated in specific subgroups. Predictive modeling offers a clinically useful approach to personalize NAT use, potentially reducing unnecessary treatment while identifying those most likely to benefit.</p>","PeriodicalId":74135,"journal":{"name":"MedComm - Future medicine","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mef2.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145572234","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}