❌

Normal view

Molecular mechanisms and therapeutic targets of acute exacerbations of chronic obstructive pulmonary disease with Pseudomonas aeruginosa infection

Respir Res. 2025 Mar 26;26(1):115. doi: 10.1186/s12931-025-03185-x.

ABSTRACT

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of global mortality, with acute exacerbations of COPD (AECOPD) significantly increasing the disease's morbidity and mortality. Among the pathogens implicated in AECOPD, Pseudomonas aeruginosa (P. aeruginosa) is increasingly recognized as a major co-infecting bacterium. Despite its clinical importance, the molecular mechanisms and therapeutic targets underlying AECOPD with P. aeruginosa infection remain inadequately understood.

METHODS: We employed a multi-omics approach, integrating proteomic analyses of bronchoalveolar lavage fluid (BALF) and plasma with transcriptomic analysis of peripheral blood. A discovery cohort of 40 AECOPD with P. aeruginosa infection patients and 20 healthy controls was analyzed, followed by validation in an independent cohort of 20 patients and 10 controls. Differentially expressed proteins (DEPs) and genes (DEGs) were identified and subjected to protein-protein interaction (PPI) network analysis, weighted gene co-expression network analysis (WGCNA), and immune infiltration analysis. Molecular docking simulations were conducted to explore potential therapeutic agents.

RESULTS: Our integrative analysis identified key biomarkers, which played critical roles in oxidative stress and neutrophil extracellular trap (NET) formation, both of which were pivotal in the pathogenesis of AECOPD with P. aeruginosa infection. The combined analysis of BALF, plasma, and peripheral blood underscored the interplay between local lung changes and systemic immune responses. Functional enrichment analyses highlighted significant pathways related to bacterial defense, inflammation, and immune activation. Validation in an independent cohort confirmed the diagnostic value of three key proteins (AZU1, MPO, and RETN), with high area under the curve (AUC) values in ROC analyses. Molecular docking indicated strong binding affinities of these proteins with Pioglitazone and Rosiglitazone, suggesting potential therapeutic utility.

CONCLUSIONS: This study provides a comprehensive understanding of the molecular mechanisms underlying AECOPD with P. aeruginosa infection, highlighting the pivotal roles of oxidative stress and NET formation in disease progression. The identified biomarkers offer promising diagnostic and therapeutic targets. Our findings pave the way for novel strategies to improve outcomes for AECOPD patients with P. aeruginosa infection. While the study design limits our ability to establish causality, these results provide important insights that warrant further investigation, particularly through longitudinal studies, to confirm the specific contributions of P. aeruginosa in exacerbations.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:40140846 | PMC:PMC11948814 | DOI:10.1186/s12931-025-03185-x

AI meets oncology: New model personalizes bladder cancer treatment

28 March 2025 at 23:25
Leveraging the power of AI and machine learning technologies, researchers developed a more effective model for predicting how patients with muscle-invasive bladder cancer will respond to chemotherapy. The model harnesses whole-slide tumor imaging data and gene expression analyses in a way that outperforms previous models using a single data type.

Liquid Biopsies in the Early Diagnosis, Prognosis, and Tailored Treatment of Colorectal Cancer

Cancers (Basel). 2025 Mar 8;17(6):927. doi: 10.3390/cancers17060927.

ABSTRACT

INTRODUCTION: Liquid biopsies provide a less-invasive option to tissue biopsies for the early diagnosis, prognosis, and tailored therapy of colorectal cancer (CRC). CRC is a major cause of cancer-related death, and early identification is essential for improving patient outcomes.

REVIEW: Conventional diagnostic techniques, including colonoscopy and tissue biopsy, may be enhanced by liquid biopsies that examine circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), extracellular vesicles (EVs), and other indicators present in body fluids. These markers provide significant insights into tumor biology, heterogeneity, and therapeutic response. CTCs detected in early-stage CRC have prognostic significance for disease recurrence and survival, while ctDNA investigation may uncover genetic mutations, epigenetic alterations, and tumor development. The identification of ctDNA in minimal residual disease (MRD) postsurgery correlates with an elevated risk of recurrence and unfavorable prognosis, underscoring its use in assessing treatment effectiveness. Furthermore, non-coding RNAs (ncRNAs) contained inside EVs provide potential prospective biomarkers and therapeutic targets, facilitating diagnosis and treatment assessment. Notwithstanding the potential of liquid biopsies, obstacles persist in assay standardization, sensitivity enhancement, and the management of tumor heterogeneity. Additional extensive research is required to determine their function in clinical practice.

CONCLUSION: Overall, liquid biopsies serve as a potential instrument for real-time monitoring, evaluating therapy responses, and directing individualized therapeutic strategies in CRC patients.

PMID:40149264 | PMC:PMC11940745 | DOI:10.3390/cancers17060927

  • ✇MRD
  • Liquid biopsies in cancer Hang Yin · Manjie Zhang · Yu Zhang · Xuebing Zhang · Xia Zhang · Bin Zhang
    Mol Biomed. 2025 Mar 20;6(1):18. doi: 10.1186/s43556-025-00257-8.ABSTRACTCancer ranks among the most lethal diseases worldwide. Tissue biopsy is currently the primary method for the diagnosis and biological analysis of various solid tumors. However, this method has some disadvantages related to insufficient tissue specimen collection and intratumoral heterogeneity. Liquid biopsy is a noninvasive approach for identifying cancer-related biomarkers in peripheral blood, which allows for repetitive s
     

Liquid biopsies in cancer

20 March 2025 at 18:00

Mol Biomed. 2025 Mar 20;6(1):18. doi: 10.1186/s43556-025-00257-8.

ABSTRACT

Cancer ranks among the most lethal diseases worldwide. Tissue biopsy is currently the primary method for the diagnosis and biological analysis of various solid tumors. However, this method has some disadvantages related to insufficient tissue specimen collection and intratumoral heterogeneity. Liquid biopsy is a noninvasive approach for identifying cancer-related biomarkers in peripheral blood, which allows for repetitive sampling across multiple time points. In the field of liquid biopsy, representative biomarkers include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and exosomes. Many studies have evaluated the prognostic and predictive roles of CTCs and ctDNA in various solid tumors. Although these studies have limitations, the results of most studies appear to consistently demonstrate the correlations of high CTC counts and ctDNA mutations with lower survival rates in cancer patients. Similarly, a reduction in CTC counts throughout therapy may be a potential prognostic indicator related to treatment response in advanced cancer patients. Moreover, the biochemical characteristics of CTCs and ctDNA can provide information about tumor biology as well as resistance mechanisms against targeted therapy. This review discusses the current clinical applications of liquid biopsy in cancer patients, emphasizing its possible utility in outcome prediction and treatment decision-making.

PMID:40108089 | PMC:PMC11923355 | DOI:10.1186/s43556-025-00257-8

  • ✇MIT Technology Review
  • How a bankruptcy judge can stop a genetic privacy disaster Keith Porcaro
    Stop me if you’ve heard this one before: A tech company accumulates a ton of user data, hoping to figure out a business model later. That business model never arrives, the company goes under, and the data is in the wind.  The latest version of that story emerged on March 24, when the onetime genetic testing darling 23andMe filed for bankruptcy. Now the fate of 15 million people’s genetic data rests in the hands of a bankruptcy judge. At a hearing on March 26, the judge gave 23andMe permission
     

How a bankruptcy judge can stop a genetic privacy disaster

28 March 2025 at 21:00

Stop me if you’ve heard this one before: A tech company accumulates a ton of user data, hoping to figure out a business model later. That business model never arrives, the company goes under, and the data is in the wind. 

The latest version of that story emerged on March 24, when the onetime genetic testing darling 23andMe filed for bankruptcy. Now the fate of 15 million people’s genetic data rests in the hands of a bankruptcy judge. At a hearing on March 26, the judge gave 23andMe permission to seek offers for its users’ data. But, there’s still a small chance of writing a better ending for users.

After the bankruptcy filing, the immediate take from policymakers and privacy advocates was that 23andMe users should delete their accounts to prevent genetic data from falling into the wrong hands. That’s good advice for the individual user (and you can read how to do so here). But the reality is most people won’t do it. Maybe they won’t see the recommendations to do so. Maybe they don’t know why they should be worried. Maybe they have long since abandoned an account that they don’t even remember exists. Or maybe they’re just occupied with the chaos of everyday life. 

This means the real value of this data comes from the fact that people have forgotten about it. Given 23andMe’s meager revenue—fewer than 4% of people who took tests pay for subscriptions—it seems inevitable that the new owner, whoever it is, will have to find some new way to monetize that data. 

This is a terrible deal for users who just wanted to learn a little more about themselves or their ancestry. Because genetic data is forever. Contact information can go stale over time: you can always change your password, your email, your phone number, or even your address. But a bad actor who has your genetic data—whether a cybercriminal selling it to the highest bidder, a company building a profile of your future health risk, or a government trying to identify you—will have it tomorrow and the next day and all the days after that. 

Users with exposed genetic data are not only vulnerable to harm today; they’re vulnerable to exploits that might be developed in the future. 

While 23andMe promises that it will not voluntarily share data with insurance providers, employers, or public databases, its new owner could unwind those promises at any time with a simple change in terms. 

In other words: If a bankruptcy court makes a mistake authorizing the sale of 23andMe’s user data, that mistake is likely permanent and irreparable. 

All this is possible because American lawmakers have neglected to meaningfully engage with digital privacy for nearly a quarter-century. As a result, services are incentivized to make flimsy, deceptive promises that can be abandoned at a moment’s notice. And the burden falls on users to keep track of it all, or just give up.

Here, a simple fix would be to reverse that burden. A bankruptcy court could require that users individually opt in before their genetic data can be transferred to 23andMe’s new owners, regardless of who those new owners are. Anyone who didn’t respond or who opted out would have the data deleted. 

Bankruptcy proceedings involving personal data don’t have to end badly. In 2000, the Federal Trade Commission settled with the bankrupt retailer ToySmart to ensure that its customer data could not be sold as a stand-alone asset, and that customers would have to affirmatively consent to unexpected new uses of their data. And in 2015, the FTC intervened in the bankruptcy of RadioShack to ensure that it would keep its promises never to sell the personal data of its customers. (RadioShack eventually agreed to destroy it.) 

The ToySmart case also gave rise to the role of the consumer privacy ombudsman. Bankruptcy judges can appoint an ombuds to help the court consider how the sale of personal data might affect the bankruptcy estate, examining the potential harms or benefits to consumers and any alternatives that might mitigate those harms. The U.S. Trustee has requested the appointment of an ombuds in this case. While scholars have called for the role to have more teeth and for the FTC and states to intervene more often, a framework for protecting personal data in bankruptcy is available. And ultimately, the bankruptcy judge has broad power to make decisions about how (or whether) property in bankruptcy is sold.

Here, 23andMe has a more permissive privacy policy than ToySmart or RadioShack. But the risks incurred if genetic data falls into the wrong hands or is misused are severe and irreversible. And given 23andMe’s failure to build a viable business model from testing kits, it seems likely that a new business would use genetic data in ways that users wouldn’t expect or want. 

An opt-in requirement for genetic data solves this problem. Genetic data (and other sensitive data) could be held by the bankruptcy trustee and released as individual users gave their consent. If users failed to opt in after a period of time, the remaining data would be deleted. This would incentivize 23andMe’s new owners to earn user trust and build a business that delivers value to users, instead of finding unexpected ways to exploit their data. And it would impose virtually no burden on the people whose genetic data is at risk: after all, they have plenty more DNA to spare.

Consider the alternative. Before 23andMe went into bankruptcy, its then-CEO made two failed attempts to buy it, at reported valuations of $74.7 million and $12.1 million. Using the higher offer, and with 15 million users, that works out to a little under $5 per user. Is it really worth it to permanently risk a person’s genetic privacy just to add a few dollars in value to the bankruptcy estate?    

Of course, this raises a bigger question: Why should anyone be able to buy the genetic data of millions of Americans in a bankruptcy proceeding? The answer is simple: Lawmakers allow them to. Federal and state inaction allows companies to dissolve promises about protecting Americans’ most sensitive data at a moment’s notice. When 23andMe was founded, in 2006, the promise was that personalized health care was around the corner. Today, 18 years later, that era may really be almost here. But with privacy laws like ours, who would trust it?

Keith Porcaro is the Rueben Everett Senior Lecturing Fellow at Duke Law School.

Spatial immune remodeling of the liver metastases: discovering the path to antimetastatic therapy

J Immunother Cancer. 2025 Mar 18;13(3):e011002. doi: 10.1136/jitc-2024-011002.

ABSTRACT

The intrinsic characteristics of metastatic tumors are of great importance in terms of the development of antimetastatic treatment strategies. Elucidation from a spatial immune perspective has the potential to provide a more comprehensive understanding of the mechanisms underlying immune escape, effectively addressing the limitations of relying solely on the analysis of immune cell subpopulation transcriptional profiles. Advances in spatial omics technology enable researchers to precisely analyze precious liver metastasis samples in a high-throughput manner, revealing spatial alterations in immune cell distribution induced by metastasis and exploring the molecular basis of the remodeling process. The aggregation of specific cell subpopulations in distinct regions not only modifies local immune characteristics but also concurrently affects global biological behaviors of liver metastatic tumors. Identifying specific spatial immune characteristics in pretreatment or early-stage treatment tissue samples may achieve accurate clinical predictions. Moreover, developing strategies that target spatial immune remodeling is a promising avenue for future antimetastatic therapy.

PMID:40107672 | PMC:PMC11927485 | DOI:10.1136/jitc-2024-011002

Circulating biomarkers in pulmonary arterial hypertension: State-of-the-art review and future directions

JHLT Open. 2024 Aug 23;6:100152. doi: 10.1016/j.jhlto.2024.100152. eCollection 2024 Nov.

ABSTRACT

Pulmonary arterial hypertension is a complex and heterogeneous condition, associated with a considerable diagnostic delay, diminished exercise capacity, and poor outcomes. In pulmonary arterial hypertension, biomarker research has become a subject of intense inquiry, and novel circulating biomarkers acknowledged in a multitude of mechanistic pathways are emerging. Beyond the widely used natriuretic peptides, novel biomarkers may provide deeper pathophysiological understanding, support clinical decision-making, and prompt the incorporation of precision medicine by enabling a more precise individual phenotyping. In this state-of-the-art review, the recent advances in circulating biomarkers in pulmonary arterial hypertension from a clinical perspective are discussed, with particular emphasis on the current state of knowledge, gaps in evidence, and future perspectives.

PMID:40145036 | PMC:PMC11935499 | DOI:10.1016/j.jhlto.2024.100152

  • ✇InfoQ
  • Applying DevOps Principles and Practices as a Quality Assurance Engineer Ben Linders
    DevOps streamlines software development with automation and collaboration between development and IT teams for efficient delivery. According to Nedko Hristov, testers' curiosity, adaptability, and willingness to learn make them suited for DevOps. Failures can be approached with a constructive mindset; they provide growth opportunities, leading to improved skills and practices. By Ben Linders
     

Applying DevOps Principles and Practices as a Quality Assurance Engineer

20 March 2025 at 19:08

DevOps streamlines software development with automation and collaboration between development and IT teams for efficient delivery. According to Nedko Hristov, testers' curiosity, adaptability, and willingness to learn make them suited for DevOps. Failures can be approached with a constructive mindset; they provide growth opportunities, leading to improved skills and practices.

By Ben Linders

Worldwide Innovative Network (WIN) Consortium in Personalized Cancer Medicine: Bringing next-generation precision oncology to patients

Oncotarget. 2025 Mar 12;16:140-162. doi: 10.18632/oncotarget.28703.

ABSTRACT

The human genome project ushered in a genomic medicine era that was largely unimaginable three decades ago. Discoveries of druggable cancer drivers enabled biomarker-driven gene- and immune-targeted therapy and transformed cancer treatment. Minimizing treatment not expected to benefit, and toxicity-including financial and time-are important goals of modern oncology. The Worldwide Innovative Network (WIN) Consortium in Personalized Cancer Medicine founded by Drs. John Mendelsohn and Thomas Tursz provided a vision for innovation, collaboration and global impact in precision oncology. Through pursuit of transcriptomic signatures, artificial intelligence (AI) algorithms, global precision cancer medicine clinical trials and input from an international Molecular Tumor Board (MTB), WIN has led the way in demonstrating patient benefit from precision-therapeutics through N-of-1 molecularly-driven studies. WIN Next-Generation Precision Oncology (WINGPO) trials are being developed in the neoadjuvant, adjuvant or metastatic settings, incorporate real-world data, digital pathology, and advanced algorithms to guide MTB prioritization of therapy combinations for a diverse global population. WIN has pursued combinations that target multiple drivers/hallmarks of cancer in individual patients. WIN continues to be impactful through collaboration with industry, government, sponsors, funders, academic and community centers, patient advocates, and other stakeholders to tackle challenges including drug access, costs, regulatory barriers, and patient support. WIN's collaborative next generation of precision oncology trials will guide treatment selection for patients with advanced cancers through MTB and AI algorithms based on serial liquid and tissue biopsies and exploratory omics including transcriptomics, proteomics, metabolomics and functional precision medicine. Our vision is to accelerate the future of precision oncology care.

PMID:40073368 | PMC:PMC11907938 | DOI:10.18632/oncotarget.28703

Scientists discover how to reactivate cancer's molecular 'kill switch'

15 March 2025 at 05:04
Researchers have discovered that cancer cells suppress 'poison exons' -- genetic elements that act as an off switch for protein production -- in a key gene called TRA2 , promoting tumor growth. By using antisense oligonucleotides (ASOs) to restore poison exon activity, the team effectively reactivated this kill switch, offering a potential new precision therapy for aggressive, hard-to-treat cancers.
  • ✇MRD
  • Importance of circulating tumor DNA in colorectal cancer B Tolmáči · A Řehulková · P Žuff · J Klein
    Klin Onkol. 2025;38(1):32-37. doi: 10.48095/ccko202532.ABSTRACTBACKGROUND: Space still exists in the management of patients with colorectal cancer (CRC) for improving risk stratification and thus the precision of treatment tailoring. Quite promising in this regard are biomarkers acquired via liquid biopsy, which is a non-invasive method of body fluid draw, most commonly peripheral blood. A variety of biomarkers associated with the tumor are analyzed, which can have either prognostic or predictiv
     

Importance of circulating tumor DNA in colorectal cancer

15 March 2025 at 18:00

Klin Onkol. 2025;38(1):32-37. doi: 10.48095/ccko202532.

ABSTRACT

BACKGROUND: Space still exists in the management of patients with colorectal cancer (CRC) for improving risk stratification and thus the precision of treatment tailoring. Quite promising in this regard are biomarkers acquired via liquid biopsy, which is a non-invasive method of body fluid draw, most commonly peripheral blood. A variety of biomarkers associated with the tumor are analyzed, which can have either prognostic or predictive value. Circulating tumor DNA (ctDNA) is one of the most explored tumor biomarkers. Initially, its utility spectrum was only in advanced or metastatic cancers and consisted of molecular profiling and detecting acquired resistance to treatment. Nowadays, the use of circulating tumor DNA has shifted to earlier cancer stages, where it can identify minimal residual disease or diagnose colorectal cancer early. Existing studies show promising potential of these biomarkers, but more information needs to be gathered and information from ongoing studies needs to be obtained in order to use them in everyday practice.

AIM: In this review article, we will discuss ctDNA, its aspects, diag- nostic possibilities and current use in CRC.

PMID:40088434 | DOI:10.48095/ccko202532

  • ✇MRD
  • Minimal Residual Disease in Metastatic Soft Tissue Sarcoma Ioannis Kournoutas · Brittany L Siontis
    Curr Treat Options Oncol. 2025 Mar 12. doi: 10.1007/s11864-025-01303-x. Online ahead of print.ABSTRACTLiquid biopsies represent a promising and minimally invasive approach to diagnosing and monitoring cancer. In recent years, studies across a multitude of solid organ malignancies have suggested the clinical utility of biomarkers such as circulating tumor DNA (ctDNA). Particular attention has been given to serial assessment of such biomarkers in an effort to detect minimal residual disease (MRD),
     

Minimal Residual Disease in Metastatic Soft Tissue Sarcoma

12 March 2025 at 18:00

Curr Treat Options Oncol. 2025 Mar 12. doi: 10.1007/s11864-025-01303-x. Online ahead of print.

ABSTRACT

Liquid biopsies represent a promising and minimally invasive approach to diagnosing and monitoring cancer. In recent years, studies across a multitude of solid organ malignancies have suggested the clinical utility of biomarkers such as circulating tumor DNA (ctDNA). Particular attention has been given to serial assessment of such biomarkers in an effort to detect minimal residual disease (MRD), in order to predict which patients may be at highest risk of relapse following curative-intent surgical or medical intervention. Such investigations are particularly relevant to sarcomas, which are highly heterogeneous malignancies and commonly develop treatment resistance. While preliminary research described herein is promising, there remain key barriers to widespread adoption of liquid biopsy in sarcoma, including the lack of standardized detection methods, high cost, and the need for large, prospective studies to validate their clinical utility. Given the high level of interest in liquid biopsy in the biomedical community, it is plausible such obstacles may be overcome in the near future. With such advancements, one can anticipate that liquid biopsies may become a key tool in the sarcoma oncologists armamentarium, and offer a path toward improved outcomes for patients with sarcoma.

PMID:40072823 | DOI:10.1007/s11864-025-01303-x

Epigenetic regulatory protein chromobox family regulates multiple signalling pathways and mechanisms in cancer

Signal transduction plays a pivotal role in modulating a myriad of critical processes, including the tumour microenvironment (TME), cell cycle arrest, proliferation and apoptosis of tumour cells, as well as th...
  • ✇TechCrunch
  • Baidu launches two new versions of its AI model Ernie Anthony Ha
    Chinese search engine Baidu has launched two new AI models — Ernie 4.5, the latest version of the company’s foundational model first released two years ago, as well as a new reasoning model, Ernie X1. According to Reuters, Baidu claims that Ernie X1’s performance is “on par with DeepSeek R1 at only half the price,”, […] © 2024 TechCrunch. All rights reserved. For personal use only.
     

Baidu launches two new versions of its AI model Ernie

17 March 2025 at 00:05

Chinese search engine Baidu has launched two new AI models — Ernie 4.5, the latest version of the company’s foundational model first released two years ago, as well as a new reasoning model, Ernie X1. According to Reuters, Baidu claims that Ernie X1’s performance is “on par with DeepSeek R1 at only half the price,”, […]

© 2024 TechCrunch. All rights reserved. For personal use only.

❌