❌

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

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

❌