Monocyte derived large extracellular vesicles in polytrauma.

Despite significant progress in the medical field, there is still a pressing need for minimal-invasive tools to assist with decision-making, especially in cases of polytrauma. Our team explored the potential of serum-derived large extracellular vesicles, so called microparticles/microvesicles/ectosomes, to serve as a supportive tool in decision-making in polytrauma situations. We focused on whether monocyte derived large EVs may differentiate between polytrauma patients with internal organ injury (ISS > 15) and those without. Thus, we compared our EV data to soluble biomarkers such as tumour necrosis factor alpha (TNF alpha) and Interleukin-8 (IL-8). From the blood of 25 healthy and 26 patients with polytrauma large EVs were isolated, purified, and characterized. TNF alpha and IL-8 levels were quantified. We found that levels of these monocyte derived large EVs were significantly higher in polytrauma patients with internal organ damage and correlated with the ISS. Interestingly, we also observed a decline in AnnV+CD14+ large EVs during normal recovery after trauma. Thus, inflammatory serological markers as TNF alpha and as IL-8 demonstrated an inability to discriminate between polytrauma patients with or without internal organ damage, such as spleen, kidney, or liver lacerations/ruptures. However, TNF and IL-8 levels were elevated in polytrauma cases overall when contrasted with healthy non-traumatic controls. These findings suggest that delving deeper into the potential of AnnV+ large EVs derived from monocytes could highly beneficial in the managment of polytrauma, potentially surpassing the efficacy of commonly used serum markers.

Liquid Biopsy in Organ Damage: small extracellular vesicle chip-based assessment of polytrauma.

Background: Despite major advances in medicine, blood-borne biomarkers are urgently needed to support decision-making, including polytrauma. Here, we assessed serum-derived extracellular vesicles (EVs) as potential markers of decision-making in polytrauma. Objective: Our Liquid Biopsy in Organ Damage (LiBOD) study aimed to differentiate polytrauma with organ injury from polytrauma without organ injury. We analysed of blood-borne small EVs at the individual level using a combination of immunocapture and high-resolution imaging. Methods: To this end, we isolated, purified, and characterized small EVs according to the latest Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines from human blood collected within 24 h post-trauma and validated our results using a porcine polytrauma model. Results: We found that small EVs derived from monocytes CD14+ and CD14+CD61+ were significantly elevated in polytrauma with organ damage. To be precise, our findings revealed that CD9+CD14+ and CD14+CD61+ small EVs exhibited superior performance compared to CD9+CD61+ small EVs in accurately indicating polytrauma with organ damage, reaching a sensitivity and a specificity of 0.81% and 0.97%, respectively. The results in humans were confirmed in an independent porcine model of polytrauma. Conclusion: These findings suggest that these specific types of small EVs may serve as valuable, non-invasive, and objective biomarkers for assessing and monitoring the severity of polytrauma and associated organ damage.

Extracellular Vesicles and Circulating Tumour Cells - complementary liquid biopsies or standalone concepts?

Liquid biopsies do promise a lot, but are they keeping it? In the past decade, additional novel biomarkers qualified to be called like that, of which, some took necessary hurdles resulting in FDA approval and clinical use. Some others are since a while around, well known and were once regarded to be a game changer in cancer diagnosis or cancer screening. But, during their clinical use limitations were observed from statistical significance and questions raised regarding their robustness, that eventually led to be dropped from associated clinical guidelines for certain applications including cancer diagnosis. The purpose of this review isn't to give a broad overview of all current liquid biopsy as biomarkers, weight them and promise a brighter future in cancer prevention, but rather to take a deeper look on two of those who do qualify to be called liquid biopsies now or then. These two are probably of greatest interest conceptually and methodically, and likely have the highest chances to be in clinical use soon, with a portfolio extension over their original conceptual usage. We aim to dig deeper beyond cancer diagnosis or cancer screening. Actually, we aim to review in depth extracellular vesicles (EVs) and compare with circulating tumour cells (CTCs). The latter methodology is partially FDA approved and in clinical use. We will lay out similarities as taking advantage of surface antigens on EVs and CTCs in case of characterization and quantification. But drawing readers' attention to downstream application based on capture/isolation methodology and simply on their overall nature, here apparently being living material eventually recoverable as CTCs are vs. dead material with transient effects on recipient cell as in case of EVs. All this we try to bring in perspective, compare and conclude towards which future direction we are aiming for, or should aim for. Do we announce a winner between CTCs vs EVs? No, but we provide good reasons to intensify research on them.

Liquid Biopsies in Hepatocellular Carcinoma: Are We Winning?

Hepatocellular carcinoma (HCC) represents the sixth most common cancer worldwide and the third most common cause of cancer-related death. One of the major problems faced by researchers and clinicians in this area is the lack of reliable disease biomarkers, which would allow for an earlier diagnosis, follow-up or prediction of treatment response, among others. In this regard, the "HCC circulome", defined as the pool of circulating molecules in the bloodstream derived from the primary tumor, represents an appealing target, the so called liquid biopsy. Such molecules encompass circulating tumor proteins, circulating tumor cells (CTCs), extracellular vesicles (EVs), tumor-educated platelets (TEPs), and circulating tumor nucleic acids, namely circulating tumor DNA (ctDNA) and circulating tumor RNA (ctRNA). In this article, we summarize recent findings highlighting the promising role of liquid biopsies as novel potential biomarkers in HCC, emphasizing on its clinical performance.

EVs as Potential New Therapeutic Tool/Target in Gastrointestinal Cancer and HCC.

For more than a decade, extracellular vesicles (EVs) have been in focus of science. Once thought to be an efficient way to eliminate undesirable cell content, EVs are now well-accepted as being an important alternative to cytokines and chemokines in cell-to-cell communication route. With their cargos, mainly consisting of functional proteins, lipids and nucleic acids, they can activate signalling cascades and thus change the phenotype of recipient cells at local and systemic levels. Their substantial role as modulators of various physiological and pathological processes is acknowledged. Importantly, more and more evidence arises that EVs play a pivotal role in many stages of carcinogenesis. Via EV-mediated communication, tumour cells can manipulate cells from host immune system or from the tumour microenvironment, and, ultimately, they promote tumour progression and modulate host immunity towards tumour's favour. Additionally, the role of EVs in modulating resistance to pharmacological and radiological therapy of many cancer types has become evident lately. Our understanding of EV biology and their role in cancer promotion and drug resistance has evolved considerably in recent years. In this review, we specifically discuss the current knowledge on the association between EVs and gastrointestinal (GI) and liver cancers, including their potential for diagnosis and treatment.

Evaluation of the shear stability of aerobic granular sludge from a pilot-scale membrane bioreactor: Establishment of a quantitative method.

This work established a quantitative method to access the shear stability of aerobic granular sludge (AGS) and validated its feasibility by using the mature AGS from a pilot-scale (50 tons/day) membrane bioreactor (MBR) for treating real municipal wastewater. The results showed that the changing rate (ΔS) of the peak area (S) of granule size distribution (GSD) exhibited an exponential relationship (R2≥0.76) with the shear time (y=a-b·cx), which was a suitable indicative index to reflect the shear stability of different AGS samples. The limiting granule size (LGS) was defined and proposed to characterize the equilibrium size for AGS after being sheared for a period of time, whose value in terms of Dv50 showed high correlation (R2=0.92) with the parameter a. The free Ca2+ (28.44-34.21 mg/L) in the influent specifically interacted with polysaccharides (PS) in the granule's extracellular polymeric substance (EPS) as a nucleation site, thereby inducing the formation of Ca precipitation to enhance its Young's modulus, while Ca2+ primarily interacted with PS in soluble metabolic product (SMP) during the initial granulation process. Furthermore, the Young's modulus significantly affected the parameter a related to shear stability (R2=0.99). Since the parameter a was more closely related (R2=1.00) to ΔS than that of the parameter b or c, the excellent correlation (R2=0.99) between the parameter a and the wet density further verified the feasibility of this method.